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w Correlation of accommodation and asthenopia in hyperopic patients
w Biomarkers and surrogate endpoints in glaucoma
w Granuloma macular por tuberculose
w Perda visual irreversível após uso de Paclitaxel
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SOCIEDADE BRASILEIRA DE OFTALMOLOGIA
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Publicação bimestral
Rev Bras Oftalmol, v. 74, n. 4, p. 197-268, Jul./Ago. 2015
Contents - Sumário
Editorial
201
Triamcinolone for diabetic retinopathy
Triancinolona no tratamento da retinopatia diabética
Otacílio de Oliveira Maia Júnior
Originals Articles
203
Prevalence of adenoviral conjunctivitis at the ophthalmologic clinic on municipality of
Viçosa/MG
Prevalência de conjuntivite adenoviral em clínica oftalmológica no município de Viçosa/MG
Euldes Nei Rosado-Filho, Silvia Almeida Cardoso, Lorena Nacif Marçal, Eliziária Cardoso dos Santos, Eduardo
de Almeida Marques da Silva, Sérgio Oliveira de Paula, Leandro Licursi de Oliveira
209
Life quality of low-vision elderly people: before and after hearing and speech intervention
Qualidade de vida de idosos com baixa visão adquirida: pré e pós intervenção fonoaudiológica
Mayla Myrina Bianchim Monteiro , Keila Miriam Monteiro de Carvalho
216
Health and vision related quality of life among patients with choroidal neovascular age
related macular degeneration
Qualidade de vida relacionada com a visão em doentes com degeneração macular
relacionada à idade neovascular
Maria Picoto, José Galveia, Sara Patrício, António Rodrigues, Fernanda Vaz
222
Chalazion and demographic characteristics of patients in a population sample
Calázio e características demográficas dos portadores em uma amostra populacional
Marjorie Fornazier do Nascimento, Ana Claudia Viana Wanzeler, Roberta Lilian Fernandes Sousa, Larissa
Horikawa Satto, Carlos Roberto Padovani, Silvana Artioli Schellini
200
225
Correlation between the use of the accommodation and symptoms of asthenopia in hyperopic patients
Correlação entre o uso da acomodação e sintomas de astenopia em pacientes hipermétropes
Juan Carlos Luna da Costa , Ian Beltrão de Sá Martins, Larissa Tavares Albuquerque Nóbrega, Maria Odília
Navarro Medeiros, Luciana Maria Palitot, Marília Bezerra Cavalcanti Dias, Tarcízio José Dias
231
Eyelid disorders: frequency of occurrence and profile of carriers in a Brazilian population sample
Alterações palpebrais: frequência de ocorrência e perfil dos portadores em amostra
populacional brasileira
Ana Cláudia Viana Wanzeler, Marjorie Fornazier do Nascimento, Roberta Lilian Fernandes Sousa, Carlos
Roberto Padovani, Silvana Artioli Schellini
235
Patient’s perception on glaucoma and different types of treatment (medical versus surgical
treatment)
Percepção dos pacientes portadores de glaucoma sobre sua doença e os diferentes tipos de
tratamento (clínico versus cirúrgico)
Augusto Alves Pinho Vieira, Ricardo Augusto Paletta Guedes, Rita de Cássia Padula Alves Vieira, Vanessa
Maria Paletta Guedes
Case Report
241
X-linked juvenile retinoschisis
Retinosquise juvenil ligada ao X
Cesar Gomes da Silveira, Gabriela Hertz Soares, Jacqueline Provenzano
244
Atypical presentation of Graves’ ophthalmopathy
Apresentação atípica da oftalmopatia de Graves
Flávia Marques Rodrigues, Nilson Lopes da Fonseca Junior, José Ricardo Carvalho Lima Rehder , Celso Lopez
Fernandez, Debora Mayumi Sugano
248
Retro-orbital tumor suggestive of optic nerve sheath meningocele
Tumoração retroorbitária sugestiva de meningocele da bainha do nervo óptico
Michelle Rodrigues Gonçalves Dias Chaves, Isabella Bezerra Wanderley de Queiroga, Mario Augusto Pereira
Dias Chaves, Fernando Melo Gadelha, Debora Apolônio Vieira
251
Macular granuloma due to tuberculosis without pulmonary symptoms
Granuloma macular por tuberculose sem manifestação pulmonar
Albert Costa Rebello, João Helio Leonardo de Sousa, José Gilberto de Sá, Karime Kalif de Sousa Rebello
254
Irreversible visual loss after use of Paclitaxel
Perda visual irreversível após uso de Paclitaxel
Maria Helena Lopes Amigo, Paulo Falabella, Ângela Bettarello, Wagner Ghirelli
Review Article
257
Biomarkers and surrogate endpoints in the glaucomatous optic neuropathy: new
developments and a review
Biomarcadores e desfechos substitutos na neuropatia óptica glaucomatosa: novos
desenvolvimentos e uma revisão
Niro Kasahara
Instruções aos autores
266
Normas para publicação de artigos na RBO
EDITORIAL
201
Triamcinolone for diabetic retinopathy
Triancinolona no tratamento da retinopatia diabética
T
he current therapeutic approach to diabetic retinopathy, based on the high level of scientific evidence, includes
drugs administered via intraocular injection into the vitreous cavity associated or not to laser photocoagulation of
the retina, besides a multidisciplinary approach for systemic metabolic control. The treatment is indicated in the
proliferative form of the disease and/or diabetic macular edema (the main cause of visual loss). The ETDRS - Early Treatment
Diabetic Retinopathy Study – has defined the laser treatment strategies in the diabetic retinopathy according to the classification,
assessing the effects of panphotocoagulation at earlier stages and macular photocoagulation for macular edema1,2.
As for drugs, we have some available for exclusive use in the eye (ranibizumab and aflibercept) and the ones used in
an “off label” way with extensive global experience as for the effectiveness (triamcinolone and bevacizumab). Invariably,
patients are involved in the discussion about the choice of drug, convenience, power, cost and side effects. Among them, an
important factor for access to treatment is the cost, being it the great competitive advantage of the “off label” drugs.
The triamcinolone approach in this editorial is due to our view that it is an excellent treatment choice for selected
patients due to the properties it has regarding the pathophysiology of diabetic retinopathy, in addition to the low cost of
application. It is believed that the mechanism of action of triamcinolone in diabetic retinopathy produces an
antiinflammatory effect not only by reducing cellular mediators of inflammation, but also by stabilizing the blood-retinal
barrier3,4. On the other hand, the diabetic macular edema is thought to be a multifactorial disease with the action of
inflammatory and VEGF (Vascular Endothelial Growth Factor) factors. Studies have shown the superiority of anti-VEGF vs
Laser, and currently there is pharmacological treatment indication of the diabetic macular edema in patients with an
edema involving the center of the macula, defined as the central subfield thickness e” 250 microns and as visual acuity as
Snellen equivalent of 20/32 to 20/3205. However, evidence has shown that interleukin 8 (IL-8) may play an important role
in cases refractory to anti-VEGF, and that triamcinolone could be an option for said cases. The presence of IL-8 supports the
hypothesis that non-responsive patients to anti-VEGF seem to have the preponderance of inflammatory effects in the
genesis of the macular edema. Joen et al. showed low levels of VEGF in the aqueous humor at the moment of injection of
triamcinolone, inferring that only the reduction of VEGF was not enough to cure the macular edema6.
The DRCR net group in a phase 3 study did not observe any difference in the visual acuity between intravitreal
triamcinolone plus laser treatment (n=203) and laser monotherapy (n=186) after one year. However, the subgroup of
pseudophakic eyes treated with triamcinolone and laser showed better results in the visual acuity compared to only laser7.
Another study in this group showed a similar effect of triamcinolone and ranibizumab in pseudophakic patients or with
minimal change of crystalline8. Thus, triamcinolone can be considered the drug of first choice in patients with pseudophakic
diabetic macular edema and who did not present ocular hypertension and/or glaucoma9.
Pioneering studies showed a favorable effect of intravitreal triamcinolone as an adjuvant to the laser treatment in
patients with proliferative diabetic retinopathy and macular edema in relation to those treated only with laser therapy10,11.
This finding was confirmed in a multicenter study of DRCR net, and currently the triamcinolone may be an option in
patients with proliferative diabetic retinopathy and macular edema undergoing laser treatment12.
Recently, it was demonstrated that not only triamcinolone raises the intraocular pressure (IOP). Continuous treatment
with ranibizumab may increase the risk of raising the IOP or the need for an ocular hypotensive13. We must be judicious
regardless of the drug chosen and conduct a closer post operative evaluation. While most of these complications are
transient and/or treatable, the retinologist must consider them when assessing the risks and benefits of the treatment, and it
is important to report to the patients the possibility of adverse effects of these medications.
Therefore, the use of triamcinolone in diabetic retinopathy can be considered in selected patients, and a careful
analysis of cost-effectiveness is imperative for adhesion to the treatment. It gives a more universal access to the drug
benefits in the treatment of this multifactorial disease.
Otacílio de Oliveira Maia Júnior
Assistant at São Rafael Hospital – Monte Tabor Foundation, Salvador – BA.
Rev Bras Oftalmol. 2015; 74 (4): 201-2
202
Maia Júnior OO
REFERENCES
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Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy
Study Report Number Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1987;94(7):761-74.
2.
Techniques for scatter and local photocoagulation treatment of diabetic retinopathy: Early Treatment Diabetic Retinopathy Study
Report no. 3. The EarlyTreatment Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin. 1987;27(4):254-64. 3.Wilson CA,
Berkowitz BA, Sato Y, Ando N, Handa JT, de Juan E Jr. Treatment with intravitreal steroid reduces blood-retinal barrier breakdown due
to retinal photocoagulation. Arch Ophthalmol. 1992;110(8):1155-9.
4.
Funatsu H, Noma H, Mimura T, Eguchi S, Hori S. Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology. 2009;116(1):73-9.
5.
Wells JA, Glassman AR, Ayala AR, et al; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for
diabetic macular edema. N Engl J Med. 2015;372(13):1193-203.
6.
Jeon S, Lee WK. Effect of intravitreal triamcinolone in diabetic macular edema unresponsive to intravitreal bevacizumab. Retina.
2014;34(8):1606-11.
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Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd,
Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or
deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35.
8.
Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, GlassmanAR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt
laser for diabetic macular edema. Ophthalmology. 2011;118(4):609-14.
9.
Dewan V, Lambert D, Edler J, Kymes S, Apte RS. Cost-effectiveness analysis of ranibizumab plus prompt or deferred laser or triamcinolone
plus prompt laser for diabetic macular edema. Ophthalmology. 2012;119(8):1679-84.
10. Bandello F, Polito A, Pognuz DR, Monaco P, Dimastrogiovanni A, Paissios J. Triamcinolone as adjunctive treatment to laser panretinal
photocoagulation for proliferative diabetic retinopathy. Arch Ophthalmol. 2006;124(5):643-50.
11. Maia OO Jr, Takahashi BS, Costa RA, Scott IU, Takahashi WY. Combined laser and intravitreal triamcinolone for proliferative diabetic
retinopathy and macular edema: one-year results of a randomized clinical trial. Am J Ophthalmol. 2009;147(2):291-7 e2.
12. Diabetic Retinopathy Clinical Research Network, Googe J, Brucker AJ, Bressler NM, Qin H, Aiello LP, Antoszyk A, Beck RW, Bressler SB,
Ferris FL 3rd, Glassman AR, Marcus D, Stockdale CR. Randomized trial evaluating short-term effects of intravitreal ranibizumab or
triamcinolone acetonide on macular edema afterfocal/grid laser for diabetic macular edema in eyes also receiving panretina photocoagulation. Retina. 2011 Jun;31(6):1009-27.
13. Bressler SB, Almukhtar T, Bhorade A, Bressler NM, Glassman AR, Huang SS, Jampol LM, Kim JE, Melia M; for the Diabetic Retinopathy
Clinical Research Network Investigators. Repeated intravitreous ranibizumab injections for diabetic macular edema and the risk of
sustained elevation of intraocular pressure or the need for ocular hypotensive treatment. JAMA Ophthalmol. 2015 Feb 26. doi:10.1001/
jamaophthalmol.2015.186. [Epub ahead of print]
Rev Bras Oftalmol. 2015; 74 (4): 201-2
ORIGINAL ARTICLE
203
Prevalence of adenoviral conjunctivitis at the
ophthalmologic clinic on municipality of Viçosa/MG
Prevalência de conjuntivite adenoviral em
clínica oftalmológica no município de Viçosa/MG
Euldes Nei Rosado-Filho1, Silvia Almeida Cardoso2, Lorena Nacif Marçal3, Eliziária Cardoso dos Santos3, Eduardo de
Almeida Marques da Silva4, Sérgio Oliveira de Paula4, Leandro Licursi de Oliveira4,
ABSTRACT
Objective: The aim of this study was to evaluate the prevalence of Adenovirus as a etiologic agent of conjunctivitis on a ophthalmic clinic
in Viçosa, Minas Gerais, Brazil. Methods: Samples of conjunctival secretion from 91 patients clinically diagnosed with conjunctivitis were
subjected to polymerase chain reaction (PCR) using degenerate primers targeted to the gene encoding the structural protein II. Positive
samples were subsequently subjected to sequencing and genotyping. Results: PCR results showed 36.3% prevalence of Adenovirus. No
differences between the sexes and was found to be higher in the age group 26-65 years with 60.60% of the positive cases. Sequencing of
positive cases showed the presence of Adenovirus serotypes 3, 4, 7, 8, and 34 circulating in the region. Conclusion: In Viçosa two in five
cases of conjunctivitis has Adenovirus as etiologic agent.
Keywords: Virology; Adenovirus/epidemiology; Conjunctivitis viral/etiology; Conjunctivitis viral/diagnosis; Polimerase chain reaction
RESUMO
Objetivo: O objetivo deste estudo foi avaliar a prevalência de Adenovirus como agente etiológico da conjuntivite, em clínica médica
oftalmológica especializada, em Viçosa, Minas Gerais, Brasil. Métodos: Amostras da secreção conjuntival de 91 pacientes clinicamente
diagnosticados com conjuntivite foram submetidas à reação em cadeia da polimerase (PCR) utilizando primers degenerados para a
região codificadora do gene da proteína estrutural II. Posteriormente as amostras positivas foram submetidas a sequenciamento e
genotipagem. Resultados: A análise dos resultados de PCR revelou prevalência de 36,3% de Adenovirus. Não havendo distinção
entre os sexos e com maior prevalência na faixa etária de 26 a 65 anos com 60,60% dos casos positivos. O sequenciamento dos casos
positivos por Adenovirus revelaram a presença dos sorotipos 3, 4, 7, 8 e 34 circulante na região. Conclusão: No município de Viçosa,
dois em cada cinco casos de conjuntivite são de etiologia adenoviral.
Descritores: Virologia; Adenovirus/epidemiologia; Conjuntivite viral/etiologia; Conjuntivite viral/diagnóstico; Reção em cadeia
da polimerase
1
2
3
4
Department of General Biology, Federal University of Viçosa – UFV – Viçosa (MG), Brazil. Department of General Biology
Department of General Biology, Federal University of Viçosa – UFV – Viçosa (MG), Brazil.
Department of General Biology, Federal University of Viçosa – UFV – Viçosa (MG), Brazil. Department of General Biology
Associate Professor, Federal University of Viçosa – UFV – Viçosa (MG), Brazil. Department of General Biology
Study conducted at the Federal University of Viçosa – UFV – Viçosa (MG), Brazil.
The authors declare no conflists of interest
Received for publication 29/10/2012 - Accepted for publication 28/01/2013
Rev Bras Oftalmol. 2015; 74 (4): 203-8
204
Rosado-Filho EN, Cardoso SA, Marçal LN, Santos EC, Silva EAM, Paula SO, Oliveira LL
INTRODUCTION
METHODS
onjunctivitis is considered one of the most common
disorders of ophthalmic emergency worldwide (1). It has
viruses and bacteria as its main etiologic agents, is highly
contagious and can occur in outbreaks(2,3). The viral conjunctivitis
has in most cases the adenovirus (AdVs) as the causative agent,
which are viruses with double-stranded DNA, non-enveloped,
lytic and with icosahedral morphology.
There are more than 55 AdVs serotypes already identified.
They are classified into seven distinct groups (AdV A-F), based
on their biological phytochemical, and genetic characteristics(4).
Adenoviral conjunctivitis cases are caused most often by AdV3 (AdV-B), AdV -4 (AdV-E), AdV -8, -19a, -37, -53, and -54
(AdV-D) (4, 5).
Conjunctivitis can also be caused by other viruses such as
Herpes Virus, Coxsackievirus, Rhinovirus, Echovirus, Enterovirus,
Molluscum Contagiosum Virus, among others. The Enterovirus
70 and Coxsackievirus A4 are both related to the hemorrhagic
form of viral conjunctivitis(6).
Most eye disorders secondary to the infection with
Adenovirus are presented in the form of simple follicular
conjunctivitis, faringoconjuntival fever and epidemic
keratoconjunctivitis. Simple follicular conjunctivitis is usually selflimited, transitory and non-associated to systemic dysfunctions(7).
The serotypes 1 to 11 and 19 are the primary cause of nonspecific follicular conjunctivitis(8-10). Faringoconjuntival fever, most
commonly caused by serotypes 3, 4, 5 and 7 of the Adenovirus, is
characterized by fever, headache, pharyngitis, follicular
conjunctivitis, and preauricular adenopathy. In some isolated
cases, the systemic signs can mimic an infection caused by the
influenza virus(11,12). The epidemic keratoconjunctivitis is often
caused by serotypes 8, 19 and 37 of group AdV-D, with significant
involvement of the cornea. In most patients it is presented in the
bilateral form, preceded by upper respiratory tract infection(13).
The assessment of systemic signs associated with precise
molecular biology techniques is key for the clinical diagnosis
and prevention of epidemics during the acute phase of
adenoviral conjunctivitis (3) . Some of the most important
conventional techniques for the clinical diagnosis of viral
conjunctivitis include, among others, cytological investigation
of the conjunctiva, assessment of the cytopathic effect in
susceptible cell lines, detection of antigens in the cells of
conjunctiva by direct fluorescence or detection of antibodies.
Despite the sensitivity of detection of the same, these
techniques are time consuming and costly from an economic
point of view, what becomes a challenge for detection and a
rapid diagnosis of AdV as caused by conjunctivitis. Other
important, relatively simple, fast, highly sensitive and low cost
diagnostic method which has been used a lot in the last decade
is the polymerase chain reaction (PCR)(13-16).
Considering the importance of accuracy of early diagnosis
and specific treatment of adenoviral conjunctivitis, the objective
of the present study is to evaluate the frequency of Adenovirus
in the conjunctival secretion of the patients assisted in eye clinic
located in the municipality of Viçosa, Minas Gerais, Brazil, in
the period from May 2009 to January 2011, using PCR as the
technique.
This is a cross-sectional study on patients assisted in a
specialized eye clinic located in the municipality of Viçosa-MG, in
the period from May 2009 to January 2011. A total of 91 patients
of both genders aged between 1 and 74 years with symptoms
indicative of viral conjunctivitis (hyperemic eyes, watery discharge
and discomfort) underwent ocular inspection followed by
thorough ophthalmologic assessment. After assessment, patients
with diffuse conjunctival hyperemia presenting ocular discomfort,
palpebral edema and tearing with watery secretion, follicular
reaction in the tarsal conjunctiva, satellite lymphadenopathy and
keratitis with multiple sub-epithelial infiltrates were considered
as possible cases of conjunctivitis of adenoviral etiology.
After the diagnosis confirmation, the patients were
informed about the possibility of Adenovirus prevalence as the
causative agent of the disease, and were invited to participate in
a clinical research for the detection of the same. The 91 patients
who volunteered signed a written consent to participate in the
study after being aware of the clinical implications of the same.
The principles of Bioethics were guaranteed to all participants,
according to regulation 196/96 of the National Health Council
determining the ethical aspects necessary for conducting research
in humans (CEPH-167741).
Subsequently, a conjunctival secretion was collected from
the anterior eyeball of each patient with aid of a sterile rayon
swab soaked in solution of 0.9% sodium chloride, using slit lamp
(Topcon 3E). The material obtained was placed in sterile 1.5 ml
polypropylene tubes previously identified and containing
phosphate buffered saline solution (PBS), and freezed for
subsequent viral DNA extraction, PCR and gene sequence
analysis for the identification of the serotype responsible for the
infection.
The viral DNA of all samples of conjunctival secretion
supposedly infected by Adenovirus have been extracted using a
specific kit for viral RNA and DNA extraction (QIAamp
UltraSens Virus-Quiagen). The extraction was carried out
according to the manufacturer’s instructions. Then, 500mL of
sample were treated with 500mL of buffer AR and 20mL of
proteinase K, and incubated at 40°C for 10 min. Later 300mL of
buffer AB were added and the material was applied to a QIAamp
affinity column, washed and eluted with 30mL of buffer AVE.
The eluted material was used for the PCR reactions; samples of
patients with a healthy conjunctiva and with no sign of infection
were used as negative control.
The total DNA extracted was then subjected to PCR using
degenerate primers hex1deg (5’-GCC (C,G)CA (AG)TG
G(G,T)C (A,T)TA CAT GCA CAT C-3’) with 25 nucleotides
and hex2deg (5’-CAG CAC (C,G)CC (A,T,C,G)GG (A,G)AT
GTC AAA-3’) with 21 nucleotides(17). The primers generate an
amplicon between position 21 and 322 of the coding region of
the structural gene II protein, which is sensitive to multiple
serotypes of Adenovirus to amplify a fragment of approximately
301 bp of DNA. The PCR reaction was processed in a
thermocycler (Mastercycler, Eppendorf) using the following
parameters: 1 cycle at 94°C for 2 min. (denaturing) followed by
30 cycles of 94°C for 30 seconds (denaturing), 55°C for 30 seconds
(annealing) and 72°C for 30 seconds (synthesis) and 1 cycle of
72°C for 10 minutes (extension). The PCR reaction product was
subjected to electrophoresis on 1.5% agarose gel containing 1.0
µg/mL of red gel (Uniscience) using Read-load 100pb DNA
C
Rev Bras Oftalmol. 2015; 74 (4): 203-8
Prevalence of adenoviral conjunctivitis at the ophthalmologic clinic on municipality of Viçosa/MG
Ladder as a standard molecular marker (Invitrogen, LT) with 60
mV for approximately 1.5 hours as sieving parameters. After the
electrophoresis sieving the gel was visualized under a UV
irradiation chamber and with digital photo documentation.
The bands of the positive samples confirmed by
electrophoresis were cut out of the gels and subjected to
sequencing for confirmation of identity of the viral isolate.
Sequencing was performed on ABI Prism 377 DNA Sequencer
device according to the Protocol described in the kits used
(Templiphi DNA amplification, Amersham Biosciences; Big
DyeTM Terminator Cycle Sequencing Ready Reaction, PE Applied
Biosystems).
The nucleotide sequences obtained were aligned with the
aid of the program CAP 3 to obtain the final consensus sequence
of viral DNA. The identity was analyzed using the Blast program
of the ‘National Center for Biotechnology Information’ (NCBI)
(http://www.ncbi.nlm.nih.gov). The alignment of the consensus
sequences was performed by the program Multalin (INRA)
(http://prodes.toulouse.inra.fr/multalin/multalin.html).
205
60.60% of cases confirmed (Figure 2B). There was a high incidence
of confirmed cases by Adenovirus in children under two years
of age (75%).
RESULTS
Of the 91 patients clinically diagnosed with conjunctivitis
and who had the conjunctival secretion collected for analysis,
36.3% (33) of the cases were confirmed as having conjunctivitis
from adenoviral source. The distribution of positive cases in the
PCR analysis during the study was more prevalent between May
and June 2009, a period in which there was an outbreak of the
disease in the city. The presence of Adenovirus in the secretions
collected from patients was also found considerable in the
months of February, November, December 2010, and in a lesser
proportion in January 2011 (Figure 1).
Figure 2: Prevalence of conjunctivitis cases according to sex (A)
and age (B).
Figure 1: Distribution of conjunctivitis cases from May 2009 to
January 2011. The samples were tested by PCR for positive or
negative reaction to the detection of Adenovirus in conjunctival
swabs.
The prevalence of adenoviral conjunctivitis, when compared
between genders in the period of the study, was a little different,
and the percentage of women and men with the disease
confirmed represented 55.17% and 45.83% respectively (Figure
2A). Regarding the distribution of conjunctivitis cases by age
group, a higher prevalence among individuals in the economically
active age group (26 to 65 years) was observed, accounting for
Regaring the different serotypes of Adenovirus as causative
of conjunctivitis in the municipality, serotypes 3, 4, 7, 8 and 34 were
identified in the samples from confirmed cases (Figure 3A). Of
these, serotype 8 proved to be more prevalent with approximately
33.33% of the cases evaluated, followed by serotype 4 with 25%,
serotype 7 presented 17% and serotypes 3 and 34 presented less
than 10% of cases. Other unidentified serotypes in the sequencing
(8.33%) were also detected in the period of the study (Figure
3A). Regarding the group of Adenovirus as causative of
conjunctivitis, groups B and D presented 33.33% of cases each,
followed by group E with 25% of cases; groups A, C and F were
not found in the present study, and 8.33% of non-identified
Adenovirus were group NI (Figure 3B).
The signs and symptoms presented by patients during
the detailed ophthalmic assessment before the collection and
analysis of conjunctival secretion were used to supplement the
laboratory detection diagnosis of Adenovirus in the secretions
analyzed (table 1). All patients assessed (91 cases) had ocular
hyperemia and tearing, common signs of conjunctivitis. When
the signs and symptoms strongly related to adenoviral
conjunctivitis were analysed, it was found that patients with
satellite lymphadenopathy 66.67% (22 cases), conjunctival
chemosis 81.82% (27 cases) and nummular keratitis 75.76%
(25 cases) were more expressive in the cases confirmed of
adenoviral conjunctivitis.
Rev Bras Oftalmol. 2015; 74 (4): 203-8
206
Rosado-Filho EN, Cardoso SA, Marçal LN, Santos EC, Silva EAM, Paula SO, Oliveira LL
Figure 3: Identification of the etiological agent causative of adenoviral conjunctivitis. Serotypes identified by sequencing (A). Prevalence of
conjunctivitis causative groups (B).
Table 1
Evaluation of frequency of conjunctivitis symptoms
Non-adenoviral conjunctivitis
Signs and symptoms
Ocular hyperemia
Tearing
Serous secretion
Purulent secretion
Satellite lymphadenopathy
Conjunctival chemosis
Conjunctival membrane
Subconjunctival haemorrhage
Discomfort
Moderate pain
Severe pain
Corneal wound
Nummular keratitis
Fever
General malaise
Nº cases
(n=58)
%
Nº cases
(n=33)
58
58
51
3
12
21
3
3
35
18
0
1
7
7
22
100.00
100.00
87.93
5.17
20.69
36.21
5.17
5.17
60.34
31.03
0.00
1.72
12.07
12.07
37.93
33
33
32
1
22
27
7
7
15
11
7
4
25
6
16
DISCUSSION
It is established in the scientific literature that Adenovirus
is responsible for epidemic outbreaks of conjunctivitis worldwide,
affecting all age groups in varied chronology and in different
orders of gravity (18-20). The early diagnosis and efficacy in
controlling the infection is a key process to minimize the incidence
of the disease(17,20).
One of the methods considered as gold standard to detect
Adenovirus is the qPCR and the real-time PCR due to the fast
analysis, high sensitivity and precision on molecular identification
of the different serotypes involved in ocular disease (20-22).
According to Allard et al. degenerate primers for the coding
region of the structural protein gene II of Adenovirus has been
shown to be effective in highlighting different serotypes of AdVs
in epidemiological studies(17). Considering these findings, the PCR
reaction using these primers was the method used to analyze the
frequency and detect different serotypes causative of adenoviral
Rev Bras Oftalmol. 2015; 74 (4): 203-8
Adenoviral conjunctivitis
%
‘100.00
100.00
96.97
3.03
66.67
81.82
21.21
21.21
45.45
33.33
21.21
12.12
75.76
18.18
48.48
conjunctivitis in the municipality of Viçosa/MG in the period
from May 2009 to January 2011 without the need of culture of
viral isolation.
The prevalence of positive samples analyzed for adenoviral
conjunctivitis was 36.3% in the present study. Previous studies
have demonstrated prevalence ranging from 15%(23), 70%(24),
and 82%(20). Different environmental factors may be related to
these discrepancies.
Scientific literature has reported differences in the
seasonality for the emergence of Adenovirus as a causative agent
of conjunctivitis worldwide. According to Matsui et al. in a study
conducted in Japan, Adenovirus keeps a low frequency
throughout the year; however an outbreak was reported in
September(20). Another study by Maranhão et al. in Brazil which
was related to the seasonal distribution of eye infections by AdV
in the years from 2004 to 2007 showed the occurence of only one
outbreak in April 2004, with no constancy over the years of
study(3). The present study presented the differences in relation
Prevalence of adenoviral conjunctivitis at the ophthalmologic clinic on municipality of Viçosa/MG
to this seasonal distribution, and AdV was more frequent in the
months of May and June, a period of disease outbreak in the city.
A possible explanation for said differences may be related to
weather conditions, because a higher prevalence of cases has
occurred in early winter.
Allard et al. analyzed secretion samples from 40 patients
with clinical symptoms of conjunctivitis caused by AdV
considering the age of the patients, and they found a very
heterogeneous distribution, with a frequency ranging from 9
months to 74 years of age(17). This finding is in agreement with
our approach, despite the higher frequency of cases in this study
has occurred in the age group between 26 and 65 years.
In order to determine the serotypes present in the samples
confirmed of adenoviral conjunctivitis, the PCR products were
characterized by sequencing(17). There was a predominance of
serotype 8 (33.33%), followed by 4 (25%) associated to keratitis,
as well as in the study of Jin et al. in Hanoi, Vietnam(25). The
presence of serotype 7 (17%) brought particular concern, since
this serotype has been associated to more severe cases of
infection by Adenovirus, such as pneumonia and myocarditis,
with a possible adverse development to respiratory and
cardiovascular failure(5).
The main clinical symptoms presented by the patients
with conjunctivitis were ocular hyperemia, serous secretion
and tearing. Patients with adenoviral conjunctivitis showed a
greater frequency of satellite lymphadenopathy, conjunctival
chemosis and nummular keratitis. Keratitis usually appear on
the 5th day after the onset of conjunctivitis, followed by the
rise of corneal nummular opacity on day 7, as it is reported by
various authors (26,27).
4.
5.
6.
7.
8.
9.
10.
11.
12.
CONCLUSION
13.
The present study revealed that in Viçosa two out of five
cases of conjunctivitis are of adenoviral etiology. Considering
the possibility of adenoviral conjunctivitis outbreaks throughout
the year, and the different serotypes that can lead to eye disease,
the study highlights the importance of conducting rapid
diagnostic tests such as PCR for the recognition of the serotype
and specific treatment as a potential measure to reduce the virus
and consequently the potential for transmission.
14.
ACKNOWLEDGEMENTS
The funding agencies: the State of Minas Gerais Research
Support Foundation (FAPEMIG) and the National Council of
Scientific and Technological Development (CNPq).
15.
16.
17.
18.
19.
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Corresponding author
Leandro Licursi de Oliveira
Av. PH Rolfs, s/n Campus Universitário
ZIP Code: 36570-000-Viçosa (MG), Brazil.
E-mail: [email protected]
ORIGINAL ARTICLE
209
Life quality of low-vision elderly people:
before and after hearing and speech intervention
Qualidade de vida de idosos com baixa visão adquirida:
pré e pós intervenção fonoaudiológica
Mayla Myrina Bianchim Monteiro1 , Keila Miriam Monteiro de Carvalho
2
ABSTRACT
Aim: To evaluate life quality of elderly people with acquired low vision before and after hearing and speech intervention. Methods: This
was a descriptive cross-sectional study. The study was made with 52 elderly people with acquired low vision. Two questionnaires that
measures life quality were used in this study. The first was ‘Low Quality of Life Vision (LVQOL)’ and the second the ‘National Eye
Institute Visual Function Questionnaire (NEIVFQ-25)’. The study included people with more than 60 years with acquired low vision and
who accepted to participate signing the consent form. The hearing and speech therapy were made into three months, one meeting a week.
The questionnaires were applied in the first and last day of the intervention. Results: The age ranged between 60 and 91 years. The macular
disorder (38%), such as age-related macular degeneration, macular hole and high myopia were the main causes of visual loss. Although
the tests show superior performance after the intervention, there was no statistically significant difference. On the question about
difficulties seeing in general, 17 participants answered that they had much more difficulty before the intervention and only 5 participants
have reported having much difficulty after the intervention. Conclusion: The intervention trended to positive results, and after the
meetings, participants showed improvements in aspects of the two questionnaires used in the study, decreasing the degree of difficulty in
performing activities.
Keywords: Quality of life; Low vision; Elderly; Questionnaire; Rehabilitation
RESUMO
Objetivo: Avaliar a qualidade de vida de idosos com baixa visão adquirida antes e depois de intervenção fonoaudiológica. Métodos:
Foi realizado um estudo descritivo e transversal. A população do estudo foi constituída por 52 idosos com baixa visão adquirida. Dois
questionários que mensuram qualidade de vida foram aplicados neste estudo. O primeiro foi “Low Quality of Life Vision” (LVQOL)
e o segundo the “National Eye Institute Visual Function Questionnaire” (NEIVFQ-25). Foram incluídos na pesquisa sujeitos com mais
de 60 anos, portadores de baixa visão adquirida e que assinaram o Termo de Consentimento Livre e Esclarecido. A intervenção
fonoaudiológica tinha duração de três encontros, um por mês. Os questionários foram aplicados no primeiro e no ultimo dia da
Intervenção. Resultados: A idade variou entre 60 e 91 anos. A alteração macular (38%), como degeneração macular relacionada à
idade, buraco macular e alta miopia foram as principais causas da perda visual. Apesar dos testes mostrarem um desempenho
superior após a intervenção, não houve diferença estatisticamente significativa. Na questão sobre dificuldades de ver em geral, 17
sujeitos responderam que tinham muita dificuldade antes da intervenção, e após a intervenção somente 5 sujeitos relataram ter
muita dificuldade. Conclusão: A intervenção tendenciou à resultados positivos, e após os três encontros, os idosos apresentaram
melhoras em aspectos avaliados nos dois questionários usados no estudo, diminuindo o grau de dificuldade na realização de
atividades.
Descritores: Qualidade de vida; Baixa visão; Idoso; Questionário; Reabilitação
1
2
Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.
Departament of Oftalmology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.
Study carried out at Subnormal Vison Ambulatory, Departament of Oftalmology, Hospital de Clinicas, Universidade Estadual de Campinas
Campinas, SP, Brasil.
The authors declare no conflicts of interest
Received for publication 19/03/2013 - Aceito para publicação em 08/01/2014
Rev Bras Oftalmol. 2015; 74 (4): 209-15
210
Monteiro MMB , Carvalho KMM
INTRODUCTION
I
n the last decade, life quality related to health has become an
important issue and also the need of researches regarding
this issue.
Investigations of the conditions that allow life quality in
old age and also the variations that the best age provides is
getting great scientific and social importance and attention.
Attempting to answer the apparent contradiction that exists
between old age and wellbeing, or even the association between
old age and diseases, researches may contribute towards
understanding the aging process and the limits and attainability
of human development. In addition to this, such investigations
will give the possibility of creating alternatives for interventions
aimed at promoting wellbeing at the best age(1).
According to the World Health Organization (WHO) (2),
health is a state of complete physical, mental and social wellbeing
and not merely the absence of disease. The term “quality of
life” (QOL) is the subjective perception of wellbeing and
wholeness. It is a broad concept affected in a complex way by a
person’s physical health, psychological state, level of
independence, social relationships, and his or her relationship
to the salient features of his or her environment(3).
There is a need on measure the results of low-vision
rehabilitation to be able to discuss the case of low-vision
assessment within manage care plans, to improve services
offered, and to secure and enhance funding for low-vision
services(4,5).
Several questionnaires were developed to measure the
life quality of people with visual impairments(6). There are
non disease-specific vision-related QOL instruments that
include: the National Eye Institute Visual Function
Questionnaires (NEIVFQ and NEIVFQ25) and the Low Vision
Quality of Life (LVQOL) described by Wolffsohn and
Cochrane(7).
Most of the instruments contain measures that capture a
combination of visual symptoms, visual physical function,
performance and participation of the low vision elderly in daily
activities. In vision rehabilitation, an instrument to specifically
address restriction of participation (handicap) is necessary to
add to measures of impairment such as visual acuity and
subjective or objective measures of activity limitation (8).
Patient-reported outcomes (PROs) are the measurement
of patients’ perception of the impact of a disease and its
treatment(s), which are typically reported by questionnaire.
PROs are increasingly being accepted as the primary endpoints
of clinical trials in health research. Therefore, it is critical that
data collected by PROs are accurate and reliable, which is only
possible when patients are able to understand the questions
asked and select response categories that represent their status.
Poorly understood questions, or underutilized rating scale
categories can seriously impair the accuracy and reliability of
PRO measurements(9,10).
The role of speech therapy in the rehabilitation of visually
impaired elderly aims to maintain communication, both oral
and written, in full use. Some studies related that there is a
decrease of written communication between the effects of visual impairment.
The aim of this study was to evaluate life quality of lowvision elderly before and after Hearing and Speech
Intervention.
Rev Bras Oftalmol. 2015; 74 (4): 209-15
METHODS
The research was conducted through longitudinal study.
The study was approved by the Committee of Ethics in Research
of the Faculty of Medical Sciences, State University of Campinas
under the protocol number 1041/2010.
The study was made with 52 elderly participants. The
inclusion criteria were: participants over 60 years, according to
the World Health Organization - WHO; acquired low vision (visual acuity equal or less than 6/18 (0.3), according to WHO);
attended at Outpatient Low Vision/HC/UNICAMP (VSN-HCUNICAMP); with no other associated disabilities and/or mental
illness; subjects who participated in three meetings called Hearing
and Speech´ Intervention consecutively; participants who
answered both questionnaires before and after Hearing and
Speech´ Intervention; Inclusion voluntary, by signing Consent
Form for the period from February 2011 to June 2012 (16 months).
Two questionnaires that deal with quality of life were
chosen for use in this study.
The first questionnaires was the ‘Low Quality of Life Vision’
(LVQOL) which contains 25 questions specifically for low vision,
and evaluated sub-items for each point analyzed, for instance,
the basic aspects, mobility, adaptation, reading and working. In
this study, it was used a Portuguese version, which is a result of
the thesis entitled “Low Vision Elderly: Causes, Functional Status,
Perceptions of Constraints and Visual Rehabilitation Unit at
University Hospital” by Prof. Dr. Keila M. M. de Carvalho (11),
obtained in 2007. The questionnaire consists of 23 questions.
Some items from life quality questionnaire addressed to
the topic of low vision, LVQOL, Low Vision Quality of Life as
described by Wolffsohn and Cochrane(7), translated and
subjected to changes given the local reality, were used to prepare this instrument.
The second questionnaire, the VFQ-25 is a version that
reliable and valid 25-item National Eye Institute. The National
Eye Institute (NEI) sponsored the development of the VFQ-25
in order to create a survey that would measure the dimensions
of self-reported health of vision that are most important for
people who have chronic eye diseases. Based on this goal, the
study measures the influence of visual disability and visual
symptoms on generic health domains such as welfare and social
and emotional functioning, as well as oriented tasks related to
the daily visual operation (12).
Simon et al investigated its reliability and validity in a group
of Brazilian patients with different eye conditions in Minas Gerais. The version used in the 2008 study, was also used in this
research (13).
When one participant arrived at the Outpatient Low Vision/
HC/UNICAMP (VSN-HC-UNICAMP), he/she was invited to
participate on the study. Once agreed, two questionnaires were
applied and the three meetings were scheduled. At the end of
the third meeting, both questionnaires were reapplied for
comparison of responses.
The questionnaires were applied by the researcher. The
reading of the questionnaire was made reliably for both
questionnaires.
Intervention Speech was accomplished through three
meetings, monthly. The meetings were conducted in groups,
lasting 50 minutes.
- 1st meeting: The theme was activities of daily living.
Perform activities of daily living with facilitators. In this meeting,
Life quality of low-vision elderly people: before and after hearing and speech intervention
the researcher stressed the need of the use of communication in
routine tasks like grocery shopping, taking a bus, leave a note or
ask someone for some information on the street. All these
activities require the use of communication, both oral and written;
- 2nd meeting: The theme was the optical and non-optical
aids. If the participant had the need of prescription use, frequency
of use and improved vision. The optical aids had been previously
prescribed by the ophthalmologist for the subjects during the
consultation at the outpatient Low Vision. However, to date the
intervention, some subjects had still not managed to get the aid,
or saw no need to use it. Optical aids are generally used in closely
activities, especially for reading. Thus at this meeting, was
necessary the use of an optical aid to perform readings.
- 3rd meeting: The theme of the meeting was reading and
writing. The use, frequency, difficulty, use of optical and non optical
aids to carry out the activities, the importance of continuing these
activities. This meeting covered an important area of the Hearing
and Speech Pathology. Reading and writing not only refers to writing
code or decipher them, we must interpret and use them socially.
During the meetings, the researcher offered new options
for participants conduct their daily activities, as well answered
questions regarding optical and non-optical aids and reading
and writing. Patients were encouraged to discuss on the issues
and also share their own experiences.
Life quality was measured after the intervention to verify
if it had an impact on the visual function and life quality by
comparing the results obtained by the two quizzes. VEM-test
was performed for question 7 and 18 and descriptive analyses
was used for other data for questionnaire 1 (LVQOL).
211
For questionnaire 2 (VFQ-25) the average SCORE for
each sub domain was calculated and the t-test was performed to
observe if the treatment lead to an improvement of visual function
and the communication. The difference between the measures
before versus after the treatment were compared and values
with interval equal to or greater than zero, were considered a
confidence level of 95%. The choice of t-test was due to paired
terms. The same test was applied to the check difference between
the VEM before versus the intervention.
RESULTS
Seventy-one subjects were selected to participate on the
study, but only fifty-two subjects participated in all phases. The
participants’ age was from 60 to 91 years. Most participants were
retired, and among them, 70% were retired due to visual problems.
The educational level of the participants is low: 81% have primary
education.
The results involving issues of Q1 - LVQOL are presented
below.
The q7 sought to examine the degree of difficulty in
performing some activities. Table 1 (q7) presents the comparison
for conducting such activities before and after the intervention.
The statistical test showed no significant improvement after
the intervention, however, by observing the table above it is
possible to infer that the VEM value to each question is a little
different, there was a tendency to improvement. Despite the
statistics have shown that there was no significant difference
before and after the intervention, it was possible to observe an
Table 1
Comparison of pre and post intervention speech: degree of difficulty performing activities of daily living (Questionnaire 1)
Before Intervention
Difficulty in
some activities
NONE
(1)
After Intervention
A LOT
(4)
MEDIA
FEW
(2)
VEM A LOT
(PRE)
(4)
1. To see generally?
17
26
9
0
3.2
5
2. To use vision for
22
22
8
0
3.3
23
16
14
0
3.2
MEDIA
FEW
(2)
NONE
(1)
VEM
(POST)
31
10
3
2.8
9
30
7
3
2.9
12
28
6
3
3.0
long time?
3. To use the night vision
at home?
4. To see with glare?
17
25
10
0
3.1
16
23
7
3
3.1
5. To see street signs?
24
18
10
0
3.3
15
26
5
3
3.1
6. To watch TV?
18
23
11
0
3.1
8
31
7
3
2.9
7. Seeing objects that move? 20
23
9
0
3.2
23
18
5
3
3.2
22
11
0
3.3
24
17
5
3
3.3
25
18
9
0
3.3
26
16
4
3
3.3
24
18
10
0
3.3
23
19
4
3
3.3
26
17
9
0
3.3
25
17
4
3
3.3
8. To calculate the distance
between you and an object? 29
9. To see steps or holes in
the sidewalk ?
10. To walk on the
neighborhood ?
11. To cross the street with
traffic?
Rev Bras Oftalmol. 2015; 74 (4): 209-15
212
Monteiro MMB , Carvalho KMM
improvement in the items 1-5 that the VEM decreased after
speech therapy and in items 7-11, the results of VEM remained
the same, showing no improvement or worsening after the
intervention. In the question about difficulty seen in general
(item 1), 17 subjects reported that they had much more difficulty
before the intervention, whereas after the intervention only 5
subjects still reported such problem.
The q8 questions are about use and types of optical aids
used, before and after Intervention. For better visualization, the
responses to q8 are divided into two tables presented below:
table 2 and table 3. Note that not all participants in the study to
make use of optical aids both pre and post intervention.
Table 3
Comparison of before and after intervention speech:
types of optical aids used (Questionnaire 1)
Table 2
Yes
No
Total
Before
Intervention
37
15
52
Before
Intervention
Glasses
Magnifying glasses
Others
Do not use
Total
27
10
4
15
52
After
Intervention
52%
19%
8%
39%
100%
31
18
5
7
52
60%
35%
10%
14%
100%
*Multiple Answers
Comparison of before and after intervention speech:
using optical aids (Questionnaire 1)
Use of optical aids
(N=52)
Types of optical aids
(N=52)
61%
39%
100%
Q12 is questioned on the purpose of using the optical
feature. The answers are manifold, because the subjects were
free to choose more than one answer. On this issue there was
also an increase of the activities for which the subjects are using
their optical devices (Table 4).
For Q18 and Q19 also statistical test was used VEM. The
two questions sought to know the great difficulty performing
certain activities using optical aids (Table 5).
After
Intervention
45
7
52
86%
14%
100%
Table 4
Comparison of before and after intervention speech: intended use of the optical feature (Questionnaire 1)
Intended use of the optical feature
Before Intervention (N=37)
To read close, yes or no?
To read
To watch tv, yes or no?
To write, yes or no?
To do manual work, yes or no?
To walk on the street, yes or no?
After Intervention (N=45)
YES
NO
YES
NO
YES
NO
YES
NO
27
14
15
20
19
15
10
23
31
17
18
22
73%
38%
33%
54%
51%
41%
27%
62%
67%
46%
49%
59%
36
12
15
34
30
18
9
33
31
11
15
27
80%
27%
33%
76%
67%
40%
20%
73%
67%
24%
33%
60%
Table 5
Comparison of before and after intervention speech: difficulty with activities performed with optical aids (Questionnaire 1)
Before Intervention
Using optical aids, the degree
of difficulty you have to (n=52)
To read large letters in newspaper?
To read text of journal or book?
To read labels for medicines?
To read letters?
To thread the needle?
To cut with scissors?
To write?
To read what you write?
To do housework?
A LOT MEDIA FEW
8
11
12
12
16
16
11
11
11
13
15
15
14
10
10
10
11
11
NONE VEM(PRE) A LOT MEDIA FEW NONE VEM (PRE)
12
8
7
8
8
8
11
12
8
For Q2 - VFQ-25 was also performed a comparison before
and after the intervention. For a confidence level of 95% using
the t test concluded that there is no difference in the results of
the responses given by patients after treatment (p-value> 0.05).
Rev Bras Oftalmol. 2015; 74 (4): 209-15
After Intervention
4
3
3
3
3
3
5
3
7
2.68
2.92
2.97
2.95
3.05
3.05
2.73
2.81
2.70
4
7
25
23
26
26
13
11
6
26
26
10
12
8
8
20
22
23
11
8
7
7
8
7
9
9
11
4
4
3
3
3
3
3
3
3
2.67
2.80
3.27
3.22
3.27
3.30
2.96
2.91
2.71
But there was a tendency to improvement, post intervention,
the sub domain related to: vision (q20), psychological aspects
(q3, q21, q22, q25), difficulties everyday (q17, q18), dependence
(q20, q23, q24), peripheral vision (q10) (Table 6).
Life quality of low-vision elderly people: before and after hearing and speech intervention
213
Table 6
Comparison of pre and post intervention speech: medium SCORE for sub domain of questionnaire 2
Sub domains VFQ (N=52)
Before intervention
(average)
After intervention
(average)
46
61
61
46
42
39
53
56
54
0
50
44
46
58
62
48
43
42
50
48
50
0
52
42
Geral health
Vision
Ocular pain
Closer activities
Far activities
Social aspects
Psychological aspects
Daily life activities
Dependency
Ability to drive motor
Color vision
Peripheral vision
The statistical analysis of the overall VFQ-25 in this study
is not presented statistical variation between subdomains. Five
subdomains showed statistical improvement after the
intervention, and five did not. Two subdomains showed no
differences before and after the intervention.
DISCUSSION
The purpose of this study was to know if there was an
improvement on life quality of those people who attended the
research, after hearing and speech intervention. The impact of
the eyesight loss has adverse individual and collective
consequences, giving rise to psychological, social and economic
problems, because implies loss of self-esteem, status in
occupational restrictions and consequent income decrease
(14,15).
Low-vision rehabilitation maximizes a person’s residual
vision, with the use of visual aids and adaptive skills, improving
their ability to perform specific tasks that were previously
considered difficult (16).
Macular disease (38%) such as age-related macular
degeneration, macular hole and high myopia syndrome, were
the related causes regarding visual loss. Similar data were found
in others studies about low vision in the elderly (17).
Visual rehabilitation aims to enhance an individual’s
functional ability and independence, as well as maximize their
use of any residual vision. Approximately 90% of visually impaired
patients have sufficient residual vision to allow them to benefit
from low-vision rehabilitation. At the present, there is no
literature available to demonstrate which strategies are the most
effective for low-vision rehabilitation. Part of the difficulty in
collecting such information lies in the numerous forms of lowvision rehabilitation strategies available. Low-vision
rehabilitation is becoming increasingly important in the wider
community, once visual impairment affects approximately 314
million people worldwide. The number is about to rise with
increased life expectancy and, therefore, more age-related visual
problems are appearing. (18,19).
Recognizing that the Hearing and Speech therapist is a
professional who works in the habilitation and rehabilitation of
Difference pre x post
0
-3
1
2
1
3
-3
-7
-5
0
2
-2
Itens num
1
1
2
3
3
2
4
2
3
2
1
1
Questions
1
2
4,19
5,6,7
8,9,14
11,13
3,21,22,25
17,18
20,23,24
15,16
12
10
communication between people, their participation in this process
for people with low vision is extremely important, considering
that subjects with visual impairment need to use different means
from those used for effective communication, thus enabling the
continuity of social relationships, so important to life quality (20).
The difficulties presented by the elderly involves both
activities near and far, showed that the visual impairment brought
involvement in various activities of the daily life. This whole impact
of impairment in vision entails a greater reliance of the elderly.
Such dependence is closely linked to poorer mental health in the
elderly with low vision or blind, as well as the loss of social life,
relationships with friends and family. The visual impairment
influences not only the near vision and also as far peripheral
vision, leading the elderly has greater insecurity to get around or
run errands. All these findings demonstrate the great impact
that the visual impairment brings to life of the elderly, as well as
its consequences interact, causing a vicious cycle (21).
The number of participants using optical aids increased after
the intervention. As this was one of the topics discussed during
the intervention, it was expected that this number actually increased
and that more seniors begin to make use of the aids (17, 20).
During the appointment the help was rewritten, perhaps
because the participants had no questions about the help that
only arise with their use. It is important that local professionals
and the elderly people are able to train using their aids, since this
helps in better quantitative and qualitative vision. Without doing
the training, it is possible that the elderly gives up from using the
aids and then becomes unused.
Moreover, during the intervention was enhanced the
explanation about the use of optical aids. The researcher
demonstrated how to use each aid, and stressed that training is
necessary to use them correctly. Activities with reading and
writing were conducted with the participants to show its
effectiveness in carrying out this activity.
Question 12 asks the surveyed to consider in which
activities the optical aids are used, and also a comparison of the
use of optical aids before and after the intervention. For closer
reading activities, write and walk down the street, the use of
aids was increased after the intervention. As for the reading
activities of posters, watching television and crafts, the use of
optical aids has decreased.
Rev Bras Oftalmol. 2015; 74 (4): 209-15
214
Monteiro MMB , Carvalho KMM
Relate to the use of optical aids, participants have reported
that the degree of difficulty in relation to read large print in a
newspaper, read a text book or newspaper, write, read what you
write and do housework, has decreased. Related on how to read
labels of remedies, threading the needle and cut with scissors,
there was no change in the degree of difficulty after the
intervention. As those activities requires more accurace of vision,
then are considered more difficult to realize.
The “VFQ” evaluates both quality of life and visual function.
For this reason, the option was use “VFQ” as an instrument for
evaluation of elderly life quality; moreover, this questionnaire was
already validated for utilization with the Brazilian population (22).
In relation to overall health, there was no significant
difference before and after intervention. As for vision,
psychological, everyday difficulties, dependence and peripheral
vision significantly improved after the intervention.
Analyzing the answers, it was expected that the vision (with
the increased use and time of optical aids using), the vision has
improved and everyday life difficulties had decreased. One of
the intervention goals was to introduce strategies to improve
visual functionality during daily tasks so could continue to be
performed by the elderly without help (17).
A dependency is a factor directly proportional. The lower
the difficulty in performing activities, the less dependency is
expected.
The psychological aspects showed up as a surprise
satisfactory, since it is known psychological impairment of people
with visual impairment acquired (23).
In the sub domains of ocular pain, near and distance
activities, color vision has improved after intervention, although
were not significant.
The VFQ-25 has three relevant items to mobility of people
with low vision. As this issue was not addressed during the
intervention, it won´t be discussed in this study. It is understood
the importance of orientation mobility and to improve the life
quality of elderly visually impaired, and it is known that these
aspects influences its independence and autonomy (12).
The majority aspects of the two questionnaires used in the
study tendency to improvement after intervention. There was
no statistically significant overall improvement. We believe that
this is due to the short time intervention (three sessions). But
we believe that if the intervention lasted a little longer, we would
have less surveyed interested to participate in the entire study.
Other professionals participated in the evaluation and
prescription of optical aids, they were ophthalmologists and
educator, who were in the subjects appointment at the Low
Vision Clinic of UNICAMP. The subjects passing by this
appointment are referred to the Visual Rehabilitation Group
in another center within the UNICAMP own. There is an
interdisciplinary team for Visual Rehabilitation in this center,
consisting of a social worker, educator, occupational therapist,
psychologist, computer science and orientation and mobility
professor. Some subjects who participated in this study has
also participated in Visual Rehabilitation Groups previously,
others don´t.
We should also take into consideration the participation
of other professionals, previously consulted, in improving the
quality of life of participants in this study.
Rev Bras Oftalmol. 2015; 74 (4): 209-15
CONCLUSION
After three meetings of Hearing and Speech
Intervention, the communication and life quality of elderly with
acquired low vision had improvements in the aspects regarding
the questioned items in the two questionnaires used for this
research: LVQOL and VFQ-25.
AUTHORS CONTRIBUTIONS
Both, the authors Mayla Myrina Bianchim Monteiro and
Keila Miriam Monteiro de Carvalho participated in the design,
analysis of results, and contributed effectively in the realization
of this manuscript.
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AL. The Brazilian version of the 25-Item National Eye Institute
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MC. [Visual impairment impact on the quality of life of the elderly population that uses the public health care system from the
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Oftalmol. 2012;75(3):161-5. Portuguese.
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P. Impact of bilateral visual impairment on health-related quality
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Corresponding author:
Mayla M. B. Monteiro
Rua Renato Portioli, 509 Jardim Itapema, Mogi Mirim, SP
Zip code: 138010-036; Brazil
Fax: 19 3862-1839
E-mail: [email protected]
Rev Bras Oftalmol. 2015; 74 (4): 209-15
ORIGINAL ARTICLE
216
Health and vision related quality of life
among patients with choroidal neovascular
age related macular degeneration
Qualidade de vida relacionada com a visão em doentes
com degeneração macular relacionada à idade neovascular
Maria Picoto1, José Galveia1, Sara Patrício1, António Rodrigues1, Fernanda Vaz2
ABSTRACT
Purpose: To describe the impact of aged-related macular degeneration (AMD) on vision-related quality of life (QOL) on a sample of
portuguese patients and explore the association with vision, Central Foveal Thickness (CFT) and demographic variables in a Portuguese
population. Methods: Observational, interview study of 68 patients with clinical diagnosis of NV AMD seen between January and April
2011 at the Ophthalmology Department of Centro Hospitalar de Lisboa Ocidental. Health-related quality of life (HRQL) was measured
with a Portuguese version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Scores were analysed and
correlated with age, gender, laterality of the disease, initial and final visual acuity (VA), CFT and duration of follow-up. Results: Worst eye
VA had predictive value in the following scores: global, distance activities, color vision, peripheral vision, role difficulties, social functioning
and mental health (p<0.05). In a multivariable model with inclusion of all the parameters studied, the analysed variables explained 60%
of the variability of the Global Score, with a predictive value of 0.08 (R2 0.57, p=0.088). Conclusion: NV AMD is associated with
impairment in reported vision related QOL in our group of patients. The VA of the worst eye has a predictive value in NEI VFQ-25 scores.
Keywords: Quality of life; Macular degeneration; Visual acuity; Mental health; Questionnaires; Chronic disease
RESUMO
Objetivo: Avaliar o impacto da degeneração macular relacionada à idade (DMRI) na qualidade de vida relacionada com a visão
(QVRV) numa amostra de pacientes portugueses. Métodos: Estudo observacional em corte transversal, não comparativo no qual
foram incluídos 68 pacientes seguidos no Departamento de Retina Médica do Serviço de Oftalmologia do Centro Hospitalar de
Lisboa Ocidental, entre Janeiro e Abril de 2011. A QVRV foi avaliada por meio do questionário National Eye Institute Visual
Functioning Questionnaire (NEI-VFQ-25), traduzido para português. Os scores obtidos foram analisados e correlacionados com os
seguintes parâmetros idade, sexo, lateralidade da doença, tempo de follow-up, acuidade visual (AV) e EFC iniciais e finais do melhor
(MO) e pior olho (PO). Resultados: A AV do PO apresentou valor preditivo nos scores global, atividade para longe, visão cromática,
visão periférica, desempenho, função social e saúde mental (p<0,05). Num modelo de multivariáveis com inclusão de todos os
parâmetros clínicos analisados, as variáveis estudadas explicaram 60% da variância do score global (SG) com um valor preditivo de
0,08 (R2 0,57, p=0,088). Conclusões: A DMRI NV está associada a uma diminuição da QVRV. A AV do PO tem valor preditivo nos
scores do NEI-VFQ-25.
Descritores: Qualidade de vida; Degeneração macular; Acuidade visual; Saúde mental; Questionário; Doença crônica
1
2
Egas Moniz Hospital, West Lisbon Hospital, Lisbon, Portugal.
Department of Medical Retina, Egas Moniz Hospital, West Lisbon Hospital, Lisbon, Portugal.
The authors declare no conflists of interest
Received for publication 19/05/2013 - Accepted for publication 29/09/2013
Rev Bras Oftalmol. 2015; 74 (4): 216-21
Health and vision related quality of life among patients with choroidal neovascular age related macular degeneration
INTRODUCTION
A
ge-related macular degeneration (AMD) is the leading
cause of severe vision loss in people older than 65 years1,2.
Its incidence increases exponentially with age. The
Framingham study3 showed an incidence of 11% in people aged
between 65 and 74 years, and 30% between 75 and 85 years old.
Although only 10 to 20% of AMD cases are identified as
exudatively, it accounts for 80-90% of cases of blindness in this
pathology3.
This disease shows a progressive loss of central vision with
a measurable impact on the quality of life of the patient4.
When evaluating the impact of a disease, four categories of
markers are considered. The physiological markers (eg:
glycosylated Hb in Diabetes Mellitus), clinical markers (eg: VA
measurement), markers reported by the clinician from their
perception of the impact of the disease, and at last the markers
reported by the patient.
The objective clinical measurement of the visual function
in a patient such as VA provides quantitative data5. However,
this analysis does not reflect the impact of the visual impairment
(VI) in the daily activities (DA) of the patient.6.
The quantification of vision-related quality of life (VRQL)
provides extra information on the impact of a disease in the
function, particularly in the DA. This measurement is important
in patients with AMD, because in addition to having high
propensity to depressive disorder 7, they show a VI that
compromises DA and mobility, which according to Williams et al.
is higher in patients of the same age and comparable to patients
with chronic disease4.
The impact of VRQL on health professionals and
community members is low8. Brown et al., Stein et al., Hart et
al. found that these groups, including ophthalmologists,
underestimate the impact of mild, moderate and severe AMD
in VRQL9,10,11.
The primary objective of this study was to determine the
impact of AMD NV in the vision-related quality of life (VRQL)
in a sample of Portuguese patients. The secondary objectives
were to understand the impact of some variables in the VRQL,
namely the presence of unilateral versus bilateral diseases, the
value of VA of the best and worst eye (BE and WE) and the
EFC of the BE and WE. And finally, interpret a global model of
interaction of the variables studied.
METHODS
An observational study of 68 patients followed in a retinal
consultation by AMD NV between January and April 2011 in the
West Lisbon Hospital. The inclusion criteria were: signing an
informed consent for participation in the study; age greater than
or equal to 50 years old; clinical diagnosis of AMD NV. The
exclusion criteria were: follow-up of less than 6m; history of eye
disease besides AMD which might compromise the VA (i.e.,
amblyopia, uncontrolled glaucoma with IOP > 30 mmHg, ischemic
optic neuropathy, diabetic macular edema clinically meaningful,
significant diabetic retinopathy, active uveitis, clinical signs of
myopic choroiditis or refraction > -8D in the current prescription;
clinical evidence of thinning of the sclera.
217
The study participants received a questionnaire VFQ-25
translated into Portuguese during the routine consultation.
The revised parameters were as follows: age; sex; number
of anti-VEGF injections performed; laterality of the disease; initial
VA determined in the appointment before the treatment by the
Snellen chart and by the same orthotics technician; final visual
acuity assessed at the last follow-up appointment by the Snellen
chart and by the same orthotics technician; EFC determined by
TD OCT (Stratus, Carl Zeiss Meditec, Inc.) in two occasions.
Measurement of EFC
EFC (average thickness in 1000ìm of the core diameter)
was determined using the TD OCT (Stratus, Carl Zeiss Meditec,
Inc) and by a single experienced operator in the two stages. Only
the scans of sufficient amount were accepted (signal strength e”
8, cuts without areas with absent or reduced signal, core cuts in
the macula and correct segmentation limits). Participants were
in an iatrogenic mydriasis (pupil diameter e” 6mm) using
tropicamide 0.5%, and were instructed to establish an internal
fixation target. After the focus adjustment was made and a good
central fixation was acquired, the process started. The thickness
maps were calculated from the analysis software of the appliance.
Questionnaire VFQ-25
The patients rated themselves in 12 dimensions: (1) general health; (2) overview; (3) nearsightedness; (4) activities related
to farsightedness; (5) eye pain; (6) social function related to vision;
(7) performance related to vision; (8) mental health related to
vision; (9) dependence related to vision; (10) difficulties in driving;
(11) color vision and (12) peripheral vision.
The total score ranges from 0 (worst possible function)
and 100 (best possible function).
For the statistical analysis of the results we determined:
- Average age, standard deviation and distribution by age
groups;
- Number of female and male patients;
- Number of patients with unilateral and bilateral disease;
- Average time of follow-up and standard deviation;
- Mean initial and final visual acuity and the respective
standard deviation;
-Mean injections and standard deviation;
- Mean baseline scores for each dimension studied of the
questionnaire VFQ-25 and the respective standard deviation;
- Impact of VA factors, laterality, age, sex and EFC
independently in the scores of the questionnaire VFQ-25 (analysis
of variance - ANOVA);
- Impact of the factors mentioned in line 8) along with the
scores of questionnaire VFQ-25 (analysis of variance - ANOVA).
RESULTS
Sixty-eight patients with AMD participated in the study
conducted in medical routine appointments in the West Lisbon
Hospital. The average age was 79.2 years, with 75% of the sample
aged over 75 years. All patients were caucasian. Most were women
(n=44). The final average VA of BE was 0.55 ± 0.27 and WE of
0.22 ± 0.22. The final VA of BE was e” to 0.5 in 42 patients (62%),
and the final VA of WE was < 0.1 in 34 patients (50%). The
distribution of VA of BE and WE are listed in table 1.
Rev Bras Oftalmol. 2015; 74 (4): 216-21
218
Picoto M, Galveia J, Patrício S, Rodrigues A, Vaz F
Table 1
Table 3
Distribution of VA of BE and WE by subgroups
Analysis of variance (p-value) of the scores of VRQL
(NEI-VFQ 25) according to the VA of BE and WE
≥ 0.1 e < 0.25 ≥ 0.25 e <0.5
≥ 0.5
AV
<0.1
BE Final
3 (4%)
8 (12%)
15 (22%)
42 (62%)
WE Final
34 (50%)
12 (18%)
10 (15%)
12 (18%)
VA: visual acuity; BE: best eye; WE: worst eye
Regarding the laterality of the disease, 44 patients (68%)
had one eye disease and 21 (32%) had bilateral disease. The
average time of follow-up was 22.63 ± 13.11. The mean number
of anti-VEGF injections per patient was 3.73 ± 3.06.
The scores obtained in each domain of the questionnaire
VFQ-25 are described in table 2.
Table 2
Scores of VRQL of NEI-VFQ 25
Score NEI-VFQ-25
n
Mean (%)
General health
Overview
Eye pain
Farsightedness
Nearsightedness
Social function
Mental health
Performance
Dependence
Driving
Color vision
Peripheral vision
Total score
68
68
68
68
68
67
68
68
68
25
65
66
68
27
43
76
51
53
66
47
45
77
54
75
64
57.4
R2
General health 0.16
Overview
0.15
Eye pain
0.1
Farsightedness 0.25
Nearsightedness 0.34
Social function 0.51
Mental health
0.42
Performance
0.45
Dependence
0.27
Driving
0.25
Color vision
0.22
Peripheral vision 0.49
Total score
0.44
BW (p)
0.18
0.96
0.86
0.42
0.81
0.41
0.75
0.79
0.96
0.81
0.42
0.76
0.90
WE (p)
0.996
0.19
0.35
0.22
0.02
0.01
0.01
0.01
0.06
0,998
0.0463
0.0024
0.0092
Interaction (p)
0.61
0.0071
0.70
0.39
0.17
0.04
0.62
0.16
0.28
0.32
0.41
0.05
0.02
SD (%)
20
19
26
26
32
36
26
36
28
36
38
35
23
Except for the score of driving, the response rate was close
to 100%. The highest mean values were observed in the scores
of dependence (77%), eye pain (76%) and color vision (75%).
The lower mean scores were of general health (27%), overview
(43%), performance related to vision (45%), mental health (47%)
and farsighted activities (53%).
Table 3 shows the p-values for the impact of the VA of BE
and WE independently. The results of ANOVA are presented
for each one of the dimensions studied.
The VA of BE and WE explained more than 40% of the
variance observed in the following scores of NEI-VFQ 25: social
function related to vision (51%), peripheral vision (49%),
performance related to vision (45%) total score (44%) and mental health (42%).
In relation to the specific effect of VA of each eye in the
dimensions studied, the p-values had a statistically significant
value (p<0.05) for the impact of the WE in the following
dimensions: peripheral vision (p=0.002), total score (chart 1,
p=0.009), performance related to vision (p=0.01), mental health
(p=0.01), social function related to vision (p=0.01), nearsighted
activities (p=0.02) and color vision (p=0.046). The impact of BE
in the scores analyzed showed no statistical significance.
Rev Bras Oftalmol. 2015; 74 (4): 216-21
Score
NEI-VFQ-25
Chart 1
Impact of VA of WE in the total score (p=0.0092)
A significant interaction between the VA of BE and WE
was observed in the following dimensions: overview (p=0.007),
social function related to vision (p=0.04), peripheral vision
(p=0.05) and total score (p=0.02).
Regarding the laterality of the disease, patients with bilateral disease had worse results in scores except for the dimension
of driving, as described in chart 2. However, the difference in
value between the scores was not statistically significant. See
table 4.
Regarding the study on the impact of the variable sex in
the results of the scores, there was no statistically significant
difference between the two sexes in the dimensions studied.
Stratifying the sample by 4 age groups (group 1: < 65 years;
group 2: 65-74 years; group 3: 75-84 years; group 4: 85-91 years)
there was no statistically significant difference for the dimensions
studied (Chart 3).
Health and vision related quality of life among patients with choroidal neovascular age related macular degeneration
219
Chart 2
Table 4
VRQL Scores of NEI-VFQ 25 according
to the laterality of the disease
Analysis of variance (p-value) of the scores of VRQL
(NEI-VFQ 25) according to the laterality of the disease
Chart 3
Analysis of variance of the total score by age groups
Score
NEI- VFQ-25
n
Unilateral
disease
Bilateral
Unilateral
disease /bilateral disease
(p-value, T (student)
General health
68
25%
30%
0.37
Overview
68
43%
43%
0.92
Eye pain
68
76%
79%
0.68
Farsightedness
68
55%
44%
0.18
Nearsightedness
68
56%
48%
0.32
Social function
67
70%
58%
0.24
Mental health
68
49%
44%
0.54
Performance
68
51%
35%
0.102
Dependence
68
78%
75%
0.64
Driving
25
65%
33%
0.11
Color vision
65
76%
73%
0.73
Peripheral vision
66
67%
58%
0.39
Total score
68
59%
54%
0.42
Analyzing the final EFC for BE and WE, a statistically
significant predictive value of final EFC for WE was seen in the
dimensions performance related to vision (p=0.03) and peripheral
vision (p=0.03).
Finally, by means of the analysis of variance we assessed
the impact of the variables studied in each one of the scores of
VRQL. We found that the variables studied explain more than
40% of the variance of scores (Table 5).
Table 5
Analysis of variance (ANOVA) of the scores of VRQL, NEI-VFQ25 according to the variables studied
Score NEI
- VFQ-25
n
R2
Age
(p)
Initial
VA of
Initial
VA of
Final
VA of
Final
VA of
BE(p)
WE(p)
BE(p)
WE(p)
Initial
EFC of
Initial
EFC of
Final
Final
No de
Follow
EFC of EFC of Injections - up
BE(p)
WE(p)
BE(p)
WE(p)
General health
68
0.61
0.51
0.66
0.03
0.95
0.26
0.24
0.60
0.31
0.0085
0.26
0.0085
Overview
68
0.66
0.3
0.02
0.92
0.11
0.41
0.33
0.15
0.18
0.89
0.64
0.64
Eye pain
68
0.4
0.54
0.59
0.33
0.14
0.09
0.19
0.57
0.18
0.4
0.67
0.35
Farsightedness
68
0.63
0.3
0.0063
0.66
0.42
0.87
0.33
0.07
0.36
0.57
0.39
0.33
Nearsightedness
68
0.63
0.28
0.00
0.61
0.14
0.31
0.03
0.93
0.03
0.04
0.87
0.067
Social function
67
0.53
0.46
0.04
0.76
0.07
0.27
0.45
0.24
0.24
0.34
0.71
0.11
Mental health
68
0.4
0.56
0.09
0.99
0.64
0.6
0.16
0.71
0.12
0.47
0.82
0.28
Performance
68
0.46
0.57
0.15
0.96
0.11
0.83
0.52
0.9
0.27
0.87
0.34
0.87
Dependence
68
0.67
0.16
0.0032
0.3194
0.9771
0.0069
0.116
0.72
0.08
0.445
0.850
0.011
Color vision
65 0.38
0.14
0.15
0.84
0.78
0.84
0.18
0.78
0.11
0.96
0.57
0.95
Peripheral vision
65 0.58
0.4
0.11
0.17
0.1
0.2
0.41
0.2
0.15
0.26
0.57
0.09
Total score
68 0.6
0.37
0.0076
0.71
0.27
0.3
0.16
0.21
0.09
0.36
0.86
0.37
Rev Bras Oftalmol. 2015; 74 (4): 216-21
220
Picoto M, Galveia J, Patrício S, Rodrigues A, Vaz F
This model built from the analysis of multivariate variance
explains 60% of the variance of the total score, with a predictive
value of 0.08 (Chart 4).
Chart 4
Analysis of variance of the total score (total score= 0.773 + 0.0076 age + 0.0076 No. inj + 0.625 VA BE + 0.032
VA WE + 0.271 VA BE – 0.287 VA WE – 0.001 EFCi BE +
0.001 EFCi WE + 0.0016 EFC BE + 0.003 EFC WE)
DISCUSSION
The demographic characteristics of the sample, 75% of
patients over 75 years old and predominance of females, are in
accordance with the normal distribution of a population of
patients with AMD12.
The results of the study clearly show that the VA has a
greater impact on VRQL, a finding already documented in other
studies7,8. Regarding the use of the questionnaire NEI-VFQ 25
as a way of measuring the VRQL, to date several researchers
have consistently found associations between low VA and low
VRQL using this assessment tool5,13.
This effect is particularly important in QOL in elderly
patients, to the extent that it leads to dependence, disability,
anxiety and depression. Some areas were more affected than
others by the VA. The impact was virtually non-existent in eye
pain (R2=0.1) and in general health (R2=0.15), unlike the domains
of social function related to vision (R2=0.51), peripheral vision
(R2=0.49), performance related to vision (R2=0.45), total score
(R2=0.44) and mental health (R2=0.42), in which the impact was
pretty strong.
This result is consistent with previous studies 4. The
symptomatic profile of the disease, in which there is a progressive
loss of the central vision, explains the changes reported by the
patients in activities that rely on it, including reading labels of
medicines and daily shopping at the supermarket. The low scores
on mental health, social function and performance related to
vision show the insulating effect of this disease and reflect the
loss of independence and increased anxiety.
It was observed that the VA of the WE had a higher
predictive value than the VA of the BE in the following scores
on the questionnaire: peripheral vision, total score, performance
related to vision, mental health, social function, nearsighted
activities and color vision. This finding is supported by several
studies described in the literature.
Rev Bras Oftalmol. 2015; 74 (4): 216-21
In the study of Berdeaux8 et al., the VA of the WE had a
measurable impact on mental health, dependence, color vision
and farsightedness.
In the Los Angeles Latino Eye Study14, patients with VA in
the WE < 20/200 had worse scores in all dimensions, except for
general health and eye pain.
According to the study by Azen et al. 15 both eyes contribute
independently to the VRQL, and the preservation of a minimal
VA in the WE may contribute to the VRQL.
Moreover, patients with worse views, even if only in one of
the eyes and without reflection on binocular vision, had higher
rates of depression, which has an impact on the VRQL, as
reported by several researchers4,7.
The findings in the aforementioned studies confirm
previous publications on the influence of VA of the WE on the
VRQL in ophthalmic diseases. The final impact of VA of the WE
was initially demonstrated in articles about the benefits of cataract
surgery in the second eye14. Subsequent articles have confirmed
these results to other ophthalmic pathologies characterized by
chronic loss of visual function, particularly gaucoma, AMD and
uveitis.
The impact of VA of the WE can be explained by the
phenomenon of visual inhibition, where binocular vision is worse
than the vision of the BE in 1 or more lines. The Los Angeles
latino Eye Study 14 demonstrated that a high proportion of
individuals may be affected by this phenomenon. Thus the
evaluation of binocular vision should be a primary measure in
the study of vision difficulties, since it reflects the usual mode of
operation.
In this study, it was observed that the impact of unilateral
and bilateral disease in VRQL was comparable. That is, in spite
of the VRQL scores in patients with bilateral disease are lower
than in patients with unilateral disease, there was no difference
between these two groups, both having similar effects on the
VRQL. This finding has several implications. Given the current
economic situation, sometimes the treatment of AMD NV in a
second eye has to be considered, especially when the VA if it is
very low and worse than the 1st eye treated. The decision may be
not treating the 2nd eye if the greatest improvement of VA and
VRQL occurs after the treatment of the first eye. In this study,
since it was observed that the unilateral disease has an impact
similar to the bilateral disease and that the VA of the WE has a
greater impact on the VRQL, treating the second eye may be
recommended, even though it has a VA worse than the first eye
treated. These findings were also described by Varma et al.5, and
Javitt et al.16,17 regarding other ocular pathology, cataracts.
From the multivariable model with inclusion of all clinical
parameters analyzed, it was found that the variables studied
explain 60% of the variance of the global score (GS) with a
predictive value of 0.08 (R2 0.57, p 0.088). However, individually
basis the variables age and sex don’t explain the variance of
scores, such as the EFC for most scores. These results are
important, given that age and sex are often factors that confuse
the analysis of QOL, which was not the case in our sample.
Regarding the EFC, this is an anatomical measurement and that
often has no correlation with the functional aspects, particularly
when a psychosocial functional dimension is assessed.
Furthermore, despite the AMD the value of EFC can be high or
low in patients with low VA, either by intraretinal edema or by
atrophy of the retinal layers.
Currently, the treatment of AMD tends to preserve mostly
the vision and entails heavy financial burden. The cost-benefit
Health and vision related quality of life among patients with choroidal neovascular age related macular degeneration
analysis is essential in the decision to treat a patient with NV. The
evaluation of VRQL may be an extra tool in the decision-making
for both the beginning as for the maintenance of the therapy in
case this translates into an improved VRQL.
This study has several limitations, including the sample size
and the age of the patients, which may put some bias in the
application of a questionnaire. In addition, the sample was not
controlled for the degree of differentiation.
The VRQL of patients with NV, assessed by NEI-VFQ 25,
reveals an association to the VA of the patient. Unilateral and
bilateral diseases have similar impact on the VRQL. The
preservation of the VA in the WE is important in maintaining
the VRQL. This study suggests that the WE should be treated
for maintaining a good long-term VRQL. The assessment of the
VRQL should be included in future studies aimed at a better
understanding of the impact of this disease on patients’ lives and
a better assessment of the effect of the treatment of this disease.
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maculopathy. The Beaver Dam Eye Study. Ophthalmology.
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M, Kramer CF, et al. The prevalence of age-related maculopathy
in the Rotterdam Study. Ophthalmology. 1995;102(2):205-10.
Leibowitz HM, Krueger DE, Maunder LR, Milton RC, Kini MM,
Kahn HA, Nickerson RJ, Pool J, Colton TL, Ganley JP, Loewenstein
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a general population of 2631 adults, 1973-1975. Surv Ophthalmol.
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Williams RA, Brody BL, Thomas RG, Kaplan RM, Brown SI. The
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Berdeuax GH, Nordmann JP, Colin E, Arnould B. Vision-related
quality of life in patients suffering from age-related macular
degeneration. Am J Ophthalmol. 2005;139(2):271-9.
Brown GC, Brown MM, Sharma S. Difference between ophthalmologists’ and patients’ perceptions of quality of life associated
with age-related macular degeneration. Can J Ophthalmol.
2000;35(3):127-33.
Stein JD, Brown MM, Brown GC, Hollands H, Sharma S. Quality of
life with macular degeneration: perceptions of patients, clinicians,
and community members. Br J Ophthalmol. 2003;87(1):8-12.
Hart PM, Chakravarthy U, Stevenson MR. Questionnaire-based
survey on the importance of quality of life measures in ophthalmic practice. Eye (Lond). 1998;12(Pt 1):124-6.
Delcourt C. Epidemiology of AMD. In: Silva R., coordinator. AMD
Age-related macular degeneration. GER Group; 2010. p.11-20.
Cahill MT, Banks AD, Stinnett SS, Toth CA. Vision-related quality
of life in patients with bilateral severe age-related macular degeneration. Ophthalmology. 2005;112(1):152-8.
Globe DR, Wu J, Azen SP, Varma R; Los Angeles Latino Eye
Study Group. The impact of visual impairment on self-reported
visual functioning in Latinos: The Los Angeles Latino Eye Study.
Ophthalmology. 2004;111(6):1141-9.
Azen SP, Varma R, Preston-Martin S, Ying-Lai M, Globe D, Hahn
S. Binocular visual acuity summation and inhibition in an ocular
epidemiological study: the Los Angeles Latino Eye Study. Invest
Ophthalmol Vis Sci. 2002;43(6):1742-8.
Javitt JC, Steinberg EP, Sharkey P, Schein OD, Tielsch JM, Diener
M, Cataract surgery in one eye or both. A billion dollar per year
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eyes, Arch Ophthalmol. 1993;111(5):686-91.
Corresponding author:
Maria Picoto
Rua: Silva e Albuquerque, 15, rc dto,
Zip Code: 1700-360, Lisbon, Portugal.
E-mail: [email protected],
Rev Bras Oftalmol. 2015; 74 (4): 216-21
ORIGINAL ARTICLE
222
Chalazion and demographic characteristics
of patients in a population sample
Calázio e características demográficas dos
portadores em uma amostra populacional
Marjorie Fornazier do Nascimento1, Ana Claudia Viana Wanzeler1, Roberta Lilian Fernandes Sousa1, Larissa Horikawa
Satto1, Carlos Roberto Padovani 2, Silvana Artioli Schellini1
ABSTRACT
Purpose: To show the frequency of occurrence of chalazion in a population sample, as well as the characteristics of patients. Methods: A
cross-sectional study using randomized population sample was carried out during 2004/2005, in the Midwest region of the state of São
Paulo. Participants were evaluated according to demographic variables and ocular examination. Results: The frequency of occurrence of
chalazion was 1.56‰, more common in women, people with astigmatism or low hyperopia, with wide variation in age of onset. It was
necessary to prescribe optical correction and surgery in a significant number of cases. Conclusion: The chalazion has low frequency of
occurrence in the general population. It occurs predominantly in women and there is a significant association with refractive error.
Keywords: Chalazion/epidemiology; Hordeolum; Eyelid/injuries; Refractive errors
RESUMO
Objetivo: Apresentar a frequência de ocorrência do calázio em uma amostra populacional, assim como as características de seus
portadores. Métodos: Estudo transversal utilizando amostra populacional aleatorizada, realizado nos anos 2004/2005, na região
centro-oeste do estado de São Paulo. Os participantes foram avaliados segundo variáveis demográficas e exame oftalmológico.
Resultados: A frequência de ocorrência do calázio foi de 1,56‰, sendo mais frequente em mulheres, portadores de astigmatismo ou
hipermetropia de pequenos graus, com grande variação de idade de acometimento. Foi necessária prescrição de correção óptica e
cirurgia em número expressivo de casos. Conclusão: O calázio tem baixa frequência de ocorrência na população geral. Ocorre
predominantemente em mulheres e há associação importante com ametropia.
Descritores: Calázio/epidemiologia; Terçol; Pálpebra/lesões; Erros de refração
1
2
Department of Ophthalmology of the Medicine College of Botucatu, São Paulo State University “Júlio de Mesquita Filho”, Botucatu, SP, Brazil.
Department of Biostatistics of the Biosciences Institute of Botucatu, São Paulo State University “Júlio de Mesquita Filho”, Botucatu, SP, Brazil.
Study conducted at the Medicine College of Botucatu, São Paulo State University “Júlio de Mesquita Filho” Botucatu, SP, Brazil
The authors declare no conflicts of interest
Received for publication 08/03/2014 - Accepted for publication 23/10/2014
Rev Bras Oftalmol. 2015; 74 (4): 222-4
223
Chalazion and demographic characteristics of patients in a population sample
INTRODUCTION
RESULTS
he chalazion is the most common inflammatory lesion of
the eyelid, and is a granulomatous reaction caused by the
retention of the secretion from the Meibomian glands
due to chronic inflammation resulting from an internal
hordeolum or meibomitis.1
It is commonly caused by Staphylococcus sp and may be
treated with medical therapy; but when there is no resolution
and there chronicity of the process, it may require surgery.2-5
After the removal, a histological examination is needed,
particularly in the case of recurrent injuries due to the possibility
of a malignant tumor, such as sebaceous cell carcinoma.6-8
Although it is common in eye care services, there are no
studies on the distribution of chalazion in the general population,
which motivated this study aimed at observing the frequency of
occurrence of chalazion in a given population and describing the
demographic profile of carriers.
Twelve cases of chalazion were found in the general
population in the Midwest of São Paulo, resulting in 1.56% of
frequency of occurrence of the disease.
Analyzing the characteristics of the patients, 11 (91.7%)
were female, with a wide range of age of occurrence, which was
between 31 and 77 years.
Nine (75%) cases were observed on the right side.
The main complaint was a foreign body sensation,
reported by 33%.
There was no link between chalazion and systemic or
local diseases.
The visual acuity (VA) presented (uncorrected) was > 0.7
in 25%, from 0.3 to 0.7 in 66.7% and < 0.05 in 8.3% of cases.
When the corrected VA was assessed, 91.7% showed AV > 0.7
and 8.3% from 0.3 to 0.05 (Fig. 1).
The refraction test showed that 58.3% of patients with
chalazion were emmetropic, 33% were hyperopic (ranging from
+1 to +3.75), and 41.7% were astigmatic (ranging from -0.50 to
-2.00). The treatment was the prescription of optical correction
to 41.7% of patientes, and 75% were referred for surgical
treatment (Fig. 2).
T
METHODS
The analysis of patients with chalazion was based on data
from a cross-section, observational study made with a randomized
population sample conducted between March 2004 and June
2005. The study was conducted in nine cities of the Midwest
region in the state of São Paulo, for which the reference center is
the city of Botucatu.
The research protocol was reviewed
and approved by the Research Ethics Committee of the Medicine
College of Botucatu - UNESP.
Participants were sorted taking into account the place of
residence according to the IBGE census tract (Census, 2000).
The sample size of 8,010 individuals was stablished, of which
7,654 people were examined. The sample size was based on the
total number of inhabitants of the study area and on the
prevalence of blindness and low vision in the population studied.
The subjects were invited to participate and an appointment
was scheduled.
The study population was approached by a Mobile
Ophthalmic Unit, registering the identification data, clinical
history, and ocular and systemic background of the participants.
Then an eye examination was performed with the assessment of
visual acuity (VA) by means of the Snellen chart for the illiterate
placed 5 meters away and with good lighting conditions, with
and without optical correction. The external ocular exam was
performed with a hand-held flashlight. The static and dynamic
refractometry values were recorded using an auto-refractor
(Topcon KR-7000, Japan) and a phoropter (Topcon VT10,
Japan). The biomicroscopy assessment was performed using a
slit lamp (Shin-Nippon, Japan), and the indirect fundoscopy was
performed using 90D Volk lens (Mentor, USA).
In individuals aged below 40 years, cycloplegia was obtained
by instilling a droplet of cyclopentolate eyedrops (Cicloplégico,
Allergan, São Paulo-Brazil), with examination after 30 minutes.
Individuals with a spherical component between -0.50 and
+0.50 were considered emmetropic, hyperopic with a degree
greater than +0.50, and astigmatic with a degree lower than -0.50.
All data obtained was categorized and transferred to an
Excel table, being statistically treated for the frequency analysis
of occurrence of the phenomena observed.
Figure 1: Distribution of visual acuity (VA) uncorrected and with the
best optical correction in patients with chalazion.
Figure 2: Distribution of patients with chalazion regarding the refractive
error and the treatment adopted.
Rev Bras Oftalmol. 2015; 74 (4): 222-4
224
Nascimento MF, Wanzeler ACV, Sousa RLF, Satto LH, Padovani CR, Schellini SA
DISCUSSION
The main value of the present study was to randomly assess
participants, which helped identify the frequency of occurrence
of chalazion in the general population. This injury is very common
in optometrists’ offices, and when it is searched in a sample that
is not the convenient one, it shows a low prevalence.
The lesion was predominant in females, as described by
others.9,10
There was a wide variation in the age of the carrier,
predominantly in the elderly, which was surprising, since the
chalazion is an infection that occurs more frequently in youngsters.9,10
There was no relation between the presence of chalazion
and ocular or systemic background, although the association
with conditions such as blepharitis, acne rosacea and seborrheic
keratosis is known.3,9,11
The uncorrected visual acuity was greater than 0.3 for
91.7% of patients with chalazion. With the best optical correction,
there was an improvement of the VA, which was above 0.7 in
91.7% of individuals.
The association between chalazion and refractive errors
of low degree is classic. When it comes to recurrent lesions,
ametropia is often associated. The present study confirms this
association, with astigmatism and hyperopia being often
observed in association with the presence of chalazion, including
requiring optical correction. In addition, astigmatism can be
induced chalazion, particularly when located on the upper eyelid,
due to causing corneal flattening and deformity.12,13
Although some cases had shown improvement with
conservative measures as warm and moist compresses3,4,5,14, the
clinical treatment is only effective in the acute inflammatory
phase, i.e., in the styes. In the chronic phase, when the
granulomatous process is already installed, only small chalazions
may cure spontaneously. In our sample, there was indication for
surgical excision for most of the cases, and no indication of
removal for small lesions carriers.
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multiple chalazion. Ann Ital Chir. 2013;23:84(ePub). pii:
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Matayoshi S, Forno EA, Moura EM. Manual de cirurgia plástica
ocular. São Paulo: Roca, 2004. 370p.
Arbabi EM, Kelly RJ, Carrim ZI. Chalazion. BMJ. 2010;341:c4044.
Gilchrist H, Lee G. Management of chalazia in general practice.
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Duarte AF, Moreira E, Nogueira A, Santos P, Azevedo F. Chalazion surgery: advantages of a subconjunctival approach. J
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tratamento. 4 ed. Rio de Janeiro: MEDSI, 2001. 592p.
Pereira PR, Odashiro AN, Rodrigues-Reyes AA, Correa ZM, de
Souza Filho JP, Burnier MN Jr. Histopathological review of sebaceous carcinoma of the eyelid. J Cutan Pathol. 2005;32(7):496-501.
Ozdal PC, Codère F, Callejo S, Caissie AL, Burnier MN. Accuracy of
the clinical diagnosis of chalazion. Eye (Lond). 2004;18(2):135-8.
Nemet AY, Vinker S, Kaiserman I. Associated morbidity of chalazia. Cornea. 2011;30(12):1376-81.
Netto AA, Rolim APQ, Müller, TPS. Prevalência de doenças
palpebrais no serviço emergencial de oftalmologia do Hospital
Universitário da Universidade Federal de Santa Catarina. Arq
Catarin Med. 2006;35(4):64-9.
Bagheri A, Hassani HR, Karimian F, Abrishami M, Yazdani S.
Effect of chalazion excision on refractive error end corneal topography. Eur J Ophthalmol. 2009;19(4):521-6.
Santa Cruz CS, Culotta T, Cohen EJ, Rapuano CJ. Chalazioninduced hyperopia as a cause of decreased vision. Ophthal Surg
Lasers. 1997;28(8):683-4.
Honda M, Honda K. Spontaneus resolutions of chalazion after 3
to 5 years. Eye Contact Lens. 2010;36(4):230-2.
Nemet AY, Vinker S, Kaiserman I. Associated morbidity of blepharitis. Ophthalmology. 2011;118(6):1062-8.
CONCLUSION
The chalazion occurred in 1.56% of the inhabitants in the
area studied, predominantly in women, with a wide range of age
of occurrence. There was a significant association with low
ametropias, requiring the prescription of optical correction and
surgery in a significant number of cases.
Rev Bras Oftalmol. 2015; 74 (4): 222-4
Corresponding author:
Marjorie Fornazier do Nascimento.
Rua Antonio Amando de Barros, 241 - Botucatu (SP) - 18601-260
- Brazil.
E-mail: [email protected]
ORIGINAL ARTICLE
225
Correlation between the use of the accommodation
and symptoms of asthenopia in hyperopic patients
Correlação entre o uso da acomodação e sintomas
de astenopia em pacientes hipermétropes
Juan Carlos Luna da Costa1 , Ian Beltrão de Sá Martins1, Larissa Tavares Albuquerque Nóbrega1, Maria Odília Navarro
Medeiros1, Luciana Maria Palitot1, Marília Bezerra Cavalcanti Dias1, Tarcízio José Dias1
ABSTRACT
Purpose: The objective of this paper was to compare the symptoms of asthenopia in patients at different levels of hyperopia and corrected
for different accommodative efforts. Methods: This study is an experimental design and quantitative approach. Sixty-nine hyperopic
patients aged between 15 and 40 were selected. Individuals with a diagnosis of accommodative insufficiency and paralysis, accommodative
spasm or any type of ocular deviation were excluded. Subjects were randomly divided into four groups. Each one performed a nearvision task with different corrective lenses, varying the value of the accommodative effort. Results: There is significant reduction in the
asthenopia score during the near-vision task when leaving 35% or more of the amplitude of accommodation in reserve. The linear
regression showed that the variables total hyperopia (r = 0.109) and the difference between static and dynamic refraction (r = 0.135) did
not obtain significant linear relationship to the asthenopia score. Conclusions: There is significant reduction in the asthenopia score
when leaving 35% or more of the amplitude of accommodation in reserve. The symptoms of asthenopia are not associated to the severity
of the hyperopic refractive error. The search for symptoms before the near vision task, using a questionnaire, related to the symptoms
during the accommodative effort task, revealing the importance of searching for complaints about asthenopia during anamnesis, which
can help ophthalmologists with prescriptions of glasses for hyperopic patients with asthenopia.
Keywords: Accommodation, ocular; Hyperopia; Asthenopia; Refraction, ocular; Eyeglasses
RESUMO
Objetivos: O presente estudo objetivou avaliar os efeitos do esforço acomodativo e do poder do erro refrativo nos sintomas de
astenopia. Métodos: Trata-se de um modelo de estudo experimental e abordagem quantitativa, cuja amostra consistiu de 69 pacientes hipermetropes entre 15 e 40 anos de idade. Foram excluídos os indivíduos com diagnóstico de insuficiência ou paralisia da
acomodação, espasmo de acomodação ou qualquer tipo de desvio ocular. Os pacientes foram alocados aleatoriamente em quatro
grupos. Cada grupo realizou o trabalho de visão para perto com correções diferentes, variando o valor do esforço acomodativo.
Resultado: Houve melhora significativa dos sintomas de astenopia com correções que proporcionaram mais de 35% da amplitude
de acomodação em reserva. Não houve relação estatisticamente significativa entre os sintomas e o valor do erro refrativo. Conclusão:
Há uma redução significativa dos sintomas quando os pacientes mantêm 35 % ou mais de sua acomodação em reserva. Os sintomas
de astenopia não estão associados à gravidade do defeito hipermetrópico. A pesquisa de sintomas antes do teste, através de um
questionário, foi o fator que melhor se relacionou com os sintomas durante o teste de visão para perto, revelando a importância da
pesquisa das queixas de astenopia durante anamnese na prescrição de lentes para visão de perto.
Descritores: Acomodação ocular; Hiperopia; Astenopia; Refração ocular; Óculos
1
Centro Oftálmico Tarcízio Dias, João Pessoa, Paraíba, Brazil.
The authors declare no conflicts of interest
Received for publication 29/09/2014 - Accepted for publication 08/03/2015
Rev Bras Oftalmol. 2015; 74 (4): 225-30
226
Costa JCL , Martins IBS, Nóbrega LTA, Medeiros MON, Palitot LM, Dias MBC, Dias TJ
INTRODUÇÃO
H
yperopia is the condition of the eye where incoming
rays of light reach the retina before they converge into
a focused image. Total hyperopia is divided into latent
hyperopia and manifest hyperopia. Latent hyperopia is the one
which is physiologically supplanted by the tonus of the ciliary
muscles. Manifest hyperopia is divided into facultative hyperopia
and absolute hyperopia. Facultative hyperopia is the one which
can be overcome by the accommodative effort, while this is not
possible in the case of the absolute hyperopia(1).
For several ophthalmologists, the prescription for the near
vision is based on the claim that only half or two-thirds of an
individual’s amplitude of accommodation is sustainable for an
extended period of time(2). Donders (1972) recommended, for
the correction of hyperopia, the value of the manifest hyperopia
added to a fourth of the latent hyperopia(3). A rule of thumb
which received wide acceptance is that the lens used for near
vision should allow that half of the patient’s amplitude of
accommodation remain in reserve(4).
The younger the patient, the more active is the
accommodation; therefore, less correction for the hyperopia is
needed. In normal individuals, right after birth the hyperopia is
about 2 to 3 diopters. It can increase slightly in the first years of
life, but it rapidly and gradually diminishes according to the
somatic growth until after the puberty, in which the individuals
tend to become emmetropic. After the growth period, refraction
tends to remain stationary. In old age, the tendency to hyperopia
is greater, due to modifications in the curvature and in the
refraction indexes of the crystalline lens layers(1,5).
There is also an apparent increase of hyperopia due to
progressive insufficiency of accommodation. With the decrease
of the ciliary muscle tonus, part of the latent hyperopia also
manifests itself and with the reduction of the accommodation
capacity, most of the facultative hyperopia becomes absolute.
Therefore, in the beginning of life, unless the error is very high,
the accommodation capacity is able to correct it entirely, if absolute
hyperopia is absent. After the age of 65 virtually all the error
becomes absolute(4).
The symptoms of eye strain are, in part, due to extreme
accommodation and to the extra convergence effort. Asthenopia
is the term used to describe the sensation of extreme effort and
weakness or eye fatigue derived from the use of vision. It is a
common manifestation in many patients with convergence
insufficiency, accommodation insufficiency, refractive error and
strabismus. Its symptoms are headache, diplopia, difficulty in
focusing the image, fatigue, reading problems, blurred vision(6).
Accommodative fatigue can be described as the reduction
of the performance of the accommodation system due to a
prolonged or repetitive accommodative effort(7). In near vision,
the temporary insufficiency of the ciliary muscle to maintain
contraction can result in visual impairment, on the other hand
extreme accommodation or spasm of the ciliary muscle, may
cause an artificial condition of myopia(8).
Accommodation is a key factor in the correction of
hyperopia(5), which motivated us to construct a diagram (diagram
J) to correlate the refractive error with the amplitude of
accommodation and find the ideal value of the most comfortable
reading prescription for the hyperopic patients. In the diagram,
the j value can be found relating the values of total hyperopia of
the patient to his accommodation and represents the comfortable
Rev Bras Oftalmol. 2015; 74 (4): 225-30
refraction for near vision. This way, the diagram can be constructed
according to the adequate refraction to hold a determinate fraction
of the accommodation in reserve. In other words, the fraction of
the accommodation not used by the eyes while fixing in a point in
space, avoiding over or undercorrection. The j(50) means the
value in the diagram calculated to leave in reserve 50% of the
patient’s accommodation. The value of j can be found through the
following equation, in which jc is the value of prescription for
certain accommodative reserve C; D is the value of the hyperopia
in diopters; P is the additional dioptric power for near vision; AA
is the amplitude of accommodation in diopters and C is the value
of the accommodative reserve in percentage:
j(C)= D + P – [AA(100-C).10-2]
The deduction of this equation is based on the maintenance
of a fraction of the accommodation during near vision effort.
Hence, near vision requires the total correction D summed to
the value of P (3 diopters in usual conditions), but in these
circumstances the prescription of lens would cancel the
accommodative effort. The reduction of this value would imply
in a progressive increase in the use of accommodation to the
maximum of the individual’s accommodation capacity. An
evidence of this effort would be the increase of the reduction
factor “AA(100-C).10 -2”. Therefore, it was observed that the
higher the accommodative reserve C, the lower the
accommodative effort, in a way that a correction j(100) would
cancel the reduction factor and, consequently, accommodation.
This equation explains why individuals with high amplitude of accommodation tend to tolerate higher degrees of
hyperopia. For instance, a five-year-old child’s amplitude of
accommodation is about 16D. Considering that this child is
hyperopic and his/her hyperopia measures two diopters, in order
to hold 50% of his/her accommodation in reserve while he/she
reads from a distance of 33cm, the ideal prescription would be:
j(50) = +2 +3 – [16(100-50).10-2] = -3D. The value of -3D implies
that, at this moment, it is not necessary to correct this patient’s
near vision, while symptoms are absent. With aging and loss of
accommodation, the hyperopic patients tend to present
symptoms of asthenopia. Thus, a patient with the same 2 diopters
of hyperopia will need +1,5 D correction when his/her amplitude is reduced to 7D (which happens approximately at 30 years
of age), to ensure that 50% of his/her accommodation remains
in reserve and the patient will be able to read comfortably.
Despite the fact that, according to many ophthalmologists,
the prescription for near vision is based on the claim that only
half or two-thirds of the amplitude of accommodation is
sustainable for an extended period of time, a research developed
by Wolffsohn et al. showed that adults’ accommodation system
is robust and resistant to fatigue during an intensive and
prolonged task(2) . Besides, a greater proportion of the amplitude of accommodation can be exercised in a continuous way, in
spite of what was suggested previously. Alves suggests the
correction of hyperopia for occasional use, for reading or any
other activity that requires accommodative effort, in those cases
where there is difficulty to relate the symptoms(5).
Based on this dissent, one of the objectives of the present
article is to compare the symptoms of accommodative effort in
patients with correction for j(20), j(35), j(50) e j(60) during a
sustained and intensive task for near vision.
Correlation between the use of the accommodation and symptoms of asthenopia in hyperopic patients
The main objective of this paper was to compare the
symptoms of asthenopia in patients at different levels of
hyperopia and corrected for different accommodative efforts.
The specific objectives were: to compare the relation between
the level of asthenopia before and after near vision task; to
evaluate the symptoms of accommodative effort in patients with
correction for j(20), j(35), j(50) e j(60); to relate the symptoms of
asthenopia with the value of refractive error; to construct a
diagram to guide the ophthalmologist in prescribing glasses for
near vision.
METHODS
This study is an experimental design and quantitative
approach. The sample consists of hyperopic patients treated at
Instituto Visão para Todos (IVPT) of Centro Oftálmico Tarcízio
Dias, in João Pessoa – State of Paraíba, Brazil, from January, 2013
to April, 2014.
Hyperopic patients aged between 15 and 40 were selected.
Individuals with a diagnosis of accommodative insufficiency and
paralysis, accommodative spasm or any type of ocular deviation
were excluded from the study.
All the individuals were carefully evaluated with regard to
the amplitude of accommodation, refractive error, visual acuity
and ocular deviation. The push-up method was adopted in order
to obtain the amplitude of accommodation. The method consists
of Snellen optotypes for near vision 40 cm distant from the eye
with corrected ametropia. In this method the patient is oriented
to find the best optotype of the chart that could be clearly seen.
Then the chart is placed closer to the patient until a blurred
vision of the letters is obtained. This distance is converted into
diopters, which corresponds to its amplitude of accommodation(9).
Automated refraction without cyclopegia was conducted
with the Huvitz MRK-3100 Premium refractor. The total
hyperopia was evaluated with the same refractor 40 min after
the instillation of Cyclopentolate 1%. Over recent years, several
studies comparing the cycloplegic effect of various drugs to the
required number of drops have proved that the instillation of a
drop of Cyclopentolate 1% is sufficient to obtain adequate
cycloplegia(10-13). The individuals were requested to return one
week after the refractive evaluation for an accommodative effort
task. Before the near-vision task, all the individuals answered
the asthenopia symptoms survey (ASS), a questionnaire about
symptoms of asthenopia, which was translated to Portuguese.
The questionnaire consists of eight questions, which involve
symptoms during near-vision task (discomfort, headache, eye
pain, blurred vision, double vision, burning sensation, eye strain).
Each symptom is graded in five points according to its severity(14).
The participants were randomly divided into four groups.
Each one performed the near-vision task with different
corrections: j(20), j(35), j(50) and j(60). Diagrams that relate the
amplitude of accommodation with the total hyperopia were used
to find a prescription for each group. The right eye underwent a
20-minute near-vision task, consisting of the use of a computer
monitor 33 cm distant from the eye, showing a 2.0 mm wide and
3.0 mm long rectangular white line on a black background. The
rectangle was programmed to randomly move, every 4 seconds
in the same position of its geometric center, in the following
directions: vertical, horizontal, and diagonal. The patients were
requested to read the rectangle and inform its direction. This
modality was chosen because of the fact that it was ensured that
the individuals evaluated kept focusing on their target during
most part of the time in order that the blur could be identified as
the patient’s difficulty to define the directions. Furthermore, the
227
eye movement effort, which is commonly used in reading, was
eliminated in order to evaluate the symptoms related solely to
accommodation. By means of monocular testing, we minimized
the convergence effort. In order to minimize the dry-eye effect,
all the patients received one drop of carmellose sodium 5mg/ml
on both eyes before the near-vision task. Astigmatism was
completely corrected with cylindrical lens. The average luminance
in the monitor position was of 290 Lux, measured with the digital CEL luxmeter, model LD-511.
The data was registered on a formulary containing
information about the symptoms experienced (headache, blurred
vision, double vision, pain, burning sensation, eye strain) and the
moment when they occurred. Each of the five symptoms was
classified into a scale from 0 to 1, taking into account the time
(T) when the symptom appeared. Thus, punctuation 0 means
that the symptom did not occur during the 20-minute test; the
punctuation tends to the maximum of 1 when the symptom occurs
at the very beginning of the test. The resulting asthenopia score
was the sum of the punctuation of all the symptoms:
Asthenopia Score during the task = Σ (1 – T/20).
The IBM SPSS Statistics® software version 18 for Windows
was used in the data analysis. ANOVA (analysis of variance),
Turkey HSD test and linear regression were used. A significance
level of 5% was adopted.
The project was approved by the Research Ethics Committee
from Paraíba-Brazil (Protocol ID: 652.767).The patients’ identification
data were kept confidential during their collection and they were not
exposed in the study. Informed consent was obtained.
RESULTS
Sixty-nine individuals were evaluated (30 male and 39 female).
The average age was 26.77, with standard deviation of 6.975.
The linear regression showed that the variables age (r =
0.006), total hyperopia (r = 0.109) and the difference between
static and dynamic refraction measured by autorefractor (r =
0.135) did not obtain significant linear relationship to the
asthenopia score. The factor that contributed the most to the
prediction of the symptoms was the Asthenopia Symptoms
Survey ASS (r = 0.39), which corresponded to a direct and positive
relation (Figure 1).
Figure 1: Graph of linar regression that shows the relation between
the asthenopia symptoms score during the test (r=0,39) and the
Asthenopia Symptoms Survey (ASS).
Rev Bras Oftalmol. 2015; 74 (4): 225-30
228
Costa JCL , Martins IBS, Nóbrega LTA, Medeiros MON, Palitot LM, Dias MBC, Dias TJ
There was not a linear relationship between the groups
and the asthenopia score during the task, but there was a
significant decrease in the asthenopia score between the j(20) and
j(35) groups, remaining unchanged after the j(35) (Figure 2).
Figure 2: Graph the relates the symptoms scores during the nearvision task (mean and confidence interval) the groups tested.
Analysis of variance (one-way ANOVA) and Turkey HSD
test revealed a statistical difference between level of
accommodation and the asthenopia score (F-value = 5.553; p =
0.002). The tests show difference between groups j(20) and
j(35) (p=0.03). ANOVA also shows difference between j(20)
and j(50) (p=0.033). Groups j(20) and j(60) were statistically
different as well (p=0.005). But there was no difference in the
following analysis: j(35) versus j(50) (p=0,870), j(35) versus
j(60) (p=0.999), j(50) versus j(60) (p=0.931) (Table 1). The j(20)
group was paired with the other groups concerning their
gender and age, without interference of such factors. Analysis
of variance (one-way ANOVA) showed no significant difference
between groups concerning the intensity of hyperopia (F-value
= 1.445; p = 0.238).
Table 1
Relation between the level of accommodation and the variables age, gender and asthenopia score during the nearvision task. One-way ANOVA showed difference between group j(20) and the other groups concerning the asthenopia
score (F-value = 5,553; p = 0,002).
Group
n
Age in years
(mean ±SD)
Gender
M
F
20% of accommodation in reserve: j(20)
17
27.80 (±6.66)
8
9
1.479 (±0.31)
35% of accommodation in reserve: j(35)
19
30.13 (±5.18)
7
12
0.786 (±0.735)
50% of accommodation in reserve: j(50)
17
24.93 (±7.92)
8
9
0.932 (±0.534)
60% of accommodation in reserve: j(60)
16
24.20 (±6.85)
7
9
0.812 (±0.591)
DISCUSSION
The value of total hyperopia and the difference between
the pre-cycloplegia and the post-cycloplegia refraction measured
by the autorefractor were not associated to the symptoms
presented during near vision effort. In his book, Duke-Elder
states that symptoms do not appear in the proportion of severity
of causal defect. The symptoms vary from individual to individual, reaching surprising levels without any apparent cause(1).
Among the variables of the study, the one that contributed
the most to the linear prediction of the symptoms was the
Asthenopia Symptoms Survey (ASS). The pre-test complaint
scores had a positive relation with the complaints during the
test, regardless of the group tested. Thus, it is possible to conclude
that some research on the symptoms of asthenopia during
anamnesis is valid in order to help in the refraction and
prescription of glasses for near vision.
There was no linear relationship between the treatment
groups and the asthenopia score during the near vision task.
Nevertheless, it could be concluded, from the results, that the
prescription of lenses over j (35) considerably reduces the
symptoms of asthenopia. Hence, there are no guarantees that
the prescription of highly positive lenses, such as the prescription
over j(50), will reduce more the patients’ symptoms of asthenopia.
We will illustrate the findings of the results into the following
example: a 25-year-old individual (amplitude of accommodation
Rev Bras Oftalmol. 2015; 74 (4): 225-30
Asthenopia score during the task
(mean ±SD)
of 8.5 D), with total hyperopia of +3.0 D spherical, has a correction
of +0.50 D spherical in diagram J35 (Figure 3); the same individual presents a correction of +1.75 D spherical in diagram J50 for
near vision lenses. The results pointed out significant
improvement in +0.50 D or over lenses prescription. The
prescription of highly positive lenses, namely over +1.75 D, does
not ensure improvement in relation to +0.50 D.
Therefore, it is possible to infer that, in isolation, the power
of accommodation does not explain the symptoms of asthenopia
in a linear way. The use of extrinsic muscles was minimized by the
test methodology, reducing the biases of the variable in the study.
Several studies in the medical literature search for other factors
as the causes of eye strain. Studies have shown the effects of
psychological and environmental factors, such as stress at work,
burnout, luminous intensity, thermal comfort in the ocular
complaints at work(15-17). The discovery of this effect may have an
ergonomic influence on health, safety and comfort conditions.
The complaints during the test could be interpreted as the
result of the uninterrupted use of accommodation for 20 min. It
is important that longer accommodative effort tests be performed
and that new studies aim at evaluating the appearance of
symptoms due to prolonged accommodative effort or with pauses for resting.
We conclude, therefore, that the accommodative effort, in
isolation, does not explain the symptoms presented by patients;
however, there is significant reduction in the asthenopia score
when leaving 35% or more of the amplitude of accommodation
Correlation between the use of the accommodation and symptoms of asthenopia in hyperopic patients
in reserve. It was also concluded that the symptoms of asthenopia
are not associated to the severity of the hyperopic refractive
error. The search for symptoms before the near vision task was
the factor that correlated the most with the symptoms during
229
the accommodative effort test, revealing the importance of
searching for complaints about asthenopia during anamnesis,
which can help ophthalmologists with prescriptions of glasses
for hyperopic patients with asthenopia.
Figure 3: Diagrams J(20), J(35), J(50) and J(60). Colored cell: diopter is zero or negative, it may not be prescribed for hyperopia. Blank cell:
diopter is positive, it may be prescribed for hyperopia.
Rev Bras Oftalmol. 2015; 74 (4): 225-30
230
Costa JCL , Martins IBS, Nóbrega LTA, Medeiros MON, Palitot LM, Dias MBC, Dias TJ
ACKNOWLEDGEMENTS
We are very grateful to translators Rodrigo Araújo e Castro and Raquel Rossini Martins Cardoso.
REFERENCES
1.
Duke-Elder S. Refração Prática. Rio de Janeiro: Rio Med Livros;
1997.
2. Wolffsohn JS, Sheppard AL, Vakani S. Davies LN. Accommodative amplitude required for sustained near work. Ophthalmic
Physiol Opt. 2011;31(5):480-6.
3. Donders FC. On the anomalies of accommodation and refraction
of the eye. Boston: Milford House; 1972
4. Yanoff M, Duker JS. Oftalmologia. 3a ed. Rio de Janeiro: Elsevier; 2011.
5. Alves AA. Refração. 5a ed. Rio de Janeiro: Cultura Médica, 2008.
6. Abdi S, Lennerstrand G, Pansell T, Rydberg A. Orthoptic findings
and asthenopia in a population of Swedish schoolchildren aged 6
to 16 years. Strabismus. 2008;16(2):47-55.
7. Hasebe S, Graf EW, Schor CM. Fatigue reduces tonic accommodation. Ophthalmic Physiol Opt. 2001;21(2):151-60.
8. Kasthurirangan S, Vilupuru AS, Glasser A. Amplitude dependent accommodative dynamics in humans. Vision Res. 2003;43(27):2945-56.
9. Duane A. Normal values of the accommodation at all ages. JAMA.
1912; 59(2):1010–13.
10. Celebi S, Aykan U. The comparison of cyclopentolate and atropine in patients with refractive accommodative esotropia by
means of retinoscopy, autorefractometry and biometric lens thickness. Acta Ophthalmol Scand. 1999;77(4):426-9.
Rev Bras Oftalmol. 2015; 74 (4): 225-30
11. Hertwig RV, Netto AL , Souza-Dias CR. Acomodação residual
sob o efeito cicloplégico do cloridrato de ciclopentolato a 1%.
Arq Bras Oftalmol. 1994;57(6):407-10,
12. Stolovitch C, Loewenstein A, Nemmet P, Lazar M. Atropine cycloplegia: how many instillations does one need? J Pediatr
Ophthalmol Strabismus. 1992;29(3):175-6.
13. Pinheiro RK, Netto AL . Estudo comparativo da acomodação
residual após instilação de colírios de tropicamida a 1%,
ciclopentolato a 1% e associação de tropicamida a 1% +
ciclopentolato a 1%. Arq Bras Oftalmol. 2000;63(6): 475-9.
14. Chatterjee D, Kothari M, Mody K. Anomalies of accommodation,
fusion and refraction in patients with low asthenopia symptom
survey score. AIOC Proceedings; 2010.
15. Ostrovsky A, Ribak J, Pereg A, Gaton D. Effects of job-related
stress and burnout on asthenopia among high-tech workers. Ergonomics. 2012;55(8):854-62.
16. Azmoon H, Dehghan H, Akbari J, Souri S. The relationship between thermal comfort and light intensity with sleep quality and
eye tiredness in shift work nurses. J Environ Public Health.
2013;2013:639184.
17. Ustinaviciene R, Januskevicius V. Association between occupational asthenopia and psycho-physiological indicators of visual
strain in workers using video display terminals. Med Sci Monit,
2006; 12(7): CR296–301.
Corresponding author
José Faustino Cavalcanti
700, Pedro Gondim, João Pessoa, Paraíba, Brazil. Zip code: 58031180.
Phone: +55 83 88082328.
E-mail: [email protected].
ORIGINAL ARTICLE
231
Eyelid disorders: frequency of occurrence and
profile of carriers in a Brazilian population sample
Alterações palpebrais: frequência de ocorrência e perfil
dos portadores em amostra populacional brasileira
Ana Cláudia Viana Wanzeler1, Marjorie Fornazier do Nascimento1, Roberta Lilian Fernandes Sousa1, Carlos Roberto
Padovani2, Silvana Artioli Schellini1
ABSTRACT
Purpose: to show the frequency of occurrence of the eyelid disorders in a Brazilian population sample, as well as the characteristics of
the carriers. Methods: a transversal study using a random population sample was carried out in the years 2004/2005, involving nine cities
of the middle west region of the State of São Paulo - Brazil. We had 7654 participants which were evaluated according to demographic
variables and complete ophthalmological examination. The eyelid disorders were detected using a lantern and slit lamp. Data were
statistically analyzed. Results: eyelid disorders such as of trichiasis and ectropion were more related to the characteristics men, whites,
complaining of reduced near visual acuity and 72.7% of trichiasis underwent surgical treatment, as well as 28.5% of patients with
ectropion. Ptosis was related to the females, whites, complaining of reduced near visual acuity and 26.3% required surgery. Entropion
was detected only in one case, male, white and a case of epiblepharon was observed in a female, brown. Conclusion: the most frequent
palpebral disorder observed in the Brazilian general population is trichiasis, followed by ptosis and ectropion. The authors call attention
to the fact that carriers do not have complaints related to the eyelid disorders.
Keywords: Eyelid diseases/epidemiology; Population studies; Brazil
RESUMO
Objetivo: apresentar a frequência de ocorrência das alterações palpebrais em uma amostra populacional brasileira, assim como as
características de seus portadores. Métodos: estudo transversal utilizando uma amostra populacional aleatorizada, realizado nos
anos de 2004/2005, em nove cidades da região centro-oeste do estado de São Paulo. Foram examinadas 7654 pessoas sendo os
participantes avaliados segundo variáveis demográficas e exame oftalmológico completo. As alterações palpebrais foram avaliadas
por meio de exame externo usando lanterna e lâmpada de fenda. Os dados obtidos foram analisados estatisticamente. Resultados:
as alterações palpebrais como a triquíase e o ectrópio foram mais relacionadas às características homens, brancos, queixa de redução
de acuidade visual para perto. Foi realizado tratamento cirúrgico em 72,7% das triquíases detectadas, assim como 28,5% dos
ectrópios. Já os casos de ptose palpebral, foram relacionados ao sexo feminino, brancos, com queixa de diminuição da acuidade visual
para perto e 26,3% necessitaram de cirurgia. Entrópio foi detectado em um caso, masculino, branco e epibléfaro foi observado em
um indivíduo do sexo feminino, parda. Conclusão: a alteração palpebral mais presente na população geral brasileira é a triquíase,
seguida da ptose palpebral e do ectrópio. Os autores chamam a atenção para o fato dos portadores não possuírem queixas
relacionadas às alterações palpebrais.
Descritores: Doenças palpebrais/epidemiologia; Estudos populacionais; Brasil
1
2
Department of Ophthalmology, Medicine College of Botucatu, São Paulo State University “Júlio de Mesquita Filho” Botucatu, SP, Brazil.
Department of Biostatistics, Institute of Biosciences of Botucatu, São Paulo State University “Júlio de Mesquita Filho” Botucatu, SP, Brazil.
Study conducted at the Medicine College of Botucatu - UNESP
The authors declare noconflicts of interest
Received for publication 07/10/2014 - Accepted for publication 16/03/2015
Rev Bras Oftalmol. 2015; 74 (4): 231-4
232
Wanzeler ACV, Nascimento MF, Sousa RLF, Padovani CR, Schellini SA
INTRODUCTION
The eyelids are part of the protective mechanism of the
eyes. They are structures composed of very delicate tissues
that move constantly, with the possibility of undergoing
changes due to external factors or alterations of senility, with
the arisal of deformities 1. They have sweat and sebaceous
glands in their composition, besides the eyelashes which are
differentiated hair follicles that grow with a convexity that
takes them away from the eyes, so that the base of the follicle
is closer and the end of it more distant to the eye bulb2.
Keeping the eyelids opposite to the eye bulb is important
for the integrity and distribution of the tear film. When there
is eversion, inversion of the eyelid margin, or even loss of
convexity of the eyelashes, the eye bulb suffers from failure of
the protective mechanism, with the possibility of installation
of inflammation and infections of the margin or the ocular
surface, which highlights the importance normal positioning
of the eyelids3.
There is no data on the presence and distribution of the
eyelid position changes in the general population. But there
is data available on the eyelid changes in convenience samples,
as well as in the elderly, which led us to this study developed
with the aim of describing the eyelid changes most commomly
found in a randomized population sample, as well as the
demographic characteristics of the patients.
METHODS
Analyses were made on the eyelid position changes based
on data from a cross-sectional study of a randomized population
sample conducted between March 2004 and June 2005 in nine
cities of the Midwest region of the state of São Paulo. The
research protocol was analised and approved by the Research
Ethics Committee of the Medicine College of Botucatu UNESP.
Participants were sorted taking into account the place of
residence according to the IBGE census tract (Census, 2000).
The sample size of 8,010 individuals was stablished, of which
7,654 people were examined. The sample size was based on the
total number of inhabitants of the study area and on the
prevalence of blindness and low vision in the population
studied. The subjects were invited to participate and an
appointment was scheduled with the approach of a Mobile
Ophthalmic Unit.
Participants’ identification data, clinical history, and ocular and systemic background were registered. Then a complete
eye examination was performed with the assessment of visual
acuity (VA) by means of the Snellen chart for the illiterate,
external examination (using hand light), slit lamp examination
in (Shin Nippon SL-203, Japan) and refractometry. For the
present study a sub-sample of patients with eyelid changes was
analyzed. When necessary, the subjects underwent surgical
treatment.
Trichiasis was defined when there were lashes touching
the eye, in that while deployed in the anterior lamella, they
were abnormally curved and directed to eye surface4. Ectropion
is the eyelid malpositioning characterized by the eversion of
the eyelid margin away from the eye bulb. Eyelid entropion
means reversing the edge of the eyelid, causing the eyelashes
to touch the eyeball1. Ptosis is a condition in which the upper
eyelid edge is located below its normal position of 2 mm, covering
the superior limbus in the primary position of the eye look3.
The data was categorized and transferred to an Excel
table, being statistically treated for the frequency analysis of
occurrence of the phenomena observed.
RESULTS
The most significant change observed was the trichiasis,
with 22 cases detected, and a frequency of occurrence of
0.29%, 59% being in men, 86.3% in white elderly, 63.6% with
complaint of visual acuity reduction to near vision. Surgical
treatment was necessary and performed in 72.7% of cases.
There were 19 cases of ptosis, with a frequency of
occurrence of 0.24%, 63.1% in females, 84.2% in white elderly
complaining of visual acuity (VA) reduction to near vision at
52.6%, and 26.3% had surgery.
Ectropion was observed in 14 cases, with a frequency of
occurrence of 0.18%, 78.5% in males, 100% white elderly with
a main complaint of VA reduction to near vision (50%) and
ocular hyperemia (42.8%) with the need of surgery in 28.5%
of cases.
Entropion was detected in one case in a white male, and
one case of epiblepharon in a brown female (Table 1). The
frequency of occurrence of these two conditions was 0.01%.
For all the conditions detected except ptosis the lower
eyelid was the most affected.
Table 1
Frequency of occurrence of eyelid changes in the Midwest region of the State of São Paulo, Brazil.
Change
Ectrópio
Ptose
Triquíase
Entrópio
Epibléfaro
Nº cases
14
19
22
1
1
Sex
78.5%
63.1%
59%
100%
100%
Rev Bras Oftalmol. 2015; 74 (4): 231-4
males
females
males
males
females
Skin color
100%
84,2%
86.3%
100%
100%
white
white
white
white
brown
Complaints
BAV PP (50%) /Hyperemia(42.8%)
52.6% BAV PP
63.6% BAV PP
100% whatery eyes
BAV PP and Hyperemia
Surgical treatment
28.5%
26.3%
72.7%
0%
0%
233
Eyelid disorders: frequency of occurrence and profile of carriers in a Brazilian population sample
Figure 1: Frequency of occurrence of eyelid changes in inhabitants of
the Midwest region of the State of São Paulo - Brazil
DISCUSSION
The main value of the present study was that the evaluation
was performed in a randomized population sample, which
allowed us to know the frequency of occurrence of eyelid position
changes in the general population without considering
convenience samples. Knowing the frequency of occurrence of
eyelid changes is interesting due to characteristics of individuals
living in a given area, as it is important to plan the training for
residency programs.
The most frequent change found in the eyelids was trichiasis,
which is an acquired condition usually due to chronic
inflammation of the eyelid margin as blepharitis and meibomites,
cicatrization conjunctival diseases and cicatrization anomalies of
the eyelid margin associated or not to previou surgeries 4.
Dermatoses as well as the effect of solar radiation on the delicate
skin of the lower eyelid are also important2 with the coincidence
of trichiasis being observed primarily in white men who probably
worked exposed to the sunlight, as the area under study is
primarily agricultural. Another cause of trichiasis and entropion
is trachoma, which was very prevalent in the rural area of São
Paulo at the beginning of last century, with the characteristic of
affecting the upper eyelid where the tarsal plate is wider and
being reported that the disease is more frequent in women5,6.
Ptosis was observed in 0.24% of the study population,
predominantly in females and white people. The prevalence of
ptosis in another region was higher than that observed in the
present study7, probably due to the presence of older patients in
that group of patients or the type of selection that was proposed
for the studies. There is no sufficient data available about the
frequency of occurrence of ptosis, but it is known that there is
equal frequency among different races and between sexes8. The
surgery was performed in only 26.3% of patients with ptosis.
Surgical treatment is mandatory only in severe ptosis which can
lead to serious functional deficit9.
Ectropion corresponds to the lower eyelid eversion and
may be due to congenital or acquired causes, and the involutional
type is the most frequent one10. A study involving only the elderly
in São Paulo pointed out the prevalence of ectropion in 2.9% of
cases, whereas in the general population we found ectropion in
0.18%. It was found mostly in males and white people, with the
consensus that men are more prone to eye disorders, perhaps
due to having professions in which they are more exposed to
risk factors11. Several patients with ectropion (42.8%) had ocular hyperemia, which can be explained by the concomitance of
meibomitis, blepharitis and keratitis with the ectropion position
of the eyelid2,12. However, the surgery was performed in only
28.5% of cases, most likely due to the non-adherence to surgical
treatment of patients who did not have great complaints.
Regarding entropion, the frequency of occurrence was
0.01%, while an entropion of 2.1% have been found when
assessing only the elderly. The involutional entropion is the most
frequent, and affects only the lower eyelid14.
The epiblepharon is clearly influenced by race, being much
more frequent in Japanese children, with a prevalence of 4.3%,
with no sex preference, with lower eyelids affected and bilateral
involvement15. It is rare in our country, being detected in 0.01%
of the study participants. By representing a skin fold, most often
in the lower eyelid and pushing the eyelashes against the eye
bulb2 which can be reduced with the growth of the face in general, surgery is not necessary, as it happened to the subject who
was part of this study.
It is very important to point out that the vast majority of
patients with eyelid position changes complained only about
concomitant refractive errors, which values the need for
comprehensive eye exams.
CONCLUSION
The most present eyelid change in the general population
of a region of São Paulo, Brazil was trichiasis, followed by ptosis
and ectropion. The authors emphasize the fact that patients have
no complaints about the changes of the eyelid position.
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Corresponding author:
Ana Cláudia Viana Wanzeler
Rua Antônio Amando de Barros, 241 – Botucatu (SP)
ZIP Code: 18601-260
Email: [email protected]
ORIGINAL ARTICLE235
Patient’s perception on glaucoma and different types
of treatment (medical versus surgical treatment)
Percepção dos pacientes portadores de glaucoma sobre sua doença
e os diferentes tipos de tratamento (clínico versus cirúrgico)
Augusto Alves Pinho Vieira1, Ricardo Augusto Paletta Guedes2, Rita de Cássia Padula Alves Vieira3, Vanessa Maria
Paletta Guedes4
ABSTRACT
Objective: To identify the meaning and impact on their quality of life of having glaucoma and to understand the patients’ perception on
the different types of treatment (medical or surgical). Methods: Through a qualitative research, focus groups were conducted with
patients in clinical treatment (group 1) and patients who underwent glaucoma surgery in both eyes and were without medication (group
2). The responses were analyzed using the technique of content analysis. Results: Fear of blindness and lack of information about the
disease were the most cited issues in relation to how it is like to having glaucoma. Medication costs, impact of drops on patients’ daily lives
and the side effects were the main points discussed in relation to medical treatment. All patients in the surgical group preferred the current
situation (without medication) when compared to the need for chronic use of medication. In the two groups, both glaucoma and its
treatment had a profound impact on people, not only from a psychological standpoint, but also affecting their daily lives. Patients
operated on for glaucoma appear to have less impact on their daily lives, but the concern about the disease persists. Conclusion: We
identified the most significant negative aspects of glaucoma and its treatment from patients’ perspectives. Confidence in the correct
indication of the type of treatment, clinical or surgical, and a solid relationship between the patient the doctor are determining factors for
extra peace of mind of patients being treated for glaucoma.
Keywords: Glaucoma, open-angle/psychology; Glaucoma, open-angle/therapy; Glaucoma, open-angle/surgery; Quality of life
RESUMO
Objetivo: Identificar a percepção dos pacientes sobre o significado de ser portador de glaucoma e a percepção que tem sobre o
tratamento clínico ou cirúrgico. Métodos: Para a coleta dos dados utilizou-se a pesquisa qualitativa através da estratégia de grupos
focais realizados com pacientes em tratamento clínico (grupo 1) e pacientes submetidos à cirurgia antiglaucomatosa (grupo 2). A
análise e a interpretação dos resultados foram feitas pela técnica da análise de conteúdo. Resultados: O medo da cegueira e a
desinformação sobre a doença foram os aspectos negativos mais encontrados com relação a ser portador de glaucoma. O grupo
cirúrgico preferiu a situação atual quando comparada à necessidade do uso de medicação. Verificou-se que tanto o glaucoma quanto
o seu tratamento impactaram profundamente esses pacientes e que, embora a preocupação com a doença ainda persista, os
pacientes operados demonstraram apresentar menos impacto no seu cotidiano. Foram determinantes para a aceitação da indicação
da cirurgia a falta de controle da doença e a confiança no médico, sendo esta última considerada um fator primordial nos dois grupos
pesquisados, o que aponta para sua importância, independente da decisão tomada pelo paciente na convivência com sua doença.
Conclusão: Identificaram-se os aspectos negativos mais relevantes com relação ao glaucoma e ao seu tratamento. A confiança na
correta indicação do tipo de tratamento, clínico ou cirúrgico, e uma relação sólida entre o paciente o médico são os fatores determinantes
para uma maior tranquilidade dos pacientes em tratamento de glaucoma (clínico ou cirúrgico).
Descritores: Glaucoma de ângulo aberto/psicologia; Glaucoma de ângulo aberto/terapia; Glaucoma de ângulo aberto/cirurgia;
Qualidade de vida
Hilton Rocha Foundation, Belo Horizonte, MG, Brazil.
Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
3
College of Health and Medical Sciences of Juiz de Fora, Juiz de Fora, MG, Brazil.
4
Ophthalmology Service of the Charity Hospital of Juiz de Fora, Juiz de Fora, MG, Brazil.
The authors declare no conflicts of interest
Received for publication 04/03/2015 - Accepted for publication 29/03/2015
1
2
Rev Bras Oftalmol. 2015; 74 (4): 235-40
236
Vieira AAP, Guedes RAP, Vieira RCPA, Guedes VMP
INTRODUCTION
T
he maintenance and/or improvement of the quality of life
at a reasonable cost should be seen as the highest goal of
the glaucoma treatment.1,2 The quality of life is closely
related to: the stage of visual function damage of the patient; the
psychological impact of the disease and its treatment; the
doctor-patient relationship; the cost and side effects of the
treatment; the independence to perform household and work
tasks, such as driving and reading; the inconvenience of
instilling eyedrops; and disbelief in its true usefulness and
efficiency due to missinformation. 3-11
To achieve properly and efficiently the goal of the glaucoma
treatment, patient education and counselling by the doctor are
very important in the pursuit of establishing a therapeutic regimen
capable of overcoming the following barriers: age, ethnicity, sex
and social class.2,4 There are also other more subjective factors
that may serve as barriers to the treatment proposed, such as:
values, beliefs and culture of the patients.11,12
Basically the glaucoma treatment is accomplished through
the proper control of intraocular pressure, which may be done
with medication (eyedrops), laser or surgery.13The guidelines
for glaucoma treatment advise to always start the treatment with
eyedrops, and classically surgery is left for cases where medical
treatment is not well indicated (intolerance, cost, low adherence
and persistence) or is not enough.14,15
There is no evidence in the literature of what kind of
glaucoma treatment is preferred by the patients. What is the
impact of having glaucoma for the patient? What do they think
about the treatment? How is the possible need for surgery
understood and how it influences the treatment? These are some
examples of questions that would be very difficult to be answered
with a quantitative methodology. In the medical literature
qualitative studies that attempt to clarify the beliefs and values
assigned by glaucoma patients themselves to the type of
treatment (medical or surgical) proposed by the doctor are
virtually absent.
This study aimed to identify, from the perspective of
patients, the meaning of being a glaucoma carrier, emphasizing
the impact of this disease on their quality of life and in the
perception (values, beliefs, fears) that had about the type of
treatment (clinical versus surgical).
METHODS
The clinical data of the patients was obtained through
the analysis of their medical records, and were used to
characterize the research participants. The study groups were
formed of patients in clinical treatment (group 1) and patients
who had undergone the glaucoma surgery (group 2), and the
criteria for inclusion in the study were: patients over 21 years
old with controled and in advanced stage primary open-angle
glaucoma (index Mean Deviation of computerized campimetry
< -12.00 dB) in at least 1 eye. In group 1 patients were in
continuous use of antiglaucoma eyedrops in both eyes, and in
group 2 they underwent surgery in both eyes at least one year
before. We excluded those patients who had been operated
and that had returned to the chronic use of antiglaucoma
eyedrops, as well as patients whose desease were not considered
controlled by the attending physician (Table 1).
The selection of patients who meet the inclusion criteria
was made through invitation to them when they went to their
appointment consecutively until completing the number of 10
patients per group. All the patients read, agreed and signed the
Informed Consent Term approved by the Research Ethics
Committee of the SCMJF.
For the focal group, we used a script of questions
previously elaborated based on guiding questions (Example:
How do you deal with the fact of having glaucoma? What do
you think about the treatment? How do you understand the
need for surgery and how it influences the treatment?). The
questions were pre-tested with patients with the same
characteristics of the future survey subjects.
The meetings with the groups were in different days, and
data collection was interrupted when the “saturation point”
was reached, i.e., when information obtained during the group
dynamics and the interviews became recurrent.
The discussions and interviews were recorded on
electronic media, and later literally transcribed. The content
obtained was organized and categorized along with the
document research based on the operation summarized in
Minayo16, which consists of three steps: pre-analysis; study of
the material; and treatment of the results obtained and
interpretation.
The procedures for the data analysis were based on the
content analysis technique. Finally, the data obtained was
related to the theoretical framework adopted, in order to
apprehend the subjects’ perception on the core question of
this study, i.e., the perception of subjects surveyed about
glaucoma and its treatment.
RESULTS
The method proposed for this study is based on the
assumptions of qualitative research, where we work with the
notions of meaning, beliefs, aspirations, reasons, values and
attitudes, seeking an approch with the object of study, as proposed
by Minayo.16
The field of study chosen was a private clinic specialized in
glaucoma, and the research project was approved by the Research
Ethics Committee of the Charity Hospital of Juiz de Fora
(SCMJF) by Opinion No. 040/2011.
As methodological strategy for collecting data, this study
used focus groups (discussions and presentation of ideas in group)
and individual semi-structured interviews, when necessary, used
to complement the data obtained during the group discussion.
Rev Bras Oftalmol. 2015; 74 (4): 235-40
From the 10 patients selected to bex each sample group,
only 9 attended the meeting. The characteristics of each one of
the participants are described in Table1, and the subjects in group
1 are coded by numbers (1 to 9) and in group 2 by letters (‘A’
through ‘I’).
The medical discourse and common sense contribute at
the same time to the meaning of the “having glaucoma”,
unanimously translated by fear of blindness, mentioned several
times by the subjects interviewed (Table 2). Some patients have
reported lack of knowledge about glaucoma before being
diagnosed with the disease. Speeches like “I got gcared for not
Patient’s perception on glaucoma and different types of treatment (medical versus surgical treatment)
237
Table 1
Características dos participantes da pesquisa:
Group 1:
Clinical
treatment
Patient
Patient
Patient
Patient
Patient
Patient
Patient
Patient
Patient
1
2
3
4
5
6
7
8
9
Group 2:
Clinical
treatment
Patient
Patient
Patient
Patient
Patient
Patient
Patient
Patient
Patient
A
B
C
D
E
F
G
H
I
Age
(years)
75
63
69
65
93
72
63
72
83
Age
(years)
78
59
80
55
81
47
70
68
58
Ethnicity
Sex
Education
white
black
black
black
white
white
white
white
white
M
F
F
F
F
M
F
M
M
High school
Elementary
Graduated
Elementary
Elementary
Graduated
Elementary
Elementary
Graduated
Ethnicity
Sex
Education
black
black
white
white
white
white
white
white
white
M
F
F
M
F
M
F
F
F
Elementary
Elementary
High school
Graduated
High school
Elementary
Graduated
High school
Elementary
knowing it” (Patient 1) and “I had never heard about this particular desease” (Patient 1) are examples of how lack of knowlege
can generate an even greater negative impact in the diagnosis of
glaucoma.
Patients mentioned that giving up activities that gave them
pleasure or that were part of their routine was a difficult change
to accept. Some examples are as follows: “I stopped working
earlier than I wanted to. For example, driving. I’ve always wanted
to get my license, but I never could (Patient 6); “When I knew I
Table 2
Examples of speeches about the subjet “having glaucoma”.
Patient 4
“At first, I was very worried about blindness.
I couldn’t read.”
Patient 5
“Really worried about being blind. I was afraid
of falling; I was really concerned.”
Patient 8
“I heard glaucoma was blindness for sure. But
the doctor said it wasn’t true at all.”
Patient 9
“I got, like, really worried. My mother was
blind before dying.”
had glaucoma, I had to stop working, and now I don’t work
anymore, you know…” (Patient 7).
During the meetings of the focus groups, the speeches about
the use of eyedrops were recurrent, even in patients who had
Time since the discovery
of the disease (anos)
7
3
10
11
2
4
15
1
20
Time since the discovery
of the disease (anos)
12
25
16
13
6
34
26
30
10
Number of droplet
per day per eye
5
3
1
5
6
3
6
3
3
Number of droplet
per day per eye
2
5
3
3
2
5
5
4
3
undergone surgery and were no longer using them. The need
for chronic use of eyedrops generated discussions related to the
concern of relying on an expensive drug, as well as the discomfort
represented by the change of routine due to the care involved in
the correct use of eyedrops.
Patients in the clinical group were the ones who talked the
most about the cost of the drug treatment. All patients in this
group were unanimous when reporting the problems related to
the chronic use of medication. Table 3 gives some examples of
speeches about the patients’ perception on the routine of the
chronic treatment with eyedrops.
The pharmacological treatment then becomes a necessary
discomfort, according to the speeches of all patients interviewed.
In the clinical group, living with the eyedrops is considered a
dependence of which they complain, claiming concern for
forgetting or having difficulties in the transportation because of
the need to keep some medicines under refrigeration. The
concern with time was dominant, and some even affirmed they
make use of the most diverse and creative resources, such as the
use of warnings or “timers”.
In the surgical group we noted a kind of freedom in relation
to such routine. This group showed satisfaction with the freedom
that surgery provided; however, they were still concerned about
the disease and the possible need to use the medication again.
Table 4 shows examples of speeches about the patients’
perception regarding the surgical treatment of glaucoma. Side
effects were remembered by patients in the surgical group, such
as: bitter taste, blurred vision after instillation, dry eye and allergy,
confirmed by the patients in the clinical group, which still make
chronic use of same.
Rev Bras Oftalmol. 2015; 74 (4): 235-40
238
Vieira AAP, Guedes RAP, Vieira RCPA, Guedes VMP
Table 3
Table 4
Examples of speeches about the difficulties and
concerns an the clinical treatment of glaucoma
Examples of speeches about the patients’ perception
regarding the surgical treatment:
Patient A
“...anyway I would choose surgery... eyedrops
are expensive and you’ll be using and not
solving the problem of pressure.””…but the
doctor seems confident.”
Patient B
“…I really prefer the surgery. And trust in
God first and then the doctor.”
Patient D
“...surgery is the last stage.””So I think there
are many risks in it (Authors’ note: regarding
the indication of treatment), especially the
trust relation between the patient and the
doctor. Many times the doctor is more
important than the medical or surgical
treatment.”
Patient E
“...I feel better after the surgery because I
think I’m free from the evil....””And when we
find a doctor who gives us attention, who speaks
clearly, objectively, we trust them and go on.”
Patient F
“…I trust better the surgery. Surgery nipped
the evil in the bud.”
Patient G
“…my eye got very red when I instilled
eyedrops. I prefer surgery.”””..in my case
eyedrops were not working, so I had to go on
surgery. But always trusting, because I knew
God and the doctor were there for me.”
DISCUSSION
Patient H
“The eyedrops were not working for me… I
was afraid of being blind.””We must trust the
doctor.”
When trying to understand the meaning of “having
glaucoma”, other aspects should be considered besides the
biological and physiological ones, and the treatment of the sick
body. The glaucoma patient assimilates what society offers in
terms of values, information, ideas, and theories, building from
that their own history, becoming a socio-historical-cultural
being. 17,18
The visual assessment itself is often more valued (clinical
data of ophthalmological examination) than the impact of vision
loss, or even the threat that this loss may represent on these
people lives, because “having glaucoma” is the same as no longer
being productive, no longer being independent, is facing the
unknown, a situation the patient fears. The lack of information
about the disease and the fear of blindness were themes really
mentioned by the patients in this study. “Having glaucoma” for
some patients means certain blindness, and the lack if information
generated anxiety and fear about the disease.
Education about the disease becomes important not only
to the patient already diagnosed with the disease, but also to the
general population. A more conscious society on glaucoma would
help reduce the psychological impact of “having glaucoma”.
The clinical treatment of glaucoma can paradoxically
compromise the quality of life of the patient. Need for chronic
use of medication, possible side effects, concerns and anxieties
Patient I
“...I am allergic to drops. I can not use any
eyedrops! So I had to go on surgery, you
know...””...I also prefer the surgery because I
really trust the doctor. First God, then her.”
Patient 2
“Besides price, what I think is absurd is the
amount. The amount is minimal! If we miss
one drop, it is worth gold!”
Patient 3
“In one month the situation got worse: three
people using eyedrops” (in the family).
Patient 4
“But it’s so expensive, so expensive that I
came came up with the decision of asking the
doctor if I could change the medicine”
Patient 2
“I put my eyedrops in two shelves, in the
bathrooms... with a warning!”
Patient 6
“To me, it’s so bad to use eyedrops every ten
minutes. I need a timer… to track time.”
Patient 8
“In this sense, this thing of instilling eyedrops
at a certain time bothers me and makes me
very uncomfortable.”
For patients in surgical treatment group, the main
motivation for undergoing surgery was the medical
indication, given the inability to control glaucoma only with
topical medication. The fear of being blind, even though in
treatment with eyedrops, made patients accept the surgical
indication as a valid option.
Rev Bras Oftalmol. 2015; 74 (4): 235-40
about the daily routine of treatment are some examples
mentioned by patients in the presnet study about the negative
impact on the quality of life of the patients chronicaly using
eyedrops. Another important factor is the cost of the treatment.
Speeches like type “each droplet is worth gold” were reccurent
during the interviews. The need to sacrifice part of the family
budget also has a big impact, since the patient gives up “extra”
activities. Such activities which rely on part of their salary now
spent on medication could represent an improvement of the
same quality of life. In this context are includes trips, special
meals, leisure, among others.
Glaucoma and its chronic course requires prolonged
treatment and follow-up, and a high cost that can compromise
25% or more of the patient’s family income. A Brazilian study
found out that the lack of financial resources was reported by
47.6% of respondents as the main cause of treatment
discontinuation, making the adhesion difficult and being
responsible for the loss of visual field.8 The difficulties in using
Patient’s perception on glaucoma and different types of treatment (medical versus surgical treatment)
eyedrops are added to the cost itself, since each lost droplet has
to be administered again.
Studies comparing the different kinds of glaucoma
treatment using the quality of life as an outcome are rare.
Encouraged by the clinical impression that the glaucoma-operated
undergoing have a better quality of life than those in chronic use
of eyedrops, researchers in the United States (Collaborative
Initial Glaucoma Treatment Study - CIGTS), randomized newly
diagnosed glaucoma patients for clinical or surgical treatment
(Trabeculectomy). Both groups had worse quality of life indexes
soon after the diagnosis. The indexes were improving during the
follow-up (9 years), demonstrating that patients tend to get used
to the disease and its treatment. Patients in the surgical group
had a slight worsening of quality of life in the early postoperative
stage, directly linked to the local effects of the surgery. In the
long term, the quality of life indexes did not differ. 19
In Brazil, Paletta Guedes et al. identified, also by means of
a questionnaire, that patients with early-stage of glaucoma
showed an association between surgical treatment and lower
indexes of quality of life, which did not happen to more advanced
stages of the disease. The most affected dimension in these cases
was the psychological one, leading to the belief that a surgery for
early glaucoma patients can give a great psychological impact.20
The question of patient preference on the type of treatment
(medical or surgical) is difficult to be elucidated with quantitative
research, as mentioned above. The CIGTS could not answer this
question, and it can be seen in the research of Paletta Guedes et.
al. 20 that choosing the type of treatment may have a nonnegligible psychological impact for some patients.
Before surgery, the patients in this study who had
undergone surgical treatment were chronic users of eyedrops
for a long time, and now were free of this commitment. So they
had a unique condition of having lived the problem both from a
clinical treatment point of view and from the point of view of the
surgical treatment. When asked about their preference between
the two conditions (clinical treatment versus surgical treatment),
they were unanimous in reporting that they preferred surgery,
and despite the discomfort of using eyedrops, confidence in the
medical indication and a good control of the disease were the
most important factors for this treatment option.
Confidence in the indication of the type of treatment, clinical
or surgical, and a solid relationship between doctor and patient
are the most important findings of the present study. A similar
result was found by Lemaitre et al.21 In a study carried out with
glaucoma patients who required a filtering surgery, these authors
found that both the disease and the surgical procedure are sources
of anxiety. The relationship between doctor and patient and the
confidence in the indication of the treatment appeared as key to
decreasing the preoperative anxiety reported by the patients.21
A limitation of the present study is that the sample may
not be representative of the entire population of primary openangle glaucoma patients. This fact is inherent in any survey
conducted by the qualitative method because it is intended to
deepen the most the question to be answered, and not generalize it. The saturation point for the qualitative methodology is an
indication that a larger sample would be unnecessary to achieve
the goal proposed in this research. A deep understanding of
values, beliefs, concerns, anxieties and fears is only possible by
means of a qualitative research.
Another limitation is that patients in the surgical group
may have been influenced by the conduct of the attending
239
physician (type of surgical technique). Also as a limitation we
can mention the fact that the research was conducted in a private
practice environment, which may influence the perception of the
patients. We believe that values, beliefs and culture base are
different between patients attending a private clinic and those
who are seen at the Single Health System (SUS). Another similar study with patients enrolled in the Single Health System
(SUS) could clarify this point. However, these limitations do not
invalidate our results.
In conclusion, glaucoma gives patients a deep sense of fear
and concern not about the loss of vision, but also about the
impact of the disease and its treatment on their daily lives. The
cost and side effects of the clinical treatment were the main
negative factors raised by the patients. The patients in the surgical
group were unanimous in preferring surgery in relation to the
chronic use of eyedrops. Glaucoma-operated patients seem to
have less negative impact on their daily lives, but the concern
about the disease persists.
The confidence in the doctor and the correct indication of
proper treatment, be it clinical or surgical, is a major factor for
extra peace of mind of the patient. The ophthalmologist is
privileged with regard to the possibility of contributing to the
reduction of the patient’s anxiety about the procedures necessary
to a better quality of life.
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patients. J Glaucoma. 2012; 22(5):369-73.
21. Lemaitre S, Blumen-Ohana E, Akesbi J, Lapalce O, Nordmann
JP. Evaluation of preoperative anxiety in patients requiring glaucoma filtration surgery. J Fr Ophtalmol. 2014; (1):47-53.
Corresponding author:
Augusto Alves Pinho Vieira.
Rua Dr. Asclepíades da Paixão Lucas 147, Portal da Torre.
36037-462 Juiz de Fora MG.
Phone:(32) 3231 2111; (31) 8811 3691
E-mail: [email protected]
CASE REPORT
241
X-linked juvenile retinoschisis
Retinosquise juvenil ligada ao X
Cesar Gomes da Silveira1, Gabriela Hertz Soares2, Jacqueline Provenzano3
ABSTRACT
Report the case of a male 28 years-old patient, who was referred to Centro de Estudos e Pesquisas Oculistas Associados – RJ, to retina
assessment and presented the tipical findings of the X-Linked Juvenile Retinoschisis: A cystoid maculopathy with formation of foveal
cysts and schisis of the peripheral retina. It was carried out the conservative management, with attention to the complications.
Keywords: Retinoschisis/diagnosis; Genetic diseases, X-linked/diagnosis; Case reports
RESUMO
Relatar o caso de um paciente masculino de 28 anos, que foi encaminhado ao Centro de Estudos e Pesquisas Oculistas Associados – RJ,
para avaliação de retina e apresentou os achados típicos de Retinosquise Juvenil Ligada ao Cromossomo X: maculopatia cistóide com
formação de cistos na fóvea e retinosquise periférica. Foi realizado o manejo conservador, com atenção para as complicações.
Descritores: Retinosquise/diagnóstico; Doenças genéticas ligadas ao cromossomo X/diagnóstico; Relatos de casos
1
3
Third-year resident physician of the Study and Research Center Opticians Associates - Rio de Janeiro, RJ, Brazil.
PhD at. Head of the Study and Research Center Opticians Associates - Rio de Janeiro, RJ, Brazil.
The authors declare no conflicts of interest
Received for publication 18/11/2011 - Accepted for publication 20/01/2013
Rev Bras Oftalmol. 2015; 74 (4): 241-3
242
Silveira CG, Soares GH, Provenzano J
INTRODUCTION
X
-linked juvenile retinoschisis (XJR) is a inherited
recessive vitreoretinal degeneration more common in
young men characterized by bilateral maculopathy with
associated peripheral retinoschisis in 50% of patients. (1-6) A
prevalence of 1:5000 to 1:28000 is estimated.(1,3)
There are descriptions of mutations in the XLRS1 gene(13,7)
, responsible for coding of retinoschisis - a protein that provides
adhesion and interaction among cells and among the retinal layers.
Defects or absence of its secretion may reduce the adherence
between the layer of nervous fibers and the remainder of the
sensory retina, forming cystic cavities.(1,6)
XJR manifests with reduced visual acuity (VA) between
the ages of five and ten years of age, and evolves with progressive
visual loss during the first two decades of life. There is the
possibility of stabilization of the VA until the fifth or sixth decade,
when it can worsen due to macular atrophy, no longer showing
the cystic aspect.(5)
The visual acuity may be less than 20/200, keeping an average
of 20/70 in young adults. Abnormalities in the angle of the anterior chamber such as occlusion angle, strabismus and nystagmus
are described as other findings. Vitreous hemorrhage and retinal
detachment are the main complications.(1,3,5)
The foveal retinoschisis is characterized by the “wagon
wheel” standard of radial streaking due to changes in the layer
of nerve fibers related to a defect of the Müller cells.(8) Despite
the cystic appearance, the exam of fluorescein angiography does
not evidence the progressive extravasation characteristic of
cystoid macular edema and contributes to the differential
diagnosis between pathologies. (8) Peripheral retinoschisis
predominantly involves the inferior temporal quadrant, often
with large detachments of the inner retinal layers. These changes
of the inner layers of the retina predispose vitreous hemorrhage
and retinal detachment.(8)
of macular and peripheral retinal images. These findings
corroborate the diagnosis of X-linked juvenile retinoschisis.
A new fluorescein angiography (Figure 3) was made in
2011 showing similar appearance to that found in the previous
exam. The exam of optical coherence tomography (OCT) (Figure 4) also held in 2011 showed an image of subfoveolar cystic
confluence, further changing the fovea architecture and justifying
the visual impairment.
Figure 1: Simple retinography (on the left): macular changes in
retinoschisis or “wagon wheel”. Fluorescein angiography (on the right):
absence of contrast extravasation. 2008.
CASE REPORT
MJS, male, 28, white, single, born and raised in Rio de Janeiro - RJ was referred to the Study and Research Center Opticians
Associates - RJ (CEPOA) in February 2011, for retinal evaluation
with the diagnosis of XJR. When asked about his family history,
he mentioned a brother with whom he is no longer in contact,
but who suffers from the same pathology diagnosed.
He brought additional exams from 2008, in which the redfree photography showed the standard of foveolar retinoschisis
that extends circumferentially to the parafovelar area. Fluorescein
angiography demonstrates cystic changes in the macula without
fluid leakage through the subcystoid space (Figure 1). Optical
coherence tomography (OCT) (Figure 2) shows foveal cysts
with retinal cleavage between the outer and inner plexiform
layers in both eyes (BE).
In the eye exam held on 02/01/2011 the visual acuity was 20/
60 in BE, with the best correction. The biomicroscopy of the anterior segment shows no changes. The intraocular pressure was 17
mmHg at 04pm in BE. The retinal mapping performed showed a
macular image in foveolar retinoschisis and inferior temporal
retinoschisis in the right eye. The left eye showed the same pattern
Rev Bras Oftalmol. 2015; 74 (4): 241-3
Figure 2: OCT images from 2008. Presence of foveal cysts in both
eyes.
DISCUSSION
X-linked juvenile retinoschisis is a relatively rare disorder
which determines low visual acuity, mainly by foveolar
retinoschisis.(1-6)
The inferior temporal bilateral presentation is considered
the classic pattern of disease, and the most frequent complications
and of worst prognosis are vitreous hemorrhage and retinal
detachment.(5)
243
X-linked juvenile retinoschisis
The treatment aims to prevent complications that increase
visual loss, since nothing has been proven effective in preventing
the development of the disease.(2) The possibility of treatment
with topical dorzolamide is being studied, but still remains
unproven. (6,9,10)
In cases of vitreous hemorrhage, some authors suggest
the use of photocoagulation of the vessels responsible for the
bleeding.(11,12) But in cases of retinal detachment, a tamponade
on the rupture and vitrectomy via pars plana are indicated.(2,11)
Children who have concomitant strabismus deserve
attention, and factors that can induce amblyopia should be
minimized. Aid for low vision, and adaptive skills training can
help individuals who develop visual loss. Genetic counseling can
help identify family members who are carriers of the gene XLRS1,
in order to avoid further damage.(2)
REFERENCES
Figure 3: Simple retinography (on the left): macular changes in
retinoschisis or “wagon wheel”. Fluorescein angiography (on the right):
absence of contrast extravasation. 2008.
Figure 4: OCT images from 2011. Presence of foveal cysts in both
eyes
The fluorescein angiography reaffirms the diagnosis, ruling
out the possibility of cystoid macular edema, since there is no
extravasation of dye through the macula.(4,5)
The optical coherence tomography (Figures 2 and 4) show
changes in the evolving foveolar architecture (foveal thickness
changes in BE), resulting from cysts on the layer of nerve fibers.
These cystic formations are also found in the retinal periphery,
where they may break to the vitreous and the retina, causing
retinal ruptures and hemorrhages.(1,5)
The electroretinogram is important in the diagnosis of this
disease. The wave amplitude A is normal or close to normal, but
wave B has a very reduced amplitude. This reduction in the wave
of the B is justified by the change in the initiation of the electrical
impulse in the Müller cells.(5)
Literature considers the possibility of stabilization of VA
around 20/70 during the second decade of life, with possible
progression to atrophic maculopathy around 60 years old.(5,9)
1.
Song MK, Small KW, Jayne RP, Law SK, Charles S, Brown LL, et
al. Retinoschisis, juvenile [Internet]. [cited 2013 Jan 12]. Available from: http://emedicine.medscape.com/article/1225857-overview.
2. Kugler M. Juvenile retinoschisis: causes progressive loss of vision
[Internet]. [cited 2013 Jan 13]. Available from: http://
rarediseases.about.com/od/rarediseasesr/a/retinoschisis05.htm
3. Puech B. X-linked juvenile retinoschisis. Orphanet Encyclopedia.
May 2004. Disponível em: http://www.orpha.net/data/patho/GB/
uk-XLRS.pdf
4. Edwards AO, Robertson JE. X-linked juvenile retinoschisis. In:
Ryan SJ, editor. Retina. 3rd ed. St. Louis: Mosby; 2001. p. 487-90.
5. Cunha AA, Picanço BC, Almeida GA, Rodrigues NH, Rocha
GM. Retinosquise juvenil: relato de caso. Arq Bras Oftalmol.
2008;71(6):878-80.
6. Caye LM, Barbosa PH, Scheid KL, Cardoso IH, Fortes Filho JB.
Uso da dorzolamida tópica em paciente portador de retinosquise
juvenil ligada ao X. Rev Bras Oftalmol. 2010;69(2):129-31.
7. Sauer CG, Gehrig A, Warneke-Wittstock R, Marquardt A, Ewing
CC, Gibson A, et al. Positional cloning of the gene associated with
X-linked juvenile retinoschisis. Nat Genet. 1997;17(2):164-70.
8. Shukla D, Rajendran A, Gibbs D, Suganthalakshmi B, Zhang K,
Sundaresan P. Unusual manifestations of x-linked retinoschisis:
clinical profile and diagnostic evaluation. Am J Ophthalmol.
2007;144(3):419-23.
9. Bastos AL, Freitas BP, Villas Boas O, Ramiro AC. Use of topical
dorzolamide for patients with X-linked juvenile retinoschisis: case
report. Arq Bras Oftalmol. 2008;71(2):286-90.
10. Apushikin MA, Fishman GA. Use of dorzolamide for patients
with X-linked retinoschisis. Retina. 2006;26(7):741-5. Erratum
in: Retina. 2007;27(1):128.
11. George ND, Yates JR, Moore AT. X linked retinoschisis. Br J
Ophthalmol. 1995;79(7):697-702. Review.
12. Gopal L, Shanmugam MP, Battu RR, Shetty NS. Congenital
retinoschisis: successful collapse with photocoagulation. Indian J
Ophthalmol. 2001;49(4):265-6.
Rev Bras Oftalmol. 2015; 74 (4): 241-3
244
CASE REPORT
Atypical presentation of Graves’
ophthalmopathy
Apresentação atípica da oftalmopatia de Graves
Flávia Marques Rodrigues1, Nilson Lopes da Fonseca Junior 2, José Ricardo Carvalho Lima Rehder3 , Celso Lopez Fernandez 4,
Debora Mayumi Sugano 5
ABSTRACT
Graves ‘ophthalmopathyis themost commonorbital diseaseand affects25-50% of the patients withGraves’ disease. It`s morecommon in
females, between the second andfifth life`s decade. The disease hasanacute andachronic stage, slowly progressing until it stabilizes, with
rarecasesof spontaneous resolution.The treatment depends on thestage andthe disease ismainly treated withoralor intravenous
corticosteroids with or without radiotherapy;colchicine is usedin individual cases. In the followingcase report, we discuss an
atypicalmanifestation ofGraves’ ophthalmopathyin an euthyroid patientwith negative antibodiesin the inicial presentation.
Keywords: Graves’ ophthalmopathy;Euthyroid;Atypical manifestation; Negative antibodies; Colchicine; Case reports
RESUMO
A oftalmopatia de Graves é a doença orbitária mais comum e acomete 25 a 50 % dos pacientes portadores da Doença de Graves
sendo mais frequente no sexo feminino, entre a segunda e quinta décadas de vida. A doença apresenta uma fase aguda e uma crônica,
evoluindo lenta e progressivamente até estabilizar, sendo raros os casos de resolução espontânea. O tratamento dependerá da fase
em que a doença se encontra sendo baseado principalmente na corticoterapia via oral e endovenosa e/ou radioterapia, sendo a
colchicina empregada em casos isolados. No seguinte relato de caso, abordaremos uma forma atípica de manifestação clínica da
Oftalmopatia de Graves em paciente eutireoidéia com anticorpos negativos na sua apresentação inicial.
Descritores: Oftalmopatia de Graves; Eutireoidea; Manifestação atípica; Anticorpos negativos; Colchicina; Relatos de casos
1
2
3
4
5
Sector at the Medicine College of ABC – FMABC - Santo André (SP) - Brazil
Medicine College of ABC - FMABC - Santo André (SP) - Brazil.
FMABC - Santo André (SP) - Brazil.
Medicine College of ABC
Medicine College of ABC
Study conducted in the Discipline of Ophthalmology at the Medicine College of ABC - FMABC - Santo André (SP) - Brazil.
The authors declare no conflicts of interest
Received for publication 11/06/2012 - Accepted for publication 03/09/2012
Rev Bras Oftalmol. 2015; 74 (4): 244-7
245
Atypical presentation of Graves’ ophthalmopathy
INTRODUCTION
T
he Graves ophthalmopathy is the most common orbital
disease, and it affects 25-50% of patients with Graves’
disease(1). It is an autoimmune disease characterized by
the deposition of immune complexes antithyroglobulin in the
extraocular muscles. In the early stages of the disease, there is an
infiltration of adipose, muscle, and connective tissues in the orbit
by T lymphocytes, mast cells, macrophages and plasma cells(2-4). It
is believed that activated T lymphocytes directed against the
thyroid follicular cells recognize and bind to similar antigens
present in the orbital tissues. Macrophages and dendritic cells
initiate the immune response, which is propagated by the
recruitment of sensitized T cells(2-4). Then various inflammatory
mediators are released (IFN gamma, TNF, IL-1), which stimulate
fibroblasts to produce glycosaminoglycans, which have a
hydrophilic characteristic that draws water into the fat, muscle
and connective tissues, causing edema and consequently fibrosis
of all the periorbit, with hypertrophy of the extraocular muscles,
particularly the medial and lower rectus and orbital fat, resulting
in increased orbital volume, causing mainly proptosis(2-4).
Although the Graves ophthalmopathy is more common
between the second and fifth decades of life, it can occur in any
age group. It is eight times more frequent in women, but in men
the involvement is more serious. It usually occurs when there is
thyroid dysfunction, but the ocular or orbital changes may precede or follow the thyroid dysfunction in up to 18 months(2).
Currently there are important systems to rate the severity
and activity of the disease. In this context we may mention the
NOSPECS which includes the following criteria: class 0 for
patients who have no signs or symptoms, class 1 for presenting
only signs (retraction of upper eyelid, stare, retraction of the
upper eyelid to look down and proptosis above 22mm) and
without symptoms, class 2 in those with soft tissue involvement
(symptoms and signs), class 3 in patients with proptosis, class 4
when there is involvement of the extraocular muscles, class 5
when there is corneal involvement and class 6 in those with a
loss of visual acuity (involvement of the optic nerve) and CAS
(clinical activity score), including signs of acute inflammation such
as hyperemia, pain, edema, and secondary functional impairment
to the presence of inflammation(1-3).
The disease develops slowly and progressively until
stabilization, with rare cases of spontaneous resolution being
reported. It usually manifests clinically in the acute phase with
ocular hyperemia, chemosis, eyelid edema, proptosis of varying
degrees, diplopia, impairment of ocular extrinsic muscles, with
the most affected muscles being the lower, the medial, the upper
and finally the side rectus, respectively. The most frequent signs
are: retraction of the upper eyelid when looking down (lidlag),
retraction of the lower eyelid (which worsens in the attempt to
look up), reduced frequency of blinking, decreased convergence,
inability to keep fixation on the side look and look scared in
the attempt to fixate (Kocher’s sign). In the chronic phase of
the inflammatory process, some patients develop restricted,
fibrotic muscles which can increase the deviation observed in
the acute phase(2,3).
The treatment is based on the phase in which the disease is
(acute or chronic). In the acute phase, the anti-inflammatory
treatment of choice is the corticosteroid therapy orally or
intravenously. Corticosteroid therapy is associated with the use
of radiation, using the linear accelerator in ten continuous
sessions in the most severe cases or ten weekly sessions with
total doses of 2000cGy. Another drug treatment option is the
use of colchicine, with a dosage of 0.5 to 1.5 mg/day, alone or
combined with radiotherapy and/or corticosteroids, with good
therapeutic response.
Except for the emergency cases in which there is the risk
of vision loss by exposure of the cornea or compressive optic
neuropathy, surgical treatment should be indicated in the inactive
phase of Graves’ orbitopathy. This treatment consists of orbital
decompression, treatment of strabismus, and correction of eyelid
retraction and aesthetic blepharoplasty, in that order(2,3).
The following case report will discuss an atypical form of
clinical manifestation of Graves’ ophthalmopathy.
CASE REPORT
EMS, 49, female, brown, single, general services assistant,
from São Bernardo do Campo – SP, referred to the Orbit Sector
in the Discipline of Ophthalmology at the Medicine College of
ABC complaining of pain in the left eye for 5 months associated
to red eye, double vision, blurred vision, eyelid swelling and
intense pain on eye movement. She denied personal and family
history of eye disease. As systemic personal history she had a
history of cervical cancer treated 8 years ago.
The visual acuity with the best correction was 20/25 RE
and 20/40 LE. Upon inspection changes were found only in the
left eye: bipalpebral edema 2+/4+, exotropia and conjunctival
hyperemia 2+/4+. The ocular extrinsic motility presented
limitation to lateroversions, being mild to adduction and severe
to abduction. Direct and consensual pupillary light reflexes were
preserved. The intraocular pressure was measured with the
flattening technique and presented 12 mmHg in the RE and 36
mmHg in the LE (01pm). There were no changes in the anterior
segment or in fundoscopy. Initially the following serum dosages
were asked: TSH, free T4, anti-thyroglobulin antibody (anti-TG
Ab), anti-thyroid peroxidase antibody (Anti-TPO Ab) and TRAb,
Antinuclear (ANA) Ab, Anti-native DNA Ab, Anti-Sm Ab, Antihistone Ab, VDRL, CH50, ACE, Lysozyme, Calcium, RF, ANA,
HSS, c-ANCA and p-ANCA. In addition to said dosages, the
following tests were requested: PPD, chest X-ray, abdominal
ultrasonography, orbit CT, urinary calcium dosage and complete
gynecological examination. Colchicine was introduced orally (0.5
mg every 12 hours), timolol maleate and brimonidine tartrate
both 1 droplet every 12 hours in the left eye.
After 4 weeks, the patient returned with partial reduction
of pain, eyelid edema and conjunctival hyperemia, but still
complaint of diplopia. The IOP measured was: RE - 13 mmHg,
and LE - 16 mm Hg (01pm). The extrinsic motility showed
limitations to lateroversions and supraversion of the LE. Among
the exams requested, only the following were outside the normal range: 1) The orbit CT (Figure 1) showed a thickening of the
medial rectus muscle of the left eye, 2) PPD (19mm = strong
reactor), 3) HSS of the first hour (40mm) and 4) the chest X-ray
revealed the presence of multiple diffuse consolidations in the
pulmonary parenchyma in the hilar region, suggestive of
pulmonary cicatrization change (Figure 2). Thus, a biopsy of the
medial rectus muscle of the LE under general anesthesia was
suggested, and the patient was referred for assessment of the
Pulmonologist who requested: 1) computed tomography of the
chest showing multiple hyperattenuating lesions in the lung
parenchyma suggestive of calcification and ancient cicatrization
process (Figure 1), direct BK search with negative result.
Rev Bras Oftalmol. 2015; 74 (4): 244-7
246
Rodrigues FM, Fonseca Junior NL, Rehder JRCL , Fernandez CL, Sugano DM
The results of all the exams described above and the clinical
approval for the surgical procedure proposed were obtained after
7 weeks. On hospitalization the patient had were significantly better
in signs and symptoms of the LE and acute impairment of the RE.
At extrinsic motility, there were moderate limitations to
lateroversions and supraversions of the RE (Figure 3). So the choice
was a new imaging study (orbit CT), and after the analysis of the
images (Figure 1) the biopsy of medial and lower rectus of the RE
was indicated under general anesthesia, and also a new serum dosage
of TSH, free T4 , Anti-TG Ab, Anti-TPO Ab and TRAb.
The anatomic and pathological study revealed the presence
of striated skeletal muscle tissue with intense lymphoplasmocytic
inflammatory infiltrate with a predominance of T lymphocytes
and the presence of macrophages found consistent with the
inflammatory phase of Graves’ ophthalmopathy. The serum
dosage of TRAb was 35U/L, interpreted as a positive result. The
other results are within the normal limits.
Figure 3: Clinical picture. Clinical presentation in the immediate
preoperative period. Presence of conjunctival hyperemia, bipalpebral
edema and limitation of ocular extrinsic movement in the right eye,
and significant reduction of signs and symptoms in the left eye.
DISCUSSION
Figure 1: Computed tomography of orbit - A) Coronal section (soft
tissue window). B) Axial section (soft tissue window). Thickening of
the medial rectus muscle of the left eye with tendon involvement at
the time of initial care of patient. C) Coronal section (soft tissue
window). D) Axial section (soft tissue window). Diffuse thickening of
the extraocular muscles of the right eye before surgery immediately
before the biopsy.
Figure 2: Image Exam. A) Chest X-ray - presence of multiple diffuse
consolidations in the pulmonary parenchyma in the hilar region
suggestive of pulmonary cicatrization change. B) Computed
tomography of the chest - presence of multiple hyperattenuating
lesions in the lung parenchyma suggestive of calcifications and ancient
cicatrization process.
Rev Bras Oftalmol. 2015; 74 (4): 244-7
Thyroid ophthalmopathy is classified into acute or
inflammatory disease, progressive and histologically associated
to lymphocytic infiltration and edematous changes, and in chronic
or inactive disease associated with fibrotic changes and fat
infiltration in the retro-orbital tissues, especially the extraocular
muscles(5,6). The acute phase of the disease presents as main
symptoms: pain, conjunctival hyperemia, edema and eyelid
hyperemia, proptosis, caruncle edema, chemosis, diplopia and
blurred vision(3). The involvement is bilateral in 80% of cases;
and usually manifests in patients with hyperthyroidism, involving
two or more extraocular muscles without tendon involvement(7).
In this case, the initial manifestation was unilateral, involving
only one extraocular muscle (MRI LE) and its respective tendon
in a patient in clinical and laboratory euthyroid state. The
literature reveals that only 10% of patients with thyroid
ophthalmopathy do not develop hyperthyroidism as the initial
manifestation of the disease (7). From these, 3% presented
hypothyroidism, and 7% euthyroid(7). Among the euthyroid
patients (7%), only 2.5% did not have positive results for AntiTG Ab, Ant-TPO Ab and/or TRAb, revealing the atypical form
of the initial clinical presentation of the disease in this case.
The biopsy should be indicated in cases where the diagnosis
is doubtful based only on the clinical profile and additional exams
or when there is recurrence or resistance to the treatment being
very important to rule out differential diagnoses.
Colchicine, a drug used to treat the patient in question,
inhibits mobility, chemotaxis, adhesion and phagocytosis of
granulocytes; reduces the levels of adhesion molecules; inhibits
the action and proliferation of fibroblasts and lymphocytes, and
inhibits the synthesis of collagen. This drug was indicated due to
the patient being strong reactive to PPD, in this case being
contraindicated the use of systemic corticosteroids.
One study compared the use of colchicine to prednisone
in the treatment of 22 patients during the inflammatory phase of
Graves’ ophthalmopathy. All the patients were similar regarding
age, sex and smoking habits, and suffered euthyroidism for at
least 3 months. They were randomized into 2 groups. Group 1
247
Atypical presentation of Graves’ ophthalmopathy
(G1) received colchicine (1.5 mg/day), and group 2 (G2) was
treated with prednisone (0.75 mg/kg/day). Although it was
verified a reduction in the clinical activity of the disease in the 2
groups, the patients treated with colchicine did not suffer the
side effects of prednisone such as weight gain, stomach problems,
weakness, depression and changes in blood pressure, as observed
in the present case(8).
The orbital radiotherapy is an important adjuvant
treatment of severe Graves’ orbitopathy in activity due to its
anti-inflammatory effects and local immunosuppressants. About
60% of patients treated showed a favorable response(9). The
successful approach will depend on the correct selection of
patients, showing better results the earlier it is established.
REFERENCES
1.
2.
3.
4.
Kuriyan AE, Phipps RP, Feldon SE.The eye and thyroid disease.
Curr Opin Ophthalmol.2008;19(6):499-506.
Höfling Lima AL, Morales PH, Manso PG, Farah ME. Alterações
oculares de doenças sistêmicas: retinopatia diabética e
oftalmopatia de Graves. RBM Rev Bras Med.2006;63(5).
Saraci G, Treta A.Ocular changes and approaches of ophthalmopathy in basedow - graves- parry- flajani disease. Maedica
(Buchar). 2011;6(2):146-52.
Weetman AP. Thyroid-associated eye disease: Pathophysiology.
Lancet. 1991;338(8758):25-8. Review.
5.
6.
7.
8.
9.
Fung S, Malhotra R, Selva D. Thyroid orbitopathy. Aust Fam Physician. 2003;32(8):615-20. Review.
Yokoyama N, Nagataki S, Uetani M, Ashizawa K, Eguchi K. Role of
magnetic resonance imaging in the assessment of disease activity in
thyroid-associated ophthalmopathy.Thyroid. 2002;12(3):223-7.
Stamato FJ, Manso PG, Maciel JR, Wolosker AM, Maciel RM,
Furlanetto RP. Colchicine as a new option for the clinical treatment of Graves’ ophthalmopathy. Proceedings of the VIth International Symposium on Graves’ Ophthalmopathy, Amsterdam,
November 27 to 28, 1998, p. 22.
Stamato FJ, Maciel RM,Manso PG, Wolosker AM, Paiva ER,
Lopes AC,et al. Colchicina no tratamento da fase inflamatória da
oftalmopatia de Graves: um estudo prospectivo e randomizado
com prednisona. Arq Bras Oftalmol.2006;69(6):811-6.
Pitz S, Kahaly G, Rösler HP, Krummenauer F, Wagner B, Stübler
M, et al. [Retrobulbar irradiation for Graves’ ophthalmopathy —
long-term results]. Klin Monbl Augenheilkd. 2002;219(12):87682.German.
Corresponding author:
Flavia Marques Rodrigues
Rua de Ceuta 222 Jardim Lusitânia São Paulo (SP) ZIP Code
04031-01
Email: [email protected]
Rev Bras Oftalmol. 2015; 74 (4): 244-7
248
CASE REPORT
Retro-orbital tumor suggestive
of optic nerve sheath meningocele
Tumoração retroorbitária sugestiva de
meningocele da bainha do nervo óptico
Michelle Rodrigues Gonçalve Dias Chavess 1, Isabella Bezerra Wanderley de Queiroga 2, Mario Augusto Pereira Dias
Chaves 1,3,4, Fernando Melo Gadelha 1,2 , Debora Apolônio Vieira 2
ABSTRACT
Meningocele of the optic nerve sheath is an extremely rare condition with a few cases reported in literature. Image studies reveal tubularcystic enlargement of the optic nerve although with the same thickness. Symptoms are often related to the involvement of the optic nerve,
leading from slow to accelerated decreasing of the visual acuity. The early surgical treatment is the decompression of the optic nerve
sheath, which it could provide improvement of visual function. We are presenting a case report of a patient who showed clinical and
radiological signs of this rare pathological condition. Male patient attended at service complaining of proptosis of right eye (OD) since
birth, in progress during the last months associated to stabbing pain. Best corrected visual acuity (BCVA) of OD was movements at 50
cm far; OS showed no abnormalities. Nuclear Magnetic Resonance of the OD showed expansive formation with cystic aspect,
defined boundaries, located in an intraconal situation on the right orbit cavity and in a closing anatomical relationship to the optic nerve,
inducing compression, deformity and anterior displacement of this eye besides presenting signal similar to spine liquor in all sequences
obtained. The first hypothesis was meningocele of right optic nerve sheath. Then, patient was referred for surgical decompression.
Keywords: Meningocele/diagnosis; Exophthalmia; Optic nerve/pathology; Neoplasms; Case reports
RESUMO
Meningocele da bainha do nervo óptico é uma condição extremamente rara, com poucos casos relatados na literatura. Exames de
imagem revelam alargamento tubular-cístico do nervo óptico, com espessamento do mesmo. Os sintomas são muitas vezes relacionados com o comprometimento do nervo, ocasionando diminuição de lenta a acelerada da acuidade visual. O tratamento cirúrgico
precoce por meio da descompressão da bainha do nervo óptico pode proporcionar melhora da função visual. Apresenta-se um
caso de paciente com as características clínicas e radiológicas desta condição patológica rara. Paciente masculino, atendido no serviço
com queixa de proptose do olho direito (OD) desde nascimento, com progressão nos últimos meses associada à dor. Melhor
acuidade visual corrigida de conta dedos a 50 cm do OD. Olho esquerdo sem anormalidades. Ressonância Magnética de OD
demonstrou formação expansiva cística de limites definidos em situação intraconal em órbita direita, em íntima relação com nervo
óptico, determinando compressão, deformidade e deslocamento anterior do bulbo ocular, além de apresentar sinal semelhante ao
líquor em todas as sequências obtidas. Suscitou-se hipótese diagnóstica de meningocele da bainha do nervo óptico direito e o
paciente foi encaminhado para cirurgia descompressiva.
Descritores: Meningocele/diagnóstico; Nervo óptico/patologia; Neoplasias; Exoftalmia; Relatos de casos
1. Hospital Visão, João Pessoa (PB), Brasil.
2. Centro de Referência Oftalmológica do Hospital Universitário Lauro Wanderley, Universidade Federal da Paraíba, João Pessoa (PB), Brasil.
3. Centro de Estudos Oftalmológicos Renato Ambrósio (CEORA) do Hospital Oftalmológico de Brasília (HOB), Brasília (DF), Brasil.
4. Fundação Altino Ventura (FAV), Recife (PE), Brasil
The authors declare no conflicts of interest
Received for publication 09/07/2012 - Accepted for publication 31/03/2013
Rev Bras Oftalmol. 2015; 74 (4): 248-50
249
Retro-orbital tumor suggestive of optic nerve sheath meningocele
INTRODUCTION
ptic nerve sheath meningocele (ONAM) is an extremely
rare condition, with few cases reported in the literature,
being it defined as a sheath swelling of the optic nerve
by spinal fluid. There is an expansion of the cerebrospinal fluid
space around the optic nerve without associated inflammation,
cerebral or orbital neoplasia. Imaging exams show a tubularcystic enlargement of the optic nerve / sheath-optical complex
with thickening of the optic nerve. The differential diagnosis
includes tumors of the optic nerve as meningioma, vascular
hamartoma, glioma, neurofibromatosis, Von Hippel-Lindau
desease, hemangioendothelioma, or skull-orbital fracture(1).
The symptoms are often related to nerve impairment, classically
causing headaches or progressive, slow or fast visual decline(2).
This paper aims at reporting the case of a patient whose
clinical data and imaging exams are highly suggestive of optic
nerve sheath meningocele, and stressing the main features of
this rare disease.
O
in the RE. The physical examination of the RE showed significant
improvement in ocular proptosis, but with persistence of
corrected visual acuity of hand movements, esotrope, direct
photomotor reflex and consensual absent; onset of conjunctival
and corneal lesion, superior temporal quadrant of the cornea,
extending until close to the visual axis (Figure 5). The pathology
report showed that the withdrawal piece was a “typical
fibroadipous hyaline tissue without epithelial lining, compatible
with benign cystic lesion wall.”
Figure 1: Patient in initial eye exam during inspection, demonstrating
important ocular proptosis in the RE
CASE REPORT
Male patient, 28, attended at the Lauro Wanderley
University Hospital complaining of congenital exophthalmos in
the right eye (RE) in progress during the last months associated
with pain in sporadic twinge. Background: 28 weeks of pre-term,
delayed neuro-psycho-motor development. Inspection: Proptosis
of the RE (Figure 1). Visual acuity (VA): RE: Counting fingers at
50 cm and 20/20 (1.0) LE (-4.50 D -1.00D 170o). Bio: RE: Cortical
cataract 2+/4; LE with no abnormalities. Fundoscopy: RE: Posterior pole choroidal with significant optic atrophy and wide area
of atrophy of the Retinal Pigment Epithelium associated to the
hyperpigmentation area adjacent to the optical disc. LE:
Excavation/cup relationship increased, characteristic macular
color, vascular arcades of usual conformity and applied retina.
IOP: RE: impracticable, LE: 12mmHg.
RE ultrasound showed cystic, retro orbital lesion in the
optic nerve topography, with other exams being asked. Computed
tomography (CT) showed the ventricular system with normal
dimensions, morphology and topography, basal cisterns of normal aspect, brain structures with normal radiographic density,
observing fusiform thickening of the right optic nerve associated
to ipsilateral exophthalmos, with no changes in the optical channel
or the intracranial route of the optic nerve. Nuclear magnetic
resonance (NMR) in the RE showed expansive formation of cystic
aspect with defined limits and thin walls located in intrachoanal
situation in the right orbit, with close anatomical relation with the
topography of the optic nerve, determining anterior compression,
deformity and displacement of the ipsilateral eye bulb, besides
showing a signal similar to CSF in all sequences obtained, with size
of 3.4 x 3.2 x 3.1 cm (Figures 2, 3 and 4).
There was no significant anomalous impregnation of the
paramagnetic contrast (GADOLINIUM) in the walls or within
the lesion. The extraocular muscles were displaced by said
formation, determining compression, deformity and proptosis
of the RE eye bulb. Being it very characteristic, the first diagnostic
hypothesis raised was rioght optic nerve sheath meningocele.
The patient was then referred to decompression surgery,
returning eight months after surgery with no complaints of pain
or headache, however reporting persistence of low visual acuity
abducens nerve
aortic siphon
Figure 2: Pre-contrast axial section weighted in T1 showing isosignal
of mass lesion, leading to proptosis of the RE
Figure 3: . Axial MRI, heavy sequence in T1 with fat saturation.
Lesion with low signal after the use of paramagnetic contrast,
highlighting significant dilation of the optic nerve sheath, with
consequent proptosis of the RE.
DISCUSSION
According to Garrity et al. (2) the pathology in question
arises from the perineural subarachnoid space of the optic nerve,
and should be differentiated from congenital cerebrospinal fluid
accumulation (CSF) in the perioptic subarachnoid space. In such
case, the lesion arises from an abnormal CSF flow through a
diverticulum in the arachnoid membrane. They also report the
cases of 13 patients with MBNO, with blurred vision and headache
being the main symptoms.
Rev Bras Oftalmol. 2015; 74 (4): 248-50
250
Chaves MRGD, Queiroga IBW, Chaves MAPD, Gadelha FM, Vieira DA
Figure 4: Axial section, heavy sequence in T2 with fat saturation.
Lesion with high signal, highlighting significant dilation of the optic
nerve sheath.
Mesa-Gutiérrez et al. reported the case of a patient, 53,
with MBNO associated to intracranial hypertension, but with
visual acuity corrected to 20/20 (1.0), with +2.00D in the initial
exam. The diagnosis was confirmed only with imaging studies.
The MRI identified a dilation of the optic nerve sheath caused
by a fluid with characteristics consistent with cerebrospinal
fluid. There were no changes in the optic nerves, as well as
there was also no evidence of brain or orbit tumors. The
lumbar puncture was performed with opening pressure of 22
mmHg, and the chemical analysis of cerebrospinal fluid was
normal. After neurosurgical evaluation, the patient was only
clinically treated with acetazolamide for three months,
remaining stable over the 24 months of follow-up. In all
follow-up examinations, the nerve function was normal, with
a visual acuity of 20/20 without optical correction after
treatment. The authors conclude that surgery should be
reserved to severe cases with pain, considerable proptosis, or
rapid and progressive decrease in visual acuity.
Spooler et al. (5) describe a case of a child with multiple
congenital anomalies, including unilateral MBNO with rapid
expansion and displacement of the lateral orbit, resulting in
severe cosmetic deformity and complete blindness in his left eye,
which was treated with surgical decompression. The authors also
rectify that surgical decompression is the standard treatment,
with improvement or progression interruption in most cases.
CONCLUSION
Figure 5: Patient in physical exam after surgery, in inspection to a
greater lower increase, showing significant reduction in the proptosis
of the RE
Lunardi et al. (1) reviewed the existing literature, finding
only about 31 cases of MBNO throughout literature, and they
describe the disease as primary cysts of the optic nerve sheath
without apical mass or malformation of the skull-orbital junction.
The symptoms are often related to the involvement of the optic
nerve, with a slow or rapid decrease in visual acuity. Additional
tests such as CT and MRI revealed a tubular-cystic enlargement
of the optic nerve sheath, with thickening of the same. The authors
suggest that early surgical intervention by means of the optic
nerve sheath decompression enables an improvement of visual
function with minimal morbidity in patients with a rapid decrease
of visual acuity within 3-6 months.
Shanmuganathan et al. reported the case of an adult, 59,
with symmetrical bilateral proptosis and complaint of
progressive loss of visual acuity associated to retro-orbital pain
and subsequently to cystoid macular edema (CME) in the RE.
MRI showed bilateral optic nerve sheath dilation and
enlargement, but with normal-sized optic nerve. They describe
that EMC can be caused by a tractional meningocele force on
the eyeball, and that the role of increased intracranial pressure
(ICP) is not clear yet in the etiology of the disease, as only
some of the reported cases had increased ICP, measured by
lumbar puncture. They also concluded that early surgical
decompression of the optic nerve sheath should always be
considered in cases of progressive visual loss.
Rev Bras Oftalmol. 2015; 74 (4): 248-50
The present case reports the presence of a retro-orbital
lesion in intrachoanal situation and intimately anatomically
related to the nerve, strongly suggestive of optic nerve sheath
meningocele. The diagnosis can be given by the NMR, and even
if pending histological examination, the investigative conduct is
consistent, besides the indication of decompressive surgery in
selected cases, exceptionally with rapid development and
imminent functional and anatomical impairment of the
surrounding structures (4). In conclusion, the importance of
remembering that entity is demonstrated by this case report,
despite the rarity of the disease.
REFERENCES
1.
2.
3.
4.
5.
Lunardi P, Farah JO, Ruggeri A, Nardacci B, Ferrante L, Puzzilli F.
Surgically verified case of optic sheath nerve meningocele: case
report with review of the literature. Neurosurg Rev.
1997;20(3):201-5.
Garrity JA, Trautman JC, Bartley GB, Forbes G, Bullock JD, Jones
TW Jr, et al. Optic nerve sheath meningoceles. Clinical and radiographic features in 13 cases with a review of the
literature. Ophthalmology. 1990;97(11):1519-31. Comment in
Ophthalmology. 1991;98(5):562.
Shanmuganathan V, Leatherbarrow B, Ansons A, Laitt R. Bilateral idopathic optic nerve sheath meningocele associated with
unilateral transient cystoid macular oedema. Eye (Lond).
2002;16(6):800-2.
Mesa-Gutiérrez JC, Quiñones SM, Ginebreda JA. Optic nerve
sheath meningocele. Clin Ophthalmol. 2008;2(3):661-8.
Spooler JC, Cho D, Ray A, Zouros A. Patient with congenital
optic nerve meningocele presenting with left orbital cyst. Childs
Nerv Syst. 2009;25(2):267-9.
CASE REPORT 251
Macular granuloma due to tuberculosis
without pulmonary symptoms
Granuloma macular por tuberculose
sem manifestação pulmonar
Albert Costa Rebello1, João Helio Leonardo de Sousa2, José Gilberto de Sá3, Karime Kalif de Sousa Rebello4
ABSTRACT
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The main site of involvement is the lung, but the bacillus may
spread by hematogenous/lymph systems to other organs, including the eye. The incidence of ocular TB is 1-2% of extra-pulmonary cases.
The authors present a case of a 28 years old female patient seeking medical care due to reduction of visual acuity in the left eye for 8 days.
She had the best corrected visual acuity in the affected eye of 20/200, and the opposite eye was 20/20. At fundoscopy was shown a
granuloma in the macular area of the left eye, with retinal edema and hemorrhage. After diagnostic investigation the patient was treated
with antibiotic therapy for tuberculosis during 6 months, obtaining lesion regression and visual acuity improvement to 20/50.
Keywords: Tuberculosis, ocular/diagnosis; Tuberculosis, ocular/drug therapy; Macula lútea; Uveitis/diagnosis; Uveitis/therapy; Case
reports
RESUMO
Tuberculose é uma doença infecciosa causada pelo Mycobacterium tuberculosis, também conhecido como bacilo de Koch. O principal
sítio de acometimento é o pulmonar, porém o bacilo pode disseminar-se por via linfo-hematogênica para outros órgãos, dentre eles:
o olho. A incidência de tuberculose ocular é de 1 a 2% dos casos extra pulmonares. Os autores apresentam um caso clínico de um
paciente do sexo feminino de 28 anos que procura atendimento médico devido a redução da acuidade visual em olho esquerdo há
7 dias. Apresentava a melhor acuidade visual corrigida no olho acometido de 20/200, e no olho contralateral de 20/20. Na fundoscopia
era evidenciado um granuloma em área macular do olho esquerdo, com edema e hemorragia intrarretiniana adjacente. Após
investigação diagnóstica, a paciente foi tratada com esquema antibiótico para tuberculose durante 6 meses, obtendo regressão do
granuloma e melhora da acuidade visual deste olho para 20/50.
Descritores: Tuberculose ocular/diagnóstico; Tuberculose ocular/tratamento; Macula lutea; Uveíte/diagnóstico; Uveíte/tratamento; Relatos de casos
Ophthalmology Center Rio – Rio de Janeiro, RJ, Brazil.
Municipal Hospital Jesus – Rio de Janeiro, RJ, Brazil.
3
Municipal Hospital Jesus – Rio de Janeiro, RJ, Brazil.
4
Ophthalmology Center Rio – Rio de Janeiro, RJ, Brazil.
Study conducted at the Municipal Hospital Jesus and the Ophthalmology Center Rio – Rio de Janeiro (RJ), Brazil.
11
2
The authors declare no conflicts of interest
Received for publication 10/07/2012 - Accepted for publication 26/03/2013
Rev Bras Oftalmol. 2015; 74 (4): 251-3
252
Rebello AC, Sousa JHL, Sá JG, Rebello KKS
INTRODUCTION
B
razil is one of 22 countries prioritized by the World Health
Organization (WHO) covering 80% of the global cases
of tuberculosis(1). Currently the country is in the 19th
place, and was formerly the 14th in 2004. In 2009, there were
71,700 new cases of the disease, with an incidence rate of 37 per
each group of 100 thousand inhabitants. In Rio de Janeiro the
incidence rate is 73.99 per 100,000 inhabitants, giving the state a
sad first place when compared to other States(2). According to
data collected by the Ministry of Health and the Department of
Health Surveillance, in the case of extra pulmonary tuberculosis
the incidence rate drops to 10.06 per 100,000 inhabitants in Rio
de Janeiro. This number includes the cases of pleural, lymph
node, osteoarticular, genitourinary, intestinal, peritoneal,
pericardial, central nervous system, eye and skin tuberculosis(3,4).
The authors present a case of ocular manifestation of
tuberculosis that was satisfactorily responsive to the treatment
against tuberculosis for 6 months.
CASE REPORT
Female patient, 28, white, sought medical care due to
decreased visual acuity in the left eye for 7 days, with sudden and
spontaneous onset. Past medical history without relevant data,
but reporting contact with a tuberculosis patient two years ago
in her own home.
The eye exam showed better corrected visual acuity for
farsight on the right eye: 20/20, and on the left eye: 20/200; Ocular
motility without change; Normal biomicroscopy; Tonometry RE:
12 mmHg and LE: 13 mmHg; Fundoscopy: stained buds,
physiological excavations, preserved arteriovenous ratio, presence
of a yellowish granulomatous lesion with adjacent retinal edema
and hemorrhage in the macula of the left eye (Figure 1).
Figure 1: Granulomatous lesion with hemorrhage and retinal edema.
Initial diagnostic research showed no changes in blood
count, microbiology, biochemistry and immunochemistry. It is
important to emphasize the negative serology for toxoplasmosis,
both IgM as IgG. Normal chest radiograph. Tuberculin skin test
equal to 20mm. Antituberculosis oral therapy was initiated with
follow-up in specialized unit of the public health service. To
improve the retinal edema, she received topical treatment with
dexamethasone eyedrops for 30 days, with gradual dose
reduction and monitoring of the intraocular pressure.
Rev Bras Oftalmol. 2015; 74 (4): 251-3
After follow-up for 6 months, with the respective end of
the oral treatment, the patient improved the visual acuity of the
left eye to 20/50. In the fundoscopy, the lesion improved and the
retinal edema disappeared, the hemorrhage was absorbed and
the retinal pigment epithelium in the macular area was atrophied
(Figure 2).
Figure 2: Regression of the lesion after antituberculous therapy for 6
months .
DISCUSSION
Given the high prevalence of the disease in our country, it
is always advisable to investigate tuberculosis in cases of
chorioretinitis. It is a especially important fact, considering that
some treatments directed to other etiologies may worsen the
tuberculosis condition (as an example we can mention the use of
systemic corticosteroids, used in some cases of toxoplasmosis
chorioretinitis).
The standard test for the diagnosis finding Mycobacterium
tuberculosis in ocular specimens, but due to the paucibacillary
lesions and the noble condition of the visual apparatus
significantly limit the histological study, the diagnosis of ocular
tuberculosis is supported by epidemiological data, clinical
examination, positive tuberculin skin test and laboratory exclusion
of other conditions(5), among them toxoplasmosis.
The tuberculin skin test is still the exam which guides us
about possible infections with Mycobacterium tuberculosis,
although a positive result does not mean active disease. Therefore,
other criteria are needed to confirm the diagnosis of ocular
tuberculosis. Among them are: observing if there is improvement
with the basic scheme in the first two months, if there is no
recurrence of the disease during treatment, or if there is no
recurrence in the first two years after interrupting the medication.
Otherwise, probably the etiology of tuberculosis is not
considered, forcing the search for other causes(6).
We must also take into account the differential diagnosis
with syphilis, sarcoidosis, brucellosis, histoplasmosis and
toxocariasis.
Any tissue in the eye may be affected, though the most
common site is the uvea. As illustrated in the present case, the
disease may be present even without systemic disease. The
changes can be caused by bacterial invasion or be immunological,
by hypersensitivity reaction type IV. Some of the possible ocular
manifestations are anterior, posterior, intermediate uveitis,
panuveitis, serpiginous-like choroiditis, subretinal abscesses,
253
Macular granuloma due to tuberculosis without pulmonary symptoms
serous retinal detachment, retinitis, choroiditis, retinochoroiditis,
retinal vasculitis and endophthalmitis(6).
In this case, the improved healing of the macular injury
after the use of anti tuberculous medication is an important
evidence to establish the diagnosis, along with the positive history
of contact. But also, there was healing and regression of the
lesion after the beggining of the treatment without reincidence,
and apparently it continues healed even after the end of 6-month
therapy. As the prognosis is influenced by the location of the
lesion and the adherence to treatment, in this case the significant
improvement in vision draws attention, despite the proximity
between the granuloma and the macula.
3.
4.
5.
6.
Brasil. Ministério da Saúde. Secretaria de Políticas de Saúde.
Departamento de Atenção Básica. Manual técnico para controle
da tuberculose. (Cadernos de Atenção Básica, 6). Brasília:
Ministério da Saúde; 2002.
Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde.
Departamento de Vigilância Epidemiológica. Doenças infecciosas
e parasitárias: guia de bolso. 8a ed. rev. Brasília: Ministério da
Saúde; 2010.
Lopes AJ, Capone D, Mogami R, Tessarollo B, Cunha DL, Capone
RB, et al. Tuberculose extrapulmonar: aspectos clínicos e de
imagem. Pulmão RJ. 2006;15(4):253-61.
Campos WR, Campos GS, Miranda SS. Tuberculose intraocular.
Rev Bras Oftalmol. 2011;70(6):437-51.
REFERENCES
1.
2.
Arakaki D, Oliveira G, Barreira D, Moherdaui F, Codenotti S,
Bartholomay P. Novo sistema de tratamento da tuberculose para
adultos e adolescentes no Brasil. Informe Técnico de Tuberculose.
Edição nº 5, julho de 2010. Disponível em: http://portal.saude.gov.br/
portal/arquivos/pdf/informe_tb_julho10_certo_22_07_2010.pdf
Brasil. Ministério da Saúde. Departamento de Informatica do
SUS. DATASUS. Disponível em http://tabnet.datasus.gov.br/cgi/
e http://www2.datasus.gov.br/DATASUS
Corresponding author:
Albert Costa Rebello
Av. Passos, 101 / 1609 - Centro ZIP Code: 20051-040 - Rio de
Janeiro (RJ), Brazil
Fax No.: (21) 2263-4838
E-mail: [email protected]
Rev Bras Oftalmol. 2015; 74 (4): 251-3
254
CASE REPORT
Irreversible visual loss after use of Paclitaxel
Perda visual irreversível após uso de Paclitaxel
Maria Helena Lopes Amigo1, Paulo Falabella2, Ângela Bettarello2, Wagner Ghirelli2
ABSTRACT
We describe a case of bilateral irreversible visual loss of a 64 year-old patient after prolonged use of paclitaxel. Patient presented best
corrected visual acuity of 20/400 in both eyes at first visit and optical coherence tomography showed increased macular in both eyes. After
six months of the interruption of suspension paclitaxel therapy, the patient showed slight improvement of visual acuity reaching 20/200
in both eyes, while OCT demonstrated resolution of macular edema.
Keywords: Chemotherapy/adverse effects; Paclitaxel/toxicity; Macular edema/chemically induced; Visual acuity/drug effects;
Ovarian neoplasms/drug therapy; Case reports
RESUMO
Descrevemos um caso de perda visual irreversível bilateral em uma paciente de 64 anos após uso prolongado de paclitaxel. Ao exame
oftalmológico apresentou acuidade visual (AV) de 20/400 em ambos os olhos (AO) na primeira consulta e tomografia de coerência
óptica (TCO) evidenciando espessamento macular AO. Após seis meses da suspensão do paclitaxel, a paciente apresentava melhora
discreta da AV atingindo 20/200 com correção em AO, além de TCO demostrando resolução do espessamento retiniano.
Descritores: Quimioterapia/efeitos adversos; Paclitaxel/toxicidade; Edema macular/induzido quimicamente; Acuidade visual/
efeitos de drogas; Neoplasias ovarianas/quimioterapia; Relatos de casos
1
2
Ophthalmology Center Tadeu Cvintal – São Paulo (SP), Brazil.
Retina and Vitreous Department of the Ophthalmology Center Tadeu Cvintal – São Paulo (SP), Brazil
The authors declare no conflicts of interest
Received for publication 27/07/2012 - Accepted for publication 05/12/2012
Rev Bras Oftalmol. 2015; 74 (4): 254-6
Irreversible visual loss after use of Paclitaxel
255
INTRODUCTION
P
aclitaxel is a chemotherapeutic of the taxane family
primarily used in the treatment of breast and ovarian
cancer and in a variety of other solid tumors. Among the
toxic effects are myelosuppression and peripheral neuropathy
(1)
. There are rare cases of retinal toxicity reported in the literature,
especially those culminating in visual loss due to maculopathy(2,3).
We describe below a report of irreversible low visual acuity
associated to the use of paclitaxel.
Figure 1: Retinography of both eyes (BE) showing the normal aspects
of retinal macula and periphery.
CASE REPORT
Female patient, white, 64, came to her first appointment
in February 2007 complaining of progressive low visual acuity
(VA) during the last year in both eyes (BE), and was initially
referred with a suspicion of cataract. She brought with her the
result of an electroretinography with no changes carried out
one month before the appointment, and result of nuclear
magnetic resonance imaging showed ethmoid sinusitis.
She had a history of surgery for excision of ovarian cancer
and chemotherapy with paclitaxel due to intestinal metastasis
eighteen years ago (not knowing the dose and the medication
use interval). She also reported history of facial paralysis eight
months ago and left lower limb thrombosis 7 months ago.
The eye exam showed normal external eye exam and
best corrected visual acuity of 20/400 (+0.50 spherical dioptres
in BE). Biomicroscopy: transparent cornea, deep anterior
chamber and without inflammatory cells, iris unchanged and
crystalline with mild nuclear opacity. Applanation tonometry
of 20 mmHg in BE. Fundoscopy showed signs of mild bilateral
arteriosclerosis. Macula and medium periphery with
physiological aspect. (Figure 1)
Fluorescein angiography exam revealed the presence of
hyperfluorescence of the optic nerve and macula without
extravasation signs in BE (Figure 2).
Optical coherence tomography (OCT) showed an increase
in the retinal thickness with cystic spaces and aspect of sectoral
retinoschisis. The right eye (RE) showed: total macular volume
of 9785 mm3, and foveal thicknesses of 243 (+/-91) microns; in
the left eye: total macular volume of 9415 mm3, and foveal
thicknesses of 212 (+/-41) microns. (Figure 3)
In April 2007 we chose to use acetazolamide oral and
triamcinolone acetate 4 mg intravitreal in the RE seeking
anatomical and functional improvement, but there were no
satisfactory results both in the visual acuity and retinal edema.
A literature review resulted in the location of a case report
which described a bilateral cystoid macular edema secondary
to the use of paclitaxel. In this case, suspending the medication
led to total remission of the edema and improvement of the
visual acuity after 6 weeks(3). Therefore, we decided to interrupt
chemotherapy and, after six months, the patient showed a mild
improvement of the VA and reached 20/200 with correction in
BE, whereas the OCT showed complete resolution of the
cystoid macular edema in BE. (Figure 4)
Figure 2: Retinal fluorescein angiography: hyperfluorescence in the
optic nerve, and macula with no signs of extravasation in BE.
Figure3: Optical coherence tomography: Increase in the retinal
thickness with cystic spaces and aspect of retinosquise in some places.
Presented respectively: Total macular volume in the RE of 9785
mm3, foveal thicknesses of 243 (+/-91) microns in the RE (A), and in
the LE 9415mm3 and 212 (+/-41) microns in the LE (B)..
Figure 4: OCT six months after suspending the use of paclitaxel,
showing retinal thickening improvement in the RE A) and LE B).
Rev Bras Oftalmol. 2015; 74 (4): 254-6
256
Amigo MHL, Falabella P, Bettarello Â, Ghirelli W
DISCUSSION
Ocular toxicity by paclitaxel is little known by both
ophthalmologists and oncologists. It is a chemotherapeutic
agent that inhibits the formation of intracellular microtubules,
and whose ophthalmological side effects often include low visual acuity, scintillating scotomas and changes in evoked visual
potential. Some articles have suggested the association of the
drug to the onset of cystoid macular edema, but we understand
this is the first one in which there was severe and irreversible
loss of visual acuity, even after discontinuation of medication(2,3).
We envisaged the differential diagnosis of cancer
associated retinopathy (CAR) because of low visual acuity,
which is why the electroretinography was held and the result
showed no changes. Electrophysiological assessment of vision
in patients treated with paclitaxel showed little correlation with
visual symptoms(4) as in this case, being therefore further data
to the diagnosis.
We highlight the important clinical characteristic related
to paclitaxel toxicity and the presence of cystoid macular edema
observed in the TCO associated to the absence of contrast
extravasation on fluorescein angiography. This fact has been
previously described for both paclitaxel and other
chemotherapeutic of the taxane family, docetaxel. Toxicity to
Müller cells is the theory for the pathophysiological mechanism,
with subsequent accumulation of intracellular fluid and
subclinical extracellular extravasation(3,5,6).
The irreversibility of low visual acuity even after
discontinuation of medication and subsequent settlement of
the cystoid macular edema suggests a distinct toxicity
mechanism of paclitaxel associated to permanent cell damage.
Rev Bras Oftalmol. 2015; 74 (4): 254-6
In this case report there was the relation to the use of
medication, not only with the onset of macular edema, but also
with the patient’s irreversible visual loss, emphasizing therefore
the maculotoxicity potential of paclitaxel.
REFERENCES
1.
2.
3.
4.
5.
6.
Marupudi NI, Han JE, Li KW, Renard VM, Tyler BM, BremH.
Paclitaxel: a review of adverse toxicities and novel delivery strategies. Expert Opin Drug Saf. 2007; 6 (5): 609-21.
Hofstra LS, de Vries EG, Willemse PH. Ophthalmic toxicity following paclitaxel infusion. Ann Oncol. 1997; 8 (10): 1053.
Joshi MM, Garretson BR. Paclitaxel maculopathy. Arch
Ophthalmol. 2007; 125 (5): 709-10.
Scaioli V, Caraceni A, Martini C, Curzi G, Luca G.
Electrophysilogical evaluation of visual pathways in plactaxeltreated patients. J Neurooncol. 2006; 77 (1):79-87.
Teitelbaum BA, Tresley DJ. Cystic maculopathy with normal capillary permeability secundary to docetaxel. Optom Vis Sci. 2003;
80 (4):277-9.
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Ophthalmol. 2007; 22 (3): 151-3.
Corresponding author:
Wagner Ghirelli
Rua Maria Figueiredo 283
Phone No.: 11 33713324
Email: [email protected]
REVIEW ARTICLE
257
Biomarkers and surrogate endpoints in the
glaucomatous optic neuropathy: new
developments and a review
Biomarcadores e desfechos substitutos na neuropatia óptica
glaucomatosa: novos desenvolvimentos e uma revisão
Niro Kasahara1
ABSTRACT
Glaucoma is a group of progressive optic neuropathies that have in common a slow progressive degeneration of retinal ganglion cells
and their axons, resulting in a distinct appearance of the optic disc and a concomitant pattern of visual loss. Biomarkers are characteristics
objectively measured and evaluated as indication of normal biologic processes, pathogenic processes, or pharmacologic responses to a
therapeutic intervention. Several biological markers have been implicated with glaucoma, especially genetics, proteomics, autoimmune
and other molecular biomarkers, although, most awaits clinical validation. There are clear potential benefits in using biomarkers.
Information can be obtained earlier, faster, and less costly. This review summarizes the latest developments and approaches in glaucoma
biomarkers and its possible uses in the diagnosis, staging, and as predictors of response to treatment.
Keywwords: Glaucoma; Optic nerve diseases; Biological makers
RESUMO
O glaucoma compreende um grupo de neuropatias ópticas progressivas que tem em comum a degeneração lenta e progressiva das
células ganglionares e seus axônios, resultando em aparência única do disco óptico e, simultaneamente, um padrão correspondente
de perda visual. Biomarcadores são características medidas objetivamente e avaliadas como indicadores de processo biológico
normal, processos patológicos ou respostas farmacológicas à uma intervenção terapêutica. Vários marcadores biológicos foram
associados com glaucoma, especialmente os genéticos, proteômicos, autoimunes e outros biomarcadores moleculares, embora a
maioria ainda necessite de validação clínica. Existem potenciais benefícios em usar biomarcadores. Informações podem ser obtidas
mais precocemente, de forma mais rápida e menos onerosa. Esta revisão resume os últimos avanços e métodos em biomarcadores
de glaucoma e seu possível uso no diagnóstico, estadiamento e como preditores da resposta ao tratamento.
Descritores: Glaucoma; Doenças do nervo óptico; Marcadores biológicos
1
Departamento de Oftalmologia, Irmandade da Santa Casa de Misericórdia de São Paulo; Faculdade de Ciências Médicas da Santa Casa de
São Paulo, São Paulo, SP, Brazil.
The authoes declare no conflicts of interest
Received for publication 21/08/2014 - Accepted for publication 17/12/2014
Rev Bras Oftalmol. 2015; 74 (4): 257-65
258
Kasahara N
B
iomarkers are characteristics objectively measured and
evaluated as indication of normal biologic processes,
pathogenic processes, or pharmacologic responses to a
therapeutic intervention.(1) Although what the marker marks is
clearly defined as being intrinsic, the marker itself can be either
intrinsic or extrinsic. Intrinsic markers can be physical (clinical
or radiographic) or laboratorial (physiological, pharmacological,
genetic, biochemical, etc.). An example of an extrinsic marker is
cigarette consumption in lung cancer.(2) A surrogate marker or
surrogate endpoint has been defined as a biomarker intended
to substitute for a clinical endpoint, the latter being a
characteristic or variable that reflects how a patient feels,
functions, or survives.(1)
Both biomarkers and surrogate endpoints can be used in
diagnosing, staging, and monitoring disease, and in determining
its response to therapy.
The difference between a biomarker and surrogate
endpoint is that a biomarker is a “candidate” surrogate marker,
whereas a surrogate marker is a test used, and taken, as a
measure of the effects of a specific treatment.(3) Biomarkers are
often cheaper and easier to measure than true endpoints and
can be measured more quickly and earlier. There may also be
ethical issues associated with measuring true endpoints. For
example, in paracetamol overdose it is unethical to wait for
evidence of liver damage before deciding whether or not to treat
a patient; instead, a pharmacological biomarker, the plasma
paracetamol concentration, is used to predict whether treatment
is required.(2)
Biomarkers can be used at any point in the chain of events
that leads from the pathogenesis of a disease to its clinical
manifestations, whether at the molecular, cellular, or organ levels.
Likewise, a therapy might be developed to tackle any one of
these links, in order to try to treat the disease. Any measurement
short of the actual outcome could be regarded as a surrogate
endpoint biomarker. However, although all surrogate endpoints
are biomarkers, not all biomarkers are useful surrogate
endpoints.(2)
Surrogate endpoints are used in clinical trials and, as such,
it is defined as a response variable for which a test of the null
hypothesis of no relationship to the treatment groups under
comparison is also a valid test of the corresponding null
hypothesis based on the true endpoint.(4) It’s use, however,
introduces heterogeneous variance and the problem of regression
to the mean.
In clinical practice, biomarkers are used frequently and
without notice. In a patient with cancer, a clinician measures the
time to relapse as a surrogate endpoint for survival time.
Ophthalmologists measure intraocular pressure (IOP) instead
of loss of vision in patients with glaucoma. Physicians use
biomarkers to stage disease (e.g., the number of lymph nodes
affected by cancer), in diagnosis (e.g., magnetic resonance
imaging, electrocardiography, and autoimmune antibodies), and
to monitor the progress of a disease or its treatment (e.g., serum
glucose concentration and blood pressure).(2)
The increased sensitivity and the developments of genomic,
proteomic, and metabolomic research techniques have caused
the potential to identify molecules that may serve as potentially
useful markers, including (1) markers for early detection of a
disease, (2) markers to predict disease severity, (3) markers to
predict the rate of disease progression, and (4) markers to serve
as predictors of response to treatment.(5)
Rev Bras Oftalmol. 2015; 74 (4): 257-65
Glaucoma is a group of progressive optic neuropathies
that have in common a slow progressive degeneration of retinal
ganglion cells and their axons, resulting in a distinct appearance
of the optic disc and a concomitant pattern of visual loss.(6) It is
estimated that glaucoma affects more than 66 million individuals
worldwide with at least 6.8 million bilaterally blind.(7) Although
not completely understood, it is a multifactorial complex
neurodegenerative disease triggered by different factors
including mechanical stress due to intraocular pressure,
decreased blood flow to retina, reperfusion injury, oxidative
stress, glutamate excitotoxicity, and aberrant immune response.
The discovery of clinically useful biomarkers in glaucoma
is constantly expanding and includes from genes to proteomic
markers, and analyses of serum antibodies to retina and optic
nerve proteins. We summarize herein the current knowledge
regarding the factors related to the diagnosis, progression, and
response to treatment of glaucoma, which have not been
definitely established but represent biomarker candidates to be
validated. These markers include clinical, genetic, proteomic,
autoimmune, and neurodegenerative candidates yet to be
corroborated.
Clinical biomarkers
Automated perimetry, IOP, optic disk, and retinal nerve fiber
layer are surrogate markers for glaucomatous optic neuropathy
used in clinical practice and as outcome measures in research.
From another standpoint, biomarkers are biological quantitative
measurements that may differentiate suspected disease from
healthy individuals, and predict the course of disease, or treatment
response. So far, we recognize some of the risk factors for glaucoma,
such as elevated IOP, although it is not always present in every
patient. A combination of two or more biomarkers such as optic
nerve structure, visual function and IOP, is a “biosignature” of
glaucoma disease, just as measurements of high density lipoprotein
(HDL), low density protein (LDL), and cholesterol have become
biosignatures of cardiovascular disease.(8)
Intraocular pressure
A number of randomized clinical trials have convincingly
shown that elevated IOP is the leading risk factor for glaucoma
development and that IOP reduction can significantly reduce
the incidence and progression of the disease. However, IOP can
be deceiving in that it is not a defining criterion for primary
open-angle glaucoma (POAG). Population surveys show that up
to 50% of open-angle glaucoma patients have an IOP of 21 mm
Hg or lower.(9,10) Besides, the effect of IOP fluctuation, either
diurnal or long-term visit to visit, on the risk of developing POAG
is still controversial.(11)
Some investigators propose a joint analysis approach to
assess whether variability of IOP as a biomarker is
independently predictive of clinical outcomes. Using data from
two long-term clinical trials of the efficacy of IOP lowering
medication in the prevention of glaucoma (the Ocular
Hypertension Treatment Study - OHTS and the European
Glaucoma Prevention Study - EGPS), they determined if longterm IOP fluctuation is independently predictive of POAG. A
linear mixed model incorporating patient-specific variance
describes the trajectory of IOP, and its association with the
time to POAG is assessed using both semi-parametric and full
parametric survival models. Substantively, the authors results
show that IOP variability is independently predictive of POAG
Biomarkers and surrogate endpoints in the glaucomatous optic neuropathy: new developments and a review
in the OHTS, and the subjects with high IOP fluctuation have
an increased risk of developing POAG.(12)
Visual function: automated perimetry
The loss of retinal ganglion cells in glaucoma leads to
characteristic visual field defects as evaluated by automated
perimetry, although a great amount of axons has to be lost
before initial visual field defects can be detected. To patients,
visual function may be the clearest marker of glaucoma. There
seems to be a clear relationship between visual function and
quality of life.(13) Automated perimetry is a particularly useful
clinical biomarker to predict disease severity, since the visual
fields of apatient immediately give an appraisal about the
amount of damage, and also the amount of residual vision that
is available before the patient will suffer definite and clear loss
of quality of life.
Nevertheless, automated perimetry do have some
limitations as a biomarker. Visual field defects are not disease
specific. Although visual field defects in glaucoma follows
typically a ganglion cell loss pattern, other optic neuropathies
do cause ganglion cell loss and visual field defects similar to
glaucoma.(14) The visual field index (VFI) has been developed
to evaluate progression of glaucoma in time.(15) As a marker to
predict the rate of disease progression, automated perimetry is
not ideal, since it is usually necessary to perform a number of
tests to assess progression. Besides, as a psychophysical test it
is dependent on patient response and can be very variable
from one exam from another. Automated perimetry is not a
useful marker for early detection of a disease since a large
amount of ganglion cells must be lost before initial visual field
defects can be detected.
Structural measures: optic nerve and retinal nerve fiber layer
Direct assessment of the optic nerve and the retinal nerve
fiber layer is of paramount importance in glaucoma diagnosis
and progression. Progressive optic disc damage is highly
predictive for the development of functional loss in glaucoma.
Some changes in the optic disk are typical of the glaucomatous
optic neuropathy, however, there is a number of patients with
suspicious looking disks in which the structural evaluation per
se is not enough for diagnosis. Although ephemeral and not very
frequent, disk hemorrhage is a very typical feature in glaucoma
patients and almost pathognomonic of glaucoma. It may be a
marker of rapid glaucoma progression, in that localized subclinical
structural change predisposes to disk hemorrhage, after which
subsequent disease progression is accelerated, and recurrent
optic disk hemorrhages are related to rapid structural progression
of glaucomatous damage.(16) The development of new imaging
devices provides better access to view the optic disk and the
nerve fiber layer as potential biomarkers. Optic coherence
tomography is a useful device to assess the optic nerve, and
careful monitoring of the optic disc appearance is important to
evaluate glaucoma progression. However, whether changes
detected by imaging instruments are associated with future
progression remains a key question and the ability to
longitudinally evaluate imaging instruments is difficult as the
technology is always evolving.
Genetic biomarkers
Family history is a risk factor of glaucoma. In fact, about
20% of glaucoma patients have family history of the disease and
the prevalence of open-angle glaucoma increases up to 13.5%
259
among relatives of glaucoma patients indicating an important
genetic component.(17,18) Genetic biomarkers might be invaluable
tools to identify individuals at risk for disease as well as serving
to measure the outcomes of therapies. One drawback is that no
all genes can function as biomarkers. In order to have a large
effect size the allele frequency has to be low; conversely, a high
allele frequency has low effect size. Besides, most gene mutations
and polymorphism are population specific; so one particular gene
mutation in Europeans descendents may not be implicated in an
African population.
Model-dependent linkage analyses using multiplex POAG
pedigrees have generated a number of potential loci (GLC1A–
GLC1H and GLC1L) however, only three genes have been
recognized.
MYOC (myocilin) was the first gene identified from the
GLC1A locus. (19,20) Myocilin is an extracellular protein of
unknown ocular function. Missense mutations account for 3%
to 5% of POAG cases.(21,22) The underlying genetic mechanism is
possibly gain-of function or dominant-negative effect, since the
loss of protein function does not result in glaucoma.(23-25) The
disease-associated missense changes reduce the solubility of the
protein, causing it to aggregate in the endoplasmic reticulum and
preventing its secretion to the extracellular matrix.(26) The absence
of protein does not cause disease, however, intracellular
accumulation of myocilin aggregates may sensitize trabecular
meshwork cells to apoptosis.(27)
The second gene optineurin (OPTN) was identified at
GLC1E (10p15-p14) and is primarily responsible for rare cases
of familial normal tension glaucoma. (28-30) Optineurin may
possibly influence ganglion cell apoptosis directly through rab8
signaling.(31,32)
WD repeat domain 36 (WDR36) at GLC1G (5q21.3-q22.1)
seems to be related to POAG severity in some cases, although it
is neither necessary nor sufficient for disease development.(33,34)
A zebrafish homolog of WDR36 stimulates apoptosis mediated
by p53, implying a possible role for the gene in retinal ganglion
cell susceptibility to apoptotic cell death.(35)
Genome-wide scans using nonparametric linkage methods
in different populations of POAG pedigrees identified 10 genomic
regions that may harbor POAG susceptibility genes (2p14, 2q3334, 10-12-p13, 14q11-q22, 17p13, 17q25, 19q12-q14).(36-38) Using
ordered subset analysis with the mean family age of onset as a
covariate, a follow-up study of the scan performed on European
descent pedigrees, distinguished some families with significant
linkage to 15q11- q13, designated GLC1I.(39)
TANK-binding kinase 1 is an enzyme encoded by TBK1
that can mediate NFKB activation in response to certain growth
factors. The gene is specifically expressed in retinal ganglion cells
affected by glaucoma. Located in chromosome 12q14, duplications
of the gene were discovered in normal tension glaucoma patients.
This duplication leads to increased transcription of TBK1.(40,41)
Besides, TBK1 associates with the product of OPTN. (42)
Nevertheless, this is a rare observation, given that, only 1% of
patients displayed duplication of the TBK1 gene in a multicenter
case-control study.(43)
Useful genetic screening tests for POAG are not
available.(44) Currently only 30% of individuals at risk for earlyonset forms of glaucoma cases can be identified.(45) Continuing
research using genome-wide association in large population may
reveal new genetic biomarkers and useful screening tests.(46)
Rev Bras Oftalmol. 2015; 74 (4): 257-65
260
Kasahara N
In order to use genes as biomarkers, one needs to have
causative genes or to have genes that are associated with disease.
At present, gene-based risk prediction and prognosis at early
stages of the disease are possible; however, studies that isolate
genes associated with late onset forms of glaucoma are still
underway. Most of the genes associated with glaucoma are
causative, so that, a molecular diagnosis and genetic counseling
with families who carry disease are possible. Future research will
aim to target newly identified genes with clinical phenotypes and
outcomes, to identify genes associated with POAG, and to
correlate genetic variation with disease, clinical outcome, and
treatment response.
Proteomic biomarkers
The term proteomics was first introduced in 1994 for the
aim of global characterization of a proteome (referring the
proteins expressed by the genome), including protein expression,
structure, modifications, functions, and interactions.(47) The
proteome is the entire set of proteins, produced or modified by
an organism or system.(48)
Proteomics is one of the most important post-genomic
approaches to improve the understanding of gene function.
Nevertheless, when compared to genome, proteome is a much
more complex and dynamic system. Although proteins provide
the most important clues to disease mechanisms, their analysis is
difficult due to large diversity in properties, such as molecular
size, dynamic range in quantity, and their hydrophilicity or
hydrophobicity.(49) Conversely, since blood samples can be easily
collected, the proteins detectable in serum or plasma have formed
the basis of commonly used tests to screen and monitor disease
biomarkers in various fields.
Proteomics is highly useful in the identification of candidate
biomarkers (proteins in body fluids that are of value for
diagnosis), identification of the bacterial antigens that are targeted
by the immune response, and identification of possible
immunohistochemistry markers of infectious or neoplastic
diseases.(50) Recent studies of glaucoma using proteomics analysis
techniques have resulted in a lists of differentially expressed
proteins in human glaucoma and animal models. The global
analysis of protein expression in glaucoma has been followed by
cell-specific proteome analysis of both retinal ganglion cells and
astrocytes. The proteomics data have also guided targeted studies
to identify post-translational modifications and protein-protein
interactions during glaucomatous neurodegeneration. In
addition, recent applications of proteomics have provided a
number of potential biomarker candidates.(49)
To date, most of the studies in glaucoma molecular
biomarkers comprise the studies of autoantibodies and their
target antigens. A panel of antigenic proteins that elicit serum
immunoreactivity at a high frequency among glaucoma patients
can provide an effective tool for biomarker screening. (49)
However, a much lower abundance of most protein biomarkers
than some disease-irrelevant serum proteins poses a challenge
of serum biomarker detection.
Currently, 22 proteins were detected in glaucoma patients
and included immune mediators and components of cell death
signaling which may serve as biomarker candidates (Table 1).(49)
Nevertheless, the clinical validation of candidate molecules still
poses a major challenge. Large studies of heterogeneous cohorts
for appropriate statistical power and blinding are deemed
necessary to eliminate false positives and to calculate the
Rev Bras Oftalmol. 2015; 74 (4): 257-65
sensitivity and specificity of candidate molecules for clinical
prediction.(51,52) Besides, given the highly complex pathogenesis
and the characteristic inter-patient heterogeneity of glaucoma, a
panel of biomarkers, rather than a single biomarker, is needed
to provide appropriate sensitivity and specificity needed.(49)
Table 1. Potencial glaucoma protein biomarkers
candidates (adapted from Tezel49).
Protein name
Accession number*
A-kinase anchor protein 10,
mitochondrial precursor
gi|21493033
Actin, cytoplasmic
gi|45011885
Heterogenius nuclear
ribonucleoprotein C-like
gi|282396082
Insulin-like growth factor
2 mRNA-binding protein 2 isoform b
gi|56118219
Rho guanine nucleotide exchange
factor 40
gi|50843837
Toll-like receptor 8 precursor
gi|20302168
Tripartite motif-containing
protein 5 isoform delta
gi|203046698
RNA polymerase I-specific
transcription initiation factor RRN3
gi|93102377
Minichromosome maintenance complex
component-like isoform a
gi|209954821
Hypothetical protein LOC100510472
gi|310133112
GRIP and coiled-coil
domain-containing protein 2
gi|31563507
DNAJ homolog subfamily C
member 7 isoform 2
gi|221219056
Zinc finger protein 804B
gi|31791053
1-phosphatidylinositol-4,5-biphsophate
phosphodiesterase gamma-1 isoform b
gi|33598946
C-Jun-amino-terminal
kinase-interacting protein 1
gi|4885433
Kinesin-like protein KIF17 isoform a
gi|170784807
NACTH, LRR and PYD
domains-containing protein 6
gi|21264320
Sialic acid-binding Ig-like lectin 5 precursor gi|4502659
Testis-specific serine/
threonine-protein kinase 2
gi|194294513
Poly [ADP-ribose] polymerase 1
gi|156523968
NACTH, LRR and PYD
domains-containing protein 8
gi|33667040
Protocadherin gamma-A11
isoform 1 precursor
gi|11128039
* GenInfo Identifier (gi) was an early system used in bioinformatics to
access GenBank and related databases. A gi number was assigned to
each nucleotide and protein sequence accessible through the NCBI
search systems, and was a means of tracking changes to the sequence.
It is an unique identifier given to a DNA or protein sequence record
to allow for tracking of different versions of that sequence record
and the associated sequence over time in a single data repository.
Biomarkers and surrogate endpoints in the glaucomatous optic neuropathy: new developments and a review
Autoimmune biomarkers
There is growing evidence implying an autoimmune
involvement in the pathogenesis of glaucoma. A number of
studies provide fundamental insights into neurodegenerative
properties of autoreactive IgG antibodies, which impair retinal
ganglion cells (RGC) survival by specific binding, and assume
direct and indirect triggered pathways for cell death in vivo.(53)
Additional evidence of the role of autoimmunity in
glaucoma is provided by the finding of elevated levels of
antibodies against small heat shock proteins (a-A-crystalline, aBcrystalline, and HSP27) in normal tension glaucoma
patients.(54,55) Disease-specific changes in complex profiles of
naturally occurring IgG autoantibodies were detected in the sera
of glaucoma patients.(56-58) Increased antibody levels (e.g. HSP70,
anti-phosphatidylserine, g-enolase, glycosaminoglycans, neuron
specific enolase, glutathione-S-transferase, a-fodrin, vimentin,
MBP, glial fibrillary acidic protein, and retinal S-antigen) were
identified and implicated as player for autoimmunity in glaucoma
and also significant and selective downregulations (e.g. anti-GFAP,
anti-14-3-3) could be detected in glaucoma patients.(59-68) However,
whether the autoantibodies have a causative effect or appear as
an epiphenomenon of the disease is yet to be unraveled. The
downregulations are possibly related to a loss of natural
protective autoimmunity and a disbalance of naturally occurring
autoantibodies promoting neurodegenerative processes. (69,70)
This unsteadiness may shift the physiological balance of protective
immunity into a neuroinflammatory degenerative process leading
to a predisposition for glaucoma which raises the question
whether elicited autoimmunity can cause RGC loss.(53)
There is a controversial debate whether autoantibodies are
aberrant and contribute to disease pathogenesis or are beneficial,
being part of a protective mechanism. Contradicting the principle
that autoantibodies are always associated with pathological
conditions, cumulative evidence demonstrate that natural
autoantibodies entail protective characteristics and that
autoimmunity can be protective in some situations. (71,72)
Accordingly, the downregulation of some autoantibodies in
glaucoma patients could lead to a loss of protective
autoimmunity.(53)
As a parameter associated with the presence and severity
of specific disease states, autoantibody patterns are useful
biomarkers for glaucoma diagnosis before its clinical
manifestations. Using mass spectrometry-based proteomics to
compare the autoantibody profiles in body fluids (serum,
aqueous humor or tears) from patients with glaucoma with those
obtained from healthy individuals, autoantibody patterns that
are the most discriminating can be classified.(53) Autoantibody
profiles are useful laboratory markers for the diagnosis of
diseases such as cancer, rheumatoid arthritis and Alzheimer’s
disease.( 73-75) In glaucoma, the complex antibody profiles are
stable and consistently exist among different study
populations.(65) As described previously, many autoantibody
reactivities are significantly increased or decreased in glaucoma
patients as compared to non-glaucoma control group. Using a
pattern recognition algorithm such as artificial neural networks
for unique serum autoantibody patterns, it is possible to
differentiate between sera of POAG patients and healthy subjects
with a sensitivity and specificity of approximately 93%.(53) Hence,
autoantibodies can be highly-specific and accurate useful
biomarkers for glaucoma diagnosis by simple blood testing.
261
Miscellaneous
Some non-genetic molecular candidate biomarkers
includes hormones such as erythropoietin, which exert its
neuroprotective effect by reducing the nitric oxide-mediated
formation of free radicals or antagonizing their toxicity, and
hepcidin that regulates of iron efflux from numerous cell types
and is expressed in the Müller cells, photoreceptors, and retinal
pigmented epithelium. Table 2 depicts a list of potential nongenetic glaucoma biomarkers.(76)
New proteins detected in the aqueous humor of
glaucoma patients are involved in molecular events that resemble
those that occur during atherosclerosis, such as, endothelial
dysfunction, lipoprotein alteration, modification of smooth
muscle cell functions, oxidative damage, inflammation, loss of
intercellular adhesion, mitochondrial failure, and apoptosis.(77)
As a whole, these observations indicate that a remarkable
endothelial damage affects the anterior chamber in glaucoma,
especially in the trabecular meshwork. From a biological point
of view, the anterior chamber is a space that is surrounded by an
endothelium and a path by which a liquid travels, so it can be
considered as being similar to a vessel. (78) Hence, these new
proteins are referred as vascular biomarkers ( Table 2).
Neurodegenerative markers
Neurodegenerative diseases are slowly progressive and
irreversible disorders of the nervous system. Early detection of
disease is possible by means of neurochemical measurements
and neuroimaging biomarkers specifically related to the
pathogenic events.(79,80) Parkinson’s and Alzheimer’s disease are
typical neurodegenerative diseases and although its primary causes are different from the glaucomatous optic neuropathy, they
share close similarities in several pathological findings.(81)
Retinal ganglion cell bodies are located within the eyeball
and its axons emerge the eye forming the optic nerve, chiasm
and optic tract. As retinal ganglion cell axons project to the central nervous system, their number within the retrobulbar optic
nerve may be a suitable surrogate marker for optic atrophy.(82)
Thinning of the retrobulbar optic nerve has been reported both
in histological and diagnostic imaging studies suggesting that the
diameter of the nerve may correlate with the extent of the optic
atrophy. (83-87) High-resolution magnetic resonance imaging
(MRI) using an ultra fast HASTE-sequence at 3 T sequences of
the optic nerve can portray axonal loss in the optic nerve
comparing closely with the retinal nerve fiber layer-related
parameters and could be used as a biomarker for axonal loss in
glaucoma.(82) 3-T diffusion tensor imaging of the optic nerve in
patients with glaucoma displays good correlation with the retinal
nerve fiber layer thickness measured by OCT and may serve as
a biomarker of disease severity.(88)
The majority of the ganglion cells axons terminate in the
lateral geniculate nucleus (LGN), the major relay station between
the retina and the visual cortex.(89) In an experimental glaucoma
model on monkeys, the loss of optic nerve fibers leads to
degenerative changes in the LGN, with decrease in number and
size of neurons and overall nucleus shrinkage.(90,91) These findings
provide evidence of trans-synaptic degeneration in glaucoma,
and may be relevant to understanding disease spread in select
patients.(81) In vivo MRI evidence of LGN degeneration in human
glaucoma is consistent with ex vivo primate and human
neuropathological studies. LGN atrophy may be a relevant
biomarker of visual system injury and/or progression in some
cases of moderate to severe glaucoma patients.(92)
Rev Bras Oftalmol. 2015; 74 (4): 257-65
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Kasahara N
Table 2. Non genetic candidate biomarkers in glaucoma
(adapted from Kokotas et al76).
Candidate biomarker
Type
Source
3 α -HSD
enzyme
blood
Ankyrin-2*
protein
AH
ANGPTL7
protein
TM and AH
Antibody for
glycosaminoglycans
antibody
serum
Antibody for GST
antibody
serum
Antibody for NSE
antibody
serum
Antibody for heat
shock proteins
antibody
serum
Antibody for anti-Helicobacter pylori
antibody
AH and serum
Antibody for Chlamydia
pneumoniae
antibody
serum
nucleotide
AH
AP4A compound
Apoliprotein B and D*
proteins
AH
BDNF
protein
serum
Caspase-14
enzyme
AH
CD44H
protein
TM and AH
Cellular senescence
antagonistic
pleiotropic response
AH
Citrate
multifunctional acid
Plasma
Cystatin C
protein
AH
Cytokines
proteins
TM, AH, and serum
ELAM1*
protein
AH
Erythropoietin
hormone
AH
GRP78
protein
TM
Heat shock 60 and 90
proteins
AH
kDa*
Hepcidin
hormone
AH
Homocysteine
amino acid
AH, plasma, and
tear fluid
Hydroxyproline
imino acid
AH and plasma
Malondialdehyde
aldehyde
AH and plasma
Myoblast determination
protein 1*
protein
AH
Myocilin
protein
AH and TM
Myogenin*
protein
AH
Myotrophin*
protein
AH
Nitric oxide synthase
enzyme
TM, Schlemm’s canal,
and collecting channels
PGDS
enzyme
AH, TM, and serum
enzyme
TM
Phospholipase A2
Phospholipase C β and γ* enzyme
AH
Transferrin
protein
AH
Transthyretin
protein
AH
Tumor necrosis factor α protein
AH
Ubiquitin fusion
degradation 1-like*
protein
AH
Vasodilator stimulated
phosphoprotein*
protein
AH and TM
AH: aqueous humor; TM: trabecular meshwork; * vascular biomarkers77
Rev Bras Oftalmol. 2015; 74 (4): 257-65
Future developments and conclusion
In summary, a biomarker is an anatomic, physiologic,
biochemical, or molecular parameter associated with the presence
and severity of specific disease states. A biomarker may be
detectable and measurable by a variety of methods, including
physical examination, laboratory assays, and medical imaging. As
a laboratory measurement or physical sign used in therapeutic
trials as a substitute for a clinically meaningful endpoint, surrogate
endpoints are used as direct measures of how a patient feels,
functions, or survives and are expected to predict the effects of
the therapy. For validation, a biomarker has to exhibit the
capability to capture the net effects of treatment on clinical
outcome, using an established scientific framework or body of
evidence that elucidates the physiologic, toxicologic,
pharmacologic, or clinical significance of the test results.(5)
The glaucomatous optic neuropathy encompasses a
number of different forms of disease, from childhood, early onset
juvenile glaucoma to secondary and adult glaucoma. The discovery
of specific biomarkers for each particular glaucoma is deemed
necessary and poses a challenge to researchers. Hence, there is
probably no single ‘ideal’ glaucoma biomarker that is going to
cover all aspects of clinical disease including early detection,
severity prediction, progression, and response to treatment.(5)
Despite the plethora of candidates biomarkers discusses
in this review, there are still unmet needs for glaucoma. What are
the candidate genes that affect connective tissue biomechanics
and how would that relate to glaucoma susceptibility? Is there
any biomarker that indicates the speed of disease progression?
Future research should focus on these issues.
In the near future, as physicians, we expect to be able to
establish a patient’s risk for POAG using a combination of genetic,
clinical and biochemical markers, to assess the ganglion cell
disease by novel imaging techniques, and initiate appropriate
therapy to restore ganglion cell health.(76)
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Corresponding author:
Alameda Madeira, 258 – sala 1206 -Alphaville – Barueri - SP
CEP: 06454-010
Email: [email protected]
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266
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B) Segunda folha
Resumo e Descritores: Resumo, em português e inglês, com
no máximo 250 palavras. Para os artigos originais, deverá ser
estruturado (Objetivo, Métodos, Resultados, Conclusão), ressaltando os dados mais significativos do trabalho. Para Relatos de
Caso, Revisões ou Atualizações, o resumo não deverá ser
estruturado. Abaixo do resumo, especificar no mínimo cinco e
no máximo dez descritores (Keywords) que definam o assunto do
trabalho. Os descritores deverão ser baseados no DeCS Descritores em Ciências da Saúde - disponível no endereço eletrônico http://decs.bvs.br/
Abaixo do Resumo, indicar, para os Ensaios Clínicos, o número de registro na base de Ensaios Clínicos (http://clinicaltrials.gov)*
C) Texto
Deverá obedecer rigorosamente a estrutura para cada categoria de manuscrito.
Em todas as categorias de manuscrito, a citação dos autores
no texto deverá ser numérica e sequencial, utilizando algarismos
arábicos entre parênteses e sobrescritos. As citações no texto deverão ser numeradas sequencialmente em números arábicos sobrepostos, devendo evitar a citação nominal dos autores.
Introdução: Deve ser breve, conter e explicar os objetivos e o
motivo do trabalho.
267
Métodos: Deve conter informação suficiente para saber-se o
que foi feito e como foi feito. A descrição deve ser clara e suficiente para que outro pesquisador possa reproduzir ou dar continuidade ao estudo. Descrever a metodologia estatística empregada
com detalhes suficientes para permitir que qualquer leitor com
razoável conhecimento sobre o tema e o acesso aos dados originais possa verificar os resultados apresentados. Evitar o uso de
termos imprecisos tais como: aleatório, normal, significativo, importante, aceitável, sem defini-los. Os resultados da pesquisa devem ser relatados neste capítulo em seqüência lógica e de maneira concisa.
Informação sobre o manejo da dor pós-operatório, tanto em
humanos como em animais, deve ser relatada no texto (Resolução nº 196/96, do Ministério da Saúde e Normas Internacionais
de Proteção aos Animais).
Resultados: Sempre que possível devem ser apresentados em
Tabelas, Gráficos ou Figuras.
Discussão: Todos os resultados do trabalho devem ser discutidos e comparados com a literatura pertinente.
Conclusão: Devem ser baseadas nos resultados obtidos.
Agradecimentos: Devem ser incluídos colaborações de pessoas, instituições ou agradecimento por apoio financeiro, auxílios técnicos, que mereçam reconhecimento, mas não justificam a
inclusão como autor.
Referências: Devem ser atualizadas contendo, preferencialmente, os trabalhos mais relevantes publicados, nos últimos
cinco anos, sobre o tema. Não deve conter trabalhos não referidos no texto. Quando pertinente, é recomendável incluir trabalhos publicados na RBO. As referências deverão ser numeradas
consecutivamente, na ordem em que são mencionadas no texto
e identificadas com algarismos arábicos. A apresentação deverá
seguir o formato denominado “Vancouver Style”, conforme modelos abaixo. Os títulos dos periódicos deverão ser abreviados
de acordo com o estilo apresentado pela National Library of
Medicine, disponível, na “List of Journal Indexed in Index
medicus” no endereço eletrônico: http://www.ncbi.nlm.nih.gov/
entrez/query.fcgi?db=journals.
Para todas as referências, citar todos os autores até seis. Quando em número maior, citar os seis primeiros autores seguidos da
expressão et al.
Artigos de Periódicos:
Dahle N, Werner L, Fry L, Mamalis N. Localized, central optic
snowflake degeneration of a polymethyl methacrylate intraocular
lens: clinical report with pathological correlation. Arch
Ophthalmol. 2006;124(9):1350-3.
Arnarsson A, Sverrisson T, Stefansson E, Sigurdsson H, Sasaki
H, Sasaki K, et al. Risk factors for five-year incident age-related
macular degeneration: the Reykjavik Eye Study. Am J Ophthalmol.
2006;142(3):419-28.
Livros:
Yamane R. Semiologia ocular. 2a ed. Rio de Janeiro: Cultura
Médica; 2003.
Capítulos de Livro:
Oréfice F, Boratto LM. Biomicroscopia. In: Yamane R.
Semiologia ocular. 2ª ed. Rio de Janeiro:
Cultura Médica; 2003.
Dissertações e Teses:
Cronemberger S. Contribuição para o estudo de alguns aspectos da aniridia [tese]. São Paulo: Universidade Federal de São
Paulo; 1990.
Publicações eletrônicas:
Herzog Neto G, Curi RLN. Características anatômicas das vias
lacrimais excretoras nos bloqueios funcionais ou síndrome de
Milder. Rev Bras Oftalmol [periódico na Internet]. 2003 [citado
2006 jul 22];62(1):[cerca de 5p.]. Disponível em:
www.sboportal.org.br
Tabelas e Figuras: A apresentação desse material deve ser
em preto e branco, em folhas separadas, com legendas e respectivas numerações impressas ao pé de cada ilustração. No
verso de cada figura e tabela deve estar anotado o nome do
manuscrito e dos autores. Todas as tabelas e figuras também
devem ser enviadas em arquivo digital, as primeiras preferencialmente em arquivos Microsoft Word (r) e as demais em arquivos Microsoft Excel (r), Tiff ou JPG. As grandezas, unidades e
símbolos utilizados nas tabelas devem obedecer a nomenclatura nacional. Fotografias de cirurgia e de biópsias onde foram
utilizadas colorações e técnicas especiais serão consideradas
para impressão colorida, sendo o custo adicional de responsabilidade dos autores.
Legendas: Imprimir as legendas usando espaço duplo, acompanhando as respectivas figuras (gráficos, fotografias e ilustrações) e tabelas. Cada legenda deve ser numerada em algarismos
arábicos, correspondendo as suas citações no texto.
Abreviaturas e Siglas: Devem ser precedidas do nome completo quando citadas pela primeira vez no texto ou nas legendas
das tabelas e figuras.
Se as ilustrações já tiverem sido publicadas, deverão vir acompanhadas de autorização por escrito do autor ou editor, constando a fonte de referência onde foi publicada.
O texto deve ser impresso em computador, em espaço duplo,
papel branco, no formato 210mm x 297mm ou A4, em páginas
separadas e numeradas, com margens de 3cm e com letras de
tamanho que facilite a leitura (recomendamos as de nº 14). O
original deve ser encaminhado em uma via, acompanhado de
CD, com versão do manuscrito, com respectivas ilustrações,
digitado no programa “Word for Windows 6.0.
A Revista Brasileira de Oftalmologia reserva o direito de não
aceitar para avaliação os artigos que não preencham os critérios
acima formulados.
Versão português-inglês: Seguindo os padrões dos principais
periódicos mundiais, a Revista Brasileira de Oftalmologia contará
com uma versão eletrônica em inglês de todas as edições. Desta
forma a revista impressa continuará a ser em português e a versão
eletrônica será em inglês.
A Sociedade Brasileira de Oftalmologia, Sociedade Brasileira
de Catarata e Implantes Intraoculares e Sociedade Brasileira de
Cirurgia Refrativa, se comprometem a custear a tradução dos
artigos para língua inglesa, porém seus autores uma vez que
tenham aprovado seus artigos se disponham a traduzir a versão
final para o inglês, está será publicada na versão eletrônica
antecipadamente a publicação impressa (ahead of print).
* Nota importante: A “Revista Brasileira de Oftalmologia” em
apoio às políticas para registro de ensaios clínicos da Organização
Mundial de Saúde (OMS) e do Intemational Committee of Medical
Joumal Editors (ICMJE), reconhecendo a importância dessas
iniciativas para o registro e divulgação internacional de informação
sobre estudos clínicos, em acesso somente aceitará para
publicação, a partir de 2008, os artigos de pesquisas clínicas
que tenham recebido um número de identificação em um dos
Registros de Ensaios Clínicos validados pelos critérios
estabelecidos pela OMS e ICMJE, disponível no endereço: http:/
/clinicaltrials.gov ou
no site do Pubmed, no item
<ClinicalTrials.gov>.
O número de identificação deverá ser registrado abaixo do
resumo.
Os trabalhos poderão ser submetidos pela Internet, pelo site rbo.emnuvens.com.br
Rev Bras Oftalmol. 2015; 74 (4): 266-8
268
Revista
Brasileira de
Oftalmologia
Declaração dos Autores (é necessária a assinatura de todos os autores)
Em consideração ao fato de que a Sociedade Brasileira de Oftalmologia está interessada em editar o manuscrito a ela
encaminhado pelo(s) o(s) autor(es) abaixo subscrito(s), transfere(m) a partir da presente data todos os direitos autorais para a
Sociedade Brasileira de Oftalmologia em caso de publicação pela Revista Brasileira de Oftalmologia do manuscrito............................................................. . Os direitos autorais compreendem qualquer e todas as formas de publicação, tais como na
mídia eletrônica, por exemplo. O(s) autor (es) declara (m) que o manuscrito não contém, até onde é de conhecimento do(s)
mesmo(s), nenhum material difamatório ou ilegal, que infrinja a legislação brasileira de direitos autorais.
Certificam que, dentro da área de especialidade, participaram cientemente deste estudo para assumir a responsabilidade por
ele e aceitar suas conclusões.
Certificam que, com a presente carta, descartam qualquer possível conflito financeiro ou de interesse que possa ter com o
assunto tratado nesse manuscrito.
Título do Manuscrito___________________________________________________________________________
Nome dos Autores_______________________________________________________________________________
_____________________________________________________________________________________________
Minha assinatura abaixo indica minha total concordância com as três declarações acima.
Data____________Assinatura do Autor____________________________________________________________
Data____________Assinatura do Autor____________________________________________________________
Data____________Assinatura do Autor_____________________________________________________________
Data____________Assinatura do Autor_____________________________________________________________
Data____________Assinatura do Autor____________________________________________________________
Data____________Assinatura do Autor_____________________________________________________________
Rev Bras Oftalmol. 2015; 74 (4): 266-8