Volumen IX
No.3
Septiembre 2010
CLINICAL APPLICATIONS OF GASES IN OPHTHALMOLOGY
Mário Junqueira Nóbrega MD
EFECTOS DE LA CAPA LIPÍDICA DE LA PELÍCULA LAGRIMAL EN LA
EVAPORACIÓN DEL COMPONENTE ACUOSO DE LA LÁGRIMA
Juan Carlos Arciniega MD; James Parker McCulley MD FACS FRCOphth (UK)
UVEAL MELANOMA ASSOCIATED WITH BILATERAL DIFFUSE UVEAL
MELANOCYTIC PROLIFERATION
Virginia L.L. Torres MD; Lynn Schoenfi Eld MD; Arun D. Singh MD
USO DE LÍQUIDO AMNIÓTICO TÓPICO EN LA
QUERATOCONJUNTIVITIS SICCA: ESTUDIO PRELIMINAR
Ximena Velasteguí Camorali MD, María Isabel Freile Moscoso MD, Manolita Guijarro MD
HOSPITAL PÚBLICO DO BRAZIL: OUTCOMES IN KERATOPLASTY AFTER
INFECTIOUS KERATITIS IN A PUBLIC HOSPITAL FROM BRAZIL
Glauco Reggiani Mello1; Marcos Longo Pizzolatti; Fernando M. Pradella; Gleisson R. Pantaleão; Ana
Paula Nudelmann Gubert; Hamilton Moreira
THE NEW FERRARA RING NOMOGRAM: THE IMPORTANCE OF CORNEAL
ASPHERICITY IN RING SELECTION
Paulo Ferrara MD PhD; Leonardo Torquetti MD PhD
4 :
PAN-AMERICA
Septiembre
Febrero 2010
2009
Mark J. Mannis, MD
University of California, Davis
Sacramento, California
Editor-in-Chief
Cristián Luco, MD
Santiago, Chile
Associate Editor
Teresa J. Bradshaw
Arlington, Texas
Managing Editor
Terri L. Grassi
Arlington, Texas
Production Editor
EDITORIAL BOARD
Eduardo Alfonso, MD
Miami, Florida USA
Alfredo Sadun, MD
Los Angeles, California USA
Eduardo Arenas, MD
Bogotá, Colombia
Allan Slomovic, MD
Toronto, Ontario, Canada
J. Fernando Arévalo, MD
Caracas, Venezuela
Luciene Barbosa de Sousa, MD
São Paulo, Brazil
José A. Roca Fernández, MD
Lima, Perú
Lihteh Wu, MD
San José, Costa Rica
Denise de Freitas, MD
São Paulo, Brazil
Paulo Dantas, MD
São Paulo, Brazil
Marian Macsai, MD
Chicago, Illinois USA
Chun Cheng Lin Yang, MD MSc
San José, Costa Rica
David E. Pelayes, MD PhD
Buenos Aires, Argentina
OFFICERS
Cristián Luco MD
Santiago, Chile
President, Pan-American Association of Ophthalmology
Nelson R. Marques
São Paulo, Brazil
Chairman of the Board,
Pan-American Ophthalmological Foundation
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Special thanks to Mapy Padilla
and Cristián Luco for assistance
in translation.
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PAN-AMERICA
MENSAJE DEL PRESIDENTE / MESSAGE FROM THE PRESIDENT
Cristián Luco, MD
President PAAO 2009-2011
Editorial
Editorial
La educación es uno de los pilares que justifica la existencia
de una sociedad supranacional como la PAAO (utilizamos estas siglas para no confundirla con la APAO – Asia Pacific Association
of Ophthalmology). Nuestra asociación tiene muchas instancias en
que ejercita esta actividad.
Los Congresos Panamericanos son un gran foro, el mayor de los
países de habla luso-hispana y semejante al de los Estados Unidos.
De 15 a 20 salas simultáneas están entregando conocimiento en cursos básicos, cursos adelantados, wet labs y simposios. Estos son en
los tres idiomas tradicionales y pronto esperamos que el francés de
Canadá se agregue. La industria farmacéutica además presenta, a su
manera, sus productos más recientes y sus innovaciones, y los presentan en un horario destinado especialmente para ellos.
La información entregada es desde los conceptos básicos de la
oftalmología hasta los resultados de la investigación básica y clínica
que aún puede estar en discusión. Los asistentes son desde residentes hasta oftalmólogos que quieren conocer los avances en disciplinas que no son las que ven a diario y les sirve para ponerse al día.
La discusión de temas alrededor de una mesa es un gran elemento de educación por la posibilidad de interactuar en forma próxima e inmediata con el docente. Esta metodología la incluiremos en
nuestros congresos, pero no en la madrugada y además le daremos
un toque latino.
Los grandes congresos reúnen de cuatro a cinco mil asistentes
por lo que es necesario efectuarlos en países con infraestructura
de centros de convención, hoteles y transporte entre otros, con capacidad para los mil asistentes más los acompañantes y todos los
representantes de la industria.
Nuestro próximo Congreso Panamericano será en Argentina en
julio de 2011. Nos vemos en Buenos Aires.
Dr. Cristián Luco
Presidente, PAAO
Education is one of the pillars that justify the existence of a
supranational society such as the Pan-American Association of
Ophthalmology – PAAO. Our Association has many instances in
which to engage in educational activity.
The Pan-American Congresses represent a very large forum, the
biggest of the Spanish-Portuguese speaking countries and similar to those in the United States. Fifteen to twenty simultaneous
halls are used to deliver knowledge through basic and advanced
courses, wet labs and symposia in the three traditional languages.
We hope soon to include Canadian French. Also, the pharmaceutical industry displays its most recent products and innovations in a
special programs especially dedicated to them.
The information presented ranges from basic concepts of ophthalmology to results of basic and clinical research that may still be
under discussion. Participants can be residents or practicing ophthalmologists who want to learn about the advances in disciplines
that are not seen in their daily practice that will be useful updates.
The round table discussion of topics is a huge element of
education and allows close and immediate interaction with the
speakers. We will include this methodology in our congresses,
(although not so early in the morning, adding a Latin touch!)
The Pan-American congresses gather four to five thousand
people including ophthalmologists, ancillary personnel and industry. These congresses are held in cities with a convention center and infrastructure with capacity for all these attendees.
Our next Pan-American Congress will be held in Argentina in
July 2011 See you in Buenos Aires.
Cristián Luco MD
PAAO President
Septiembre 2010
What doe the Pan-American Ophthalmological Foundation do? / O que faz a Fundação Pan-Americana de Oftalmologia?
Nelson R.A. Marques
PAOF President
Editorial
Editorial
A resposta mais objetiva é a de que a Fundação é o braço financeiro da Associação.
The most objective answer is that the Foundation is the financial arm of the PAAO.
2010 começou com o devastador terremoto no Haiti. A Associação Pan-Americana de Oftalmologia esteve entre as primeiras entidades a mobilizar-se para auxiliar os médicos oftalmologistas do
Haiti. A Fundação iniciou com um “pledge” de US$ 10,000.00 uma
campanha de arrecadação de fundos para os oftalmologistas do Haiti.
Temos a felicidade de reportar que obtivemos cerca de 120 doações
em dinheiro de indivíduos, famílias, fundações familiares, sociedades e entidades oftalmológicas nacionais, regionais e internacionais.
Conseguimos totalizar US$ 55,000.00, distribuídos, a princípio em
alimentos e produtos essenciais, e atualmente em processo de distribuição para atividades de educação e intercâmbio para nossos amigos do Haiti. Talvez nunca na história da Pan-Americana tenhamos
demonstrado juntos a imensa força do que é Panamericanismo.
The year 2010 began with a devastating earthquake in Haiti.
The Pan-American Association of Ophthalmology was among the
first entities to mobilize for aid to the ophthalmologists of Haiti.
The Foundation began a campaign to collect funds for Haitian ophthalmologists with a pledge of $10,000 US. We obtained a total of
$55,000 US, distributed initially as food and essential goods, and
we are currently in the process of funds distribution for educational
activities and exchange for our colleagues in Haiti. Perhaps never
in the history of the Pan-American Association have we demonstrated the immense power of Pan-Americanism.
Estamos coordenando a criação de um portal da PAAO,sob inspiração do Dr. Luco, que substituirá brevemente a nossa webpage.
A partir de Dezembro teremos novo portal eletrônico, com módulos de e-learning (incluindo fóruns de discussão e intercâmbio),
e-commerce (para inscrição em atividades da PAAO), e-publishing
(com a publicação virtual da revista Vision Pan-Americana).
Propusemos uma nova identidade visual para a Associação PanAmericana e para a Fundação Pan-Americana, em que nossa união
e força ficam claramente identificadas visualmente.
Finalmente entre as missões da Fundação está uma visão estratégica, que garanta a perenidade da Associação. Estamos em
processo de término de um planejamento estratégico que inclui um
plano operacional para os próximos 3 anos e que, a partir de agora,
será revisto e atualizado a cada triênio.
Meus agradecimentos aos Professores Cristián Luco (atual presidente da PAAO), Mark Mannis (Presidente Eleito para o biênio
2011/13) e à Teresa e Terri, todos de fundamental importância para
que conseguíssemos uma perfeita integração e harmonia para estas importantes conquistas.
We are coordinating the creation of a new online portal for
the PAAO, inspired by Dr. Luco, that will soon replace our current webpage. By December, the new electronic portal will have
modules for e-learning (including discussion and exchange forums), e-commerce (for subscription to activities and products of
the PAAO), and e-publishing (with the virtual publication of our
journal, Vision Pan-America).
We have proposed a new logo for both the Pan-American Association as well as the Pan-American Foundation that will clearly
identify us as a unified force.
Finally, among the missions of the Foundation is a strategic
vision that guarantees programmatic continuity of the organization. We are in the process of completing a strategic plan that
includes an operational plan for the next three years, and this plan
will be reviewed triennially.
My thanks to Professor Cristian Luco (current president of the
PAAO), Mark Mannis (President Elect for 2011/2013), and, of course,
Teresa Bradshaw and Terri Grassi, all of whom are of fundamental importance for us to succeed in these significant efforts.
Nelson R.A. Marques
PAOF President
Nelson R.A. Marques
Presidente, Fundação Pan-Americana de Oftalmologia
PAN-AMERICA : 67
REVIEW
Clinical Applications of Gases in Ophthalmology
Mário Junqueira Nóbrega MD(1,2,3)
1
Sadalla Amin Ghanem Eye Hospital, Joinville (SC), Brazil
University of Joinville, Joinville (SC), Brazil
3
Pan-American Association of Ophthalmology (PAAO), Brazilian
2
Delegate 2009-2011
RESUMO:
Atualmente, os gases intraoculares são utilizados de rotina para
o tratamento de várias doenças do segmento anterior e posterior,
propiciando resultados melhores e mais rápidos. Os gases intravítreos
são frequentemente usados para a terapia de descolamento de retina,
buraco macular, hemorragia intravítrea e submacular e como coadjuvante em cirurgia vítrea. A aplicação de gases na câmara anterior é
principalmente empregada no tratamento de hidrópsia corneana aguda,
descolamento da membrana de Descemet e como adjuvante em ceratoplastia lamelar. Este artigo de revisão discute aspectos relacionados
às atuais aplicações clínicas de gases para o tratamento de diferentes
doenças oculares e também os possíveis efeitos adversos associados
à injeção de gases na cavidade vítrea ou na câmara anterior.
ABSTRACT:
Intraocular gases in present day use are routinely implemented
for therapy of several diseases of the anterior and posterior segment, leading to better and faster outcomes. Intravitreous gases
are frequently used for therapy of retinal detachment, macular hole,
intravitreous and submacular hemorrhage and as a coadjuvant during vitreous surgery. Intracameral gases are mainly employed for
treatment of acute corneal hydrops, Descemet´s membrane detachment and as adjuvant for lamellar keratoplasty. This review article discusses details concerning the current clinical applications
of gases for treatment of different ocular diseases as well as the
potential adverse events associated with gas injection in the vitreous cavity or in the anterior chamber.
Introduction
Although the first description of use of intravitreous air to fix
retinal detachments is from 1911, by Ohm 1, the widespread use
of gases in Ophthalmology came after the 1960’s, with Norton et
al., who employed them for treatment of selected forms of rhegmatogenous retinal detachments 2-4 and with Machemer et al., the
precursors of the modern vitreous surgery 5-7.
Gases have important physical properties such as a high surface tension and high buoyant force that permit a better mechanical endotamponade than any other substitute and an adequate
pressure of a detached tissue against the attached one leading
to a firm adhesion. Additional advantageous properties of gases
include the fact that they are chemically inert, colorless, odorless and nontoxic.
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PAN-AMERICA
Intraocular gases in present day use are routinely implemented for therapy of several ocular diseases, contributing to better
and faster results than results from past decades.
According to different clinical situations, nonexpanding or expanding gases are utilized. Air is the most common nonexpanding
gas while sulfur hexafluoride (SF6) and perfluorocarbon gases (mainly
perfluoroethane (C2F6) and perfluoropropane (C3F8) are the most frequent expanding gases used in Ophthalmology.
Longevity of intraocular gases is variable. For a complete reabsorption in the vitreous cavity, air may take 7 days while pure
SF6, C2F6 and C3F8 may take 14 days, 35 days and 65 days,
respectively.
POSTERIOR SEGMENT INDICATIONS
The principal indications of injection of intravitreous gases include retinal detachment, macular hole repair, intravitreous and submacular hemorrhage and as a coadjuvant during vitreous surgery.
1. Retinal detachment
Pneumatic retinopexy is a technique to solve uncomplicated forms
of rhegmatogenous retinal detachments, principally those caused by
a small break in the superior 8 clock hours without proliferative vitreoretinopathy. It consists of intravitreous injection of a pure expanding
gas (0,5 ml of SF6 or 0,3 ml of C3F8) followed by laser photocoagulation or cryotherapy around the break and appropriate head positioning
for approximately 5 days. It is successful in the majority of these cases
and it does not cause the surgical trauma frequently observed in other
techniques of retinopexy 8-9.
In scleral buckling procedures or after external drainage of
subretinal fluid, gases are very useful to restore intraocular volume,
to smooth a retina with large meridional folds and to prevent a “fishmouth“ phenomenon. Air and SF6 18% are the preferred choices in
these situations due to their rapid reabsorption.
In complicated types of retinal detachment such as caused by
multiple retinal breaks, posterior breaks, giant tears or associated with
proliferative vitreoretinopathy, a complete vitrectomy in conjunction with
a fluid-gas exchange and a long-acting gas endotamponade have permitted better anatomical and functional results. Perfluorocarbon gases
are the best option, notably C2F6 16% and C3F8 14%, because of their
slower reabsorption and more prolonged effect (Figure 1) 10-13.
Septiembre 2010
Figure 1 – Partially gas filled vitreous
cavity three weeks after a pars plana
vitrectomy, fluid-gas exchange and
endotamponade with C3F8 14%.
2. Macular hole
A continued investigation about
pathophysiology of macular hole and the
development of vitreoretinal surgery techniques, equipments (principally optical
coherence tomography) and instrumentation have allowed remarkable results.
In addition to a conventional pars plana
vitrectomy with complete removal of the
posterior hyaloid and fluid-gas exchange,
the use of SF6 or perfluorocarbon gases in
a nonexpanding concentration is mandatory to close the hole. Nowadays, although
the internal limiting membrane peeling is
usually carried out for treatment of stage 3
or 4 macular holes, its indication for stage
2 macular holes remains controversial, as
does the need for postoperative face-down
positioning and its subsequent duration in
the postoperative course 14-17.
3. Intravitreous hemorrhage
Previous vitrectomized patients that
have recurrent vitreous hemorrhage, mainly in proliferative diabetic retinopathy or
after branch retinal vein occlusion, can
be managed through a fluid-gas exchange
due to its efficiency, practicality and safety
profile. Generally, it is performed by local anesthesia with a head rotation towards
the injection site and the introduction of a
30-gauge needle in the vitreous cavity 3 to
4 mm posterior to the limbus. Air or SF6
18% are usually injected in small quantities alternating with aspiration of the intravitreous fluid so that the vitreous cavity is
gradually filled by gas 18.
4. Submacular hemorrhage
A pneumatic displacement of submacular hemorrhage can be achieved after re-
cent episodes of bleeding caused by subretinal neovascular membranes, polypoidal
choroidal vasculopathy, traumatic choroidal ruptures and retinal arterial macroaneurysms. A 0,5 ml intravitreous injection of
pure C2F6 or C3F8 is expanded from 1,5 ml
to 2,0 ml after 6 to 8 hours so that the gas
can dislodge the subretinal hemorrhage.
Subsequently, the patient is instructed to
preserve a 40 degree gaze down position
for 20 minutes every hour while awake for
some days (Figure 2). When the submacular hemorrhage is thick, a pars plana vitrectomy and a subretinal injection of tissue
plasminogen activator may be indicated in
conjunction with pneumatic displacement
in order to maximize the effect and the
functional results 19-21.
5. Coadjuvant in vitreous surgery
During vitrectomy, a fluid-gas exchange
and maintainance of air under pressure inside
the vitreous cavity improve intraoperative visualization of the retina and allow a more adequate treatment of the underlying disease 22.
In sutureless small-gauge pars plana vitrectomy, besides making tunneled incisions
for insertion of the microcannulas, replacing
30% of vitreous volume with air at the end
of the surgery may help a better closure of
sclerotomies and consequently, it may decrease the risk of postoperative hypotony or
endophthalmitis 23, 24.
Furthermore, in aphakic eyes that need endotamponade with silicone oil, keeping an intracameral air bubble before air-silicone exchange
can avoid postoperative silicone prolapse
and corneal endothelium decompensation.
ANTERIOR SEGMENT INDICATIONS
The use of gases for treatment of anterior
segment diseases is more recent than the
application for posterior segment diseases.
Nevertheless, they are also fundamental in
different situations like acute corneal hydrops,
Descemet´s membrane detachment and as
adjuvant for lamellar keratoplasty.
1. Acute corneal hydrops and
Descemet´s membrane detachment
Intracameral nonexpanding gases (air,
SF6 18% or C3F8 14%) may close intrastromal clefts in advanced keratoconus or pellucid
marginal degeneration and promote resolution
of acute corneal hydrops as well as they may
reattach Descemet´s membrane tear after
complicated cataract surgery or deep lamellar keratoplasty (Figures 3 and 4). In these
conditions, Pilocarpine drops administration
and anterior chamber paracentesis precede
the gas injection. Nonexpanding C3F8 (14%)
is preferred because it stays longer inside the
eye and minimizes the need of other injections. The results are usually observed after
some days of intracameral gas tamponade
and supine positioning 25-31.
2. Adjuvant for lamellar keratoplasty
Lamellar keratoplasty techniques have
been progressively performed worldwide due
to its safer, faster and more predictable results
when compared with penetrating keratoplasty
(PK) 32-35.
In deep anterior lamellar keratoplasty
(DALK), especially indicated for treatment of
Figure 2 – Submacular hemorrhage caused by polypoidal choroidal vasculopathy before
(A) and one day after intravitreous gas injection for pneumatic displacement (B)
PAN-AMERICA : 69
REVIEW
Figure 3 – Acute corneal hydrops treated with intracameral
C3F8 14% in a patient with pellucid marginal degeneration
(Courtesy of Dr. Newton Rodrigues Salerno)
Figure 4 – Descemet´s membrane detachment after a deep
anterior lamellar keratoplasty (A) treated with intracameral C3F8
14% (B) (Courtesy of Dr. Vinícius Coral Ghanem)
Figure 5 – Corneal intrastromal air injection in deep anterior
lamellar keratoplasty (“big-bubble technique”) (Courtesy of Dr.
Ramon Coral Ghanem)
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PAN-AMERICA
keratoconus, stromal dystrophies and postinflammatory conditions, the main surgical purpose is to reduce the irregularity of the corneal stromal bed and consequent decreased
final visual acuity. So, after lamellar trephination, a deep intrastromal air injection of
approximately 0,5 ml is performed to cleave
the stroma from the Descemet´s membrane.
It allows an easier removal of the opaque corneal tissue and a smooth donor-to-recipient
interface (Anwar´s “big-bubble” technique
36
) (Figure 5). An additional intracameral
“small-bubble” may be injected to help delineation of intrastromal “big-bubble” and
to avoid inadvertent Descemet´s membrane
perforation during the procedure 37, 38.
Techniques of endothelial keratoplasty
(deep lamellar endothelial keratoplasty
(DLEK), Descemet’s stripping endothelial keratoplasty (DSEK), Descemet’s
stripping automated endothelial keratoplasty (DSAEK) and Descemet’s membrane endothelial keratoplasty (DMEK))
are important for treatment of endothelial
disfunction of the cornea in conditions
such as Fuchs’ endothelial dystrophy,
pseudophakic bullous keratopathy, previous endothelial graft rejection and rare
endothelial dystrophies such as posterior polymorphous corneal dystrophy and
congenital hereditary endothelial dystrophy. The injection of air or SF6 18% in the
anterior chamber has been used to create
apposition between donor posterior tissue
and recipient stroma 39-42.
COMPLICATIONS
Even though gas application improves
surgical outcomes in the vast majority of
cases, it may cause serious hazards. The
most common complications are elevation
of intraocular pressure and lens opacification. Expanding gases are more susceptible
to develop such events because of their increased size and prolonged period inside
the eye. Preoperatively, patients must be
aware of these potential adverse events and
their relation to gravity 43, 44. Positioning
becomes essential for avoidance of these
complications depending on whether the
gas is used for anterior or posterior segment surgery. Patients undergoing retina
surgery with a posterior gas must avoid
sleeping on their back in order to prevent
anterior displacement of the bubble. Conversely, patient undergoing lamellar kerato-
plasty should sleep on their back to prevent
posterior diversion of air and subsequent
pupillary block glaucoma and iridocorneal
adhesions 45. Other possible hazards associated with intracameral air/gas injection
following DSAEK include corneal endothelial cell damage, fixed dilated pupil (UrretsZavalia syndrome) and anterior subcapsular
cataract formation 46, 47.
CONCLUSIONS
In the last decades, important advances
of ophthalmic techniques and technology
have allowed not only therapy of previously
untreatable diseases but also more effective and efficient outcomes than previously
described uses. The use of gases is inserted in this context because their singular
physical and chemical characteristics yield
results not seen before in many diseases
of the anterior and posterior segment. In
the future, it’s hoped that their application
in Ophthalmology will become even more
common with the development of different
types of gases and a better understanding
of the interactions between effects of gases
on the ocular tissues with limitations of
ocular complications.
ACKNOWLEDGMENT
The author thanks Dr. Vinícius Coral
Ghanem for important observations and
suggestions.
Septiembre 2010
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2006, p.2167.
23. Shimada H, Nakashizuka H, Hattori T, Mori R, Mizutani Y, Yuzawa M.
Incidence of endophthalmitis after 20- and 25-gauge vitrectomy causes and
prevention. Ophthalmology 2008;115(12):2215-20.
24. Woo SJ, Park KH, Hwang JM, Kim JH, Yu YS, Chung H. Risk
factors associated with sclerotomy leakage and postoperative hypotony after 23-gauge transconjunctival sutureless vitrectomy. Retina.
2009;29(4):456-63.
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2002;133(6):750-2.
26. Shah SG, Sridhar MS, Sangwan VS. Acute corneal hydrops treated by
intracameral injection of perfluoropropane (C3F8) gas. Am J Ophthalmol.
2005;139(2):368-70.
27. Salerno NR, Salerno LC, Souza ALS. Acute hydrops: incidence
and couse after clinical and surgical treatment. N. R. Salerno, L. C.
Salerno, and A. L. S. Souza. Invest Ophthalmol Vis Sci. 2007; 48:
E-Abstract 1836.
28. Zusman NB, Waring GO 3rd, Najarian LV, Wilson LA. Sulfur hexafluoride gas in the repair of intractable Descemet´s membrane detachment. Am J
Ophthalmol. 1987;104(6):660-2.
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detachment with perfluoropropane (C3F8). Cornea. 1998;17(2):129-34.
30. Kim T, Hasan SA. A new technique for repairing Descemet membrane detachments using intracameral gas injection. Arch Ophthalmol.
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31. Lucena Ada R, Lucena Dda R, Macedo EL, Ferreira Jde L, de Lucena
AR. C3F8 use in Descemet detachment after cataract surgery.Arq Bras Oftalmol. 2006;69(3):339-43.
32. Archila EA. Deep lamellar keratoplasty dissection of host tissue with intrastromal air injection. Cornea, 1984–85, 3(3):217–8.
33. Melles GRJ, Lander F, Rietveld FJR, Remeijer L, Beekhuis WH, Binder
PS. A new surgical technique for deep stromal, anterior lamellar keratoplasty.
Br J Ophthalmol 1999;83(3):327–33.
34. Fontana L, Parente G, Tassinari G. Clinical outcomes after deep anterior
lamellar keratoplasty using the big-bubble technique in patients with keratoconus. Am J Ophthalmol. 2007;143(1):117-24.
35. Chen ES, Terry MA, Shamie N, Hoar KL, Phillips PM, Friend DJ. Endothelial keratoplasty: vision, endothelial survival and complications in a
comparative case series of fellows vs attending surgeons. Am J Ophthalmol.
2009;148(1):26 –31.
36. Anwar M, Teichmann KD. Big-bubble technique to bare Descemet’s membrane in anterior lamellar keratoplasty. J Cataract Refract Surg
2002;28(3):398–403.
37. Parthasarathy A, Por YM, Tan DT. Use of a “small-bubble technique” to increase the success of Anwar’s “big-bubble technique” for
deep lamellar keratoplasty with complete baring of Descemet’s membrane. 2007;91(10):1369-73.
38. Price FW Jr. “Small bubble technique” helps “big bubble technique”. Br
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39. Melles GRJ, Lander F, van Dooren BTH, Pels E, Beekhuis WH. Preliminary clinical results of posterior lamellar keratoplasty through a sclerocorneal
pocket incision. Ophthalmology. 2000;107(10):1850–6.
40. Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty in the first
United States patients: early clinical results. Cornea 2001;20(3):239–43.
41. Terry MA. A new approach for endothelial transplantation: deep lamellar
endothelial keratoplasty. Int Ophthalmol Clin. 2003;43(3):183-93
42. Terry MA, Shamie N, Chen ES, Hoar KL, Friend DJ. Endothelial keratoplasty: a simplified technique to minimize graft dislocation, iatrogenic graft
failure, and pupillary block. Ophthalmology. 2008;115(7):1179 –86.
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44. Lincoff H, Weinberger D, Stergiu P. Air travel with intraocular gas. II.
Clinical considerations. Arch Ophthalmol. 1989;107(6):907-10.
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AO, Gottsch JD. Secondary angle closure caused by air migrating behind the pupil in descemet stripping endotheilial keratoplasty. Cornea.
2009;28(6):652-6.
46. Hong A, Caldwell MC, Kuo AN, Afshari NA. Air bubble-associated endothelial trauma in descemet stripping automated endothelial keratoplasty.
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REVIEW
Efectos de la Capa Lipídica de la Película
Lagrimal en la Evaporación del Componente
Acuoso de la Lágrima
Juan Carlos Arciniega MD; James Parker McCulley MD
FACS FRCOphth (UK)
Department of Ophthalmology, University of Texas Southwestern
Medical Center at Dallas, Texas, USA.
Realizado con apoyo de los grant EY12430 y EY016664 del National Institute of
Health y por un grant sin restricción de Research to Prevent Blindness, Inc, NY. USA.
Los autores no poseen ningún interés comercial en los productos o procedimientos mencionados en este artículo.
Correspondencias a:
James P. McCulley
Department of Ophthalmology, University of Texas Southwestern
Medical Center at Dallas
5323 Harry Hines Blvd., Dallas, TX, 75390-9057
Telephone: 214-648-2020, Fax: 214-648-9061
Email: [email protected]
ABSTRACT:
RESUMEN
The tear film consists of three layers: an outer thin lipid layer
that is composed in part of lipid-rich excreta called meibum, secreted by the meibomian glands; a middle aqueous-mucin layer
that nourishes the cornea and conjunctiva; and an inner mucin
layer that helps to spread the aqueous layer over the ocular surface. Changes in the quality or quantity of any of the tear film
components affect its normal protective function and promote the
development of dry eye disease.
La superficie ocular está cubierta por una delgada película, llamada película lagrimal, compuesta por 3 capas: la externa o capa
lipídica, integrada principalmente por los lípidos provenientes de
las glándulas de meibomio; la capa intermedia, acuosa, compuesta por proteínas y electrólitos; y la capa interna, compuesta en su
mayor parte de mucina. Cambios cuantitativos o cualitativos de
cualquiera de los componentes de la película lagrimal conllevan a
situaciones patológicas como el ojo seco.
Currently, a study in the U.S estimated that 3.25 million women
and 1.68 million men 50 years and older are affected, and is expected to grow even more. Previous studies have identified some
risk factors for dry eye disease such as older age, female sex, reduced androgen levels, and imbalanced diet. Dry eye disease has
been divided into two groups: 1) aqueous tear-deficient dry eye,
and 2) evaporative dry eye (also known as lipid tear deficiency
dry eye).
Actualmente, en Estados Unidos 3,25 millones de mujeres y 1,68
millones de hombres mayores de 50 anos se encuentran afectados,
y esta cifra va en aumento. Estudios previos han identificado factores de riesgo para la enfermedad entre los que se encuentran el
envejecimiento, sexo femenino, disminución de los niveles de andrógenos y dietas desbalanceadas. La enfermedad del ojo seco se
divide en dos grupos: 1) ojo seco con deficiencia del componente
acuoso, y 2) ojo seco de tipo evaporativo (también conocido como
ojo seco con deficiencia del componente lipídico).
Previous publications have postulated that an abnormal tear
film lipid layer would facilitate the evaporation from the tear film
and lead to the development of dry eye disease. In our study, using
two relatives humidities (25-35% and 35-45%) we have reported
an increase in the evaporation rate by 42.1% and 40% in dry eye
patients, compared to normal group. These results indicate that
the dry eye patients have a higher rate of evaporation from the
aqueous tear layer as compared to normal subjects.
The development of new technologies to reduce the evaporation
from the aqueous tear has been the aim of many pharmaceutical
companies. Newer lipid emulsion eye drops are becoming more
effective and popular. Recent data suggest that after the instillation
of these lipid-containing eye drops the lipid layer thickness and
ocular symptoms improved in dry eye patients, compared to other
commercially available eye drops.
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Publicaciones previas han señalado el aumento de la evaporación de la película lagrimal en presencia de una capa lipídica
disfuncional. Nuestras investigaciones (usando humedades relativas de 25-35% y 35-45%) han reportado un aumento en la evaporación de un 42.1% y 40% aproximadamente en pacientes con ojo
seco, en comparación con el grupo control. Estos resultados indican que los pacientes con ojo seco tienen una tasa de evaporación
de la película lagrimal mucho más alta a la de personas sanas.
Cada día más laboratorios invierten en el desarrollo de tecnología para reducir la evaporación de la película lagrimal. Gotas
con emulsión lipídica son cada vez más comunes y efectivas, estas gotas restauran parcialmente la capa lipídica y han demostrado
ser eficaces en el tratamiento del ojo seco de tipo evaporativo en
comparación con las gotas sin contenido lipídico.
Septiembre 2010
Introducción
La superficie ocular está cubierta por una delgada película. Esta película lagrimal es una estructura
compleja compuesta por 3 capas: la externa, llamada capa lipídica, integrada principalmente por los
lípidos provenientes de las glándulas de meibomio.
La capa intermedia, acuosa, compuesta por proteínas y electrolitos. Y la capa interna, compuesta en
su mayor parte de mucina. Cambios cuantitativos o
cualitativos de cualquiera de los componentes de
la película lagrimal, en especial las capas lipídica
y acuosa conllevan a situaciones patológicas como
el ojo seco.
Actualmente, el ojo seco es una de las enfermedades oftalmológicas con mayor prevalencia, afectando a millones de personas. Esta patología impide
el normal desarrollo de actividades como la lectura,
conducir un auto, o trabajar en la computadora.
El ojo seco se define como una enfermedad
multifactorial de la película lagrimal y superficie
ocular que resulta en síntomas de molestia y problemas visuales, con un potencial daño al epitelio
ocular.1
La fisiopatología del ojo seco se desarrolla por
un aumento de la osmolaridad e inestabilidad de la
película lagrimal. La hiperosmolaridad causa daños en
el epitelio ocular a través de la activación de la cascada
inflamatoria y la liberación de mediadores inflamatorios
en la película lagrimal, produciendo muerte celular por
apoptosis, disminución de células de Goblet y trastornos en la producción de mucina, llevando a la inestabilidad de la película lagrimal.1
Estudios previos han identificado factores de
riesgo para la enfermedad del ojo seco entre los que
se encuentran el envejecimiento, sexo femenino,
disminución de los niveles de andrógenos y dietas
desbalanceadas.2 Un estudio a larga escala en los
Estados Unidos estimó que 3,25 millones de mujeres
y 1,68 millones de hombres mayores de 50 años sufren de ojo seco, en los hombres esta cifra se espera
que ascienda a 2.79 millones para el año 2030.3, 4
El ojo seco ha sido clasificado en dos grupos: 1) ojo seco con deficiencia del componente
acuoso, y 2) ojo seco de tipo evaporativo, en el cual
una excesiva cantidad de agua se pierde desde la
superficie ocular a través de la evaporación.1
Un modelo de la capa lipídica de la película
lagrimal fue propuesto por McCulley et al.5 Este
modelo sugiere una teoría bifásica de la capa
lipídica, compuesta por una parte polar y otra no
polar. La fase lipídica polar tiene propiedades sur-
factantes facilitando la interacción entre la capa
acuosa y la fase no polar. La fase no polar ubicada
en la superficie actúa como barrera previniendo la
pérdida de agua de la película lagrimal.6
Las glándulas de meibomio son un tipo especializado de glándulas sebáceas localizadas en los
márgenes de los párpados. Estas glándulas son
responsables de la secreción de lípidos que integran
la capa lipídica de la película lagrimal. En ciertas
circunstancias existe un deterioro en la composición
de estos lípidos, conocido como disfunción de las
glándulas de meibomio. El envejecimiento y la deficiencia de andrógenos han sido asociados con el
desarrollo de esta patologia.7 Adicionalmente, las
lipasas y esterasas bacteriales también pueden
modificar estos lípidos y producir disfunción de
las glándulas de meibomio. En ambos casos, los
lípidos de meibomio tienen alterada su estructura,
afectando de manera negativa a la película lagrimal,
y predisponiendo al paciente a sufrir de ojo seco.
Después de cada parpadeo, una parte del componente acuoso de la lágrima se pierde por evaporación,
esto ocurre en situaciones normales.8 En la enfermedad del ojo seco, la evaporación de la capa acuosa se
ha considerado de fundamental importancia, debido
a que en estos pacientes el índice de evaporación es
mucho mayor al de producción lagrimal, llevando al
déficit del componente acuoso de la lágrima. La evaporación del componente acuoso varía entre un 20%
y 60% y es dependiente de condiciones ambientales
como la humedad relativa (HR).9
En previas publicaciones, hemos observado que
en condiciones de baja humedad existe un aumento
de la tasa de evaporación de la película lagrimal.10
Estos datos obtenidos en el laboratorio simulan
situaciones como vuelos comerciales o paseos a
lugares áridos, en donde las personas que padecen
de ojo seco pudieran estar severamente afectadas.
Evaporación del componente acuoso
de la lágrima y la capa lipídica.
La evaporación es la transición de una fase
líquida a una fase gaseosa desde una superficie. Entre los factores que afectan la tasa de evaporación,
se encuentran: la presión de saturación de ese
líquido, área de superficie, flujo de aire, y temperatura. En la superficie ocular la película lagrimal está
expuesta a todo lo mencionado anteriormente.
Maurice y Mishima calcularon la tasa de
evaporación desde la superficie de la cornea de
conejo por medio de cambios en el grosor de ésta.11 Ellos fueron los primeros en observar que la
capa lipídica retardaba la evaporación de la película
lagrimal.11 En seres humanos, Rolando y Refojo
PAN-AMERICA : 73
REVIEW
Gráfico
TABLA. Resultados de la Tasa de Evaporación
Humedad (HR) Normalesa,b
Ojo Secoa,b
Pc
25% to 35%
0.033±0.012 0.057±0.026
0.003
35% to 45%
0.023±0.008 0.038±0.018
0.001
a
Valores expresados en la media ± desviación estándar
Unidad: µl/cm2/min.
c
Comparación de la tasa evaporativa entre los grupos.
b
desarrollaron un instrumento que permite calcular
la evaporación de la película lagrimal, este equipo
consiste en unas gafas adaptadas al contorno del
rostro y por las cuales circula una corriente de aire
deshumificado a través de un sensor de humedad y
temperatura, en el cual se registran los cambios de
humedad provenientes de la córnea.12
En nuestras investigaciones se utilizó un equipo
similar al usado por Rolando y Refojo, pero con
algunas mejoras. La temperatura del área donde
se realizó el estudio fue controlada a 25 ± 1°C,
y el parámetro de humedad relativa fue colocado
entre 25-35% y 35-45%. Además, el parpadeo del
paciente fue estandarizado a un intervalo de 2 segundos. En pacientes con ojo seco el estudio de la
evaporometría ha sido usado para calcular la cantidad de agua perdida por la película lagrimal.
Rolando y Refojo reportaron un aumento en el
doble en la tasa de evaporación en pacientes con
ojo seco.9 En el año 2000, Craig y Tomlinson estudiaron pacientes con ojo seco, encontrando que la
tasa de evaporación, osmolaridad y temperatura en
la superficie ocular fue superior al grupo control.13
Además, Mathers reportó un aumento en la tasa de
evaporación en un 55% en pacientes de ojo seco
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comparado con personas sanas. En otro estudio
realizado por el mismo autor, la tasa de evaporación
en pacientes con ojo seco y disfunción de las glándulas de meibomio reportó ser tres veces mayor al
grupo control.14 Los resultados de McCulley y Shine
sugieren que las personas que padecen de disfunción de las glándulas de meibomio presentan una
modificación de los lípidos secretados por estas
glándulas, afectando de manera negativa la estabilidad y acelerando la tasa de evaporación de la
película lagrimal.15
Nuestros resultados se correlacionan con los
anteriormente mencionados (ver tabla). Calculando
la evaporación de la película lagrimal usando dos
humedades relativas de 25-35% y 35-45%, encontramos que el grupo conformado por pacientes con
ojo seco tuvo un aumento significativo en la tasa
de evaporación de la película lagrimal de 42.1% y
40%, comparado con el grupo control (ver gráfico).
Futuras investigaciones son necesarias, en especial las que incluyan un análisis estructural de los
lípidos de meibomio y a su vez correlacionar estos
resultados con la tasa de evaporación de la película
lagrimal.
Alternativas terapéuticas para tratar
el ojo seco
El objetivo de muchos tratamientos para el ojo
seco ha sido la reducción de la evaporación de la
película lagrimal. Análisis químicos del meibum
obtenidos de pacientes con disfunción de las glándulas de meibomio sugieren que existe una alta
proporción de ácidos grasos saturados versus no
saturados.16 Estos cambios producen un aumento
Septiembre 2010
del punto de fusión de los lípidos y explica por qué en
estos pacientes la secreción de las glándulas de meibomio posee una consistencia pastosa. Aumentando la
temperatura en el área de los párpados, la consistencia
de los lípidos debería modificarse, y pasar de pastosa
a líquida, facilitando su excreción hacia la superficie
ocular.17 Por esta razón el uso compresas tibias con
temperaturas superiores a la corporal son indicadas en
pacientes con ojo seco de tipo evaporativo.
El uso de nuevas gotas como sustitutos a las lágrimas está siendo investigado. Datos recientes sugieren
que después de instilar gotas con emulsión de lípidos,
la capa lipídica de la película lagrimal aumentó su
grosor y los pacientes reportaron una mejoría en sus
sintomas.18 Khanal et al reportó una disminución en la
tasa de evaporación de la película lagrimal de 7.25 g/
m2/h usando gotas con la emulsión lipídica, en comparación con 2.02 g/m2/h usando gotas que contenían
una solución hipromelosa.19 Resultados similares
fueron reportados por Korb et al20, donde se
observó un aumento del grosor de la capa lipídica en un
107% posterior al uso de gotas con emulsión lipídica,
contrastando con un aumento del 16% cuando se uso
una gota sin contenido lipídico.
Por otra parte, el uso de anteojos adaptados para
formar una campana húmeda en donde se reduce la
evaporación de la superficie ocular se ha empleado por
algún tiempo.21
Sin embargo, el manejo del paciente con ojo seco
es todavía un desafío. Nosotros como médicos estamos
en la necesidad de educar a nuestros pacientes sobre
todos los factores que agravan la enfermedad, así como
individualizar el tratamiento en cada caso.
BIBLIOGRAFÍA
1. The definition and classification of dry eye disease: report
of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:7592.
2. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop
(2007). Ocul Surf 2007;5:93-107.
3. Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol
2003;136:318-326.
4. Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence
of dry eye disease among US men: estimates from the Physicians’
Health Studies. Arch Ophthalmol 2009;127:763-768.
5. McCulley JP, Shine W. A compositional based model for the
tear film lipid layer. Trans Am Ophthalmol Soc 1997;95:79-88;
discussion 88-93.
6. McCulley JP, Shine WE. The lipid layer: the outer surface of
the ocular surface tear film. Biosci Rep 2001;21:407-418.
7. Sullivan BD, Evans JE, Dana MR, Sullivan DA. Influence of
aging on the polar and neutral lipid profiles in human meibomian gland secretions. Arch Ophthalmol 2006;124:1286-1292.
8. Mathers WD, Daley TE. Tear flow and evaporation in patients
with and without dry eye. Ophthalmology 1996;103:664-669.
9. McCulley JP, Uchiyama E, Aronowicz JD, Butovich IA. Impact of evaporation on aqueous tear loss. Trans Am Ophthalmol
Soc 2006;104:121-128.
10. Uchiyama E, Aronowicz JD, Butovich IA, McCulley JP.
Increased evaporative rates in laboratory testing conditions
simulating airplane cabin relative humidity: an important factor for dry eye syndrome. Eye Contact Lens 2007;33:174-176.
11. Mishima S, Maurice DM. The oily layer of the tear film
and evaporation from the corneal surface. Exp Eye Res
1961;1:39-45.
12. Rolando M, Refojo MF. Tear evaporimeter for measuring water evaporation rate from the tear film under controlled conditions in humans. Exp Eye Res 1983;36:25-33.
13. Craig JP, Singh I, Tomlinson A, Morgan PB, Efron N. The
role of tear physiology in ocular surface temperature. Eye (Lond)
2000;14 ( Pt 4):635-641.
14. Mathers WD. Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology 1993;100:347-351.
15. McCulley JP, Shine WE. Meibomian gland function and the
tear lipid layer. Ocul Surf 2003;1:97-106.
16. Shine WE, McCulley JP. Association of meibum oleic acid
with meibomian seborrhea. Cornea 2000;19:72-74.
17. Mitra M, Menon GJ, Casini A, et al. Tear film lipid layer
thickness and ocular comfort after meibomian therapy via latent heat with a novel device in normal subjects. Eye (Lond)
2005;19:657-660.
18. Scaffidi RC, Korb DR. Comparison of the efficacy of two lipid
emulsion eyedrops in increasing tear film lipid layer thickness.
Eye Contact Lens 2007;33:38-44.
19. Khanal S, Tomlinson A, Pearce EI, Simmons PA. Effect of
an oil-in-water emulsion on the tear physiology of patients with
mild to moderate dry eye. Cornea 2007;26:175-181.
20. Korb DR, Scaffidi RC, Greiner JV, et al. The effect of two novel
lubricant eye drops on tear film lipid layer thickness in subjects
with dry eye symptoms. Optom Vis Sci 2005;82:594-601.
21. Hart DE, Simko M, Harris E. How to produce moisture
chamber eyeglasses for the dry eye patient. J Am Optom Assoc
1994;65:517-522.
Gráfico. Comparación en la tasa de evaporación entre personas
sin patología ocular (normales) y pacientes con ojo seco, usando
dos humedades relativas 25-35% y 35-45%. El grupo con ojo
seco mostró un aumento en la tasa de evaporación de 42,1% y
40% en comparación al grupo control (p=0.003 y p=0.001).
PAN-AMERICA : 75
CLINICAL SCIENCES
Uveal Melanoma Associated With Bilateral
Diffuse Uveal Melanocytic Proliferation
Virginia L.L. Torres MD1,3; Lynn Schoenfield MD2; Arun D. Singh MD3
1
Escola Paulista de Medicina – Federal University of Sao Paulo, Sao Paulo, Brazil
Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio
3
Department of Ophthalmic Oncology, Cleveland Clinic Foundation, Cleveland, Ohio
2
The authors have no relevant financial interest in the products or companies
described in this article
Resumo
Proliferação melanocítica uveal difusa
bilateral (BDUMP) é uma síndrome paraneoplásica ocular rara, cujo diagnóstico
diferencial inclui melanoma uveal difuso,
carcinoma ou melanoma metastático,
linfoma intra-ocular de grandes células,
síndrome da efusão uveal idiopática e síndrome de Vogt-Koyanagi-Harada. BDUMP
está relacionada a perda visual importante
e irreversível. O reconhecimento desta
condição ajuda ao clínico diagnosticar
uma doença maligna sistêmica subclínica.
Nós apresentamos um caso de BDUMP, associado a melanoma uveal com documentação histológica, em um paciente sem o
diagnóstico clínico de doença maligna.
Abstract
Bilateral diffuse uveal melanocytic
proliferation (BDUMP) is a rare ocular
paraneoplastic syndrome whose differential diagnosis includes diffuse uveal melanoma, uveal metastatic carcinoma or melanoma, intra ocular large-cell lymphoma,
idiophatic uveal effusion syndrome, and
Vogt-Koyanagi-Harada syndrome. BDUMP
is a vision-threatening disease and always
represents a diagnostic challenge. Early
recognition of this condition can help the
clinician to identify an underlying malignancy. We report a case of BDUMP with
histopathologically documented uveal
melanoma in one eye in a patient without a
detectable systemic malignancy.
Introduction
Diffuse uveal melanocytic proliferation
is a rare but well-defined entity. This para76
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Reprints:
Arun D. Singh MD
Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic
9500 Euclid Ave, Cleveland, Ohio, 44195
e-mail: [email protected]
neoplastic syndrome was first described in
1982 by Barr and associates.[1] At that time
they reported six cases with clinical and
histopathologic descriptions and included
two previous reports from the literature, the
first publication dating from 1966 by Machemer.[2] Since then, many case reports
and small case series have been published.
[3-18]
Characteristically the disease exhibits
bilateral diffuse melanocytic proliferation
of the uvea unrelated to metastasis. In the
literature this condition is generally known
as bilateral diffuse uveal melanocytic proliferation (BDUMP). In some reports concurrent ocular and cutaneous and/or mucosal involvement is demonstrated[6, 13, 14,
19]
which lead Singh et al[6] to suggest the
term paraneoplastic melanocytic proliferation as more appropriate for this disease
since the eye, skin and mucous tissues
may share the same histopathologic features. BDUMP is associated with systemic
carcinomas and in the majority of the
cases the primary neoplasia is unknown at
the time of presentation. The mean age at
diagnosis is 63 years. The most commons
malignances associated with BDUMP are
poorly differentiated carcinomas of the
lung in men and ovarian, cervical and uterine carcinoma in women.[10]
Herein, we present a case of bilateral
diffuse uveal melanocytic proliferation
with histopathologically documented uveal
melanoma involving one eye in a patient
without a detectable systemic malignancy.
Case Report
A 65 year old man complained of blurred
vision in both eyes after recent cataract surgery. At ophthalmic examination, corrected
visual acuity was 20/70 OD and 20/25 OS.
Anterior segment examination displayed in
the right eye iris “freckle” and nevus in the
inferior quadrant, measuring 3.0 x 2.5 mm
(Figure 1A). Ophthalmoscopic examination
and image documentation were limited by
poor dilation of both pupils. In the right eye
two flat choroidal nevi in the superotemporal
quadrant and juxta-papillary nasal quadrant
were present (Figure 1B) as well as retinal
pigmentary epithelium (RPE) changes in the
posterior pole better noticed with autofluorescence examination (Figures 1C and D). In the
left eye, a triangular mildly elevated choroidal mass nasal to the disc was identified with
overlying orange pigmentation and subretinal
fluid, diagnosed as a large choridal nevus or
indeterminate melanocytic lesion. Ocular
ultrasonography detected another ciliochoroidal mass in the superior quadrant of the
left eye, which was mushroom-shaped with
prominent intrinsic vascularity, low to medium reflectivity, measuring 9.5mm in thickness (Figure 1E). As the major lesion could
not be visualized properly due to poor pupil
dilation, the patient was referred for a systemic work-up to rule out metastatic disease
and for fine needle aspiration biopsy (FNAB)
that revealed, as clinically suspected, malignant melanoma cells and an enucleation was
performed. The histopathologic features are
described below.
During the subsequent year the patient
experienced progressive deterioration of
vision. Ophthalmic examination disclosed
visual acuity of hand motion, increased iris
pigmentation and enlargement of iris lesions with neovascularization (Figure 2A),
diffuse angle pigmentation (Figure 2B),
and ultrasonography revealed diffuse choroidal thickness with focal areas of serous
Septiembre 2010
retinal detachment (Figure 2C). Clinical course of bilateral diffuse uveal involvement was suggestive of BDUMP
and dermatologic and oncologic evaluations were performed. At present, the investigations have not revealed
any evidence of systemic malignancy.
Pathology
On macroscopic examination, the eye presented
a nonpigmented mass involving the ciliary body and a
darkly pigmented area of choroidal thickening close to
the optic disc (Figure 3A). Histopathologic examination showed malignant melanoma which involved the
entire circumference of the uveal tract (iris, ciliary body
and entire choroid) (Figures 3B and C) and not just the
grossly noted masses. The thinner areas measured less
than 200 microns in thickness, and the largest tumoral
focus measured 8 mm in height. The predominant cell
type was spindle B but occasional epithelioid cells were
also present (Figure 3D). Mitoses (up to 10 per 40 power
fields) were identified circumferentially, and the proliferation rate, assessed with a Ki-67 stain by immunoperoxidase, was uniform throughout the uveal tract (Figures
3 E and F). No extraocular extension was noticed. PAS
stain showed a weak pattern of vascular mimicry.
Comments
Paraneoplastic syndromes are rare disorders triggered by an altered immune response to a neoplasm that
occurs remotely from the tumor itself and are considered
of nonmetastatic nature. The eyes manifest several symptoms and signs relating to paraneoplastic effects with
well-established entities: cancer-associated retinopathy
(CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse uveal melanocytic proliferation (BDUMP).
Examples of neuro-ophthalmologic manifestations resulting from paraneoplastic syndromes are optic neuropathy,
opsoclonus and vertical gaze paralysis [20, 21].
Gass [15] compiled five cardinal signs associated
with BDUMP based upon previous reports 1) multiple,
round or oval, subtle, red patches at the level of the retinal pigment epithelium in the posterior fundus; 2) a striking pattern of multifocal areas of early hyperfluorescence
corresponding with these patches; 3) development of
multiple pigmented and nonpigmented uveal melanocytic tumors, as well as evidence of diffuse thickness of
uveal tract; 4) exudative retinal detachment; and 5) rapid
progression of cataract. In his report he emphasized the
importance of the first two signs as both may antedate
the other three and are highly suggestive of the underly-
Figure 1. Initial presentation. Slit lamp examination of the
right eye shows iris “freckle” and nevus in the inferior quadrant
(A). Color fundus photograph of the right eye showing nevus in
the superior quadrant (B) and posterior pole with slightly RPE
changes (C) better noticed in the autofluorescence study (HRA)
(D). B-scan ultrasonography of the left eye shows a dome shaped,
low to medium reflectivity, ciliochoroidal mass with intrinsic
vascularization, and thickness of 9.3mm in the superior quadrant
compatible with melanoma (E).
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Figure 3.
Histopathology of enucleated left eye. Macroscopic appearance of a nonpigmented
ciliary body mass in superior quadrant and darkly pigmented nodule in the peripapillary area (A).
B (HE) and C (PAS): Low power resolution microscopy showing diffuse cell infiltration of uveal tract.
D (HE): melanoma spindle and epitheliod cells. E and F: Ki-67 stain immunoperoxidase assessed
proliferation rate uniformly throughout the uveal tract.
ing diagnosis. These important signs were
also stressed by Bourrat at al.[12] These authors attributed the focal areas of subretinal
red patches with early fluorescence to the
local toxic or immune reactions that cause
damage to the RPE as well as to the outer
retina. They found histopathologically a remarkable predilection for the uveal melanocytic proliferation to spare the choriocapillaris with widespread areas of degeneration
of the RPE and outer retina in large areas
where only minimal melanocytic proliferation was present.
In our case the most prominent first
sign was a tumoral mass in the left eye
that was clinically suspicious of primary
uveal melanoma. The histopathology of the
enucleated eye revealed diffuse melanoma
throughout the uveal tract with predominant
ciliary body involvement. The proliferating
uveal melanocytes in BDUMP can range in
appearance from benign to frank melanoma.
[14, 16, 19, 31]
The patient had complained of
uncharacteristic blurred vision of both eyes,
and there was progression to severe vision
loss in the right eye as well as progressive
iris pigmentation and neovascularization,
choroidal thickening, and cataract. These
findings were consistent with the diagnosis
of BDUMP. As in many cases, the primary
tumor was not known at presentation, nor
has one subsequently been identified. In
retrospect, autofluorescence (HRA) stud78
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Figure 2. One year after initial presentation. Slight
increase in size and thickness of pigmented iris lesions (A).
Gonioscopy depicts thickened iris with pigmentary and
non-pigmentary iris nodules and diffuse angle pigmentation
(B). B-mode ultrasonography (circumferential approach)
shows serous retinal detachment (white arrow) and choroidal
thickness (black arrow) (C) .
ies showed RPE changes characterized by a
mottled pattern of hypo- and hyperautofluorescence (Figure 1D).
Various hypotheses have been suggested to explain the pathogenesis in BDUMP;
1) de novo development of uveal melanocytic proliferation and systemic carcinoma
in response to a common oncogenic stimulation; [22] 2) de novo development of uveal
melanocytic proliferation in response to a
hormone-secreting visceral carcinoma, [22]
and; 3) coincidental development of bilateral “low-grade” diffuse melanomas and a
systemic carcinoma in patients genetically
predisposed to neoplasia.[23] In the first description by Barr et al, [1] they postulated
a possible action of hormonal factors activating the manifestations of the syndrome.
Unlike several paraneoplastic syndromes,
the exact mechanism in BDUMP is still not
known. In MAR and CAR syndromes studies
have identified autoantibodies toward tumor
antigens that cross-react with antigens on
retinal cells.[24]
Diffuse skin melanosis [25-29] and eruptive nevi[30] can be also be associated with
metastatic melanoma implicating melanocyte peptide growth factors such as basic
fibroblast growth factor (bFGF), alpha- melanocyte-stimulating hormone (α-MSH),
mast cell growth factor (MGF), hepatocyte
growth factor (HGF) and endothelin-1 (ET-1)
in causing the uncontrolled pigmentation. Some paraneoplastic skin pigmentation syndromes are believed to be due to
adrenocorticoticopic hormone (ACTH) and
melanocyte-stimulating hormone (MSH).
Further, Mouriaux[31] considered the tyrosine kinase receptor (c-kit) and its ligand
stem cell factor (SGF) as possibly playing
a role in the proliferation of choroidal melanocytes and its role in BDUMP. In our case,
serum ACTH and MSH levels were within
normal limits.
[29]
In summary, BDUMP is a rare ocular
paraneoplastic syndrome whose differential diagnosis includes diffuse uveal melanoma, uveal metastatic carcinoma or melanoma, intra ocular large-cell lymphoma,
idiophatic uveal effusion syndrome, and
Vogt-Koyanagi-Harada syndrome. BDUMP
is a vision-threatening disease and always
represents a diagnostic challenge. Early
recognition of this condition can help the
clinician to identify an underlying malignancy. Unfortunately, there is no ocular
treatment available for these patients and
severe visual loss is expected.
Septiembre 2010
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Uso de Líquido Amniótico Tópico en la
Queratoconjuntivitis Sicca: Estudio Preliminar
Ximena Velasteguí Camorali MD1, María Isabel Freile Moscoso MD2, Manolita Guijarro MD3
Hospital de los Valles, Clínica Oftálmica; Quito – Ecuador
1
Oftalmóloga Cirujana; Clínica Oftálmica; Hospital de los Valles; Meditrópoli;
Miembro de la Sociedad Ecuatoriana de Oftalmología
2
Oftalmóloga Cirujana; Hospital de los Valles; Topvision; Club de Leones “Villaflora”
3
Colaboradora
Relaciones Comerciales: Ninguna
Patrocinio: Ninguno
Abstract
Purpose To evaluate the effects of topic
amniotic fluid on the treatment of keratoconjunctivitis sicca.
Material and methods We studied 13
patients with moderate to severe dry eye, on
which other therapies have failed. The patients
applied topic amniotic fluid during four weeks. Weekly evaluations were made, recording:
symptoms (OSDI score), staining with fluorescein and lissamine green (Oxford score),
break-up time (BUT) and Schirmer test.
Results We found a significant difference on the symptoms on the first (p = 0,01),
third (p = 0,028) and fourth weeks (p =
0,024) of treatment, compared to the media
before it. Also there was significant difference on the BUT at first week of treatment
(p = 0,022). On lissamine green staining,
there was a statistically significant difference with the media before treatment and the
values of the first and fourth weeks after it
(p = 0,001). We did not find difference on
fluorescein staining or visual acuity.
Conclusions On this study, the amniotic
fluid demonstrated an improvement not only
on the symptoms but also on the clinical
signs of dry eye on the patients. The present
study reflects the need of larger clinical trials
in order to have more conclusive and applicable results.
Resumen
Objetivo Evaluar los efectos del líquido
80
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Corresponding Author:
Ximena Velasteguí MD
Av. Interoceánica km 12 ½ y Av. Florencia, Quito – Ecuador
Tel: (593-2) 237-8819
Email: [email protected]
amniótico tópico en el tratamiento de la queratoconjuntivitis sicca.
Materiales y métodos Se estudiaron
13 pacientes con queratoconjuntivitis sicca
moderada a severa y en los cuales fracasaron
otras terapias. Los pacientes utilizaron líquido
amniótico estéril siguiendo indicaciones preestablecidas; se aplicó el tratamiento por vía
tópica durante 4 semanas, evaluando agudeza
visual, sintomatología (escala de OSDI), tinción con fluoresceína y verde lisamina (escala
de Oxford), tiempo de ruptura lagrimal (BUT)
y test de Schirmer antes y después del tratamiento. Durante el estudio los pacientes utilizaron lágrimas artificiales según necesidad.
Resultados Se encontró una diferencia
estadísticamente significativa en la sintomatología entre el promedio pre-terapia y el
promedio a la primera (p = 0,01), tercera (p
= 0,028) y cuarta semanas (p = 0,024) de
tratamiento. En el BUT, hubo diferencia estadística a la primera semana (p = 0,022).
En cuanto a la tinción con verde lisamina,
existió diferencia significativa entre el promedio previo y la media a la primera y cuarta
semanas de tratamiento (p = 0,001). No se
encontró significancia al comparar los promedios en la tinción con fluoresceína.
Se comparó el uso de lágrimas artificiales antes de iniciar el tratamiento con líquido
amniótico y a las cuatro semanas del mismo
y se encontró una frecuencia de uso diario
significativamente menor al final del tratamiento (p = 0,041).
Conclusión El líquido amniótico tópico
mostró una mejoría tanto de la sintomatología como de las características clínicas en
los pacientes estudiados. El presente estudio muestra resultados esperanzadores en
cuanto al uso de esta nueva terapia. Sin embargo, son necesarios estudios con una mayor muestra y que incluyan un grupo control,
para poder llegar a resultados concluyentes
con el fin de aplicar este tratamiento en la
práctica clínica.
Palabras clave: Queratoconjuntivitis
sicca, líquido amniótico, ojo seco.
Introducción
La queratoconjuntivitis sicca presenta una
alta prevalencia: 14% a 33% de la población
mundial. Se han aplicado terapias para el tratamiento del ojo seco, con poco éxito.1
La membrana amniótica posee características antiinflamatorias y pro-cicatrizantes;
se ha utilizado con éxito durante décadas en
enfermedades de la superficie ocular. 2
Durante la gestación, la membrana amniótica se encuentra embebida en líquido
amniótico. Por tanto, en dicho fluido también
se han observado factores con propiedades
que estimulan la reepitelización y cicatrización; reducen la inflamación, neovascularización y contracción de heridas; además es
bacteriostático.3
Actualmente no existen estudios publicados sobre líquido amniótico tópico en enfermedades de la superficie ocular en seres
Septiembre 2010
humanos. Sin embargo, los trabajos en animales demuestran resultados prometedores.
Así, Herretes observó mejoría de la reepitelización corneal utilizando líquido amniótico
tópico en quemaduras corneales en ratas.
Castro-Coombs realizó un estudio en
cultivo de órganos in vivo, observando aceleración de la cicatrización corneal usando
líquido amniótico. 4
Lee demostró que el líquido amniótico
promueve la regeneración nerviosa, acelerando la recuperación de la sensibilidad
corneal luego de una ablación corneal por
excímer láser en conejos. 5
El objetivo del presente estudio es evaluar la eficacia del líquido amniótico tópico
en el tratamiento de pacientes con ojo seco,
con el fin de encontrar un tratamiento alternativo y útil para esta patología que muestra
una gran prevalencia y a la vez afectación del
paciente en su calidad de vida.
Materiales y Métodos
Este es un estudio preliminar prospectivo, experimental, no controlado. Fue aprobado por el Comité de Bioética de la Universidad San Francisco de Quito. Cada paciente
firmó un consentimiento informado para participar en el estudio.
Se incluyeron pacientes con ojo seco moderado a severo, evaluando la severidad del
mismo mediante la escala de OSDI (Anexo
Nº1). Además se aplicó la clasificación realizada por Behrens y col. (Dysfunctional Tear Study
Group),1 que consta en la Tabla Nº 1. Se consideró como “Ojo seco moderado” a los pacientes que presentaban el nivel 2, y “Ojo seco
severo” a los que presentaron el nivel 3 y nivel
4 de dicha clasificación. Se eligieron pacientes
que anteriormente utilizaron otras terapias para
ojo seco, sin éxito. (Tabla 1)
A cada paciente, se le entregó un frasco
estéril con líquido, conservado en un termo
de hielo (4ºC), indicándole su aplicación tópica cada 6 horas, manteniéndolo en dicho
termo. Además, el paciente podía aplicarse
lágrimas artificiales según necesidad.
Se realizó recambio semanal del frasco,
cultivando el líquido usado. Todos los cultivos fueron negativos.
Se realizó examen oftalmológico antes
del tratamiento y semanalmente durante el
mismo, por cuatro semanas, evaluando:
sintomatología (escala de OSDI), tiempo de
ruptura lagrimal (BUT) con fluoresceína sin
anestésico, test de Schirmer con anestésico, tinción vital de córnea y conjuntiva con
fluoresceína y con verde lisamina (escala de
Oxford - Anexo Nº2).
Los resultados fueron tabulados en Excel
y analizados en SPSS v.11.5. Se tomó como
valor de potencia 80% y de significancia de
95%; se utilizó como medida de ésta última
la prueba t de Student, para todas las variables estudiadas (cuantitativas).
Resultados
Se estudiaron 13 pacientes: 11
mujeres (84,6%) y 2 varones (15,4%)
con un promedio de edad de 51,0 años
(±16,66), con rango de 28 a 87 años.
Al analizar la sintomatología
(OSDI), se encontró un promedio pretratamiento de 84,90% (±13,11); a la
primera semana de tratamiento el promedio fue 73,96% (±12,33), con una
diferencia significativa comparada con
el valor previo (p = 0,01).
A las 2 semanas, la media fue 71,57%
(±10,38), sin encontrar diferencia significativa (p = 0,223).
A las 3 semanas, la media fue 47,87%
(± 32,06), siendo la diferencia significativa
(p = 0,028), comparada con la media preterapia.
A las 4 semanas el valor fue 40,46% (±
32,55), con diferencia igualmente significativa (p = 0,024). (Figura 1).
En cuanto al tiempo de ruptura lagrimal
(BUT), su promedio previo al tratamiento fue
2,08 segundos (±1,32). A la primera semana, la media fue 3,38 seg. (± 1,76), valor que
comparado con el promedio previo al tratamiento presentó una diferencia significativa
(p = 0,022). A la segunda semana, el valor
promedio fue 1,75 seg. (± 0,96); a la tercera
semana, 4,67 (± 2,31); a la cuarta semana,
6,33 (± 2,85). No se presentó diferencia significativa en estos últimos valores (p = 0,789;
0,317; y 0,731 a la segunda, tercera y cuarta
semanas respectivamente).
En el test de Schirmer, se encontró una
media previa a la terapia de 8,54 mm (±
5,17); a la primera semana de tratamiento
promedio fue 11,0 mm (± 4,43), comparado con el valor previo, presentó una diferencia significativa (p = 0,001). A la segunda
semana, el valor fue 8,75 mm (± 4,99 mm),
con una diferencia también significativa (p
= 0,018). A la tercera semana, la media
fue 5,33 (± 5,86). A la cuarta semana la
media fue 5,67 (± 4,16). No se encontró
significancia en estos últimos valores (p =
0,635 y 0,775 en la tercera y cuarta semana
respectivamente). (Figura 2).
El líquido amniótico fue obtenido por
amniocentesis previa a cesárea a término,
en condiciones estériles, por un ginecólogo
entrenado, según protocolos preestablecidos. Se realizaron exámenes serológicos a
la madre donante y al líquido extraído: HIV,
hepatitis B y C, CMV, VDRL. (Laboratorio
NetLab – ISO 9001).
El líquido amniótico con resultados negativos fue procesado de la siguiente manera (NetLab): Se centrifugó a 1800 rpm por
10 minutos. Posteriormente, se lo congeló
(-20ºC) en frascos estériles.
Fig 1. Sintomatología antes y después del tratamiento con líquido amniótico medida con la escala de OSDI.
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CLINICAL SCIENCES
Fig 2. Test de Schirmer antes y después del tratamiento con líquido amniótico.
Al evaluar la tinción con fluoresceína (Oxford), se encontró un valor promedio previo
al tratamiento de 2,4 (± 0,89). A la primera semana, la media fue 2,2 (± 0,84). A la
segunda semana fue 2,0 (± 0,0). A la tercera semana la media fue 1,33 (± 0,58). A la
cuarta semana fue 1,67 (± 0,58). No se encontró diferencia estadísticamente significativa en ninguna de las comparaciones (p = 0,374; 0,058; 0,184 y 0,225 a la primera,
segunda, tercera y cuarta semana respectivamente). (Figura 3).
Fig 3. Tinción con fluoresceína a) antes y b) 4 semanas después del tratamiento.
Al evaluar la tinción con verde lisamina (Oxford), se encontró un valor promedio previo al tratamiento de 2,61 (± 0,65). A la primera semana, la media fue 1,54 (± 0,78),
que mostró una diferencia significativa comparada con el valor previo (p = 0,001). A la
segunda semana fue 1,75 (± 0,50). A la tercera semana, la media fue 2,67 (± 0,58),
sin encontrar diferencia significativa (p = 0,215 y 0,423 a la segunda y tercera semana
respectivamente). A la cuarta semana fue 1,67 (± 0,67), presentándose diferencia significativa (p = 0,001). (Figuras 4 y 5).
Fig 4. Tinción con verde lisamina: a) antes y b) 4 semanas después del tratamiento.
El promedio de agudeza visual medido con logMAR antes del tratamiento fue de
0,57 (± 0,15), y 0,53 (± 0,12) después del mismo (a las 4 semanas). No se encontró
diferencia significativa (p = 0,808).
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En cuanto a la frecuencia de uso de lágrimas artificiales se realizó una comparación antes del tratamiento y
al final del mismo. El promedio de uso antes de iniciar la
terapia fue 9,7 veces / día (± 4,84) y a las 4 semanas de
terapia fue 3,3 veces / día (± 1,03). Al comparar los dos
valores, presentaron diferencia estadísticamente significativa (p = 0,041).
Discusión
Los resultados encontrados en el presente estudio
concuerdan con los que refieren trabajos anteriores en
animales y cultivos in vivo. En éstos, se realizaron evaluaciones histopatológicas, por lo cual no son comparables
con el presente estudio. Se están iniciando estudios de la
utilización de líquido amniótico tópico en seres humanos
en varias patologías oculares, incluyendo ojo seco, pero
todavía no se encuentran reportes publicados.
En los pacientes estudiados se encontró una mejoría
estadísticamente significativa en la sintomatología ya desde la primera semana de tratamiento, manteniéndose en
la tercera y cuarta semanas, por lo que se puede afirmar
que el efecto beneficioso de la terapia se mantiene hasta
el final del tratamiento.
En cuanto al tiempo de ruptura lagrimal (BUT), se observó una mejoría significativa a la primera semana.
De igual forma, se observó una mejoría significativa en
el test de Schirmer en la primera y segunda semanas. La
tinción con verde lisamina disminuyó significativamente a
la primera y cuarta semanas de tratamiento.
Fig 5. Tinción con verde lisamina antes y después del tratamiento con líquido
amniótico, medida con la escala de Oxford.
Niveles de Severidad del Síndrome de Ojo Seco
Severidad
Nivel 1
Síntomas leves a moderados
No signos
Signos conjuntivales leves a moderados
Nivel 2
Síntomas moderados a severos
Signos de la película lagrimal
Tinción punctata leve en córnea
Tinción conjuntival
Signos visuales
Nivel 3
Síntomas severos
Tinción punctata marcada en córnea
Tinción corneal central
Queratitis filamentosa
Nivel 4
Síntomas severos
Tinción corneal severa, erosiones
Cicatriz conjuntival
Se demostró una disminución significativa al comparar la frecuencia de uso de lágrimas artificiales antes y a
las cuatro semanas del uso de líquido amniótico.
No hubo diferencia significativa en la tinción con fluoresceína ni en la agudeza visual con el tratamiento.
Conclusiones:
El líquido amniótico ha demostrado mejoría tanto clínica como estadísticamente significativa en el tratamiento
del ojo seco en los pacientes estudiados.
Una limitante del presente trabajo es la muestra pequeña y corto periodo de seguimiento. Es por esto que es
necesario realizar a futuro estudios con un mayor tamaño
de muestra y más largo seguimiento para obtener resultados más significativos y concluyentes.
El presente es un estudio preliminar al ensayo clínico multicéntrico que se está realizando en varios países
de América; se espera que éste muestre resultados similares a los encontrados, que puedan aplicarse en la
práctica clínica.
Características
Tabla 1. Clasificación de severidad del síndrome de ojo seco según
signos y síntomas.1
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ANEXO N° 1
OSDI SCORE
(SINTOMATOLOGÍA DE OJO SECO)
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Septiembre 2010
ANEXO N° 2
ESCALA DE OXFORD
REFERENCIAS BIBLIOGRÁFICAS
(TINCIÓN CON COLORANTES VITALES)
1
Behrens A, Doyle JJ, Stern L, Chuck RS, McDonnell PJ, Azar DT, Dua HS,
Hom M, Karpecki PM, Laibson PR, Lemp MA, Meisler DM, Murube del Castillo J, O’Brien T, Pflugfelder SC, Rolando M, Schein OD, Seitz B, Tseng SC,
van Setten G, Wilson SE, Yiu SC. Dysfunctional Tear Syndrome, Cornea 2006;
25: 900-907.
2
Dua HS, Gomes JA, King AJ, Maharajan VS. The Amniotic Membrane in
Ophthalmology, Survey of Ophthalmology 2004, 49 (1) 51-57.
3
Herretes S, Suwan-Apichon O, Pirouzmanesh A, Reyes JM, Broman AT, Cano
M, Gehlbach PL, Gurewitsch ED, Duh EJ, Behrens A. Use of topical human
amniotic fluid in the treatment of acute ocular alkali injuries in mice, American Journal of Ophthalmology 2006; 142: 271-278.
4
Castro-Combs J, Noguera G, Cano M, Yew M, Gehlbach PL, Palmer J, Behrens A. Corneal wound healing is modulated by topical application of amniotic
fluid in an ex vivo organ culture model, Experimental Eye Research 2008 (87);
56-63.
5
Lee HS, Kim JC. Effect of amniotic fluid in corneal sensitivity and nerve:
regeneration after excimer laser ablation, Cornea 1996, 15: 517-524.
6
Behrens, A, Brito, B, Patent application title: Use of amniotic fluid in treating
ocular disease and injury. Whitham, Curtis & Christofferson & Cook, Reston,
VA US, 2009.
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Hospital Público do Brazil: Outcomes in
Keratoplasty after Infectious Keratitis in a Public
Hospital from Brazil
Glauco Reggiani Mello1; Marcos Longo Pizzolatti2; Fernando M. Pradella3; Gleisson R. Pantaleão4;
Ana Paula Nudelmann Gubert5; Hamilton Moreira6
1
Mestre em Cirurgia pela Faculdade Evangélica do Paraná, Fellow em Transplante de Córnea do Departamento
de Oftalmologia da Universidade Federal do Paraná, UFPR, Curitiba-PR, Brasil
2
Fellow em Transplante de Córnea do Departamento de Oftalmologia da Universidade Federal do Paraná,
UFPR, Curitiba-PR, Brasil
3
Médico Residente do Departamento de Oftalmologia da Universidade Federal do Paraná, UFPR, Curitiba-PR, Brasil
4
Especialista em Transplante de Córnea pelo Departamento de Oftalmologia da Universidade Federal do
Paraná, UFPR, Curitiba-PR, Brasil
5
Acadêmica de Medicina da Universidade Federal do Paraná, UFPR, Curitiba-PR, Brasil
6
Professor Adjunto do Departamento de Oftalmologia da Universidade Federal do Paraná, UFPR, Curitiba-PR, Brasil
Abstract
Purpose To evaluate the outcome and complications of corneal
transplant in a hospital school.
Methods Retrospective study of medical records in cases of corneal
transplantation due to infectious cause occurred in the Hospital de Clinicas, UFPR between 2002 and 2008. We included all cases with clinical
or laboratory diagnosis of eye infection with active 6 months minimum
follow up.
Results Of the 146 transplants performed in the period, 16 (10,
95%) had infectious keratitis as an indication. Regarding the etiology were found: 9 cases of bacteria (56.25%), 3 fungal (18.75%), 2
herpetic (12.25%), 1 Acanthamoeba and 1 case unknown (6.25%).
Visual acuity after the surgery had no change in 7 cases, 5 cases
had a decrease in visual acuity and there was an improvement on
4. Evaluating the predisposing factors, 8 (50%) had a history of eye
surgery, and in 5 (31.25%) there was a history of prior transplant, 2
(12.5%) cases occurred after trauma, 1 (6, 25%) case had a contact
lens related infection and in 5 (31.25%) was not found any predisposing factor. Among the complications were: recurrence of infection,
synechiae, cataract, glaucoma, OACR and need of re-suture. The corneal transparency was found in 68.75% of cases. The result after the
first surgery was satisfactory in 13 cases, and achieved eye integrity.
2 progressed to evisceration / phthisis.
Conclusions There was a rate of anatomical cure of 81.25% after
the first transplant and 87.5% at the end of treatment. These data show
undoubted success and improvement in quality of life.
Keywords: Cornea, Infectious Keratitis, Cornea Transplant, Penetrating keratoplasty, Eye Integrity, Ophthalmologic Emergency
RESUMO
Objetivo Avaliar as intercorrências e os resultados dos transplantes de córnea terapêuticos em um hospital escola.
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Nome do pesquisador: Glauco Reggiani Mello
Endereço: Rua Lamenha Lins 447 ap 21 Centro, Curitiba – PR
CEP 80250-020
Fones/ Celular: (55-41) 8808-0234
e-mail: [email protected]
Trabalho realizado no Centro da Visão, Departamento de
Oftalmologia da Universidade Federal do Paraná
Métodos Estudo retrospectivo em prontuários de pacientes submetidos a transplante de córnea devido à causa infecciosa, ocorridos
no Hospital de Clínicas da UFPR entre 2002 a 2008. Foram incluídos
todos os casos com diagnóstico clínico ou laboratorial de infecção
ocular ativa com seguimento mínimo de 6 meses.
Resultados Dos 146 transplantes realizados no período, 16
(10,95%) tiveram como indicação ceratite infecciosa. Em relação
a etiologia foram encontrados: 9 de causa bacteriana (56,25%), 3
fúngicas (18,75%), 2 herpéticas (12,25%) 1 caso Acanthamoeba e 1
caso não identificado (6,25%). A acuidade visual no pós-operatório
não se alterou em 7 casos, em 5 casos houve piora de visão e em
4 houve melhora. Avaliando-se os fatores predisponentes, 8 (50%)
apresentavam história de cirurgia ocular, sendo que em 5 (31,25%)
havia história de transplante prévio, 2 (12,5%) ocorreram após trauma, 1 (6,25%) houve uso de lente de contato e em 5 (31,25%) não
foi encontrado nenhum fator predisponente. Entre as complicações
encontrou-se: recidiva de infecção, sinéquias, catarata, glaucoma,
oclusão de artéria central de retina e necessidade de ressutura. A
transparência corneana foi obtida em 68,75% dos casos. O resultado
após a primeira cirurgia foi satisfatório em 13 casos, sendo conseguidaa cura anatômica, com 2 evoluindo para evisceração/phthisis.
Conclusões O resultado final foi de cura anatômica de 81,25%
após o primeiro transplante e 87,5% ao final do tratamento. Esses
dados apresentados mostram sucesso e melhora indubitável na qualidade de vida.
Descritores: Cornea, Ceratite infeciosa, Transplante de Cornea, Ceratoplastia penetrante, Integridade Ocular, Emergência Oftalmológica
1. INTRODUÇÃO
O transplante de córnea é um procedimento cirúrgico desafiador,
tendo indicações médicas distintas. O ritmo de pesquisas nessa área
é intenso e novos entendimentos, idéias e soluções melhoram os
resultados e expectativas do procedimento.
Septiembre 2010
Tradicionalmente, o transplante pode ser indicado com o objetivo de melhorar a visão (óptico), para
controle de doença corneana inflamatória ou infecciosa (terapêutico) e para restabelecer a integridade
estrutural (tectônico)1, 2.
A ceratite infecciosa é uma doença que ocorre
quando microorganismos como fungos, bactérias,
vírus ou parasitas suplantam os mecanismos de defesa
oculares, ocorrendo invasão e destruição tecidual com
extensão e progressão muito variável. Os oftalmologistas devem identificar os fatores de risco da infecção
ocular, realizar um exame clínico minucioso, auxiliado por exames complementares. O tratamento medicamentoso deve ser imediato e pode ser alterado de
acordo com a resposta clínica ou exames laboratoriais.
O transplante terapêutico é realizado quando a
doença corneana inflamatória ou infecciosa está em
progressão apesar do tratamento clínico medicamentoso máximo e ameaça ou compromete a integridade
do globo ocular3. A perfuração que pode ocorrer nesta
situação aumenta drasticamente o risco de endoftalmite e perda do globo ocular4.
Nesse procedimento é esperada a diminuição ou
remoção dos microorganismos da córnea a um nível
no qual a ação dos antimicrobianos e da defesa endógena do paciente passa a ser efetivo.
O sucesso do transplante de córnea está diretamente relacionado a vários fatores: a doença de base
oftalmológica5, a qualidade da córnea transplantada, a
experiência do cirurgião e aos cuidados e terapêutica
pós-operatórios.
A literatura divide os transplantes de córnea em
quatro grupos, de acordo com a doença de base oftalmológica. O de melhor prognóstico, alcançando taxa
de sucesso superior a 90%, é encontrado em casos
de ceratocone, cicatrizes centrais ou paracentrais inativas ou distrofia de Fuchs inicial. O grupo de bom
prognóstico é composto por casos de ceratopatia bolhosa do pseudofácico, distrofia de Fuchs avançada e
ceratite herpética inativa. Neste grupo espera-se um
sucesso entre 80 a 90%. As ceratites infecciosas ativas estão no grupo de prognóstico regular, com sucesso entre 50 e 80%. Casos de queimadura severa,
olho seco severo e síndrome Stevens-Johnson estão
no grupo de prognóstico ruim, com menos de 50% de
sucesso esperado6-9.
Dentre os casos de ceratite infecciosa, a expectativa de sucesso também varia conforme a etiologia,
mostrando um sucesso muito menor em casos mais
agressivos como ceratite por acanthamoeba10.
Nos casos de transplantes terapêuticos, devido
ao caráter de urgência, são utilizadas córneas com
menor qualidade (menor contagem de células endoteliais, leucoma)1. Essas córneas não seriam uti-
lizadas em um transplante com finalidade óptica, o
que aumenta a sua disponibilidade, mas pode levar
a uma taxa de sucesso menor.
O resultado também é influenciado pela técnica
cirúrgica e experiência do cirurgião. Um seguimento profissional adequado a longo prazo também é
fator determinante no resultado. Este fator é muito
mais relevante no transplante de córnea do que em
outros procedimentos oftalmológicos, como a cirurgia de catarata11.
O Hospital de Clínicas da UFPR é um hospital
escola, sendo também um centro transplantador. Todos os pacientes admitidos são do Sistema Único de
Saúde, sendo a grande maioria com baixa condição
sócio-econômica. Os transplantes de córnea são
realizados por cirurgiões em formação. Os cuidados
e medicamentos que devem ser utilizados no pósoperatório são de mais difícil acesso para o paciente
atendido neste hospital.
Devido ao fato de que essas condições são encontradas na grande maioria da população brasileira, este
estudo objetiva avaliar o resultado dos transplantes terapêuticos em um hospital escola. As intercorrências,
manutenção da integridade ocular e melhora da acuidade visual serão avaliadas, com ênfase no sucesso e
melhora de qualidade de vida para o paciente.
2. MÉTODOS
Estudo retrospectivo de prontuários de todos os
casos de transplante de córnea realizados no Hospital de Clínicas da UFPR de 2002 a 2008. A revisão
dos prontuários foi realizada no serviço de arquivo do
Hospital de Clínicas, após a aprovação no Comitê de
Ética em Pesquisa em seres humanos do Hospital de
Clínicas - UFPR.
Foram identificados os transplantes feitos devido
à causa infecciosa e os seguintes dados analisados:
sexo, idade, etiologia infecciosa, exames laboratoriais,
fatores predisponentes, necessidade de retransplante,
integridade ocular, acuidade visual e tempo de seguimento.
Critérios de inclusão: pacientes submetidos a
transplante de córnea com diagnóstico clínico ou laboratorial de infecção ocular ativa com seguimento
mínimo de 6 meses.
Critérios de exclusão: pacientes que perderam o
seguimento antes de completar 6 meses.
3. RESULTADOS
Dentre os 146 transplantes realizados no período
de 2002 a 2008, 16 (10,95%) tiveram o diagnóstico
de ceratite infecciosa. O grupo estudado foi composto por 11 mulheres (68,75%) e 5 homens (31,75%).
A idade variou de 8 a 83 anos (média 48,12 anos,
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DP±20,81). O tempo de seguimento
variou de 6 (tempo mínimo de seguimento) a 72 meses (média 19 meses,
DP±16,34). (Tabela 1).
A etiologia foi determinada pelos
exames laboratoriais (realizados em
87,5% dos pacientes). Destaca-se a
baixa sensibilidade dos exames laboratoriais, sendo que somente 42,85%
tiveram exames positivos. Os demais
casos tiveram sua etiologia sugerida
pelos achados clínicos aliados a uma
resposta adequada ao tratamento proposto. Assim foram encontrados 9
casos de causa bacteriana (56,25%),
3 fúngicos (18,75%), 2 herpéticas
(12,25%), 1 caso de Acanthamoeba (6,25%) e 1 caso não identificado
(6,25%). (Gráfico 1).
Tabela 1. Características Epidemiológicas e
Seguimento dos Transplantes de Córnea no
período de 2002–2008.
Características
Valores
Causas
Ceratite Infecciosa
16 (10,95%)
Outros (Ceratocone,
Fuchs, etc.)
Total
130 (89,05%)
146 (100%)
Sexo*
Masculino
5 (31,75%)
Feminino
11 (68,75%)
Total
16 (100%)
Idade (anos) *
Mínimo / Máximo
Média ± DP
8 / 83
48,12 ± 20,81
Seguimento (meses) *
Mínimo / Máximo
6 / 72
Média ± DP
19 / 16,34
*Somente Casos de Ceratite Infecciosa
Dados apresentados em média ± desvio padrão ou
número absoluto (porcentagem).
Entre os fatores oftalmológicos predisponentes, percebeu-se que 8 (50%)
pacientes já haviam se submetido a
uma cirurgia ocular prévia, sendo que
destes, em 5 (31,25%) casos havia
história de um transplante ocular prévio. Dois casos (12,50%) ocorreram
após um trauma, 1 caso (6,25%) tinha
relatado uso de lente de contato e em 5
casos não foi encontrado nenhum fator
predisponente. Em 50% dos transplantes realizados, havia uma perfuração
ocular no momento do procedimento, e
em outros 50%, a córnea estava íntegra,
porém com afinamento severo ou risco
de perfuração. (Gráfico 2).
Enfatiza-se que dentre os 5 casos
com história de transplante de córnea
prévio, obteve-se manutenção da integridade ocular em 4 pacientes e córneas transparente após o procedimento
em somente 1 caso.
A avaliação da acuidade visual no
pós-operatório constatou que em 7
pacientes (43,75%) não houve alteração, 5 (31,25%) pioraram a visão, e
em 4 (25%) ocorreu melhora. Em 13
(81,25%) a primeira cirurgia manteve
o olho íntegro. Dentre os transplantes
realizados em 8 (50%) se obteve transparência após a primeira cirurgia, o que
não ocorreu nos demais. (Tabela 2).
O tratamento não obteve sucesso
após a primeira cirurgia em 3 casos,
observando-se ausência da integridade
ocular no pós-operatório. Salienta-se
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que a etiologia dos 3 casos foram confirmadas como: fungo, Acanthamoeba e
pseudomonas.
No pós-operatório foram encontradas as seguintes complicações: recidiva
da infecção em 5 (31,25%), sinéquias
5 (31,25%), catarata 3 (18,75%), glaucoma 2 (12,50%), Oclusão de artéria
central da retina (OACR) e necessidade
de re-sutura 1 (6,25%).
No total, 5 pacientes foram submetidos a re-transplante, sendo que 2 destes
foram com objetivo de preservar a integridade ocular e em 3 casos foram transplantes ópticos. Considerando que a ceratite infecciosa é uma doença séria que
exige intervenção imediata, o resultado
foi satisfatório em 13 casos (81,25%) incluindo também a ausência de infecção
e a integridade do bulbo ocular. Dos 3
casos em que não foi alcançada a integridade ocular após a primeira cirurgia,
2 evoluíram para evisceração/phthisis e
em 1 caso foi realizado outro transplante
terapêutico e após foi conseguida a cura
anatômica. (Gráfico 3).
4. DISCUSSÃO
No presente estudo o percentual
de transplantes realizados por ceratite
infecciosa de 10,95%, coincide com
a literatura, onde os estudos mostram
variação de 2,6 a 17,9% entre o total
de transplantes realizados. Entretanto
quando se considera que o Hospital de
Clinicas da UFPR é um de referência
terciária como a Santa Casa de Misericórdia de São Paulo que atende grande
número de casos graves nota-se diferença, visto que neste hospital o percentual de transplantes terapêuticos
foi de 18,4%1.
A maioria dos transplantes realizados teve como causa infecção
bacteriana ou fúngica, sendo a ceratite herpética menos freqüente, o que
coincide com a literatura1.
Em nosso serviço encontramos
uma alta freqüência de pacientes
com história prévia de cirurgia ocular
(50%), em particular pacientes com
transplante prévio (31,25%). Essa alta
prevalência não foi encontrada na literatura e possivelmente devido ao fato
de nosso hospital ser referência para
todo o estado do Paraná, com outros
Septiembre 2010
serviços que realizam transplante de córnea podendo encaminhar pacientes de maior comorbidade e
conseqüentemente custo para nosso hospital. Dos
5 casos com história de transplante prévio apenas 2
tinham realizado este transplante em nosso serviço
e destes, apenas 1 desenvolveu a infecção no pósoperatório imediato. Dos outros 3 casos, apenas 1
teve infecção no pós-operatório imediato. Isso chama atenção ao cuidado no peri-operatório, pós-operatório imediato e principalmente no pós-operatório
tardio. Pacientes submetidos a um transplante de
córnea devem receber um acompanhamento freqüente e regular que não pode ser negligenciado(11).
Complicações graves como a infecção poderiam ser
tratadas mais facilmente no início e isto poderia influir positivamente no prognóstico final.
Gráfico 1.
Entre as principais complicações pós-operatórias, destaca-se recidiva da infecção em 5 casos
(31,25%), acima do índice encontrado em pesquisa
realizada em hospital público com condições semelhantes (10,1%)1. Encontrou-se também catarata em
3 pacientes (18,75%), sendo que está complicação
é freqüente em todos os tipos de transplante12,13,14 e
glaucoma em 2 (12,50%), resultado este abaixo do
encontrado na literatura15,16.
Nos 3 casos em que não houve um resultado
satisfatório na primeira cirurgia, observa-se que os
patógenos isolados foram germes (Acanthamoeba,
Pseudomonas e fungo) que de acordo com a literatura10 possuem alto grau de dano tecidual com prognóstico mais reservado.
Gráfico 2.
Encontramos córneas transparentes ao exame
clínico em 50% dos casos, resultado dentro do esperado para a gravidade dos casos (referência), tendo
ainda que se considerar que as córneas reservadas
para esse tipo de transplante normalmente tem uma
qualidade pior, o que por si só pode justificar um pior
resultado na transparência.
Todos os pacientes atendidos no Hospital de
Clínicas - UFPR são do SUS e maioria são carentes
com baixo nível sócio-econômico. Existem barreiras
econômicas e sociais que dificultam o uso correto
das medicações e também o seguimento das orientações. Todos os transplantes foram realizados por
médicos-residentes em formação, com experiência
limitada. Mesmo com todas essas adversidades,
encontramos uma taxa de cura anatômica após o
primeiro transplante de 81,25%, chegando a 87,5%
de sucesso anatômico ao final do tratamento. Esses
dados mostram melhor resultado que a literatura
mundial(8,17) na qual se espera entre 50 a 80% de
sucesso anatômico conforme observa-se na figura
abaixo. (Gráfico 4).
Gráfico 3.
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Tabela 2. Características e seguimento de pacientes com diagnóstico de ceratite
infecciosa submetidos a transplante de córnea
Paciente/
idade/sexo
Diagnóstico clínico
Cultura
Fatores predisponentes
Cura*
Seguimento
(meses)
1 / 57 / M
Úlcera Fúngica
Negativa
Trauma com cana
Sim
14
2 / 77 / F
Úlcera Bacteriana
Cocos Gram+
Facectomia
Sim
16
3/8/F
Úlcera Bacteriana
Negativa
Trauma com faca
Sim
12
4 / 83 / M
Úlcera Bacteriana
Negativa
Cirurgia ocular não especificada
Sim
7
5 / 36 / F
Úlcera bacteriana
Negativa
Nega
Sim
6
6 / 66 / M
Úlcera Fúngica
Negativa
Nega
Sim
6
7 / 24 / F
Úlcera Bacteriana
Negativa
Nega
Sim
36
8 / 26 / F
Úlcera por
Acanthamoeba
Formas trofozoitas de
ameba sp
Lentes de contato gelatinosas
Não
24
9 / 59 / F
Úlcera Bacteriana
Negativa
Facectomia
Sim
9
10 / 30 / F
Úlcera Bacteriana
Negativa
Transplante prévio (ceratocone)
Sim
54
11 / 60 / M
Úlcera Bacteriana
Negativa
Nega
Sim
20
12 / 65 / F
Úlcera Herpes Simples
Negativa
Transplante prévio (Leucoma
Herpes)
Sim
20
13 / 36 / F
Úlcera Bacteriana
Cocos Gram+
Transplante prévio (ceratocone)
Sim
6
14 / 47 / F
Úlcera Bacteriana
Pseudomonas
aeruginosa
Transplante prévio (ceratocone)
Não
6
15 / 58 / F
Úlcera Fúngica
Leveduras e
pseudófilos
Ceratopatia bolhosa
Sim
30
16 / 38 / M
Úlcera Herpes Simples
Negativa
-
Sim
24
*Cura considerada como preservação da anatomia do globo ocular, com ou sem melhora da acuidade visual
após todos os procedimentos necessários, inclusive outro transplante de córnea.
5. CONCLUSÕES
O resultado final foi de taxa de cura anatômica de
81,25% após o primeiro transplante e 87,5% ao final
do tratamento. A transparência corneana foi obtida
em 68,75% dos casos. As principais intercorrências
encontradas foram recidiva de infecção, sinéquias,
catarata e glaucoma. Esses dados apresentados mostram sucesso e melhora indubitável na qualidade de
vida do paciente quando se considera a seriedade da
doença com sua história natural de perda ocular e
caráter de emergência, com os números obtidos em
um serviço formador comparáveis com a literatura
mundial. Conclui-se ainda ao finalizar este estudo
da necessidade de acompanhamento e melhor orientação pós-operatórias de cirurgias oculares, principalmente transplantes de córnea, tendo em vista o
alto número de úlceras corneanas que evoluíram para
transplante neste grupo de pacientes que poderiam
ser evitadas.
Gráfico 3.
90
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Septiembre 2010
BIBLIOGRAFIA
1. de Oliveira F.C, Dantas P.E., de Marco E.S., de Oliveira A.C.,
Nishiwaki-Dantas, M.C. Transplante terapêutico de córnea: Resultados prolongados de séries de casos. Arq. Bras. Oftalmol,
2007; 70 (4): 625-31.
2. Killingsworth DW, Stern GA, Driebe WT, Knapp A, Dragon
DM. Results of therapeutic penetrating keratoplasty. Ophthalmology, 1993; 100 (4): 534-41.
3. Sato EH, Belfort Jr R. Tratamento cirúrgico da ceratites infecciosas. In: Kara-José N, Belfort Jr R. Córnea cirúrgica: clínica.
Roca, São Paulo, 1997. p.505-11.
4. Miedziak AL, Miller MR, Rapuano CJ, Laibson PR, Cohen
E.J. Risk factors in microbial keratitis leading to penetrating
keratoplasty. Ophthalmology, 1999; 106 (6): 1166-70; discussion 1171.
5. Coster D.J., Badenoch P.R. Host, microbial, and pharmacological factors affecting the outcome of supurative keratits. Br J
Ophthalmol, 1987; 71 (2): 96-101.
6. Buxton JN, Buxton DF, Westhalen JA. Indications and contraindications.In: Brightbill RD, editor. Cornea surgery: theory,
technique and tissue. 2 ed., Mosby-Year Book, St Louis, 1993.
p. 77-88.
7. Ti SE, Scott JA, Janardhanan P, Tan DT. Therapeutic keratoplasty for advanced suppurative keratitis. Am J Ophthalmol.
2007; 143 (5): 755-762.
8. Beckingsale P, Mavrikakis I, Al-Yousuf N, Mavrikakis E,
Daya SM. Penetrating keratoplasty: outcomes from a corneal
unit compared to national data. Br J Ophthalmol, 2000; 90
(6): 728-31.
9. Maier P, Böhringer D, Reinhard T. Clear graft survival and immune reactions following emergency keratoplasty. Graefes Arch
Clin Exp Ophthalmo, 2007; 245 (3): 351-9.
10. Kashiwabuchi RT, de Freitas D, Alvarenga LS, Vieira L,
Contarini P, Sato E, Foronda A, Hofling-Lima AL. Corneal graft
survival after therapeutic keratoplasty for Acanthamoeba keratitis. Acta Ophthalmol, 2008; 86 (6): 666-9.
11. McNeill JI. Penetrating Keratoplasty – Indications and Outcomes. in: Krachmer JH, Mannis MJ, Holland JE, ed. Cornea. 2.
ed., Elsevier Mosby, Philadelphia, 2005:1413-22.
12. Chen WL, Wu CY, Hu FR, Wang IJ. Therapeutic penetrating
keratoplasty for microbial keratitis in Taiwan from 1987 to 2001.
Am J Ophthalmol, 2004; 137 (4): 736-43.
13. Sukhija JM, Jain AK. Outcome of therapeutic penetrating
keratoplasty in infectious keratitis. Ophthalmic Surg Lasers Imaging, 2005; 36 (4): 303-9.
14. Sony P, Sharma N, Vajpayee RB, Ray M. Therapeutic keratoplasty for infectious keratitis: a review of the literature. CLAO J,
2002; 28 (3): 111-8.
15. França ET, Arcieri ES, Arcieri RS, Rocha FJ. A study
of glaucoma after penetrating keratoplasty. Córnea, 2002; 21
(3): 284-8.
16. Endriss D, Cunha F, Ribeiro MP & Toscana J. Ceratoplastias penetrantes realizadas na Fundação Altino Ventura: revisão
dos resultados e complicações. Arq Bras Oftalmol, 2003; 66 (2):
273-7.
17. Beckingsale P, Mavrikakis I, Al-Yousuf N, Mavrikakis E,
Daya SM. Penetrating keratoplasty: outcomes from a corneal
unit compared to national data. Br J Ophthalmol. 2006; 90 (6):
728-31.
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CLINICAL SCIENCES
The New Ferrara Ring Nomogram: The Importance
of Corneal Asphericity in Ring Selection
Paulo Ferrara MD PhD; Leonardo Torquetti MD PhD
Correspondence to:
Paulo Ferrara MD PhD
Clínica de Olhos Dr. Paulo Ferrara, Av. Contorno 4747, Suite 615, Lifecenter –
Funcionários – Belo Horizonte – MG - 30110-031 – Brasil
Email: [email protected]
The author has financial interest in Ferrara intrastromal cornea ring
Edited by Foxit Reader Copyright(C) by Foxit Software Company, 2005-2007 For Evaluation Only.
RESUMO
Objetivo Descrever a inclusão da asfericidade corneana (Q)
como um novo parâmetro para seleção do anel no nomograma do
anel de Ferrara.
Local Clínica de Olhos Dr. Paulo Ferrara
Materiais e Métodos Cinquenta olhos de 42 pacientes portadores de ceratocone foram submetidos ao implante do anel de
Ferrara, em maio e junho de 2009. O tempo médio de seguimento pós-operatorio foi de 5,48 ± 0,97 [DP] meses). A tomografia
corneana foi realizada pelo Pentacam (Oculus Pentacam®, USA) no
pré e pós-operatório. Avaliou-se os dados pré e pós-operatórios relativos a asfericidade (Q), acuidade visual com correção (AVCC) e
ceratometria (K).
Resultados O implante do anel de Ferrara reduziu a asfericidade
média, de – 0,86 para -0,42 (p=0,000). Observou-se uma redução
significativa nos valores de Q em todos os casos. A ceratometria
média reduziu de 49,10 para 45,90 (p = 0,000). A AVCC média
aumentou de 20/77 para 20/47 (p = 0,001).
Conclusão A consideração da asfericidade (Q) para seleção
do anel de Ferrara pode melhorar os resultados visuais após o implante do anel.
ABSTRACT
Purpose To report the inclusion of the corneal asphericity (Q) as
a new parameter for ring selection in the Ferrara Ring nomogram.
Setting Dr. Paulo Ferrara Eye Clinic
Material and Methods Intrastromal Ferrara ring segments were
placed in 50 eyes of 42 patients with keratoconus, operated in May
and June 2009. The mean follow-up time was 5.48 ± 0.97 [SD]
months). Corneal topography was obtained from Pentacam (Oculus
Pentacam®, USA). Statistical analysis included preoperative and
postoperative asphericity (Q), best-corrected visual acuity (BCVA)
and keratometry (K).
Results The Ferrara intrastromal ring implantation significantly reduced the mean corneal asphericity from – 0.86 to -0.42
(p=0.000). It was observed a significant reduction in Q values in all
cases. The mean K decreased from 49.10 to 45.90 (p = 0.000). The
BCVA improved from 20/77 to 20/47 (p = 0.001).
92
PAN-AMERICA
Conclusion The consideration of the asphericity (Q) for Ferrara
intrastromal ring selection can improve the visual results after ring
implantation.
Introduction
The Ferrara intrastromal corneal ring segment (ICRS) is an important tool for corneal surface regularization in keratoconus and similar keratectasias. Many studies have demonstrated the efficacy of
intrastromal rings to treat many corneal conditions as keratoconus,1-7
post–LASIK corneal ectasia,8 and post-radial keratotomy ectasia9.
The ICRS implantation usually improves the uncorrected visual acuity
(UCVA), best-corrected visual acuity (BCVA) by decreasing the irregular astigmatism usually found in these conditions.
Long-term stability studies10 show that the intrastromal ring flattens the cornea and keeps this effect for a long period of time. There
is no significant re-steepening of the cornea over time. Therefore the
ICRS can be a valuable tool to provide topographic and visual stability, delay the progression of keratoconus and postpone a corneal
grafting surgery.
There is a continuous improvement in the Ferrara ICRS design
and nomogram, as the knowledge about its effects evolves. In the first
generation of the nomogram (1997 – 2000) only the evolutive grade
of keratoconus was considered for ring selection (Table 1). As it was
observed that in many cases there was hipo and hypercorrection it was
replaced by the second generation of the nomogram (2002 – 2006) in
which the spherical equivalent (SE) was considered for ring selection.
Table 1. Ferrara Ring Nomogram. First
generation.
Diameter 5.00
mm
Thickness
Diopters to be corrected
0,150 mm
-2.00 to – 4.00
cone I
0,200 mm
-4.25 to – 6.00
cone II
0,250 mm
-6.25 to – 8.00
cone III
0,300 mm
-8.25 to –10.00
cone IV
0,350 mm
-10.25 to –12.00
Septiembre 2010
The third and actual generation of the nomogram
(2006 – 2009) considers the topographic astigmatism and distribution of the ectasia area over the cornea (Tables 2 and 3).
The normal anterior corneal surface is prolate, and it could be described as conic (flattening
of the radius of curvature from the apex toward the
periphery).11 In keratoconus corneas, the steepening
of the central cornea leads to an increase in cornea
asphericity (Q).
The expression “aspherical surface” simply
means a surface that is not spherical. The outer surface of the human cornea is physiologically not spherical but rather like a conoid. On average, the central
part of the cornea has a stronger curvature than the
periphery. The typical corneal section is a prolate
ellipse, consisting of a more curved central part, the
apex, with a progressive flattening towards the periphery. In the inverse profile, i.e. when the cornea is
flattened in its center and becomes steeper towards
the periphery, the term cornea oblate is used to define this condition. The asphericity of the cornea is
usually defined by determining the asphericity of the
coniconoid which best fits the portion of the cornea to
be studied. The physiologic asphericity of the cornea
shows a significant individual variation ranging from
mild oblate to moderate prolate12,13.
Most studies agree that the human cornea Q
(asphericity) values ranges from -0.01 to -0.80.11,14, 15
Currently, the most commonly accepted value in a
young adult population is approximately -0.23 ±
0.0816.
In a recent paper (to be presented at ASCRS2010
- Boston), we retrospectively reviewed the charts of
123 patients (145 eyes) and found that there was an
almost direct correlation between Q value reduction
and thickness of rings implanted; i.e., the thicker the
ring (or pair of rings) implanted the most significant
was the Q reduction (Graphic 1).
This study shows the first results of the New Ferrara ring nomogram (fourth generation) in which the
asphericity is the first parameter to be considered
ring selection.
Material and Methods
Intrastromal Ferrara ring segments were placed in
50 eyes of 42 patients with keratoconus, operated in
May and June 2009. The mean follow-up time was
5.486 ± 0.97 [SD] months. Thirteen patients had the
surgery performed in both eyes, the remainder had
the surgery done in only one eye. After a complete
ophthalmic examination and a thorough discussion of
the risks and benefits of the surgery, the patients gave
written informed consent. The main indication for Ferrara ring implantation was contact lens intolerance
TABLE 2. Ferrara Ring Nomogram – Ring
selection according to the distribution of the
corneal ectasia.
Map
Distribution of
Ectasia
Description
0 % / 100%
All the ectatic area is located at
one side of the cornea
25 % / 75%
75% of the ectatic area is located
at one side of the cornea
33 % / 66%
66% of the ectatic area is located
at one side of the cornea
50 % / 50%
The ectatic area is symmetrically
distributed on the cornea
TABLE 3. Third generation of the Ferrara Ring
Nomogram: topographic astigmatism.
Segment thickness choice in symmetric bowtie keratoconus
Topographic astigmatism (D)
Segment thickness
<1.00
150 / 150
1.25 to 2.00
200 / 200
2.25 to 3.00
250 / 250
> 3.25
300 / 300
Asymmetrical segment thickness choice in sag
cones with 0/100% and 25/75% of asymmetry
index (Table 2).
Topographic astigmatism (D)
Segment thickness
<1.00
none / 150
1.25 to 2.00
none / 200
2.25 to 3.00
none / 250
3.25 to 4.00
none / 300
4.25 to 5.00
150 / 250
6.25 to 6.00
200 / 300
Asymmetrical segment thickness choice in sag
cones with 0/100% and 33/66% of asymmetry
index (Table 2).
Topographic astigmatism (D)
Segment thickness
<1.00
none / 150
1.25 to 2.00
150 / 200
2.25 to 3.00
200 / 250
3.25 to 4.00
250 / 300
PAN-AMERICA : 93
CLINICAL SCIENCES
and/or progression of the ectasia. The progression
of the disease was defined by: worsening of UCVA
and BCVA, progressive intolerance to contact lens
wear and progressive corneal steepening documented by Pentacam.
Statistical analysis included preoperative and
postoperative asphericity (Q) at 4.5 mm optical zone
and keratometry (K). The Q-factor analysis was performed by means of the corneal topographer. The
corneal topography was obtained from Pentacam
(Oculus Pentacam®, USA). Statistical analysis was
carried out using the Minitab software (2007, Minitab Inc.). Student´s t test for paired data was used to
compare preoperative and postoperative data.
All surgeries were performed by the same surgeon (PF) using the standard technique for the ICRS
implantation, as previously described.7,8,9 The rings
were implanted according to fourth generation (Qbased) Ferrara Nomogram (Graphic 1). Based on this
nomogram, one could predict the Q-value reduction
after implantation of a specific ring (or pair of rings)
thickness; for example, a single segment of 200 μm
reduces the asphericity in 0.31 (Graphic 1), therefore
this segment would be the most appropriate in patient with a preoperative Q value of -0.54, to achieve
a postoperative Q value close to -0.23 (theoretical
normal value).
Graphic 1 - Q variation (ΔQ) from preoperative to postoperative, according to the ICRS
thickness implanted.
Results
The Q values reduced significantly after ICRS Implantation. The mean preoperative Q value was -0.86
and the mean postoperative Q value was – 0.42
(-0.44 difference, p = 0.000). The mean keratometry reduced from 49.10 to 45.90 D (3.20 difference,
p = 0.000). (Table 4)
The BCVA improved from 20/77 to 20/47 (p = 0.001)
(Graphic 2). Seventy percent of patients achieved a
20/40 or better visual acuity at last visit.
Discussion
The nomogram has evolved as the knowledge
about the predictability of results has grown. Initially,
surgeons implanted a pair of symmetrical segments
in every case. The incision was always placed on
the steep meridian to take advantage of the coupling
effect achieved by the rings.
First, only the grade of keratoconus was considered for the ring selection, which means that in keratoconus grade I the more suitable Ferrara ring for implantation was that of 150 μm and in the keratoconus
grade IV the more appropriate ring was of 350 μm.
However, some cases of extrusion could be observed
as in keratoconus grade IV the cornea usually is very
thin and the thick ring segment sometimes was not
properly fitted into the corneal stroma.
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PAN-AMERICA
Graphic 2 - Preoperative and postoperative BCVA.
Table 4. Preoperative and
postoperative parameters. The p
value was < 0.001 for all parameters
(Students’ t test)
Preoperative
Postoperative
Q value
-0,86
-0,42
Sph. Equivalent
-3,38
-0,94
BCVA
20/77
20/47
Km
49,1
45,9
Top.
Astigmatism
-3,1
-0,6
Septiembre 2010
The second generation of the nomogram considered
the refraction for the ring selection, besides the distribution of the ectactic area on the cornea. Therefore, as the
spherical equivalent increased, the selected ring thickness
also increased. However, in many keratoconus cases the
myopia and astigmatism could not be caused by the ectasia itself but by an increase in the axial length of the
eye (axial myopia). In these cases, a hypercorrection by
implanting a thick ring segment in a keratoconus in which
a thinner segment was indicated was observed.
In the third generation of the Ferrara Ring Nomogram,
ring selection will depend on the corneal thickness, the
amount of topographic corneal astigmatism (sim K) and
the distribution of the ectactic area on the cornea (Tables
2 and 3). The Ferrara ring implantation can be considered
as an orthopedic procedure and the refraction is not important on this nomogram. For symmetric bow-tie patterns
of keratoconus, two equal segments are selected. For peripheral cones, the most common form type, asymmetrical
segments are selected. It is important to emphasize that
the ring segment thickness cannot exceed 50% of the thickness of the cornea on the track of the ring.
Using this third generation of the nomogram we
usually found that in some patients there was significant
corneal flattening without considerable improvement of
UCVA and BCVA. We realized that, in this cases, the cornea usually presented oblate (positive Q values) postoperatively, what could explain the lack of significant improvement in these cases.
This finding lead us to retrospectively review the charts
of 147 eyes operated in 2008 (paper in press), concerning the asphericity changes induced by the implantation
of each thickness of ring (or pair of rings). Surprisingly,
we found a direct correlation between ring thickness and
reduction of Q values; i.e. the thicker the ring the more the
effect in the reduction of Q.
Our previous studies (Ferrara Ring: An Overview –
Cataract and Refractive Surgery Today Europe - http://
bmctoday.net/crstodayeurope/pdfs/1009_04.pdf. Accessed December 29, 2009) showed that, using the previous
nomograms, the BCVA was 20/60 or better in 70% of
patients. When using the Q-based nomogram we found a
BCVA of 20/40 or better in 70% of patients.
The results obtained through this new nomogram are very
satisfactory and reproducible since we use thinner segments
to achieve a significant amount of corneal regularization with
very satisfactory postoperative visual acuity.
REFERENCES
1. Siganos D, Ferrara P, Chatzinikolas K, et al.
Ferrara intrastromal corneal rings for the correction of keratoconus. J Cataract Refract Surg 2002;
28:1947-1951.
2. Colin J, Cochener B, Savary G, et al. Correcting
keratoconus with intracorneal rings. J Cataract Refract Surg. 2000;26:1117–1122.
3. Asbell PA, Ucakhan O. Long-term follow-up of
Intacs from a single center. J Cataract Refract Surg
2001; 27:1456–1468.
4. Colin J, Cochener B, SavaryG, et al. INTACS
inserts for treating keratoconus; one-year results.
Ophthalmology 2001; 108:1409–1414.
5. Colin J, Velou S. Implantation of Intacs and a
refractive intraocular lens to correct keratoconus. J
Cataract Refract Surg 2003;29:832–834.
6. Siganos CS, Kymionis GD, Kartakis N, et al.
Management of keratoconus with Intacs. Am J
Ophthalmol 2003; 135:64–70.
7. Assil KK, Barrett AM, Fouraker BD, Schanzlin
DJ. One-year results of the intrastromal corneal
ring in nonfunctional human eyes; the Intrastromal
Corneal Ring Study Group. Arch Ophthalmol 1995;
113:159–167.
8. Siganos CS, Kymionis GD, Astyrakakis N, et
al. Management of corneal ectasia after laser in
situ keratomileusis with INTACS. J Refract Surg.
2002;18:43–46.
9. Silva FBD, Alves EAF, Cunha PFA. Utilização
do Anel de Ferrara na estabilização e correção
da ectasia corneana pós PRK. Arq Bras Oftalmol.
2000;63:215–218.
10. Torquetti, L, Berbel RF, Ferrara P. Longterm follow-up of intrastromal corneal ring segments in keratoconus. J Cataract Refract Surg
2009;35:1768–1773.
11. Davis WR, Raasch TW, Mitchell GL, et al. Corneal asphericity and apical curvature in children: a
cross-sectional and longitudinal evaluation. Invest
Ophthalmol Vis Sci 2005; 46:1899-1906.
12. Kiely PM, Smith G, Carney LG. The mean
shape of the human cornea. Opt Acta (Lond)
1982;29:1027-1040.
13. Calossi A. The optical quality of the córnea.
Fabiano Editore, Italy, 2002.
14. Holmes-Higgin DK, Baker PC, Burris TE, Silvestrini TA. Characterization of the aspheric corneal surface with intrastromal corneal ring segments.
J Refract Surg 1999;15:520-528.
15. Eghbali F, Yeung KK, Maloney RK. Topographic determination of corneal asphericity and its lack
of effect on the refractive outcome of radial keratotomy. Am J Ophthalmol 1995;275-280.
16. Yebra-Pimentel E, González-Méijome JM,
Cerviño A, ET AL. Asfericidad corneal en una poblácion de adultos jóvenes. Implicaciones clínicas.
Arch Soc Esp Oftalmol 2004;79:385-392.
17. Torquetti, L, Ferrara P. Corneal asphericity
changes after implantation of intrastromal ring segments in keratoconus. In Press.
PAN-AMERICA : 95
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Investigadores de diversos estudios, (AGIS, Shirakashi, Shields)
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ser retiradas antes de la instilación de LUMIGAN® (bimatoprost) y pueden ser recolocadas 15 minutos después. Los pacientes deben ser advertidos de que el producto contiene cloruro de benzalconio, que es absorvido por las lentes hidrofílicas.Si más que un medicamento
de uso tópico ocular estuviera siendo utilizado, se debe respetar un intervalo de por lo menos 5 minutos entre las aplicaciones.No está previsto que LUMIGAN® (bimatoprost) presente influencia sobre la capacidad del paciente conducir vehículos u operar máquinas, sin embargo,
así como para cualquier colírio, puede ocurrir visión borrosa transitoria después de la instilación; en estos casos el paciente debe aguardar que la visión se normalice antes de conducir u operar máquinas. Interacciones medicamentosas.
medicamentosas.Considerando que las concentraciones
circulantes sistemicas de bimatoprost son extremadamente bajas después múltiplas instilaciones oculares (menos de 0,2 ng/ml), y, que hay varias vías encimáticas envueltas en la biotransformación de bimatoprost, no son previstas interacciones medicamentosas en humanos.
eacciones adversas. LUMIGAN® (bimatoprost) es bien tolerado, pudiendo causar eventos adversos oculares leves a moderados y no graves.Eventos adversos ocurriendo en 10-40% de los pacientes que recibieron doses únicas diarias, durante
No son conocidas incompatibilidades. RReacciones
3 meses, en orden decreciente de incidencia fueron: hiperenia conjuntival, crecimento de las pestañas y prurito ocular.Eventos adversos ocurriendo en aproximadamente 3 a < 10% de los pacientes, en orden decreciente de incidencia, incluyeron: sequedad ocular, ardor ocular,
sensación de cuerpo estraño en el ojo, dolor ocular y distúrbios de la visión.Eventos adversos ocurriendo en 1 a <3% de los pacientes fueron: cefalea, eritema de los párpados, pigmentación de la piel periocular, irritación ocular, secreción ocular, astenopia, conjuntivitis alérgica,
lagrimeo, y fotofobia.En menos de 1% de los pacientes fueron relatadas: inflamación intra-ocular, mencionada como iritis y pigmentación del íris, ceratitis puntiforme superficial, alteración de las pruebas de función hepática e infecciones (principalmente resfriados e infecciones
de las vías respiratorias).Con tratamientos de 6 meses de duración fueron observados, además de los eventos adversos relatados más arriba, en aproximadamente 1 a <3% de los pacientes, edema conjuntival, blefaritis y astenia. En tratamientos de asociación con betabloqueador,
durante 6 meses, además de los eventos de más arriba, fueron observados en aproximadamente 1 a <3% de los pacientes, erosión de la córnea, y empeoramiento de la acuidad visual. En menos de 1% de los pacientes, blefarospasmo, depresión, retracción de los párpados,
Posología y Administración.
hemorragia retiniana y vértigo.La frecuencia y gravedad de los eventos adversos fueron relacionados a la dosis, y, en general, ocurrieron cuando la dosis recomendada no fue seguida.Posología
Administración.Aplicar una gota en el ojo afectado, una vez al día, a la noche.
La dosis no debe exceder a una dosis única diaria, pues fue demostrado que la administración más frecuente puede disminuir el efecto hipotensor sobre la hipertensión ocular.LUMIGAN® (bimatoprost) puede ser administrado concomitantemente con otros productos oftálmicos
tópicos para reducir la hipertensión intra-ocular, respetándose el intervalo de por lo menos 5 minutos entre la administración de los medicamentos. VENTA BAJO PRESCRIPCIÓN MÉDICA.“ESTE PRODUCTO ES UM MEDICAMENTO NUEVO AUNQUE LAS INVESTIGACIONES HAYAN
INDICADO EFICACIA Y SEGURIDAD, CUANDO CORRECTAMENTE INDICADO, PUEDEN SURGIR REACCIONES ADVERSAS NO PREVISTAS, AÚN NO DESCRIPTAS O CONOCIDAS, EN CASO DE SOSPECHA DE REACCIÓN ADVERSA, EL MÉDICO RESPONSABLE DEBE SER NOTIFICADO.
1. The AGIS Investigators: The Advanced Glaucoma Intervetion Study - The Relationship Between Control of Intraocular Pressure and Visual Field Deterioration. Am. J. Ophthalmol, 130 (4): 429-40, 2000. 2. Shirakashi, M. et al: Intraocular Pressure-Dependent Progression of Visual
Field Loss in Advanced Primary Open-Angle Glaucoma: A 15-Year Follow-Up. Ophthalmologica, 207: 1-5, 1993. 3. Mao, LK; Stewart, WC; Shields, MB: Correlation Between Intraocular Pressure Control and Progressive Glaucomatous Damage in Primary Open-Angle Glaucoma. Am.
J. Ophthalmol, 111: 51-55, 1991. 4. Higginbotham, EJ et al. One-Year Comparison of Bimatoprost with Timolol in Patients with Glaucoma or Ocular Hypertension. Presented at American Academy Ophthalmology, Nov 11-14, 2001. 5. Gandolfi, S et al. Three-Month Comparison of Bimatoprost
and Latanoprost in Patients with Glaucoma and Ocular Hypertension. Adv. Ther, 18 (3): 110-121, 2001. 6. Coleman, AL et al: A 3-Month Comparison of Bimatoprost with Timolol/Dorzolamide in Patients with Glaucoma or Ocular Hypertension. Presented at American Acedemy of
Ophthalmol, New Orleans, La, 2001.
Mejor comodidad posológica:
1 vez al día.
No requiere refrigeración.
Presentación conteniendo 3 ml.