PAAO March 2012, Vol. 11(1) baja

VISION THE PAN-AMERICAN JOURNAL OF OPHTHALMOLOGY ISSN 2219-4665 March 2012, Vol. 11(1)

TO FOLLOW VIRTUE AND KNOWLEDGE Dantas tas PEC

INDUÇÃO DE LIGAÇÕES COVALENTES DO COLÁGENO (CROSS-LINKING) DA CÓRNEA PARA ESTABILIZAÇÃO DA ECTASIA PROGRESSIVA de Freitas D,, Schor S P

EFFICACY OF ONE DROP OF 2% PILOCARPINE TO REVERSE THE INTRAOCULAR PRESSURE PEAK AT 6:00 A.M. IN EARLY GLAUCOMA Cronemberger S, Calixto N, Moraes oraes MN, Castro ID, Lan Lana PCC, C, Loredo A AF

CIRUGÍA DE CATARATA POR MICROINCISIONES BIMANUALES Y COAXIALES Hernández Silva JR, López MR, Torres MR, Rodríguez YRR, Martínez ez RRR

MELKERSSON-ROSENTHAL SYNDROME: A FORGOTTEN DIAGNOSIS A CASE REPORT Karon MD, Valenzuela AA

LASER PHOTOCOAGULATION FOR I125 RADIATION-INDUCED RETINOPATHY IN CHOROIDAL MELANOMA: A CASE REPORT Fernández MG, Navarro JC, Yañes PM

ADVOCACY Izquierdo NJ

OBITUARY: Dr. Francisco Belisario-Navarro

NEW INSTRUCTIONS FOR AUTHORS

Proud to be PAN-AMERICAN

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PAN-AMERICA

March 2012, Vol. 11(1) Membership, Associations and Editorial Guidelines

Editor-in-Chief: Paulo Elias C. Dantas, MD Prof. of Ophthalmology Department of Ophthalmology Santa Casa of São Paulo, Brazil

Associate Editor-in-Chief: Lihteh Wu, MD (San José, Costa Rica)

Administrative Editorial Council: Mark Mannis, MD (PAAO President, Sacramento, CA, USA.), and Nelson Marques, MBA (PAOF Chairman, São Paulo, Brazil)

Section Editor, Cataracts: Nestor Gullo, MD (La Plata, Argentina)

Section Editor, Neurophthalmology: Karl Golnik, MD (Cincinnati, OH, USA)

Section Editor, Cornea and External Disease: Allan R. Slomovic, MD (Ontario, Canada)

Section Editor, Oncology: Rubens N. Belfort, MD (São Paulo, Brazil)

Section Editor, Prevention of Blindness: Fernando R. Barría von Bischhoffshausen, MD (Concepción, Chile)

Section Editor

Section Editor, Refractive Surgery: Luis Izquierdo Jr, MD (Lima, Peru)

Section Editor, Eye Banking: Luciene Barbosa de Sousa, MD (São Paulo, Brazil)

Section Editor, Ophthalmic Section Editor, Retina and Plastics and Orbital Diseases: Chun Cheng Lin Yang, MD MSc Vitreous: Mauricio Maia, MD (San José, Costa Rica) (São Paulo, Brazil)

Section Editor, Genetics: Eduardo José Gil Duarte Silva, MD (Figueira da Foz, Portugal)

Section Editor, Pathology: J. Oscar Croxatto, MD (Buenos Aires, Argentina)

Section Editor, Statistics and Epidemiology: Niro Kasahara, MD (São Paulo, Brazil)

Section Editor, Glaucoma: James C. Tsai, MD (New Haven, CT, USA)

Section Editor, Pediatric Ophthalmology and Strabismus: Maria Estela Arroyo Yllanes, MD (México City, México)

Section Editor, Uveitis and Immunology: Lourdes Arellanes-García, MD (Mexico City, Mexico)

Editorial Advisory Board

Editorial Review Board

Denise de Freitas, MD (São Paulo, Brazil)

Alejandro Lichtinger, MD (Toronto, Ontario, Canada)

Maria Audina Berrocal, MD (Miami, FL, USA)

Eduardo Alfonso, MD (Miami, FL, USA)

Ashley Behrens, MD (Riyadh, Saudi Arabia)

Daniel Weil, MD (Buenos Aires, Argentina)

Aims and scope:

Eduardo Arenas, MD (Bogotá, Colombia)

Ana Luisa Höfling-Lima (São Paulo, Brazil)

Marian Macsai, MD (Chicago, IL, USA)

Vision Pan-America (printed version ISSN 2219-4665, electronic version ISSN 2219-4673), the official publication of the Pan-American Association of Ophthalmology, is a quarterly fully peer reviewed scientific publication that publishes original research in Ophthalmology, including review articles on ophthalmic diseases and surgical techniques, clinical scientific studies, basic investigation, case reports, brief communications and letters to the editor in four languages: Spanish, English, Portuguese and French. In addition, the journal publishes critical reviews of new texts in ophthalmology deemed to be of importance to the Pan-American practitioner.

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Bruno Fontes, MD (Rio de Janeiro, Brazil)

Marie Eve Legare, MD (Quebec City, Canada)

Alfredo Sadun, MD (Los Angeles, CA, USA)

Carol L. Karp, MD (Miami, FL, USA)

Natalio Izquierdo, MD (San Juan, Puerto Rico)

Enrique Graue-Hernández, MD (Mexico City, Mexico)

Peter Quiros, MD (Los Angeles, CA, USA)

Eugenio Maul de La Puente (Santiago, Chile)

Renato Ambrósio Jr. (Rio de Janeiro, Brazil)

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PAOF BOARD

PAAO EXECUTIVE COMMITTEE 2011-2013 President Mark J. Mannis, MD President Elect Ana Luisa Höfling-Lima, MD Past President Cristián Luco, MD Vice President Peter A. Quiros, MD Executive Vice President J. Fernando Arévalo, MD FACS

Secretary, English Language Region James C. Tsai, MD MBA

Secretary, Spanish Language Region Lihteh Wu, MD

Associate Secretary, English Language Region Carol L. Karp, MD

Associate Secretary, Spanish Language Region Jorge E. Valdez García, MD MA

Secretary, Portuguese Language Region Paulo E.C. Dantas, MD

Executive Director Teresa Bradshaw

Associate Secretary, Portuguese Language Region Mauricio Maia, MD

Chairman of the Board Mr. Nelson Marques Past Chair Rubens Belfort Jr, MD PhD Vice Chair William C. de La Peña, MD Secretary Treasurer J. Fernando Arevalo, MD Executive Director Teresa Bradshaw

PAAO BOARD OF DIRECTORS 2011-2013 ARGENTINA Enrique S. Malbrán, Sr., MD1 Ernesto Ferrer Abad, MD1,3 Gustavo Federico Bodino, MD1 J. Ignacio Manzitti, MD1 Joaquin Alfredo Bafalluy, MD1 Juan Oscar Croxatto, MD4 Lidia López, MD4 María Celeste Mansilla, MD1 Nestor Gullo, Jr., MD4 Roberto N. Ebner, MD1 S. Fabián Lerner, MD4 BOLIVIA José Luis Sebastián Salas, MD3 José Vladimir Justiniano Talavera, MD1 Vania Licett García Aliaga, MD1 BRAZIL Bruno Machado Fontes, MD1 Eduardo Büchele Rodrigues, MD1 José Alvaro P. Gomes, MD4 Liana Maria V. de O. Ventura, MD PhD1 Luciene Barbosa de Sousa, MD4 Luciene Chaves Fernandes, MD4 Marco Antonio Rey de Faria, MD1,3 Maria Cristina Nishiwaki-Dantas, MD1 Mário Junqueira Nóbrega, MD1 Nilo Holzchuh, MD1 Paulo Augusto de Arruda Mello, MD PhD1 Rubens Belfort, Jr., MD PhD2 CANADA Allan R. Slomovic, MA MD FRCS(C)1 Paul E. Rafuse, MD PhD FACS1,3 CHILE Cristián Luco, MD2 Fernando Barría von Bischhoffshausen, MD1,4 Francisco José Conte Silva, MD1 Gonzalo Matus, MD1 Javier Lagos Rodríguez, MD1 Juan Verdaguer Taradella, MD2 Pedro Bravo C., MD1,4 COLOMBIA Alvaro Rodríguez González, MD2 Angela María Fernández Delgado, MD1,4 Angela María Gutiérrez Marín, MD1 Carlos Alberto Restrepo Pelaez, MD1 H. Fernando Gómez Goyeneche, MD1,3 Pedro Ivan Navarro Naranjo, MD1 COSTA RICA Javier A. Montero Alpizar, MD1 Joaquín Martínez Arguedas, MD3 Lihteh Wu, MD4 Teo Evans, MD1

CUBA Caridad Chiang Rodríguez, MD1 Carlos Alberto Perea Ruiz, MD1 Marcelino Rio Torres, MD3 Reinaldo Ríos Caso, MD1 DOMINICAN REPUBLIC Joaquin Lora Hernández, MD1 Miguel Angel López Pimentel, MD1 Miriam Cortina, MD3 ECUADOR Gregorio Gabela, MD1,4 Patricio Flor Arteaga, MD1 Ximena Velasteguí Camorali, MD3 EL SALVADOR Carlos Eduardo Alas Gudiel, MD1 Jaime Ricardo Avila Guerra, MD3 Rodrigo Antonio Quesada Larez, MD1 GUATEMALA Paulina Castejón, MD1 Rudy Oliver Gutiérrez Díaz, MD1,3 HAITI Frantz Large, MD3 HONDURAS Doris Alvarado de Jaúregui, MD1,3 Sergio Rolando Zúñiga Castillo, MD1 MEXICO Cecilio Francisco Velasco Barona, MD4 Enrique L. Graue Wiechers, MD2 Humberto Ruiz Orozco, MD1,3 José Luis Tovilla Canales, MD4 Lourdes Arellanes, MD4 María Estela Arroyo Yllanes, MD4 Raul Macedo Cué, MD1 NICARAGUA Sylvia Bravo Mendiola, MD1,3 PANAMA Benjamín F. Boyd, MD2 Félix Emilio Ruiz Díaz, MD1,3 Miguel Fco. Wong Tang, MD1 PARAGUAY Cirila Espinola de Ruiz Díaz, MD1,3 Miriam R. Cano, MD1 PERU Dino Fernando Natteri Marmol, MD1 Francisco Contreras Campos, MD2 Juan Carlos Corbera Gonzalo, MD1 Juan Fernando Mendiola Solari, MD1 Miguel Guzmán Ahumada, MD3 Rocío Ardito Vega, MD1

PORTUGAL Eduardo José Gil Duarte Silva, MD PhD1 Maria Manuela Pires Carmona, MD1,3 PUERTO RICO Ian Piovanetti Pérez, MD1,3 María Hortencia Berrocal, MD1 SPAIN Carlos Cortés Valdés, MD1 Luis Fernández Vega Sanz, MD3 Miguel A. Zato Gómez de Liaño, MD PhD1 URUGUAY Alicia Martínez de Pacheco, MD1 María del Rosario Varallo, MD1 Miguel Zylberglajt Cordones, MD1,3 USA Alice R. McPherson, MD2 Andrew G. Lee, MD1 Anthony C. Arnold, MD1 Arun D. Singh, MD4 Bradley Dean Fouraker, MD1 Bradley R. Straatsma, MD JD2 Carl D. Regillo, MD1 Charles M. Zacks, MD1 David K. Coats, MD1 Eduardo C. Alfonso, MD1 George A. Williams, MD1 J. Bronwyn Bateman, MD2 James P. McCulley, MD1 John A. Irvine, MD1 Nelson R. Sabates, MD1 Paul R. Lichter, MD2 Richard K. Parrish, II, MD1 Richard L. Abbott, MD2 Robert B. Bhisitkul, MD PhD1 Robert C. Drews, MD2 Robert Ritch, MD1 Ruth D. Williams, MD3 Stephanie Jones Marioneaux, MD1 Stuart R. Seiff, MD1 VENEZUELA Claudia Luz Pabón Bejarano, MD1 Luis Felipe Rivero Caret, MD1 María Angélica Cortez Bernal, MD1 Morayma Coromoto Acevedo Sorondo, MD3 Oscar Vicente Beaujón Balbi, MD1 WEST INDIES Donovan Calder, BSc MBBS FRCS3 Terrence Allan, BSc MBBS FRCS1 1

Delegate PAAO Past President President, Affiliated National Society 4 President, Affiliated Subspecialty Society 2 3

EDITORIAL

Editorial Paulo E.C. Dantas, MD Editor-in-Chief, PAAO

To follow virtue and knowledge “Considerate la vostra semenza: fatti non foste a viver come bruti, ma per seguir virtute e canoscenza”.

(Consider your origin: you were not born to live like brutes, but to follow virtue and knowledge).

Dante Allighieri, The Divine Comedy (written between1308-1321)

Taking on the role of Editor-in-Chief of Vision Pan-America (VPA) is a challenging assignment after a decade of an outstanding job, almost “with bare hands”, done by Dr. Mark J. Mannis, who is the current President of the Pan-American Association of Ophthalmology. Mark tried to improve and maintain high standards to promote the growth and success of VPA. I would like to take this opportunity to congratulate Mark and thank him for his excellent services to the journal and this decade of legacy.

In this new journey, along with my dear friend and Assistant Editor-in-Chief, Dr. Lihteh Wu from Costa Rica, I will certainly face many challenging situations, but I am confident that all that I have learned from my professors, mentors, family and life will help me to perform my best in taking this journal to a new level.

As we continue to make strides in life, it is important to look back to honor and recognize those who have paved the way and gave us the essential sense to follow virtue and knowledge. My eternal recognition and thanks to Rubens Belfort Jr, Richard L. Abbott, Cristian Luco, Mark J. Mannis, Nelson Marques and Carlos Ramos Souza-Dias.

When authors are confronted with a variety of titles to choose from for the publication of their research, they look for accessibility, speed, reliability, exposition and diffusion of their ideas. For those reasons, as soon as I began my duties as Editor, my first challenge was to look for a reliable, accessible and fast editorial managing system. We came to an agreement with The Public Knowledge Project (PKP) that is operated through a partnership among the Faculty of Education at the University of British Columbia, the Simon Fraser University Library, the

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Vis. Pan-Am. 2012;11(1):3-4

School of Education at Stanford University, and the Canadian Centre for Studies in Publishing at Simon Fraser University.

Now, virtually, anyone with computer access in the world can submit scientific papers to Vision Pan-America through the URL http://journals.sfu.ca/paao.

In the same way, editors, reviewers and our managing staff (the incredible trio: Teresa Bradshaw, Terri Grassi and Mapy Padilla) can do all the work electronically. This is an impressive achievement that certainly will increment submissions and make VPA one excellent option for publishing.

Another noteworthy addition was to include a specific and strongly indicative subtitle to our journal. From now on, our journal will be known as Vision PanAmerica, The Pan-American Journal of Ophthalmology. We think that this is a very strong branding, that also recognizes our targeted audience.

As you will notice, many layout changes were introduced to VPA. Short running head subtitles, disclaimer of proprietary interest, funding, date of submission and approval and other layout changes were introduced to deal with basic bibliometrics requirements, aimed at future indexation of our journal in scientific databases.

In face of a wide range of increasingly complex ethical issues in the editorial process, VPA will adopt a set of minimal standards of code of conducts, essentially based on the Code of Conducts and Best Practice Guidelines for Journal Editors by the Committee of Publication Ethics (COPE) (http://www.publicationsethics.org). We also prepared new guidelines for authors and reviewers, mostly based on the orientations from extremely influential associations such as International Committee of Medical Journals Editors (ICMJE www.icmje.org), the World Association of Medical Editors (WAME www.wame.org) and EQUATOR network (www.equator-network.org), to deal with contemporary questions on ethics and scientific publications.

We already started the process of submitting VPA to some of the most respected scientific databases and hope that, in the upcoming issues, we would come up with thrilling news about this special achievement.

In the meantime, I would like to invite researchers and colleagues from inside and outside the Americas to submit their scientific contributions to Vision Pan-America.

I would like also to take this moment to welcome the incoming Editorial Board, one of the brightest and prolific Editorial Board in The Americas, qualified by the Literature Selection Technical Review Committee from The National Library of Medicine as exceptionally good. I thank each of you in advance for your commitment.

As the new Editor-in-Chief of Vision Pan-America, The Pan-American Journal of Ophthalmology, I look forward to an exciting, challenging and fruitful time.

Success and bright future to VPA! Paulo E.C. Dantas, M.D. Editor-in-Chief Vision Pan-America, The Pan-American Journal of Ophthalmology pauloecdantas@uol.com.br pauloecdantas@me.com

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NOTE OF CORRECTION: Late introduction of an omitted author after paper publishing Following the Code of Conduct and Best Practice Guidelines for Journal Editors issued by the Committee on Publication Ethics (COPE), journal editors should consider issuing a correction note if the author/ contributor list is incorrect (i.e. a deserving author has been omitted or somebody who does not meet authorship criteria has been included).

In the last issue of VPA Vol X No.4 Dic 2011, the paper Complicaciones de la Válvula de Ahmed con Mitomicina C, en un Caso de Glaucoma Congénito published on page 118 to 122, had the name of first author unintentionally omitted. We apologize for that mistake and acknowledge that the correct list of authors is: Liamet Fernández Argones, M.D. Meisy Ramos López, M.D. Violeta Rodríguez Rodríguez, M.D. Yanileidy González Blanco, M.D. Ibraín Piloto Díaz, M.D. Susana Vinardell Pérez, M.D. Francisco Y. Fumero González, M.D.

Paulo E.C. Dantas Editor-in-Chief, Vision Pan-America, The Pan-American Journal of Ophthalmolohy

de Freitas & Schor. Cross-linking para tratamento do ceratocone progressivo.

Indução de ligações covalentes do colágeno (cross-linking) da córnea para estabilização da ectasia progressiva Induction of corneal colagen cross-linking for the stabilization of progressive ectasia Denise de Freitas1, Paulo Schor1

Corresponding author:

1

Professor adjunto, Departamento de Oftalmologia, Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brasil.

Funding: None

Denise de Freitas, MD Rua Onze de Junho 977 São Paulo, SP 04041-053 BRAZIL email: dfreitas.epm.unifesp@gmail.com Data de recepção: 09-01-2012 / Data da aprovação: 31-01-2012

Proprietary and/or financial interest: None

ABSTRACT

RESUMO

The induction of corneal collagen cross-linking by ultraviolet radiation (UV) over a substract of riboflavin was popularized and dubbed as CXL (cross-linking).

In 2003, this technique was introduced in the therapeutic arsenal for patients with keratoconus, aiming to halt the progression of the disease. The procedure would enhance biomechanical and biochemical corneal stability by the formation of new covalents bonds in the amino-termial sites of the collagen molecule of the anterior stroma. Such induction depended on the hydrogen singlets free radicals generated by the riboflavin photosensibilization by UV-A. CXL is indicated in corneal thinning and progressive ectasias, as it happens in keratoconus, post-LASIK ectasia and pellucid marginal degeneration. Other anecdotic indications are described in the literature such as treatment of infectious keratitis, control of bullous keratopathy and corneal melting; however, they will not be discussed in this review.

The classic technique was described in 1995 by German researchers and variations of this technique still under evaluation. The CXL is a recent procedure and, besides some favorable results, a long-term follow up (more than 5 years) is needed, to evaluate collateral side effects and potential complications.

A inducao de novas ligações covalentes entre cadeias de colágeno da córnea pela radiação ultravioleta (UV), tendo como substrato a riboflavina, foi popularizada com a sigla CXL (cross-linking). Em 2003, foi introduzida no arsenal terapêutico de pacientes com ceratocone, com o objetivo de evitar a progressão da doença.

O procedimento aumentaria a estabilidade biomecânica e bioquímica da córnea pela formação de novas ligações covalentes entre as porções amino-terminais das moléculas do colágeno no estroma anterior. Tal indução se dá às custas dos radicais livres dos hidrogênio singlets gerados na fotossensibilização da riboflavina pela luz UV-A. O CXL é indicado, em geral, nos afinamentos e ectasias da córnea de caráter progressivo, como acontece no ceratocone, na ectasia pós-LASIK e na degeneração marginal pelúcida. Outras indicações anedóticas são descritas na literatura como, por exemplo, para o tratamento de algumas ceratites infecciosas, para controle da ceratopatia bolhosa e necrólise da córnea; porém, não serão abordadas nesta revisão. O CXL para o tratamento da ectasia progressiva é um procedimento que não envolve equipamentos sofisticados, seguro (com baixas chances de complicações), de baixo custo e alta eficácia (parada da progressão da ectasia). A maioria dos pacientes submetidos tratados é de adultos jovens. Há contraindicações para o procedimento e, dentre estas, a espessura mínima de 400 μm é a mais respeitada. A técnica mais utilizada e considerada como clássica é a descrita em 1995, por pesquisadores alemães. Variações da técnica clássica estão ainda em avaliação. O CXL é um procedimento recente e apesar dos resultados até agora serem favoráveis, acompanhamento a longo prazo (mais de 5 anos) é necessário, inclusive em relação aos efeitos colaterais e potenciais complicações.

Key words: córnea, keratoconus, ectasia, crosslinking, riboflavin.

PALAVRAS CHAVE: córnea, ceratocone, ectasia, cross-linking, riboflavina.

The CXL for the treatment of progressive corneal ectasia is a procedure that does not involve sophisticated equipments. It is safe (low odds of complications), not expensive and with high efficacy (halting the progression of ectasia). The great majority of treated patients are young adults. There are some contraindications for this procedure such as minimum corneal thickness of 400 μm, which is the most feared.

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REVIEW / Vis. Pan-Am. 2012;11(1):5-13

INTRODUÇÃO As proteínas são conjuntos de aminoácidos que têm funções enzimáticas, de transporte, de armazenamento e, dentre estas, função estrutural, que fornece proteção ou resistência às estruturas biológicas. Dentre estas proteínas com função estrutural, temos o colágeno que é encontrado, por exemplo, em ossos, cartilagens, na córnea e na pele. As proteínas são classificadas quanto a sua conformação (forma) em fibrosas e globulares, sendo que as fibrosas são caracterizadas por um grupo de cadeias polipeptídicas enroladas em espiral ou hélice, formando fibras ou lâminas, com ligações cruzadas por intermédio de pontes de dissulfeto e de hidrogênio. Essas proteínas também são as que compartilham propriedades de resistência e/ou elasticidade às estruturas anatômicas onde ocorrem; são elementos estruturais básicos do tecido conjuntivo e são encontradas no colágeno e elastina (proteínas dos tendões, matriz óssea, córnea) e na queratina (cabelos, unhas, pele). A apresentação estrutural do colágeno ocorre em hélice tríplice e, tanto na a queratina, quanto no colágeno, a resistência mecânica é aumentada pelo enrolamento helicoidal de múltiplos segmentos em super-hélices, da mesma forma como os cordões são enrolados para formar uma corda resistente. A manutenção da forma tridimensional é conseguida por ligações quíicas de atração e repulsão. A resistência dessas estruturas é aumentada pelas ligações covalentes entre cadeias polipeptídicas no interior das cordas multihelicoidais e entre as adjacentes.1 O colágeno do estroma da córnea é basicamente constituído por colágeno do tipo I, embora colágenos do tipo III, V, VI também estejam presentes. O colágeno da córnea tipicamente forma fibrilas (32 nm) uniformemente espaçadas, que são arranjadas em fibras maiores, denominadas de lamelas corneais, de espessura (1-2 mm) e largura (5-100 mm) variáveis, dispostas em camadas entrelaçadas ao longo do estroma. A manutenção dessa arquitetura uniforme é crucial para a transparência relativa da córnea. O colágeno é sintetizado pelo ceratócito, na forma da sua molécula precursora, o procolágeno, que possui dois peptídios adicionais, um em cada extremidade. No espaço extracelular, enzimas especializadas conhecidas como proteinases procolágeno removem dois péptidos de extensão localizados nas extremidades da molécula. A molécula, agora transformada em colágeno, sofre modificação póstranslacional e forma fibrilas e, em seguida, fibras. Este processo, enzimaticamente controlado, envolve a enzima oxidase lisil e resulta na oxidação dos aminoácidos lisina e hidroxilisina para os seus respectivos aldeídos, que condensam com outros aldeídos para formar ligações covalentes (cross-linkings) intra e intermoleculares.2 A indução de novas ligações covalentes entre as cadeias de colágeno da córnea, induzida pela radiação ultravioleta (UV), foi popularizada com a sigla CXL (corneal cross-linking). Em 2003, foi introduzida no arsenal de tratamentos de pacientes com ceratocone, com o objetivo de evitar a progressão da doença. O procedimento aumenta a estabilidade biomecânica e bioquímica da córnea, pela formação de novas ligações covalentes entre as porções amino-terminais das moléculas de colágeno no estroma anterior. Tal indução se dá pelos radicais livres dos oxigênio singlets gerados na fotossensibilização da riboflavina pela luz UV-A. As ligações químicas propiciam a formação de ligações químicas entre cadeias de polímeros, no caso, polímeros de aminoácidos (proteínas). Estas ligações podem ser covalentes (compartilhamento de pares de elétrons entre os átomos) ou iônicas (atração eletrostática entre dois íons de cargas opostas)3 e podem ocorrer entre polímeros sintéticos ou naturais (proteínas). Nas ciências biológicas, as ligações covalentes (cross-linking) comumente referem-se a uma reação mais especificamente usada para pesquisar interações moleculares. Em tecidos biológicos, tal reação pode promover pontes entre proteínas, estabilizando e acrescentando resistência e durabilidade a estes tecidos. A indução de ligações cruzadas tem sido usada em implantes biológicos para reparo de hérnias4, na propriedade mecânica de tendões5, em cartilagens para reconstrução nasal6, na resistência de válvulas cardíacas7, no reparo da membrana timpânica8, dentre outros. Várias modificações relacionadas à idade como, por exemplo, enrijecimentos das articulações e do sistema vascular 6

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nada mais são do que resultado dos efeitos deletérios causados por um processo natural de ligações cruzadas nas moléculas de colágeno nos tecidos.9 Em 1996, Yamauchi et al comprovaram que a córnea também sofre um processo natural de indução de ligações cruzadas de colágeno, em função da idade.10 Também, Sady et al, em 1995, referiram que o diabetes, a longo prazo, causa uma reação natural de crosslinking no colágeno da córnea pela reação de Maillard (formação endógena dos produtos de glicação avançada) que predispõe a ligações covalentes.11 Ou seja, pode-se obter uma reação de cross-linking por vários mecanismos, dentre estes, a mais discutida na atualidade, a irradiação de luz UV, com ou sem uso de fotossensibilizador, além da glicação não-enzimática e reações aldeídicas12, dentre outras.

A literatura mostra que pacientes com ceratocone têm uma expressão alterada dos proteoglicanos, como o sulfato de queratan.13-18 Ainda é relatado que a menor rigidez corneal no ceratocone pode ser devida a uma redução no número de reações cruzadas do colágeno estromal e nas ligações moleculares entre os proteoglicanos estromais adjacentes19. Portanto, a indução de ligações de modo terapêutico para o ceratocone teria como objetivo aumentar o grau de ligações covalentes entre as moléculas da matriz extracelular, tais como colágeno do tipo I e proteoglicanos. Novas ligações retardariam a degradação enzimática, já descrita em casos de ectasia e, teoricamente, restringiram o deslizamento de lamelas de colágeno, resgatando a rigidez corneal e, conseqüentemente, retardando ou até mesmo estacionando a progressão do ceratocone. As ligações cruzadas geradas pelo procedimento são intramoleculares, uma vez que se tem comprovado o aumento no diâmetro molécula de colágeno em até 10% pós-CXL. Em 1998, Spoerl et al investigaram a possibilidade do CXL do colágeno do estroma aumentar a rigidez corneal, visando um futuro tratamento conservador para as ectasias20. Desencadearam, assim, uma intensa linha de pesquisa para a aplicação in vivo desta nova arma terapêutica, em especial para o ceratocone evolutivo.

CERATOCONE É uma ectasia corneal não-inflamatória, geralmente bilateral, simétrica ou assimétrica, com afinamento central ou paracentral (mais frequente na região temporal inferior), que pode ou não ter caráter progressivo.

Casos unilaterais de ceratocone são raros e podem no olho não afetado apresentar sinais de ceratocone “forma frustra” ou desenvolver a doença mais tardiamente.21-25 Aparentemente, não há variação de incidência quanto ao gênero e etnia, mas o assunto é controverso na literatura.26-30 Geralmente inicia-se por volta da puberdade e pode ser progressivo até as terceira e quarta décadas de vida quando tende a estacionar.31 A incidên-

de Freitas & Schor. Cross-linking para tratamento do ceratocone progressivo.

cia estimada varia amplamente nos diferentes estudos (17.3 a 230 casos para cada 100.000 habitantes)31-35, com um valor médio de 1 para cada 2.000 habitantes.

A prevalência mais citada é de 54 casos por 100,000 habitantes.36 Diferenças em incidência e prevalência são creditadas aos diferentes métodos empregados e às diferentes definições da doença.

A causa definitiva do ceratocone não é esclarecida. Fatores de natureza metabólica12,37, bioquímica38,39, biomecânica40,41, genética42 e de doenças relacionadas42-45 são cogitados como envolvidos na etiopatogenia da doença.46 Os achados clínicos variam com a severidade do ceratocone, sendo os mais frequentes [1] o astigmatismo irregular e a miopia, apesar de casos de hipermetropia terem sido descritos47,48, [2] perda da melhor acuidade visual corrigida (pacientes com ceratocone mais avançado, geralmente não atingem acuidade visual de 20/20 ou 6/6), [3] reflexo “em tesoura” na retinoscopia, [4] reflexo da “gota de azeite” de Charleux na retroiluminação, [5] anel de Fleisher (depósito de hemossiderina na forma de linha ou arco), [6] estrias de Vogt (diminutas linhas verticais produzidos pela compressão da membrana de Descemet; tendem a desaparecer comprimindo-se digitalmente a córnea), [7] aumento da espessura dos nervos corneais, [8] cicatrizes superficiais e profundas da córnea, [9] sinal de Munson (deformação em forma de “V” da pálpebra inferior no olhar para baixo), [10] sinal de Rizzuti (reflexo luminoso na área medial do limbo, quando a luz é projetada da região lateral)31,36,43,49. Alguns pacientes em estádio avançado da doença, podem a[resentar rupturas da membrana de Descemet, ocorrendo à difusão do humor aquoso no estroma, com formação de edema agudo de córnea (hidrópsia).

Existem classificações do ceratocone baseadas na [1] morfologia (pontiagudo - diâmetro do ceratocone ≤ a 5 mm; oval - diâmetro do ceratocone ≥ a 5 mm; globoso, quando afeta mais de 75% da córnea), [2] evolução da doença (grau 1, forma frustra ou subclínica, geralmente despercebida, a não ser que um exame de tomografia ou topografia seja realizado, visão 20/20 com ou sem óculos, ausência de sinais corneais; grau 2, forma leve com discreto afinamento de córnea, ausência de cicatrizes ou opacidades; grau 3, forma moderada com Estrias de Vogt, anel de Fleischer, afinamento de córnea significativo e astigmatismo irregular entre 2,00-8,00 dioptrias, ausência de cicatrizes ou opacidades, acuidade visual de ou próxima a 20/20 somente com a adaptação de lentes de contato; grau 4, forma severa com curvatura da córnea maior que 55 dioptrias, acuidade visual com lentes de contato menor que 20/25, presença de cicatrizes e afinamento acentuado, sinal de Munson) e [3] exames subsidiários, com índices específicos para topografia36 (valor

Tabela 1: índices baseados em sistemas de detecção de ceratocone; um valor mais alto do que o ponto de corte sugere a presença de ceratocone.36 Índice

Ponto de Corte

Valor de K

47.2

Valor I-S

1.4

KPI KCI%

Descrição

Referência

Baseado na ceratometria central

Rabinowitz YS & McDonnell PJ, 1989135

Baseado na assimetria inferior-superior dos valores ceratométricos

Rabinowitz YS & McDonnell PJ,1989135

0.23

Derivado de oito índices topográficos quantitativos

Maeda et al, 1994136

0%

Derivado doz KPI e mais quatro outros índices

KSI

0.25

Detecção do ceratocone e da sua gravidade avaliado em sistema de inteligência artificial

Smolek MK & Klyce SD, 1997138

Z3

0.00233

Baseado em valores que na topografia referiam-se a altura e foram transformados para termos do polinômio ortogonal de Zernike

Schwiegerling J & Greivenkamp JE, 1996139

KISA%

100%

KSS

0.5

Baseado na biomicroscopia, topografia corneal, poder corneal e RMS (“Root Mean Square”) das aberrações de alta ordem oriundas da análise de frente de onda da superfície da córnea.

McMahon TT et al, 2006141

CLMI

>0.45

Baseado na detecção da presença ou ausência de padrões de ceratocone e determinando a localização e a magnitude da curvatura do cone

Mahmoud AM et al, 2008142

Maeda et al, 1995137

Rabinowitz YS & Rasheed K, 1999140

Baseado nos valores de K, I-S, AST e SRAX

Adaptado de Romero-Jimenez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Contact lens & anterior eye: The journal of the British Contact Lens Association. 2012. 33(4): 157-66)36

de K, valor I-S, KPI, KCI%, KSI, Z3, KISA%, KSS, CLMI – Tabela 1), tomografia com os sistemas Scheimpflug e de coerência óptica50-53, com análise de paquimetria54, biomicroscopia ultrassônica55, análise de frente de ondas56,57, histerese e fator de resistência da córnea22,58-61, além da microscopia confocal.62 O tratamento do ceratocone é inicialmente feito com a correção refracional por meio de óculos e lentes de contato. Quando ambos os tratamentos falham, cogitase o tratamento cirúrgico, que varia desde o implante de anéis intraestromais até os transplantes de córnea, que podem ser lamelares ou penetrantes63,64. O CXL é uma alternativa nos casos de ceratocone com comprovada progressão, em qualquer estágio da doença, dentro das suas contraindicações.2,65

INDICAÇÃO E CONTRA-INDICAÇÕES O CXL é classicamente indicado para casos de ceratocone com progressão comprovada. Existe a controvérsia de indicação em casos não-progressivos, baseada no fato de que, em alguns estudo, tem sido relatado o aplanamento da curvatura e conseqüente melhora da acuidade visual.66 Não existem estudos de longo prazo avaliando o procedimento mais objetivamente para outros afinamentos progressivos, como a ectasia pós-LASIK e a degeneração marginal pelúcida. Porém, para a ectasia pós-LASIK, especula-se que os resultados esperados seriam os mesmos encontrados no tratamento do ceratocone.2 Outras indicações anedóticas são descritas na literatura como, por exemplo, tratamento de ceratites infecciosas, controle da dor na ceratopatia bolhosa e reversão da necrólise da córnea, mas o pequeno número de casos e a ausência de acompanhamento a longo prazo não embasam a indicação desse procedimento.

A maioria dos pacientes tratados na atualidade é de adultos jovens. A indicação rotineira em crianças requer evidência científica, mas na literatura há citação de tratamento em pacientes abaixo de 18 anos de idade.67-69 A indicação no paciente acima de 40 anos é menos comum, pois a doença tende a estacionar com o envelhecimento68.

As contra-indicações incluem [1] curvatura corneal ≥ 55.00 dioptrias no ápice do ceratocone, [2] espessura corneal ≤ 400 μm no ápice do ceratocone, [3] presença de opacidades de córnea por cicatrizes subepiteliais e ou estromais e estrias de PAN-AMERICA

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Vogt, [4] antecedente de herpes ocular, pelo risco de recorrência desencadeada pela luz UV, [5] doenças da superfície ocular como olho seco, displasias e tumores, disfunção da glândulas de Meibomius, incluindo possíveis dificuldades de cicatrização [6] antecedente de doença do tecido conectivo ou auto-imune de qualquer natureza, [7] alergia aos componentes utilizados no tratamento e [8] gravidez e ou amamentação, pelo fato de ser um procedimento novo na medicina.

A espessura mínima da córnea para realização segura do procedimento tem gerado controvérsia na literatura, pois o valor não é claramente descrito, nas diferentes publicações. Encontram-se variações de sua definição (paquimetria mínima), em relação à presennça ou não do epitélio corneal, sem a medida é sem ou logo apos a nstilação de riboflavina; se a riboflavina utilizada é iso ou hipo-osmótica, sem contar publicações que têm demonstrado que durante o procedimento a córnea sofre um processo de afinamento70. Tal preocupação deve-se ao fato de haver casos de córnea mais Iná, com risco maior de lesão endotelial.71 Aparentemente, a espessura da córnea deve ser de no mínimo 400 μm, sem epitélio e sem a administração de riboflavina, medida por várias vezes, imediatamente antes do início do procedimento, no ponto mais fino da córnea. Tal precisão dá-se com o auxílio de mapas paquimétricos, como os resultantes de exames tomográficos de segmento anterior, e não da ultrasonografia, que pode apontar uma área mais espessa no local presumido de maior curvatura. Por outro lado, encontram-se evidências de erros maiores em alguns sistemas de tomografia, quando realizados em córneas irregulares ou com opacidades.

CARACTERIZAÇÃO DE PROGRESSÃO Não existem parâmetros pontuais uniformemente utilizados nos diferentes estudos que caracterizem a progressão do ceratocone. Tão pouco é estabelecido o intervalo (3, 6 ou 12 meses) em que a possível progressão deveria ser checada.

Pode-se considerar como progressão clínica, a perda da acuidade visual corrigida por óculos (SCVA) acompanhada de mudanças de refração. Para tal, devem-se realizar de maneira seriada as medidas de AV, sem e com a melhor correção refracional, assim como as medidas da curvatura corneal no seu ponto mais alto (K máxima) e a avaliação da paquimetria no seu ponto mais fino, em geral no ápice do ceratocone.

Topografia e tomografia (sistemas Scheimpflug e coerência óptica) são exames subsidiários importantes e também utilizados na avaliação da progressão.72 A tomografia, em especial, pode auxiliar comprovando o aumento da profundidade da câmara anterior, a medida em que a ectasia progrida.

Estudo recente na literatura propõe um modelo de avaliação de progressão de ceratocone, que pode também ser aplicado no pós-CXL, utilizando-se topografia, aberrometria, localização do cone e pressão intraocular.73

TÉCNICA PADRÃO/CLÁSSICA DE CXL DO COLÁGENO CORNEAL A técnica considerada padrão/clássica de CXL foi a descrita na primeira publicação clínica no assunto por Wollensak et al, em 200374 e incluiu 23 olhos com ceratocone progressivo de grau moderado ou avançado. O estudo mostrou que o CXL foi eficaz em estacionar o ceratocone ao longo de um período de até quatro anos. Neste estudo, a progressão média pré-operatória da ceratometria (K) máxima de 1,42 D em 52% dos olhos nos 6 meses anteriores ao tratamento foi seguida de uma diminuição no pós-operatório em 70% dos olhos. As estatísticas também revelaram uma redução da K máxima de 2,01 D, enquanto o pós-operatório SEQ foi reduzida por uma média de 1,14 D. Ao mesmo tempo, 22% dos olhos controle não tratado sujeito tinha uma progressão pós-operatório da ectasia em média de 1,48 D. Já com algumas modificações desta, atualmente o CXL é realizado em condições estéreis de centro cirúrgico e a superfície ocular é anestesiada com colírio de cloridrato de proximetacaína 0,5%. O epitélio central da cornea é removido com espátula romba em uma área de diâmetro aproximado de 8 a 9 mm. Como fotossensibilizador, utiliza-se a solução de riboflavina isosmótica a 0,1%, que deve ser instilada 8

PAN-AMERICA

30 minutos antes da irradiação, com a aplicação de uma gota a cada cinco minutos. A riboflavina é uma macromolécula e, para que possa penetrar o estroma, o epitélio da córnea deve ser removido antes da instilação de riboflavina. A presença de coloração amarelada (riboflavina) em toda a espessura da córnea e na câmara anterior do olho ao exame na lâmpada de fenda, deverá ser confirmada antes do início da irradiação. Uma vez iniciada a irradiação, a instilação de riboflavina deve ser mantida a cada 5 minutos durante todo o período de tratamento, ou seja, 30 minutos; colírio de cloridrato de proximetacaína 0,5% também deve ser instilado, sempre que necessário, para evitar que o paciente sinta dor durante o procedimento.

Antes de iniciar a irradiação, deve-se repetir a paquimetria ultrassônica no provável ponto mais fino da córnea, baseado-se na imagem topográfica, para assegurar-se que a espessura mínima é de 400 μm. A irradiação ultravioleta (UV)-A é, então, iniciada a uma distância de 5 cm, usando-se um diodo emissor de luz UV-A do comprimento de onda livre do transporte 365-370 nanômetro (nm), com irradiância de 3 mW/cm2, o que corresponde a uma dose de energia 5,4 J/cm2. Nestes valores, o CXL ocorre nos primeiros 310 μm do estroma anterior da córnea. Após o tratamento, pomada antibiótica é aplicada até a reepitelização; mais atualmente, faz-se uso de uma lente de contato terapêutica, em média por 3 a 5 dias e uso adjunto de colírio corticoide e antibiótico profilático. É importante ressaltar que a calibragem da fonte de irradiação antes da realização do procedimento é essencial para garantir que a potência máxima não ultrapasse 3 mW/cm², evitando, assim, toxicidade aos tecidos oculares.

O CXL do colágeno da córnea com irradiação UV-A utilizando-se a riboflavina causa uma fotopolimerização por geração de radicais livres. A riboflavina no procedimento é necessária para absorver a luz UV-A e proteger as estruturas mais profundas oculares dos perigos potenciais da formação de radicais livres. Ao mesmo tempo, a riboflavina deve permitir a formação de radicais livres para indução do CXL no estroma anterior. Ou seja, a riboflavina deve ser bem balanceada na sua quantidade, de maneira a proporcionar adequada blindagem, mas também, gerar radicais livres suficientes para induzir a formação de CXL das fibras de colágeno.

A riboflavina (vitamina B2) é a precursora de coenzimas que agem no metabolismo das proteínas, gorduras e hidratos de carbono. É um componente essencial das células vivas e não é citotóxica. Age como fotomediadora aumentando de 30% a 95% a absorção da luz de UV-A no estroma corneal. Em córneas mais finas tem se preconizado o uso da riboflavina hipo-osmolar, com o objetivo de aumentar a espessura da córnea por indução de edema.75 A riboflavina 0.1% iso-osmolar é preparada diluindo-se a riboflavina-5-fosfato a 0.5% (10 mg) em Dextran T-500 a 20% (10 ml). A riboflavina hipo-osmolar é preparada diluindo-se a riboflavina-5fosfato a 0.5% (10 mg) em soro fisiológico (10 ml de

de Freitas & Schor. Cross-linking para tratamento do ceratocone progressivo.

cloreto de sódio a 0.9%). Ambas as soluções devem ser protegidas da luz e utilizadas em até duas horas.

Outras técnicas são descritas na literatura, com variação da irradiância e tempo de irradiação, como por exemplo, aplicação de 7 mW/cm2 por 15 minutos em comparação a técnica padrão de 3 mW/cm2 por 30 minutos (76), sem remoção do epitélio corneal (CXL transepitelial)77, com remoção a álcool ou a laser do epitélio, com criação de “bolsa” intraestromal para colocação da riboflavina78. A associação do CXL a outras técnicas como ceratectomia fotorrefrativa (PRK), ceratomileuse intra-estromal a laser (LASIK) e implante de anel intraestromal (ISCR) também tem sido descrita na literatura, com resultados variáveis.

RESULTADOS CLÍNICOS A microscopia confocal revela que pacientes submetidos ao CXL tem sinais de tratamento em uma profundidade média de 320 μm, variando de 270–350 μm. Imediatamente após o tratamento ocorre a rarefação de ceratócitos e nervos no estroma anterior e intermediário da córnea, correspondendo à área de tratamento. Também são observados sinais de edema estromal em até três meses pós-tratamento. Também são observados sinais de edema estromal, até 3 meses após o tratamento, que não repercute em mudanças significativas da paquimetria. Com três meses, nota-se o reaparecimento gradual dos ceratócitose e nervos no local do tratamento e o edema passa a desaparecer.79 Em média de 6 meses, o estroma apresenta-se normal após o tratamento com CXL.80 A microscopia confocal também ajuda a comprovar que áreas com epitélio preservado não apresentam CXL na mesma intensidade de áreas onde o epitélio foi retirado; ou seja, a eficácia do tratamento é menor se o epitélio for mantido intacto.81 Com a tomografia de coerência óptica do segmento anterior do olho é possível observar uma linha de demarcação que separa a área tratada da não-tratada.82 A espessura corneal diminui nos primeiros meses de pós-operatório, voltando aos valores iniciais e não se alterando a longo prazo.83 Estudos de citologia de impressão mostraram que a técnica é segura para a superfície ocular.84 A maioria dos estudos revela uma alta porcentagem de sucesso quanto ao objetivo principal de estacionar a progressão do ceratocone (Tabela 2). Alguns pacientes apresentaram diminuição das curvaturas (diminuição do K médio, do K máximo e do índice I-S, inferiorsuperior) e melhora na AV corrigida e não-corrigida, inclusive com diminuição dos valores refracionais e de equivalente esférico. Os achados topográficos e tomográficos também mostram melhoras na maioria dos estudos.74,85-93 É também descrita melhora na aberrometria pós-CXL87,94, porém nosso grupo e experiência

Tabela 2: Estudos com acompanhamento longo e maior número de casos de ceratocone e ectasia tratados com cross-linking publicados nos últimos 5 anos.143 Número de Olhos

Acompanhamento Valor de K AVCC Erro refracional (em meses) (média em D) (em linhas) (média em D) Média e Variação (regressão PO) (regressão PO) (regressão PO)

Referência

23

23.2 3 a 48

2.0

Média de 1.3

1.1

Wollensak G. et al, 200374

241

26.7 12 a 72

2.3

≥1

1.2

Raiskup-Wolf F. et al, 200886

153

27.9 12 a 90

2.2

≥1

1.3

Hoyer A. et al, 2009144

28

24 (-)

1.1

Média de 2.0

0.8

Vinciguerra P. et al, 200994

102

12 (-)

0.9

ENS

1.4

Grewal DS et al, 200988

44

52.4 48 a 60

2.0

Média de 1.9

2.1

Caparossi A. et al, 201089

10

Até 25 (-)

1.9

Média de 3

1.2

Hafezi F. et al, 200785

13

12 (-)

ENS

≥1

1.4

Vinciguerra P. et al,, 201090

K:ceratometria; D:dioptrias; PO:pós-operatório; AVCC:acuidade visual com correção; ENS: estatisticamente não significante; ≥ : maior ou igual Adaptado de Gkika M, Labiris G, Kozobolis V. Corneal collagen cross-linking using riboflavin and ultraviolet-A irradiation: a review of clinical and experimental studies. Int Ophthalmol. 2011 Aug;31(4):309-19).143

pessoal não validam tais critérios de modo a indicar o CXL em pacientes sem progressão comprovada da doença. Tais índices tem alta variabilidade e pouca precisão.

COMPLICAÇÕES E REAÇÕES ADVERSAS As complicações e reações adversas do tratamento do ceratocone com CXL são consideradas pouco freqüentes, chegando a 3,5%.91 Se o procedimento for realizado sem intercorrências e com algumas precauções95, a literatura concorda que o dano endotelial é ausente ou mínimo. Não há alterações na transparência do cristalino96, nem à retina, especialmente à mácula.

Mesmo assim, são publicados na literatura casos ou revisões que descrevem: 1.1. Infecção pós-operatória: tanto a retirada do epitélio, quanto o uso de lente de contato terapêutica e corticosteróides são fatores predisponentes importantes para o desenvolvimento de ceratite microbiana. As infecções descritas na literatura envolvem bactéria, vírus, fungo e parasita. Em relação às infecções bacterianas, elas ocorrem, em média, nos primeiros cinco dias de pós-operatório, envolvendo Escherichia coli97, Staphylococcus epidermidis98, Pseudomonas aeruginosa99; há um caso de infecção polimicrobiana (Streptococcus salivarius, Streptococcus oralis, e Staphylococcus sp coagulase-negativa) em paciente que inadvertidamente retirou sua lente de contato terapêutica no dia seguinte da realização do CXL e “limpou-a” na boca, recolocando-a em seguida no olho.100 Quanto às ceratites virais, a herpética ocorre, em geral, após quatro ou cinco dias da realização do CXL, confirmando que a irradiação UV pode induzir à recorrência do herpes simples vírus101, mesmo em pacientes que não tenham história prévia da infecção.102-104. Infecção por Fusarium sp quatro semanas PAN-AMERICA

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após a realização do cross-linking foi descrita na literatura sem fator desencadeante aparente.105 Ceratite por Acanthamoeba spp ocorreu em paciente que, sem saber que estava com uma lente de contato terapêutica, lavou o olho várias vezes com água corrente de torneira, desenvolvendo a infecção cinco dias após o procedimento.106 1.2. Ceratite estéril: Ocorre na forma de edema e infiltrados cinza-esbranquiçados, às vezes com precipitados ceráticos (PKs), que podem evoluir para necrólise, afinamento e perfuração107-110, ou para cicatrizes estromais e comprometimento da visão.86,111,112 Em um dos estudos, de 117 pacientes que realizaram CXL para ceratocone, quatro desenvolveram ceratite estéril.112 Necrólise bilateral da córnea foi descrita em paciente com Síndrome de Down que teve os dois olhos tratados simultaneamente, por sua condição mental; a espessura mínima de 400 μm necessária para a realização do procedimento não foi respeitada, sendo cogitada como possível causa da complicação.113 A etiologia da ceratite estéril pósCXL é desconhecida, mas tem sido possivelmente atribuída a [1] ausência de ceratócitos, que ocorre com o procedimento79,114,115, [2] condições especificas de saúde, sistêmica e ocular, do paciente (por exemplo, dermatite atópica), [3] uso de colírios anti-inflamatórios não-esteroides, descritos na literatura como causadores de complicações corneais116,118, [4] uso de álcool para a remoção do epitélio, apesar de que estudos têm mostrado que não há diferenças entre remoção mecânica ou com álcool quanto a dano corneal na realização de PRK119, [5] reação de hipersensibilidade aos colírios usados no procedimento, em especial a riboflavina120,121, [6] reação de hipersensibilidade a toxinas de estafilococos (Figura 4)122 e [7] falha na execução da técnica, como aproximação excessiva da irradiação no olho, quantidade irradiada maior do que a preconizada, uso inadequado da riboflavina, dentre outros.

1.3. Ceratite Lamelar Difusa (DLK): foi descrito um caso de DLK em um paciente que desenvolveu ectasia pós-LASIK e foi tratado com CXL.123 1.4. Haze e opacidade de córnea: de todas as complicações e efeitos adversos do CXL descritos na literatura, o haze e a opacidade de córnea são os mais freqüentes. Um estudo refere que de 163 olhos tratados com ceratocone grau I-III, aproximadamente 9% desenvolveram haze clinicamente significativo em um ano de pós-operatório.124 O haze pós-CXL pode ser classificado como transitório, ocorrendo nas fases iniciais de pós-operatório e com resolução por volta do terceiro mês ou permanente, sendo observado em até um ano de pós-operatório.114,125,126.

A história natural do haze corneano pós-CXL é des10

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crita como mais intensa no primeiro mês, estacionária por volta do terceiro mês, diminuindo significativamente entre três e doze meses.127 Fatores de risco para haze seriam pacientes com ceratocone avançado, córneas mais afinadas, curvaturas mais altas, idade mais avançada e presença de padrão reticular em microestrias estromais, observadas por microscopia confocal.

Foram descritos casos de cicatrizes estromais profundas em ceratocones de grau leve, de aparecimento tardio (três meses) após a realização do CXL, que, se em intensidade severa, induziram astigmatismo significativo.128 É importante também citar que foi observada uma linha de demarcação no estroma corneal, indicando a zona de transição entre a área do estroma anterior (em geral nos 300 μm iniciais), que sofreu cross-linking e a área posterior não tratada.129 A linha de demarcação é detectável precocemente no exame biomicroscópico de lâmpada de fenda, em até duas semanas após o tratamento e é melhor observada com tomografia óptica de segmento anterior do olho82.

1.5. Alteração da medida da pressão intraocular (Pio): alguns estudos têm referido que o CXL não altera a longo prazo as medidas da pressão intraocular (Pio), nem os parâmetros biomecânicos como histerese e fator de resistência corneal.130 Por outro lado, outros estudos referem aumento de valores da Pio atribuído a maior rigidez corneal que o procedimento causa131 ou mesmo aumento transitório da Pio sem alteração nos parâmetros biomecânicos, sugerindo outra causa para essa mudança que não a maior rigidez tecidual.132 Interessantemente, um estudo comprovou que após a realização do CXL, a medida da Pio fica imprecisa, sendo algumas vezes superestimada e em outras, preocupantemente, subestimada.133 É importante sempre ressaltar que a medida da Pio pode variar com a espessura da córnea e também com o método utilizado (pe,; tonometria de aplanação de Goldman e tonometria dinâmica de contorno – Pascal)134 e que os parâmetros fundoscópicos devem ser monitorizados para um bom diagnóstico de dano glaucomatoso, na imprecisão da medida da Pio. 1.6. Perda de células endoteliais: estudo comprova que, se o CXL for realizado em córneas mais finas com menos de 400 μm, sem o epitélio e antes da instilação de riboflavina, a perda endotelial pode ser significativa.71

PERSPECTIVAS FUTURAS A indução de ligações químicas que permitem aumentar a rigidez da córnea e diminuir o afinamento secundário a digestão enzimática tem sido definida como “cirurgia química” da córnea. Desenvolvimentos tecnológicos patenteados propõem o uso desse processo como “cola” em incisões, ou como “catalizador” após modificações estruturais induzidas em ortoceratologia. Tais efeitos não tem eficácia comprovada; porém, o poder do CXL parece ser menor do que o preconizado, havendo mesmo na indicação clássica, falhas de tratamento, com a progressão das ectasias.

Novas preparações de moléculas tradicionais tem sido experimentados, como as preparações anfifílicas (com comportamento hidro e lipofilico combinados) genuínas (riboflavina anfifílica) ou com poder dito anfifílico (como o cloreto de benzalcônio, que lesa a barreira epitelial e permite a entrada de preparações lipofílicas de riboflavina). Novas moléculas são descritas como possuindo o mesmo poder “estruturante”, por exemplo o decorin, que atua interligando e “bloqueando” cadeias de colágeno sem a necessidade de reação oxidativa.

A integração multidisciplinar entre oftalmologistas, bioquímicos, químicos, ópticos e engenheiros permite projetar tratamentos específicos e precisos, que atuam no microcosmo das ligações químicas, e tem como conseqüência, modificações morfológicas, ópticas e cognitivas na visão do ser humano.

de Freitas & Schor. Cross-linking para tratamento do ceratocone progressivo.

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Herpetic keratitis with iritis after corneal crosslinking with riboflavin and ultraviolet A for keratoconus. J Cataract Refract Surg 2007 Nov;33(11):1982-4.

104. Coskunseven E, Jankov MR, 2nd, Hafezi F. Contralateral eye study of corneal collagen cross-linking with riboflavin and UVA irradiation in patients with keratoconus. J Refract Surg 2009 Apr;25(4):371-6.

105. Garcia-Delpech S, Diaz-Llopis M, Udaondo P, Salom D. Fusarium keratitis 3 weeks after healed corneal cross-linking. J Refract Surg 2010 Dec;26(12):994-5.

106. Rama P, Di Matteo F, Matuska S, Paganoni G, Spinelli A. Acanthamoeba keratitis with perforation after corneal crosslinking and bandage contact lens use. J Cataract Refract Surg 2009 Apr;35(4):788-91.

107. Labiris G, Kaloghianni E, Koukoula S, Zissimopoulos A, Kozobolis VP. Corneal melting after collagen crosslinking for keratoconus: a case report. J Med Case Reports 2011;5:152.

108. Gokhale NS, Vemuganti GK. Diclofenac-induced acute corneal melt after collagen crosslinking for keratoconus. Cornea 2010 Jan;29(1):117-9.

109. Angunawela RI, Arnalich-Montiel F, Allan BD. Peripheral sterile corneal infiltrates and melting after collagen crosslinking for keratoconus. J Cataract Refract Surg 2009 Mar;35(3):606-7.

110. Mangioris GF, Papadopoulou DN, Balidis MO, Poulas JL, Papadopoulos NT, Seiler T. Corneal infiltrates

after corneal collagen crosslinking. J Refract Surg 2010 Aug;26(8):609-11.

111. Rodriguez-Ausin P, Gutierrez-Ortega R, AranceGil A, Romero-Jimenez M, Fuentes-Paez G. Keratopathy after cross-linking for keratoconus. Cornea 2011 Sep;30(9):1051-3.

112. Koppen C, Vryghem JC, Gobin L, Tassignon MJ. Keratitis and corneal scarring after UVA/riboflavin cross-linking for keratoconus. J Refract Surg 2009 Sep;25(9):S819-23.

113. Faschinger C, Kleinert R, Wedrich A. [Corneal melting in both eyes after simultaneous corneal crosslinking in a patient with keratoconus and Down syndrome. Ophthalmologe 2010 Oct;107(10):951-2, 4-5.

114. Salomao MQ, Chaurasia SS, Sinha-Roy A, Ambrosio R, Jr., Esposito A, Sepulveda R, et al. Corneal wound healing after ultraviolet-A/riboflavin collagen cross-linking: a rabbit study. J Refract Surg 2011 Jun;27(6):401-7.

115. Kymionis GD, Diakonis VF, Kalyvianaki M, Portaliou D, Siganos C, Kozobolis VP, et al. One-year follow-up of corneal confocal microscopy after corneal cross-linking in patients with post laser in situ keratosmileusis ectasia and keratoconus.

Am J Ophthalmol 2009 May;147(5):774-8, 8 e1.

116. Congdon NG, Schein OD, von Kulajta P, Lubomski LH, Gilbert D, Katz J. Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs. J Cataract Refract Surg 2001 Apr;27(4):622-31.

117. Feiz V, Oberg TJ, Kurz CJ, Mamalis N, Moshirfar M. Nepafenacassociated bilateral corneal melt after photorefractive keratectomy. Cornea 2009 Sep;28(8):948-50.

118. Ornek K, Yalcindag FN, Ozdemir O. Corneal melting associated with a fixed-dose combination of diclofenac 0.1% plus tobramycin 0.3% following cataract surgery. J Cataract Refract Surg 2008 Aug;34(8):1417.

119. de Medeiros FW, Mohan RR, Suto C, Sinha S, Bonilha VL, Chaurasia

SS, et al. Haze development after photorefractive keratectomy: mechanical vs ethanol epithelial removal in rabbits. J Refract Surg 2008 Nov;24(9):923-7.

120. Ou LS, Kuo ML, Huang JL. Anaphylaxis to riboflavin (vitamin B2). Ann Allergy Asthma Immunol 2001 Nov;87(5):430-3.

121. Masuda K, Katoh N, Mizutani H, Kishimoto S. Anaphylaxis to vitamin B2 added to an energy drink.

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122. Jayamanne DG, Dayan M, Jenkins D, Porter R. The role of staphylococcal superantigens in the pathogenesis of marginal keratitis.

Eye (Lond) 1997;11 ( Pt 5):618-21.

123. Kymionis GD, Bouzoukis DI, Diakonis VF, Portaliou DM, Pallikaris AI, Yoo SH. Diffuse lamellar keratitis after corneal crosslinking in a patient with post-laser in situ keratomileusis corneal ectasia. J Cataract Refract Surg 2007 Dec;33(12):2135-7.

124. Herrmann CI, Hammer T, Duncker GI. [Hazeformation (corneal scarring) after cross-linking therapy in keratoconus. Ophthalmologe 2008 May;105(5):485-7.

125. Strmenova E, Vlkova E, Hlinomazova Z, Pirnerova L, Dvorakova D, Goutaib M, et al. [Corneal crosslinking--modern method of keratoconus treatment].

Cesk Slov Oftalmol 2010 Dec;66(6):248-53.

126. Raiskup F, Hoyer A, Spoerl E. Permanent corneal haze after riboflavin-UVAinduced cross-linking in keratoconus. J Refract Surg 2009 Sep;25(9):S824-8.

127. Greenstein SA, Fry KL, Bhatt J, Hersh PS. Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and biomicroscopic analysis. J Cataract Refract Surg 2010 Dec;36(12):2105-14.

128. Lim LS, Beuerman R, Lim L, Tan DT. Late-onset deep stromal scarring after riboflavin-UV-A corneal collagen cross-linking for mild keratoconus. Arch Ophthalmol 2011 Mar;129(3):360-2.

129. Seiler T, Hafezi F. Corneal cross-linkinginduced stromal demarcation line. Cornea 2006 Oct;25(9):1057-9.

130. Sedaghat M, Naderi M, Zarei-Ghanavati M. Biomechanical parameters of the cornea after collagen crosslinking measured by waveform analysis. J Cataract Refract Surg 2010 Oct;36(10):1728-31.

131. Kymionis GD, Grentzelos MA, Kounis GA, Portaliou DM, Detorakis ET, Magarakis M, et al. Intraocular pressure measurements after corneal collagen crosslinking with riboflavin and ultraviolet A in eyes with keratoconus. J Cataract Refract Surg 2010 Oct;36(10):1724-7.

132. Goldich Y, Barkana Y, Morad Y, Hartstein M, Avni I, Zadok D. Can we measure corneal biomechanical changes after collagen cross-linking in eyes with keratoconus?--a pilot study. Cornea 2009 Jun;28(5):498-502.

133. Romppainen T, Bachmann LM, Kaufmann C, Kniestedt C, Mrochen M, Thiel MA. Effect of riboflavin-UVA-induced collagen cross-linking on intraocular pressure measurement.

Invest Ophthalmol Vis Sci 2007 Dec;48(12):5494-8.

134. Park SJ, Ang GS, Nicholas S, Wells AP. The Effect of Thin, Thick, and Normal Corneas on Goldmann Intraocular Pressure Measurements and Correction Formulae in Individual Eyes.

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tion methods compared with a neural network approach.

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139. Schwiegerling J, Greivenkamp JE. Keratoconus detection based on videokeratoscopic height data. Optom Vis Sci 1996 Dec;73(12):721-8.

140. Rabinowitz YS, Rasheed K. KISA% index: a quantitative videokeratography algorithm embodying minimal topographic criteria for diagnosing keratoconus.

J Cataract Refract Surg 1999 Oct;25(10):1327-35.

141. McMahon TT, SzczotkaFlynn L, Barr JT, Anderson RJ, Slaughter ME, Lass JH, et al. A new method for grading the severity of keratoconus: the Keratoconus Severity Score (KSS). Cornea [2006 Aug;25(7):794-800.

142. Mahmoud AM, Roberts CJ, Lembach RG, Twa MD, Herderick EE, McMahon TT. CLMI: the cone location and magnitude index. Cornea 2008 May;27(4):480-7.

143. Gkika M, Labiris G, Kozobolis V. Corneal collagen cross-linking using riboflavin and ultraviolet-A irradiation: a review of clinical and experimental studies. Int Ophthalmol 2011 Aug;31(4):309-19.

144. Hoyer A, Raiskup-Wolf F, Sporl E, Pillunat LE. [Collagen cross-linking with riboflavin and UVA light in keratoconus. Results from Dresden. Ophthalmologe 2009 Feb;106(2):133-40.

135. Rabinowitz YS, McDonnell PJ. Computer-assisted corneal topography in keratoconus. Refract Corneal Surg 1989 Nov-Dec;5(6):400-8.

136. Maeda N, Klyce SD, Smolek MK, Thompson HW. Automated keratoconus screening with corneal topography analysis. Invest Ophthalmol Vis Sci 1994 May;35(6):2749-57.

137. Maeda N, Klyce SD, Smolek MK. Comparison of methods for detecting keratoconus using videokeratography. Arch Ophthalmol 1995 Jul;113(7):870-4.

138. Smolek MK, Klyce SD. Current keratoconus detec-

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CLINICAL SCIENCES / Vis. Pan-Am. 2012;11(1):14-16

Efficacy of one drop of 2% pilocarpine to reverse the intraocular pressure peak at 6:00 a.m. in early glaucoma From Department of Ophthalmology, Federal University of Minas Gerais, Brazil: Sebastião Cronemberger, M.D.1, Nassim Calixto, M.D.1, Marcelo Nacif Moraes, M.D.2, Iuri David Castro, M.D.2, Patrícia Cordeiro Lana, M.D.2, Artur Furst Loredo,3 1.

Full Professor of Ophthalmology, 2. Medical Doctors, 3. Undergraduate student

Funding: This study was supported by an educational grant from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasil through the Programa Institucional de Bolsas de Iniciação Científica (PIBIC).3 Proprietary and/or financial interest: None

Sebastião Cronemberger, MD Address: Rua Martim de Carvalho, 410/501 Santo Agostinho 30190-090 Belo Horizonte, MG, Brazil Phone: 5531-33356218/Fax: 5531-32411791 Email: secronem@gmail.com Date of receiving: 12-02-2012 / Date of approval: 22-02-2012

ABSTRACT

INTRODUCTION

Purpose: To assess the efficacy of one drop of 2% pilocarpine (2% Pi) at night to reverse the intraocular pressure (IOP) peak at 6:00 a.m. in the daily curve of intraocular pressure (DCPo) of pre-perimetric open-angle glaucoma.

Primary open-angle glaucoma (POAG) is one of the main causes of irreversible blindness in the world.1 It is mostly asymptomatic, discovered unexpectedly in routine intraocular pressure (IOP) measurements and/ or in optic disc or visual field exams.¹,² There is much evidence that an elevated IOP is the principal risk factor for optic nerve damage that results in visual field loss.²

Methods: We retrospectively analyzed the charts of patients with early glaucoma. We compared the IOP values at 6:00 a.m. in the same eye of two DCPos. In the first DCPo, the patients were without medication, and in the second they were using one drop of 2% Pi between 10:00 and 10:30 p.m. for at least six months.

Each DCPo had five IOP measurements taken at 9:00 a.m., 12:00, 6:00 and 10:00 p.m. (Goldmann applanation tonometer) and in the morning of the following day at 06:00 a.m. (Perkins tonometer) in a supine position in bed and in darkness before the patient had stood up.

The pre-perimetric glaucoma patients, without medication, presented an IOP peak at 6:00 a.m. in the DCPo. This peak represents a difference ≥7 mmHg between the IOP value at 6:00 a.m. and that lesser IOP at any other time in the DCPo. An IOP peak reversion at 6:00 a.m. under 2% Pi occurred when the difference between the IOP at 6:00 a.m. and the lesser IOP was ≤5 mmHg in the DCPo. Patients with secondary glaucoma were excluded. We set the significance level at 5% (P<0.05).

Results: Sixty-one eyes of 35 patients with an average age of 56.1 years were included. Under 2% Pi the IOP peak at 6:00 a.m. reversed significantly (X2=7.96; P=0.005) in 44 (72.1%) eyes. The mean IOP dropped from 22.1±2.3 mmHg in the DCPo without medication to 16.8±2.7 mmHg in the DCPo under 2% Pi (t=7.9; P<0.001).

Conclusion: One drop of 2% Pi at night is effective to reverse the IOP peak at 6:00 a.m. in pre-perimetric glaucoma.

Key words: Glaucoma, Intraocular pressure, pilocarpine, efficacy.

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Corresponding author:

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The Advanced Glaucoma Intervention Study (AGIS) demonstrated that long-term IOP fluctuation is associated with a progression of visual field loss in patients with low mean IOPs, but not in patients with high mean IOPs.² The daily intraocular pressure curve (DCPo) is considered the most reliable method for the evaluation of IOP fluctuations in early glaucoma diagnosis, as well as in its treatment.3 Pilocarpine was one of the first drugs to be used in the treatment of POAG.4 It is a direct muscarinic cholinergic drug which increases the drainage of aqueous humor through Schlemm´s canal. It is normally used three to four times a day. After the introduction of new drugs, the use of pilocarpine decreased due to its side effects (miosis, ciliary muscle spasm, myopia, cataract, etc), although it is still one of the cheapest drugs available for the treatment of POAG.5 Studies demonstrate that aqueous humor production follows a circadian rhythm.6-8 In normal patients, the aqueous humor production decreases about 50% at night.9,10 As pilocarpine increases aqueous humor drainage, it is theoretically the most indicated drug for night use in order to reverse the IOP peak at 6:00 a.m. in preperimetric glaucoma patients.

This study aims to assess the efficacy of one drop of 2% pilocarpine (2% Pi) at night to reverse the IOP peak at 6:00 a.m. in the DCPo of glaucoma patients without visual field loss (pre-perimetric glaucoma).

Cronemberger S et al. Efficacy of one drop of 2% pilocarpine to reverse the intraocular pressure peak.

METHODS We retrospectively analyzed patients‘ charts from the Glaucoma Service of the São Geraldo Eye Hospital. The study was approved by the Ethics Committee of the Federal University of Minas Gerais, and adhered to the principles enshrined in the Declaration of Helsinki.

Informed consent was obtained from all patients. We registered the patients’ demographic data.

We compared two DCPos from the same patients.

In the first DCPo, the patients were without medication, and in the second the patients were using one drop of 2% Pi between 10:00 and 10:30 p.m. for at least six months.

The use of only one drop of 2% Pi between 10:00 and 10:30 p.m. was an endeavor to reverse the IOP peak at 6:00 a.m. that these patients presented in the absence of medication. This IOP peak at 6:00 a.m. represents a difference equal to or greater than 7 mmHg between the IOP measurement at 6:00 a.m. and the lesser IOP measurement taken at 9:00 a.m. or 12:00, or 6:00 or 10:00 p.m. in the DCPo. An IOP peak at 6:00 a.m. under 2% Pi was reversed when the difference between the IOP at 6:00 a.m. and the lesser IOP measurement in the DCPo was ≤5 mmHg which is the normal diurnal IOP fluctuation.11-14 Each DCPo consisted of five IOP measurements taken at 9:00 a.m., 12:00, 6:00 and 10:00 p.m. (Goldmann applanation tonometer) and in the morning of the following day at 06:00 a.m. (Perkins tonometer) in a supine position in bed and in darkness before the patient had stood up. The Perkins tonometer is essentially a portable Goldmann applanation tonometer that can be used with the patient in either upright or supine position.13 We included open-angle glaucoma patients with a normal visual field (pre-perimetric glaucoma) done with an Octopus 1-2-3 perimeter that, without medication, presented an IOP peak at 6:00 a.m. in the DCPo. We have only selected eyes with pre-perimetric glaucoma due to its initial glaucoma stage, which can possibly be treated effectively with a minimum dose of an antiglaucomatous drug.

Besides the normal visual field, the diagnostic criteria for pre-perimetric glaucoma were based on at least two of three following findings: 1. IOP values from 19 to 25 mmHg in isolated tonometry; 2. vertical cup disc ratio ≥0.7 with localized optic disc notching and thinning; 3. asymmetry of the cup disc ratio ≥0.3.

Due to the IOP peak at 6:00 a.m. the patients also presented an abnormal DCPo. This was demonstrated by an abnormal mean IOP (IOPm) and/or an abnormal standard deviation (SD) when compared with the normal IOPm and SD from healthy age-matched individuals previously studied in our Service by one of the authors15 (Table 1).

Table 1. Superior normal limits of mean intraocular pressure (IOPm + 2 SD) and of standard deviation (SD + 2 SD) from the DCPo of normal eyes previously studied by Calixto15 Age group (years) 15 to 25 26 to 35 36 to 45 46 to 58

n 24 22 20 20

IOPm

SD 2.28 2.28 2.63 2.22

14.62 15.93 16.66 16.92

DCPo, daily curve of intraocular pressure; IOPm, mean intraocular pressure; SD, standard deviation; n, number of eyes;

Table 2. Comparative statistical analysis between the IOP peak at 6:00 a.m. without medication and after using 2% pilocarpine in eyes with pre-perimetric glaucoma Eyes IOP peak at 6:00 a.m.

IOPm at 6:00 a.m.

Without medication

Under 2% Pi

Statistical test

P-value

N=61 (100%)

N=17 (27.9%)

X2=7.96

0.005

22.1±2.3 mmHg

16.8±2.7 mmHg

t=7.9

<0.001

IOP, intraocular pressure; IOPm, mean intraocular pressure; X2, chi-square; t, paired t test; P, probability; Pi, pilocarpine.

Patients using 2% Pi more than once a day or associated with any other antiglaucomatous drug were excluded. We also excluded patients with secondary glaucoma.

For statistical analysis, we considered both eyes of the same patient that met the inclusion criteria because each eye could have a different behavior in the two DCPos. We used the paired t test to compare the IOP values at 6:00 a.m. in the same eye in two DCPos: the first one without medication and the second after using 2% Pi for at least six months. The 17.0 SPSS was used for statistical analysis. The level of significance was set at 5% (P-value<0.05).

RESULTS Sixty-one eyes of 35 patients (27 women and 8 men) were included. The patients’ average age was 56.1 years. Seven (20%) patients were white; 21 (60%) were feodermic (Brazilian mulattos) and seven (20%) were black. Nine eyes were excluded for not presenting an IOP peak at 6:00 a.m. in the DCPo without medication. All sixty-one eyes presented an IOP peak at 6:00 a.m. without medication and a normal visual field. After using 2% Pi between 10:00 and 10:30 p.m., the IOP peak at 6:00 a.m. was reversed in 44 (72.1%) eyes with a statistically significant difference (X2=7.96; P=0.005). In 17 (27.9%) eyes, the IOP peak at 6:00 a.m. was not reversed.

The IOPm at 6:00 a.m. was 22.1±2.3 mmHg in the first DCPo without medication. This IOPm at 6:00 a.m. dropped to 16.8±2.7 mmHg in the DCPo under 2% Pi with a statistically significant difference (t=7.9; P<0.001) (Table 2). Therefore, on average, the IOP peak at 6:00 a.m. was reduced 5.3 mmHg.

DISCUSSION It is widely recognized that the IOP varies throughout twenty-four hours.16,17 The IOP reduction is the only goal in the treatment of glaucoma.2 From the best of our knowledge, this study is the first to evaluate the efficacy of one drop of 2% Pi used between 10:00 and 10:30 p.m. to reverse the IOP peak at 6:00 a.m. in the DCPo. After using 2% Pi, a high percentage (72.1%) of eyes had a reversion of the IOP peak at 6:00 a.m. There was a statistically significant reduction in the IOPm (t=7.9; P<0.001). Therefore, in agreement with Sirbat, our results demonstrate that, despite well-known adverse effects, pilocarpine remains a useful medication.5 PAN-AMERICA

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CLINICAL SCIENCES / Vis. Pan-Am. 2012;11(1):14-16

In this paper, 2% Pi was useful to reverse the IOP peak at 6:00 a.m. in a high percentage of eyes. As a consequence of the IOP peak reversion at 6:00 a.m. the 24-hour IOP control was obtained in those eyes since no IOPs changes occurred at 9:00 a.m. and at 12:00, 6:00 and 10:00 p.m.. On the other hand, in some eyes (27.9%), as happens with other antiglaucomatous drugs, 2% Pi was unable to reverse the IOP peak at 6:00 a.m. (Table 2).

The findings of this paper were not comparable with prior studies because we did not find any similar study in literature.

One question that may arise is why one drop of 2% Pi at night was chosen to reverse the IOP peak at 6:00 a.m. The principal answer is the fact that the patients included in this paper only presented an IOP peak at 6:00 a.m. without medication in the DCPo. We have chosen one drop of 2% Pi to reverse the IOP peak at 6:00 a.m. instead of a selective or non-selective beta-blocker, a α2-agonist, a topical carbonic anhydrase inhibitor or a prostaglandin analog for the following reasons: 1. Two percent Pi is the only topical antiglaucomatous drug that truly reduces the IOP by increasing the outflow facility of aqueous humor via Schlemm’s canal. As the pathogenetic mechanism of glaucoma is an increased resistance to aqueous humor drainage via Schlemm’s canal, the instillation of one 2% Pi drop should be considered the most rational choice to reverse the IOP peak at 6:00 a.m.

2. A selective or non-selective beta-blocker, a α2agonist and a topical carbonic anhydrase inhibitor diminish the IOP by reducing the aqueous humor production.

As aqueous humor production is already physiologically reduced about 50% at night,9,10 these drugs should not be the most recommended only to reverse the IOP peak at 6:00 a.m. In addition, the reduction of aqueous humor production by the above-mentioned drugs could well cause a long-term reduction of the permeability of the external wall of the trabecular meshwork due to a reduced volume of aqueous humor in circulation.10 3. The prostaglandin analogs reduce the IOP by increasing the aqueous humor outflow through the uveoscleral via.18 The patients of this study only had an IOP peak at 6:00 a.m. and no elevated IOP during the day nor visual field loss (pre-perimetric glaucoma). Therefore, the prostaglandin analogs would not be so indicated. In general, these drugs are remarkably efficient in reducing the IOP and can be prescribed for patients with an elevated IOP and advanced glaucoma. Furthermore, one drop of prostaglandin analogs is very expensive in comparison with one drop of 2% Pi, which is one of the cheapest antiglaucomatous drugs; 4. It is well known that miosis, ciliary muscle spasm and myopia are common side effects caused by pilocarpine when it is used three to four times a day.

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However, when pilocarpine is instilled only once at night in the effort to reverse the IOP peak at 6:00 a.m., those side effects are not present. In some patients, the presence of a light miosis might occur the following day; however, this does not cause any problem due to the patients’ age in this study. In this series, no patients complained the following day after using one drop of 2% Pi between 10:00 and 10:30 p.m.

Despite the limitations placed by the small sample, this paper demonstrates the benefit of using one drop of 2% Pi between 10:00 and 10:30 p.m. to reverse the IOP peak at 6:00 a.m. It reduces the IOP peak at 6:00 a.m. in the majority of eyes from pre-perimetric glaucoma patients. Consequently, the IOP fluctuation reduction might prevent the risk of glaucoma progression.16,17

CONCLUSION One drop of 2% Pi at night is highly likely to be effective to reverse the IOP peak at 6:00 a.m. in pre-perimetric glaucoma patients.

REFERENCES 1. Cronemberger S, Lourenço LFS, Silva LC, Calixto N, Pires MC. Prognosis of glaucoma in relation to blindness at a university hospital. Arq Bras Oftalmol 72:199-204, 2009.

2. The Advanced Glaucoma Intervention Study (AGIS). 7. The relationship between control of intraocular pressure and visual field deterioration.

The AGIS Investigators.

Am J Ophthalmol 130:429440, 2000.

3. Cronemberger S, Silva ACL, Calixto N. Importance of the intraocular pressure taken at 6:00 a.m. in bed and in darkness in suspected and glaucomatous patients. Arq Bras Oftalmol 73:346-349, 2010.

4. Lee DA, Higginbotham EJ. Glaucoma and its treatment: a review. Am J Heath Syst Pharm 62:691699, 2005.

5. Sirbat D. What should we think? Should diamox and pilocarpine continue to be prescribed? J Fr Ophtalmol 30:72-73, 2007.

6. Brubaker RF. Clinical measurements of aqueous dynamics: implications for addressing glaucoma.

In: Civan MM, ed. The eye´s aqueous humor, from secretion to glaucoma. New York: Academic Press, 1998:234 7. Sears J, Sears M. Circadian rithyms in aqueous humor formation. In: Civan MM, ed. The eye´s aqueous

humor, from secretion to glaucoma. New York: Academic Press, 1998:203.

8. Sit AJ, Nau CB, McLaren JW, Johnson DH, Hodge D. Circadian variation of aqueous dynamics in young healthy adults.

Invest Ophthalmol Vis Sci 49:1473-1479, 2008.

9. Liu JH. Circadian rhythm of intraocular pressure [Review]. J Glaucoma 7:141-147, 1998.

10. Becker B. Does hyposecretion of aqueous humor damage the trabecular meshwork? J Glaucoma 4:303-305, 1995.

11. Göbel K, Rüfer F, Erb C. Physiology of aqueous humor formation, diurnal fluctuation of intraocular pressure and its significance for glaucoma.

Klin Monbl Augenheilkd 228:104-108, 2011.

12. Duke-Elder S. The phasic variations in the ocular tension in primary glaucoma. Am J Ophthalmol 35:1-21, 1952.

13. American Academy of Ophthalmology. Basic and Clinical Science Course Section 10: Glaucoma . Singapore: American Academy of Ophthalmology, 2008.

14. Drance SM. The significance of the diurnal tension variations in normal and glaucomatous eyes. Arch Ophthalmol 64:494-501, 1960.

15. Calixto NS. Intraocular pressure, daily curve of intraocular pressure,

ocular rigidity, tonographic coefficients. Averages of normality in different age groups [in Portuguese].

[Thesis, Free Teaching].

Belo Horizonte: Universidade Federal de Minas Gerais, 1967.

16. Asrani S, Zeimer R, Wilensky J, Gieser D, Vitale S, Lindenmuth K. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma.

J Glaucoma 9:134-142, 2000.

17. Caprioli J, Coleman AL. Intraocular pressure fluctuation; a risk factor for visual field progression at low intraocular pressures in the advanced glaucoma intervention study.

Ophthalmology 115:11231129, 2008.

18. Santos HDM, Fernandes TAP, Souza CA, Cronemberger S, Calixto N. Efficacy of latanoprost versus travoprost assessed by daily intraocular pressure curve. [in Portuguese]. Arq Bras Oftalmol 72:13-17, 2009.

Silva JRH et al: Cirugía de catarata por microincisiones bimanuales y coaxiales

Cirugía de catarata por microincisiones bimanuales y coaxiales From Instituto Cubano de Oftalmología Ramón Pando Ferrer, La Habana, Cuba:

Autor correspondiente:

Juan Raúl Hernández Silva MD,PhD1, Meisy Ramos López MD,PhD2, Marcelino Río Torres Md,PhD2, Yanele Ruíz Rodríguez, M.D.3, Raúl Rúa Martínez, M.D.3.

Juan Raúl H. Silva,M.D. Instituto Cubano de Oftalmología Ramón Pando Ferrer, La Habana, Cuba Ave. 76 N0 3104, Mariana, La Habana, Cuba

1 . Doctor en Ciencias Médicas. Especialista de II grado en Oftalmología. Profesor Titular de Oftalmología. Investigador Auxiliar. Editor Jefe de la Revista Cubana de Oftalmología. Vicedirector de Docencia e Investigación del Centro Post grado 2 . Doctor en Ciencias Médicas.

3 . Especialista en Oftalmología.

Funding: None Proprietary and/or financial interest: None

Fecha de recepción: 04-01-2012 / Fecha de aprobación: 14-02-2012

ABSTRACT Purpose: To compare the results of the coaxial microincisions cataract surgery technique and bimanual microincisions in the Cuban Ophthalmology Institute “Ramón Pando Ferrer” from June 2009 to June 2011.

Methods: Sixty-eight patients were evaluated and diagnosed with senile or presenile cataract. Of these, 41 patients (eyes) were operated with coaxial microincisions technique and 27 patients (eyes) with bimanual microincisions technique. We determined age, hardness of the nucleus, best corrected visual acuity and uncorrected preoperative and postoperative, mean induced astigmatism, endothelial cell loss, effective phaco time and spherical equivalent. For statistical analysis, the nonparametric Mann Whitney test with a significance of 95% was used.

Results: Most patients were older than 50 years.

An ultrasound effective time of less than a minute was required to emulsify the cataractous lens, which had hardness classified as NO3 by the LOCS III for both techniques. The spherical equivalent behaved as preoperatively planned with a tendency to emmetropia. A significant correction of the keratometric and refractive cylinder was obtained. Fully corrected visual acuity was achieved with both techniques. The mean induced astigmatism was less than 0.5 diopters, with endothelial cell loss of less than 5% in both groups.

Conclusions: Both surgical techniques achieved satisfactory results demonstrating their effectiveness.

Keywords: Cataract surgery, microincisions, CoMICS, BiMICS.

microincisiones bimanuales en el Instituto Cubano de Oftalmología “Ramón Pando Ferrer” en el período de junio de 2009 a junio de 2011.

Métodos: 68 pacientes fueron evaluados y diagnosticados con catarata senil o presenil. De estos, 41 pacientes (ojos) se operaron con la técnica de microincisiones coaxiales y 27 pacientes (ojos) con la técnica de microincisiones bimanuales. Se determinó: edad, dureza del cristalino, agudeza visual mejor corregida y sin corrección preoperatoria y postoperatoria, media del astigmatismo inducido, pérdida celular endotelial, tiempo efectivo de ultrasonido y el equivalente esférico. Para el análisis estadístico, se utilizó el test no paramétrico U de Mann Whitney con una significación del 95%.

Resultados: La mayoría de los pacientes tenían edades superiores a 50 años. Se empleó un tiempo efectivo de ultrasonido menor a un minuto para emulsificar los cristalinos cataratosos, los cuales tenían una dureza clasificada como NO3 por el LOCS III para ambas técnicas. El equivalente esférico se comportó según lo planificado en el preoperatorio con tendencia a la emetropía. En el postoperatorio se obtuvo una corrección significativa del cilindro queratométrico y refractivo. Para ambas técnicas quirúrgicas mejoró en su totalidad la agudeza visual con corrección alcanzando su valor máximo. La media del astigmatismo inducido fue menor a 0,5 dioptrías, con una pérdida celular endotelial menor a un 5% en ambos grupos.

RESUMEN

Conclusiones: Para ambas técnicas quirúrgicas se lograron resultados satisfactorios que demuestran la efectividad de las mismas.

Objetivo: Comparar los resultados de la cirugía de catarata por las técnicas de microincisiones coaxiales y

Palabras clave: Cirugía de catarata, microincisiones, CoMICS, BiMICS. PAN-AMERICA

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INTRODUCCIÓN La microincisión ha representado un paso de avance en la cirugía de catarata a partir del año 2000. Muchos cirujanos se aventuraron en esta nueva tendencia como Steve Arshinoff (Biaxial phaco), Agarwal (Phakonit), Takayuki Akahoshi (Microcoaxial system), entre otros más. Estas técnicas se han ido perfeccionando a medida que se han mejorado los facoemulsificadores y el diseño de los lentes intraoculares. Esto se ha realizado con el objetivo de minimizar el uso de energía ultrasónica manteniendo la eficiencia en la emulsificación del núcleo cataratoso. Alcon, (TX, USA) introdujo su sistema torsional con la pieza de mano y punta Ozil®; AMO (CA, USA) produjo el sistema de pieza de mano WhiteStar® mejorando ambos la eficiencia de estos componentes, del followability, y decreciendo la cavitación con la consiguiente menor dispersión de energía. Otros sistemas como Aqualase® (Alcon Infiniti System, USA), Dodick LaserLysis (ARC Laser GmbH, Alemania), no ganaron popularidad para su utilización entre los cirujanos1,2.

Para lograr una reducción en el tamaño de la incisión se necesitó pasar de una punta de facoemulsificación convencional de 1 mm de diámetro para incisiones de 2,7 a 3,2 mm a una de menor diámetro para realizar las incisiones corneales de 1,8 mm para facoemulsifucación coaxial. Introducidas por el sistema Stellaris® (Bausch and Lomb, NY, USA), incisiones de 1,8 mm con punta y sleeve para facoemulsificación coaxial, y también con el sistema Infiniti® (Alcon), se diminuyó a incisiones de 2,2 mm para facoemulsificación coaxial. Los materiales de estas puntas han variado y así Optikon® (Roma, Italia) introdujo su punta de carbono para incisiones sub 2 mm en la microfacoemulsificación bimanual (BiMICS)1,2.

Esta reducción en el tamaño de la incisión permitió estabilidad en la herida quirúrgica evitando quemaduras que influían negativamente en la cicatrización. Disminuyó la inducción de astigmatismo postquirúrgico y las aberraciones corneales de alto orden. Estas quemaduras, que hay que evitar, están influidas positivamente con el uso de la modulación del poder del ultrasonido a través de los micropulsos, las variaciones del duty cycles y el rise time, para controlar la dispersión de la energía ultrasónica en la cámara anterior del ojo. Estos sistemas a su vez permiten una mejor planificación quirúrgica, disminuir la instrumentación y los resultados son mejores aún en núcleos de alta dureza1,2.

La microincisión coaxial (CoMICS) que se realiza a través de incisiones de 1,8 mm, muestra como ventaja una menor curva de aprendizaje (al estar el cirujano familiarizado con las técnicas coaxiales de facoemulsificación estándar), más estabilidad de la cámara anterior del ojo, seguridad en el uso de altos niveles de vacío y modulación de ultrasonido para generar menor energía ultrasónica3.

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La cirugía de catarata por BiMICS separa la irrigación de la aspiración con pequeñas incisiones de 1,6 a 1,8 mm en un ángulo de 90 grados, con el uso del chopper de irrigación. De esta forma se garantiza una mejor manipulación de los fragmentos nucleares en situaciones como el iris floppy, cataratas posvitrectomías en pacientes miopes altos (en los cuales la inestabilidad de la cámara anterior intraoperatoriamente se puede controlar mejor); así como la reducción de la turbulencia y la estabilidad de la misma, permitiendo remover de forma efectiva los restos corticales, disminuyendo el tiempo de emisión de ultrasonido y el astigmatismo inducido por la cirugía3.

La adecuada arquitectura de la herida en ambos casos, la disminución de la instrumentación y el correcto manejo preoperatorio de ambas técnicas garantizan una disminución de las complicaciones transquirúrgicas relacionadas con la rotura de la cápsula posterior así como de la endoftalmitis.

Nuestro propósito fue comparar los resultados de la cirugía de catarata por las técnicas de microincisiones coaxiales y microincisiones bimanuales efectuadas en el Instituto Cubano de Oftalmología “Ramón Pando Ferrer” en el período de junio de 2009 a junio de 2011.

MÉTODOS Se realizó un estudio prospectivo descriptivo de serie de casos, cuyo universo estuvo constituido por 41 pacientes (41 ojos) operados utilizando la técnica de microincisiones coaxiales y 27 pacientes (27 ojos) operados con la técnica de microincisiones bimanuales., En ambos casos fueron diagnosticados con catarata senil y presenil cuyos expedientes clínicos estaban completos, en el Instituto Cubano de Oftalmología “Ramón Pando Ferrer” en el período de junio del 2009 a junio del 2011.

El tamaño de muestra de los grupos a comparar estuvo determinado por la disponibilidad de los lentes intraoculares a utilizar en cada caso.

Se excluyó del estudio pacientes con enfermedades generales como conectivopatías y afecciones del sistema inmunológico, enfermedades de párpado (ectropión, entropión, ptosis palpebral), alteraciones de la lágrima (ojo seco), trastornos corneales (distrofias, degeneraciones, queratocono y leucoma), cataratas traumáticas, glaucoma, degeneraciones retinianas y maculares que se detectaran en el periodo preoperatorio y anomalías oculares congénitas (micro córnea, aniridia).

Para dar cumplimiento a los objetivos propuestos se consideraron las siguientes variables: dureza del cristalino (DC) según la clasificación LOCS III, mejor agudeza visual corregida (MAVC) y sin corregir (MAVSC) pre y postoperatorio, las cuales se midieron por la cartilla de Log MAR; la media del astigmatismo inducido (MAI), pérdida celular endotelial, la edad, el tiempo efectivo de ultrasonido (TEP) y el equivalente esférico (EE).

Silva JRH et al: Cirugía de catarata por microincisiones bimanuales y coaxiales

FiIGURA 1: Resultados de la cirugía de catarata por CoMICS y BiMICS. Variables Estudiadas

Técnica Quirúrgica CoMICS (n=41)

BiMICS (n=27)

Edad Promedio (años)

60±5

58±5

Tiempo Efectivo de Faco (seg)

45±10

56±9

Dureza del Cristalino (LOCS III)

ON3

ON3

Equivalente Esférico

-0.25 ± 0.5

0 ± 0.25

Astigmatismo Medio Inducido (D)

- 0.30 ± 0.5

-0.25 ± 0.25

MAVsC (Log MAR)

0,1

0,1

MAVC (Log MAR)

0,0

0,0

Pérdida celular endotelial (%)

4,8

4,5

* p>0.05 en la comparación de medias para todas las variables estudiadas (con excepción de la dureza del cristalino).

Fuente: Base de datos centro de microcirugía ocular. n=número de pacientes, TEP=Tiempo Efectivo de Facoemulsificación, DC=Dureza Nuclear, EE= Equivalente Esférico, MAI= Astigmatismo Medio Inducido, MAVSC= Mejor Agudeza Visual Sin Corrección, MAVC= Mejor Agudeza Visual Corregida.

A todos estos pacientes se les realizaron estudios de biomicroscopía en lámpara de hendidura, refracción, microscopia endotelial, test de sensibilidad al contraste y tonometría por aplanación antes de la cirugía de catarata, así como en el postoperatorio. Las evaluaciones postoperatorias se realizaron a las 24 horas, una semana, un mes y tres meses.

El cálculo del poder del lente intraocular que se implantó se realizó con el IOL Master (Carl Zeiss, Alemania) y Lenstar (Haag Streit, Switzerland). Para los casos operados por la técnica de CoMICS se implantó el LIO Miniflex, Mediphacos y para los operados por la técnica de BiMICS el LIO Acri.Smart 46 S, Acri.Tec. Se diagnosticó el eje más curvo corneal en el preoperatorio con el Pentacam (Oculus, Alemania) para personalizar el lugar de la incisión quirúrgica en córnea clara. El conteo celular endotelial se realizó con el microscopio endotelial SP 3000 de TOPCON (Topcon, Japón). Para la cirugía se utilizó la máquina de facoemulsificación Minimal stress de OPTIKON (Optikon, Italia) en todos los casos. Para ambas técnicas quirúrgicas se utilizaron los cuchilletes de BD BeaverTM XstarTM de 1,8mm 45º Bevel Up (BD, EE.UU.). Todos estos pacientes fueron operados por un mismo cirujano.

Para el análisis estadístico se utilizó el test no paramétrico U de Mann Whitney (por la n pequeña y desigual de los grupos a comparar) con un nivel de significación del 95%.

La investigación estuvo justificada desde el punto de vista ético, pues en todos los casos se contó con el consentimiento de los pacientes para la investigación acorde a la Declaración de Helsinki.

RESULTADOS Los pacientes presentaron un promedio de edad superior a los 60 años. Entre los diferentes indicadores que se tomaron para determinar los resultados se tuvo en cuenta el TEP menor a un minuto para ambas técni-

cas, aunque discretamente superior en el grupo BiMICS; el promedio de dureza del cristalino fue de ON3 en ambos grupos de estudio.

Después de realizar ambas cirugías, el promedio del equivalente esférico (EE) se redujo a -0,25 ± 0,5 y 0 ± 0,25 D respectivamente. Con relación al cilindro refractivo también evaluado por el estudio de refracción, se observó que la media del astigmatismo inducido (MAI) antes de la cirugía era de -1,0 ± 0,75 y de -1,0 ± 0,5 D para reducirse después de la cirugía a -0,30 ± 0,5 y -0,25 ± 0,25 D respectivamente.

Con relación a la mejor agudeza visual sin corregir (MAVSC) y la mejor agudeza visual corregida (MAVC), ambas aumentaron después de realizar los dos procedimientos quirúrgicos. La MAVSC varió de 1,0 a 0,1 después de realizar la CoMICS y de 0,9 a 0,1 después de la BiMICS. Por otro lado, la MAVC para ambas técnicas quirúrgicas reportó 0,0 de visión.

En la evaluación del conteo de células endoteliales obtenido por microscopía endotelial para determinar su pérdida después de ambos procedimientos, en el caso de los ojos operados por CoMICS, el promedio de pérdida celular fue de 4,8 % y en los ojos operados por BiMICS de 4,5 % (Figura1).

DISCUSIÓN En general, después de los 55 años el proceso de envejecimiento ocular produce una esclerosis del cristalino que dificulta la visión. En sus comienzos, la cirugía de catarata estaba encaminada solamente a sustituir el cristalino cataratoso. Con la introducción de la facoemulsificación, la tecnología se puso en función de la mejoría constante de la cirugía y sus resultados visuales, de ahí que en este momento se considere como una cirugía refractiva del cristalino. La calidad de la visión es otro puntal en el análisis de los resultados quirúrgicos. Actualmente los pacientes no se conforman solo con ganar en cantidad con relación a la visión. La vida social moderna y el desarrollo que avanza a pasos agigantados en la sociedad exigen además calidad en su visión. Estas exigencias hacen que el cirujano mejore constantemente su técnica quirúrgica y esté a la vanguardia en el desarrollo tecnológico.

Las nuevas máquinas de facoemulsificación tienen programas cada vez más avanzados para realizar la cirugía con el menor daño posible y la mayor calidad permisible. Los parámetros facodinámicos deben tenerse en cuenta, ya que para las técnicas de microincisiones, estas deben ser modificadas para mejorar el TEF, con relación a la dureza del cristalino, y minimizar los daños tisulares que pueden conspirar contra la mejoría visual de estos pacientes., Como se demuestra en este estudio, el promedio de opacidad del cristalino para ambos grupos fue NO3. Sin embargo, Lee y colaboradores4 en su investigación demostraron que el CoMICS a través de 2,2 mm fue efectivo para cristalinos con opacidades nucleares, mientras las incisiones de 1,8 mm PAN-AMERICA

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fueron efectivas en las opacidades corticales. Para esta investigación, aunque el promedio del TEF fue menor a un minuto en ambos grupos, el de BiMICS necesitó más tiempo con relación a la planificación de los parámetros facodinámicos, donde el vacío necesitado fue algo menor con relación al grupo CoMICS. Wang y colaboradores5 reportaron diferencias significativas en ambos grupos con un mayor TEF para el grupo BiMICS. Sin embargo, Cavallini y colaboradores6 no encontraron diferencias entre ambos grupos en su estudio. Para Kurz y colaboradores7 el TEF fue menor en el grupo BiMICS. En adición, el correcto examen preoperatorio es importante para personalizar el diagnóstico y la cirugía acorde a las necesidades visuales de cada paciente y decidir qué lente intraocular implantar en cada caso. Como resultado, el EE muestra la calidad de este diagnóstico en el postoperatorio. En este estudio se comportó de modo similar para ambas técnicas quirúrgicas, alcanzándose valores muy cercanos a la emetropía, resultado similar a otros estudios8.

La mayoría de los autores coinciden en que las incisiones sub 2 mm no modifican el astigmatismo inducido por la cirugía de catarata. Por esto, la MAI para ambas técnicas quirúrgicas, aunque se realizó la incisión corneal principal en ambos casos por el meridiano más curvo determinado en el estudio preoperatorio, tuvo un valor dióptrico menor a 0,5 D. Wilczynski y colaboradores9 encontraron una MAI sin diferencias significativas para ambos grupos de estudio con los diferentes métodos que utilizaron para analizar esta variable. Lee y colaboradores4 no encontraron diferencias significativas en el MAI en sus dos grupos de estudio.

En su conjunto, el control del EE y el bajo valor del MAI resultó en que la MAVC alcanzada para ambas técnicas quirúrgicas fuera la máxima, redundando en la satisfacción de los pacientes que vieron cumplidas sus expectativas visuales, al igual que reportaron varios autores en sus estudios respectivos4-7,10. Otra de las ventajas de las técnicas de microincisión sobre las técnicas coaxiales estándar con relación a la ganancia visual, es la prontitud de la recuperación de esta y su mayor valor en visión corregida y sin corregir como demostró Saeed11 en su estudio. Dosso y colaboradores12 mostraron la efectividad de la técnica de MICS aunque finalmente el resultado de esta y la técnica convencional coaxial fueron comparables.

Con relación al deterioro de la densidad celular endotelial para este estudio no mostró diferencias significativas para ambos grupos estudiados, demostrando la ventaja de ambas técnicas quirúrgicas con relación al daño mínimo a los tejidos vecinos, específicamente el endotelio corneal, que contribuye como otro factor en una buena MAVC por la magnífica transparencia corneal al no estar edematosa esta estructura. Resultados similares mostró Wang et al5 Kahraman13 reporta mayor pérdida celular endotelial en el grupo BiMICS, aunque finalmente no hubo diferencia significativa entre ambos grupos. Para el estudio de Kurz et al7, aunque fue realizado en casos complicados, no hubo una pérdida celular endotelial significativa relacionada con las técnicas 20

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quirúrgicas de microincisión, y Vasavada10 igualmente reporta una baja pérdida celular endotelial en su estudio. En ambos grupos de este estudio no se presentaron complicaciones pre ni postoperatorias, sin embargo Kahraman13 en su estudio no encontró diferencias significativas en las complicaciones perioperatorias de sus dos grupos de estudio. Para Kurz et al7, en ambos grupos de su estudio no se presentaron diferencias significativas en las complicaciones pre y postoperatorias, aunque estas aumentaron en el estudio de Vasavada10.

Podemos concluir que con ambas técnicas quirúrgicas, la CoMICS y BiMICS, se lograron resultados satisfactorios que demuestran la efectividad de las mismas.

REFERENCIAS BIBLIOGRÁFICAS 1. Alió JL, Rodríguez-Prats JL, Galal A. Micro incision Cataract Surgery in Phacoemulsification. Principles and Practice of Phacoemulsification. USA: Slack Pub; 2003.

2. Alió JL, Rodríguez-Prats JL, Galal A. Outcome of micro incision cataract surgery versus coaxial Phacoemulsification. Ophtalmology 2005; 112(11):1997-2003.

3. Pandey SK, Olson RJ, Werner L. Microincision intraocular lenses. Advances in Ophthalmology. EyeNet 2005:82-90 4. Lee KM, Kwon HG, Joo CK. Microcoaxial cataract surgery outcomes: comparison of 1.8 mm system and 2.2 mm system.

J Cataract Refract Surg 2009 May;35(5):874-80.

5. Wang Y, Xia Y, Liu X, Zheng D, Luo L, Liu Y. Comparison of bimanual and micro-coaxial phacoemulsification with torsional ultrasound. Int Ophthalmol 2009 Oct; 29(5):393-400.

6. Cavallini GM, Campi L, Masini C, Pelloni S, Pupino A. Bimanual microphacoemulsification versus coaxial miniphacoemulsification: prospective study. J Cataract Refract Surg 2007 Mar; 33 (3):387-92.

7. Kurz S, Krummenauer F, Thieme H, Dick HB. Biaxial microincision versus coaxial small-incision cataract surgery in complicated cases. J Cataract Refract Surg 2010 Jan; 36(1):66-72.

8. Alió JL, Rodríguez-Prats JL, Galal A. Micro incision Cataract Surgery in Phacoemulsification. Principles and Practice of Phacoemulsification. USA: Slack Pub; 2003.

9. Wilczynski M, Supady E, Piotr L, Synder A, PalengaPydyn D, Omulecki W. Comparison of surgically induced astigmatism after coaxial phacoemulsification through 1.8 mm microincision and bimanual phacoemulsification through 1.7 mm microincision. J Cataract Refract Surg 2009 Sep;35(9):1563-9.

10. Vasavada V, Vasavada V, Raj SM, Vasavada AR. Intraoperative performance and postoperative outcomes of microcoaxial phacoemulsification. Observational study.

J Cataract Refract Surg 2007 Jun;33(6):1019-24.

11. Saeed A, O’Connor J, Cunnife G, Stack J, Mullhern MG, Beatty S. Uncorrected visual acuity in the immediate postoperative period following uncomplicated cataract surgery: bimanual microincision cataract surgery versus standard coaxial phacoemulsification. Int Ophthalmol 2009 Oct;29(5):393-400. Epub 2008 Jul 23.

12. Dosso AA, Cottet L, Burgener ND, Di Nardo S. Outcomes of coaxial microincision cataract surgery versus conventional coaxial cataract surgery. J Cataract Refract Surg 2008 Feb;34(2):284-8.

13. Kahraman G, Amon M, Franz C, Prinz A, Abela-Formanek C. Intraindividual comparison of surgical trauma after bimanual microincision and conventional small-incision coaxial phacoemulsification.

J Cataract Refract Surg 2007 Apr;33(4):618-22.

Karon MD and Valenzuela AA. Melkersson-Rosenthal Syndrome: A forgotten diagnosis

Melkersson-Rosenthal Syndrome: A forgotten diagnosis. A Case Report From Department of Ophthalmology, School of Medicine, Tulane University, New Orleans, Louisiana Michael D. Karon, MD PhD1, Alejandra A. Valenzuela, MD2 1

. Resident . Associate Professor, The George Haik Sr. / St. Gile Foundation Chair Orbital & Lacrimal Diseases/Surgery Oculoplastics & Periocular Eyelid Reconstructive Surgery Orbital & Ocular Adnexal Oncology 2

Funding: None Proprietary and/or financial interest: None

Corresponding author Dr. Alejandra A. Valenzuela Department of Ophthalmology, Tulane University Medical Sciences Centre, School of Medicine 1430 Tulane Avenue, SL-69 New Orleans, LA, 70112 Phone: (504) 988-5314 Fax: (504) 988-2684 Email: avalenz1@tulane.edu

Date of receiving: 26-01-2012 / Date of approval: 04-02-2012

ABSTRACT The rare, non-caseating, granulomatous disease known as Melkersson-Rosenthal syndrome (MRS) can be diagnostically difficult especially when not presenting as the characteristic triad of facial palsy, facial edema, and fissured tongue.1 We present a case of a 65-year-old female with a 15-year history of recurrent bilateral upper eyelid swelling previously unsuccessfully treated for a presumed lid allergy and rosacea. Following imaging and histopathology results, she has now been diagnosed with MelkerssonRosenthal syndrome. Since this disease is typically refractory to treatment, she is being followed and treated with cosmetic eyelid skin reduction if necessary during inactive stages of the disease.

Key Words: Melkerson-Rosenthal syndrome, noncaseating granuloma, eyelid swelling, eyelid inflammation.

FIGURE 1: Clinical photography of a 65-year-old Caucasian female demonstrating predominately right-sided upper eyelid non-pitting swelling and mechanical ptosis secondary to Melkersson-Rosenthal syndrome.

INTRODUCTION Melkersson-Rosenthal Syndrome (MRS) is a rare condition of unknown etiology. We present a case of this disease to demonstrate the need to include this in the differential diagnoses of eyelid edema.

CASE REPORT A 65 year-old Caucasian female with no family history and consanguinity, presented with a 15-year history of non-pitting, non-pruritic, recurrent bilateral upper eyelid swelling worse on the right side.

Seven years prior, she was given a diagnosis of rosacea and lid allergies. She has been treated unsuccessfully with oral anti-allergy medications, topical

antibiotics and steroid ointments. For the last year, she has had a complaint of a mildly pruritic facial rash that worsen in sunlight.

Examination demonstrated a mild right mechanical upper ptosis and bilateral upper lid swelling more prominent on the right side (Figure 1). Her skin was brawny in color with no signs of pain, itchiness or sensory/motor defect. No significant laboratory findings were present. Her head-orbit CT was only significant for right eye preseptal soft tissue swelling (Figure 2). After excision biopsy, the histopathology showed dermal edema, ectatic vessels, and granuloma formation near dilated vessels. In addition, scattered interstitial and perivascular lymphocytes were present as well as intravascular histiocytes which stained with CD68 (Figures 3 and 4).

Due to the disease process and specifically the histopathology, her diagnosis is Melkersson-Rosenthal Syndrome. The current treatment will be observation for the underlying disease state. She will be offered upper lid skin reduction if the disease progresses.

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CASE REPORT / Vis. Pan-Am. 2012;11(1):21-22

FIGURE 2: Axial contrast head and orbit CT scan showing right pre-septal soft tissue swelling.

FIGURE 3: Low power view (40x) of skin section with prominent dermal edema, granuloma formation, and perivascular inflammation.

DISCUSSION MRS is a rare chronic condition that has relapsing-remitting course involving painless, non-pitting orofacial swelling. It may exist as a triad of symptoms including orofacial edema, relapsing facial palsy, and fissured tongue; however, this triad need not exist for the diagnosis to be made.1,2 Typically, the remainder of the ophthalmic examination is normal.3 The differential diagnosis includes thyroid-associated orbitopathy, angioedema, sarcoidosis, preseptal cellulitis, lymphoma, lymphedema, acne rosacea, and blepharochalasis.2,3 Diagnosis is usually confirmed with histopathology which is characteristically a granulomatous angiitis with perivascular inflammatory cells and variable dermal edema.5 Although, granulomas may be absent in the early stages of this disease.6 Our case study demonstrated the representative dermal edema and granuloma formation. Therapy for this syndrome typically consists of corticosteroids; however, the condition is frequently refractory to any treatment.7 In this case report, it took 15 years of symptoms before the correct diagnosis was made; however, in that time she did receive treatment with steroid ointments, which is the mainstay of treatment, without success. Because of this, we decided to take the conservative approach and proceed with observation alone at this time. If, due to recurrences, the edema is visually significant or cosmetically unacceptable, then we will proceed with upper eyelid skin reduction during an inactive phase of the condition.

MRS should be considered amongst the differential diagnosis of recurrent eyelid swelling and it can only rule out with histopathology once this condition is suspected.

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FIGURE 4: High power view (200x) of nonnecrotizing granuloma adjacent to dilated vessels.

REFERENCES 1. Shapiro M, Peters S, Spinelli HM. MelkerssonRosenthal syndrome in the periocular area: a review of the literature and case report. Ann Plast Surg 2003;50:644-8.

2. Chen C, Huilgol SC, James C et al. Melkersson-Rosenthal syndrome presenting with upper lid edema and facial palsy. Can J Ophthalmol 2002;37:361-3.

3. Hallet JW, Mitchell B. Melkersson-Rosenthal syndrome.

Am J Ophthalmol 1968;65:542-4.

4. Pierre-Filho Pde T, Rocha EM, Natalino R et al. Upper eyelid oedema in Melkersson-Rosenthal syndrome. Clin Experiment Ophthalmol 2004;32:439-40.

5. Rawlings NG, Valenzuela AA, Heathcote JG. Isolated eyelid edema in Melkersson-Rosenthal syndrome: a case series. Eye 2011; Nov 4: 1-4.

6. Akarsu C, Atasoy P, Erdogan S et al. Bilateral upper eyelid edema in Melkersson-Rosenthal syndrome. Ophthal Plast Reconstr Surg 2005;21:243-5.

7. Cocuroccia B, Gubinelli E, Annessi G et al. Melkersson-Rosenthal syndrome: new clinicopathologic findings in 4 cases. Arch Ophthalmol 2000;118:227-32.

Fernández MG et al: Laser photocoagulation for I125 radiation-induced retinopathy

Laser photocoagulation for I125 radiation-induced retinopathy in choroidal melanoma: a case report From the Retina Service, Department of Ophthalmology. Hospital Universitario Central de Asturias (Asturias, SPAIN).

Miriam García Fernández, M.D.1, Joaquín Castro Navarro, M.D.1, Purificación Mera Yañez, M.D.2

Corresponding author: Miriam García Fernández, M.D. C/Dionisio Ridruejo nº5, 11ºD. CP: 33007, Oviedo (Asturias) (SPAIN).

E-mail: migarci@hotmail.es

1

. Retina Department, Ophthalmology. University Central Hospital of Asturias. . Surgical Retina and Oncology Department, Ophthalmology. University Hospital of Santiago de Compostela, Galicia, Spain.

2

Funding: None Proprietary and/or financial interest: None

Date of receiving: 13-12-2011 / Date of approval: 08-02-2012

ABSTRACT We describe herein a case of a 25 year-old female with main complain visual acuity loss in his left eye (OS) associated to a choroidal melanoma. Treatment with plaque brachytherapy using I125 was started. It was observed improvement regarding tumor size and best-corrected visual acuity (BCVA). However, at 39 months of follow up on brachytherapy, fundoscopic signs of radiation-induced retinopathy (microaneurysms, retinal hemorrhages, hard exudates, and neovascularization) were observed.

Fluorescein angiography confirmed the diagnosis of radiation-induced retinopathy, with large areas of ischemia and neovascularization. Focal argon photocoagulation was used as treatment with excellent results in 5 years follow-up.

Keywords: choroidal melanoma, brachytherapy, radiation-induced retinopathy.

INTRODUCTION Brachytherapy with radioisotopes has become the treatment of choice for choroidal melanoma, a common primary malignant intraocular tumor, due to the given capacity for preservation of the vision and the eye. We describe herein a case of radiation-induced retinopathy in a patient treated with brachytherapy using I125, its clinical recognition and management.

FIGURE 1: First visit. A: Temporal choroidal melanoma at initial examination. B: A and B-scans ecography, showing choroidal mass, with low internal tumor reflectivity, choroidal excavation, positive kappa angle, serous retinal detachment associated with extraescleral extension. Dimensions (mm): 10,31 mm (base) x 4,36 mm (apical height). C: CT-scan showing a temporal posterior lesion in the left eye, suggestive of choroidal melanoma (white narrow).

CASE REPORT A 25 year-old female patient came to our attention in the emergency room with a 15 days history of floaters and decreasing of vision in her left eye (OS). Best-corrected visual acuity (BCVA) was 0.9 in the right eye (OD) and 0.16 in the OS. Biomicroscopy of anterior segment in both eyes was unremarkable. Funduscopic examination showed a nodular, dome-shaped and well-circumscribed mass located temporally to the macula and a serous retinal detachment. No macular involvement was detected in the left eye (Figure 1A).

A and B-scan ultrasound of the eye were performed and revealed a 10,31 x 4,36 mm dome-shaped lesion with low reflectivity, excavation of underlying uveal tissue and an acoustic quiet zone at the base of the tumor, corresponding to the typical “acoustic hollowing”. Kappa angle was observed (Figure 1B).

CT scan of the globe and orbit showed a temporal posterior mass with contrast enhancement in the left eye, suggestive of choroidal melanoma (Figure 1C). Neither orbital infiltration nor bone affectation was found.

Complementary examinations were performed such as complete blood analysis (including tumoral markers-CEA, CA 15.3, CA 19.9) and abdominal ultrasound and X-ray of the lungs. All exams were normal.

According to the findings, we decided to treat the patient with plaque brachytherapy using I125. A computer calculation was used to determine the dose and duration of plaque application (80-100 Gy to the apex of the tumor, at 50-125 cGy/h). An appropriate sized plaque was sutured temporarily to the sclera underlying the melanoma (after previous desinsertion of the external rectus muscle), considering a margin of 2 mm over the largest tumor basal dimension.

The radioactive plaque was left for 3 days, after which it was removed, with reinsertion of external rectus muscle.

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CASE REPORT / Vis. Pan-Am. 2012;11(1):23-25

FIGURE 2: Lesion appearance five months after brachytherapy treatment.

FIGURE 3: Fundus photographs appearance 39 months after plaque therapy. Hard exudates, retinal hemorrhage and capillaries dilatation, suggestive of radiation retinopathy.

After 5 months, BCVA in OS was 0.4, and funduscopic examination revealed a reduction in size of the mass (Fig. 2), and a fibrotic appearance. The ultrasound showed a considerable reduction in height of the mass (10,53 x 2,32 mm), although it demonstrated choroidal excavation and positive kappa angle. The complementary exams were repeated - especially liver function as well as the lung X ray and liver tomography - showing normal results.

Thirty-eight months after plaque therapy, BCVA had improved to 0.6. Ultrasonography showed a reduction in size of the mass (7,15 x 2,38 mm). However, hard exudates surrounding the choroidal lesion were noted.

These hard exudates were suggestive of radiation-induced retinopathy. At 39 months follow-up, signs of radiation-induced retinopathy such as microaneurysms, retinal hemorrhages, hard exudates, and neovascularization were observed (Figure 3).

By fluorescein angiography evaluation, it was observed large areas of ischemia and hyperfluorescence as well as areas of neovascularization (Figure 4).

We decided then to perform treatment with argon photocoagulation over the tumor surface and the 2 mm margin. Typical laser settings included a 100 Îźm spot size, 0.1â&#x20AC;&#x201C;0.2 ms duration, and 150-180 mW. A tight pattern of scatter laser photocoagulation was performed.

Twelve months after laser treatment, BCVA improved to 0.8, and the retinopathy showed no signs of progression. Five years after photocoagulation, the BCVA remained the same (0.8), and the lesion showed a fibrotic and stationary appearance surrounded by laser spots. Ultrasonography demonstrates no changes, except for a small retinal detachment over the lesion probably secondary to radiotherapy (Figure 5).

DISCUSSION Choroidal melanoma is the most common primary malignant intraocular tumor and the second most common type of primary malignant mela24

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noma in the body. Therapeutic options include enucleation, plaque brachytherapy or external beam radiation.

Mortality rates for medium-sized melanomas did not significantly differ between any of these treatments.

This is the main reason why brachytherapy has become the treatment of choice, given its capacity for preservation of the vision and the eye.

Several radioisotopes have been used for brachytherapy (cobalt-60, palladium-103, rutenio-106, iridium-192, and I-125). The I-125 emits low energy photons, which in theory decreases radiation-induced complications. However, it is associated with a varied range of complications, involving anterior and posterior segment of the eye such as dry eye and keratitis1,2, iris neovascularization and neovascular glaucoma3,4, radiation-induced cataract5, radiation-induced optic neuropathy and scleral necrosis6, episcleral deposits7, and radiation induced retinopathy.

The pathogenesis of this retinopathy is related to the loss of vascular endothelial cells and relative sparing of pericytes8 with local capillary occlusion and, finally, neovascularization, vitreous hemorrhage, tractional retinal detachment, and macular edema.

The prevalence of this complication varies from 10 to 63%.6,9. The risk is intimately related to radiation doses and other factors, as height and location of the tumor. It is well known that patients with lesions greater than 4 mm of thickness and close to the foveola have a higher risk to develop radiation-induced retinopathy and maculopathy3,6.

A variety of treatments have been proposed and used for this complication, including intravitreal injections of triamcinolone10 and bevacizumab11, hyperbaric oxygen treatment12 and laser photocoagulation; however, the best results have been found with laser photocoagulation. In 1997, Finger et al13 suggested that treating the irradiated zone with scatter laser photocoagulation was adequate to induce regression of radiation retinopathy associated to plaque brachytherapy. Some authors have suggested that scatter argon laser photocoagulation of the radiation targeted zone is effective in preventing or regressing radiation retinopathy14. In their study, laser photocoagulation regressed radiation retinopathy in 29 (64.4%) of the 45 patients treated after the onset of radiation retinopathy (17 with only retinopathy, 10 with a combination of retinopathy and maculopathy, and two with only maculopathy). Additionally, 16 patients received laser treatment before clinical evidence of retinopathy; only one of them developed radiation maculopathy and two developed retinopathy without maculopathy (all three responded to additional laser photocoagulation).

Other authors15, have suggested that focal laser therapy may modestly improve visual acuity and promote resolution of macular edema at 6 months, but benefit from a single treatment is not sustained at 2 years.

Fernández MG et al: Laser photocoagulation for I125 radiation-induced retinopathy

FIGURE 4: Fluorescein angiogram showing ischemic areas of neovascularization.

Despite of the fact that local tumor control rates after ophthalmic plaque radiation therapy are greater than 90% in most series, BCVA after plaque radiation therapy is, unfortunately, typically poor. This can be related to the development of ischemic retinopathy, where laser ablation of the ischemic zone may be helpful for long term BCVA maintenance resulting in stable results after 5 years of follow-up, as observed in this current case.

Acknowledgements: The authors would like to thank to Dr. Purificación Mera Yañez (Unidad de Retina Quirúrgica y Oncología Ocular, Servicio de Oftalmología, Complejo Hospitalario Universitario de Santiago de Compostela) for its cooperation in obtaining the photographs and editing the manuscript.

REFERENCES 1. Durkin SR, Roos D, Higgs B et al. Opthalmic and adnexal complications of radiotherapy. Graefes Arch Clin Exp Ophthalmol 2007; 239: 488-495.

2. Lumbroso-Le Rouic L, Charif Chefchaouni M, Levy C et al. 125I plaque brachytherapy for anterior uveal melanomas. Eye 2004; 18: 911-916.

3. Puusaari I, Heikkonen J, Kivela T. Ocular complications after iodine brachytherapy for large uveal melanomas. Ophthalmology 2004; 111: 1768-1777.

4. Detorakis ET, Engstrom Jr RE, Wallace R et al. Iris and anterior chamber angle neovascularization after iodine 125 brachyterapy for uveal melanoma. Ophthalmology 2005; 112: 505-510.

5. Collaborative Ocular Melanoma Study Group. Incidence of cataract and outcomes after cataract surgery in the First 5 Years after iodine 125 brachytherapy in the Collaborative Ocular Melanoma Study COMS Report No. 27. Ophthalmology 2007; 117: 1363-1371.

6. Stack R, Elder M, Abdelaal A, Hidajat R et al. New Zealand experience of I125 brachytherapy for choroidal melanoma. Clin Experiment Opthalmol 2005; 33: 490-494.

11. Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys 2008; 70: 974-977.

7. Toivonen P, Kivela T. Pigmented episcleral deposits after brachytherapy of uveal melanoma. Ophthalmology 2006; 113: 865-873.

12. Gall N, Leiba H, Handzel R et al.Severe radiation retinopathy and optic neuropathy after brachytherapy for choroidal melanoma, treated by hyperbaric oxygen. Eye 2007; 21: 1010-1012.

8. Archer DB, Amoaku WM, Gardiner TA. Radiation retinopathy- clinical, histopathological, ultraestructural and experimental correlations. Eye 1991; 5: 239-251.

9. Jones R, Gore E, Mieler W et al. Postreatment visual acuity in patients treated with episcleral plaque therapy for choroidal melanomas: dose and dose rate effects. Int J Radiat Oncol Biol Phys 2002; 52: 989-995.

10. Shields CL, Demirci H, Dai V et al. Intravitreal triamcinolone acetonide for radiation maculopathy after plaque radiotherapy for choroidal melanoma. Retina 2005; 25: 868-874.

FIGURE 5: A and B. Ultrassonography (A and B-scans). Choroidal mass with nodular shape (although smaller), regular structure and medium-high reflectivity (higger in regions near the surface), rectification of kappa angle, choroidal excavation, small dome-shaped retinal detachment over the lesion, no extraescleral extension. Dimensions (mm): 7,09 mm (base) x 1,96 mm (apical height). C and D. Choroidal melanoma appearance five years after laser photocoagulation, without signs of activity.

13. Finger PT: Radiation therapy for choroidal melanoma. Surv Ophthalmol 1997; 42: 215–232.

14. Finger PT, Kurli M. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol 2005; 89: 730-738.

15. Hykin PG, Shields CL, Shields JA et al. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology 1998; 105: 1425-1429.

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PAAO / Vis. Pan-Am. 2012;11(1):26

Advocacy

By Natalio J. Izquierdo, MD Chairman of the PAAO Professional Relations/Advocacy Committee

Physicians need to rediscover the leader within them. Further, we need to restore our drive to be advocates for our patients. As physicians our quest is to improve patients’ health. That is what an advocate does.

Advocacy blends science, ethics and politics. I guess we all know about the former two, but we get cautious about the latter. However, there is a need for physicians to transform medicine, and patients’ behavior by changing public health policies. I guess the best example would be smoking. It took physicians to observe lung cancer, to recommend patients to quit smoking and transform health policies by placing labels on cigarette packs and banning smoking in public spaces.

Ophthalmologists are leaders by virtue of their medical knowledge. We are leaders in both our clinical practice and team leaders in the operating rooms. However, we need to strengthen our leadership in public health issues.

Let us analyze advocacy by using 9 building blocks: First, we all have a health issue that calls our attention; something we would like to change. There is an issue that worries us the most because it impacts our patients’ lives. The questions being: Is there a solution? Is there a way to solve it? Does our community, region or nation have the resources to solve it? Will this issue solidify our physician-patient relationship? Or, will this issue divide us? If the answers are positive, go for it. This issue is worth fighting for!

The second building block is to understand the context. We need to understand the process. Concentrate on the how it is done. Forget about the why! We need to identify the decision makers, and understand the process of decision making. These concepts are important both in the legislative and executive branches of our democratic governments. Lastly we need to understand the context of laws and health policies implementation in our countries. Perhaps as leaders we may need advisors to understand all of these processes. Go hire them!

The third building block is gathering information. As leaders, we need the evidence. As physicians, we learn to observe and document, so this is an easy task.

However, the challenge is about collecting information in our communities, nations, and through supranational organizations. I guess this is the best asset of cybernetic social networks. We get together through the internet to share our ideas. Do it!

As ophthalmologists we learn how to communicate with our patients and understand their needs. We need to communicate with our peers and mentors. As leaders, we need the former for their support and the latter for inspiration. As democratic leaders, we must allow open communication and fair participation in decision making processes. Further, as leaders, we ought to represent groups’ opinions and decisions well. These will further confirm our leadership among peers. Speak up!

As ophthalmic surgeons, we always have a plan. When preparing a strategy, remember the mnemonic SMART. Our plan must be Specific in order to achieve a result.

Our results must be Measurable. The question being: are the objectives being met? Is 26

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our strategy Achievable? As leaders, we ought to walk one step at a time. Avoid big unreachable tasks. In other words, we need to be Realistic. Finally, we need a Time frame. For example: the Haiti task force decided on having a one year time frame. We achieved many goals within this time frame. Be SMART! A leader needs communication skills. Language needs to be simple and consistent with the group´s vision and voice. A message must be delivered clearly.

The message must be repeated several times. Leaders´ body language needs to be coherent with the message.

Go practice your speech!

As advocates, we need to grab the opportunity. Look around you and understand what´s happening, so you may comment wisely about it. Watch politicians closely as they make decisions on public health policies.

Finally, always be ready to deliver a speech, especially whenever you go to a meeting. Write it up!

The eighth block has to do with being accountable.

Leaders need to be able to account for every penny they spend on a campaign. Spending must be evaluated in terms of results. Keep counting!

Finally, advocates have a strategy, a different approach for every issue. This plan takes into account our patients´ priorities. This plan is designed to succeed having an impact on patients´ health. Plan ahead!

In summary, Eye MD´s are born leaders. Rediscover the leader qualities within you, and improve patients´ health. Engage your allies, as Don Quixote found his friend Sancho. Ask your mentors for guidance and your peers for support. Be pro-active, and change public health policies. You can do it!

OBITUARY

Dr. Francisco Belisario-Navarro Dr. Francisco Belisario-Navarro passed away on February 1, 2012. He was a visionary and medical pioneer with an extraordinary commitment to society who worked tirelessly from his earliest days to address the problem of prevention of blindness in Venezuela and the entire American continent. After graduating from the Central University of Venezuela with the title of medical surgeon in 1951, he decided to perform postgraduate studies in ophthalmology at the San Carlos Hospital in Madrid and the Barraquer Institute in Barcelona Spain. He subsequently completed a fellowship in glaucoma in the United States.

Returning to Venezuela, one of his first accomplishments was to open ophthalmological consulting services in a number of hospitals that lacked them and served the less privileged population. His lifelong dedication to the development of education in ophthalmology led him to participate in many medical conferences worldwide and locally. However, he was especially proud of his tenure at “Dr. Francisco Antonio Rísquez” Hospital in Caracas where he founded the ophthalmology department of that institution and later served as its department head from 1964 until 1984, there he trained generations of ophthalmologists. In 1984 he achieved another milestone in his very prolific career, he founded the “Instituto Popular para los Ojos Dr. F. Belisario-Navarro” along with his wife, Dr. Magally Hernández de Belisario, also an ophthalmologist. The Institute was started to be a non-profit nongovernmental organization that would provide attention to very low-income persons.

Dr. Belisario-Navarro was a founding member of the Venezuelan Society of Ophthalmology and a member of the Venezuelan Public Health Society, the Pan-American Association of Ophthalmology, and numerous ophthalmology societies of the Americas and Europe. He presented and published numerous scientific papers related to the prevention of blindness, leaving a very special legacy in the form of his Atlas of photographs of the different ophthalmological lesions produced by leprosy in Venezuela. Over the course of his life he was honored with many public distinctions as well as frequently recognized for his contributions by the Ministry of Health and many national and international organizations.

Venezuela and the world have lost a great gentleman who served as an example for his character, his human qualities, and his great knowledge, as well as for the innate leadership that always characterized him and allowed him to work with cheerfulness, humility, and great energy for more than five uninterrupted decades in the service of the prevention of blindness.

Our condolences to Dr. Belisario-Navarro’s family, his wife Dr. Magally Hernández de Belisario, and their children, relatives, colleagues, and many friends, for this irreparable loss. He will be greatly missed. God rest his soul…

J. Fernando Arevalo, MD FACS PAAO Executive Vice President

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INSTRUCTIONS FOR AUTHORS / Vis. Pan-Am. 2012;11(1):28-32

VISION PAN-AMERICA Instructions to Authors GENERAL INSTRUCTIONS FOR ONLINE SUBMISSIONS As off January 2012, all submissions to the journal Vision Pan-America need to be uploaded electronically at http://journals.sfu.ca/paao/index.php/journal/index through the Open Journal System software. Candidates must log in as Author with user name and password. To obtain a user name and password, please REGISTER. If, for some reason, you are unable to access the system, please contact the Editorial Office by email at terri.grassi@paao.org or tgrassi@paao.org or by phone at 817-275-7553 with Terri Grassi.

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by an established Institutional Review Board. The following disclaimer should be included in the body of the paper: “This study was evaluated and approved by the Institutional Review Board or Ethical Committee of (name of institution)”.

In countries or situations where an IRB is not available, the authors should confirm that the study and data collection comply with local legislation and with the principles of the Declaration of Helsinki (JAMA 2000;284:3043-3045).

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The entire process is electronic; therefore, all forms should be scanned and uploaded with your submission. If this is not possible, you may fax them (with designated manuscript number and identification) to 817-275-3961 at the Journal Editorial Office with attention to Terri Grassi.

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To qualify for authorship, authors must make substantial contributions to the intellectual content of the paper in each of the three suggested categories: Category 1: concept and design, data acquisition or data analysis and interpretation.

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Vision Pan-America - Instructions to Authors

Once a manuscript has been submitted, the order of authorship (including adding or removing authors) cannot be changed without written request to the Editorial Office from the corresponding author. Specifically, if an author is removed, a letter from that author agreeing to his/her removal is required. The new copyright form must show the title and authors’ names at the top of the form in the order they should appear in print and include original signatures from each. If the authors are not able to agree among themselves on authorship changes, the paper should be withdrawn.

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GUIDELINES FOR PREPARING A SCIENTIFIC MANUSCRIPT FOR SUBMISSION TO VISION PAN-AMERICA Vision Pan-America has adopted the following guidelines related to the publication of biomedical research from the original work of influential editorial groups such as: International Committee of Medical Journal Editors (ICMJE) Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. J Pharmacol Pharmacother 2010;1:42-58.

World Association of Medical Editors (WAME) at http://www.wame.org

Committee on Publication Ethics (COPE) COPE Guidelines (including Code of Conduct; Guidelines for Retracting Articles; Ethical Editing for New Editors) at www.cope.org Council of Science Editors (CSE) CSE’s White Paper on Promoting Integrity in Scientific Journal Publications at www.councilscenceeditors.org EQUATOR Network at http://www.equator-network.org

GENERAL PRINCIPLES To be published in Vision Pan-America, the text of observational and experimental original articles must be divided into the following sections: Introduction, Methods, Results, and Discussion. Other types of articles, such as case reports, reviews, and editorials need to be formatted differently. A structured abstract in two languages should accompany the text.

Double-space all portions of the manuscript— including the title page, abstract, text, acknowledgments, references, individual tables, and legends to facilitate printing for reviewing and editing.

Authors should number all of the pages of the manuscript consecutively, beginning with the title page, to facilitate the editorial process.

Reporting Guidelines for Specific Study Designs The general requirements listed in the next section relate to reporting essential elements for all study designs. Authors are encouraged also to consult reporting guidelines relevant to their specific research design. A good source of reporting guidelines is the EQUATOR Network http://www.equator-network.org/home/

A. Title Page The title page should have the following information: 1. Article title: Authors should include all information in the title that will make electronic retrieval of the article both sensitive and specific.

2. Authors’ names and institutional affiliations: Vision Pan-America publishes only one author’s highest academic degree.

3. The name of the department(s) and institution(s) to which the work should be attributed.

4. Contact information for corresponding authors: Name, mailing address, telephone and fax numbers, and e-mail address of the author responsible for correspondence about the manuscript.

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INSTRUCTIONS FOR AUTHORS / Vis. Pan-Am. 2012;11(1):28-32

5. If existent, source(s) of support in the form of grants, equipment, drugs, or all of these.

6. A running head (first author surname and initials, followed by up to four words of the title) with no more than 40 characters (including letters and spaces) at the foot of the title page.

B. Abstract Structured abstracts (Purpose, Design, Methods, Results, Conclusions and Financial Disclosure) are preferred for original research and systematic reviews. The abstract should provide the context or background for the study and should state the studyâ&#x20AC;&#x2122;s purpose, basic procedures (selection of study subjects or laboratory animals, observational and analytical methods), main findings (giving specific effect sizes and their statistical significance, if possible), principal conclusions, and funding sources.

Articles on clinical trials should contain abstracts that include the items that the CONSORT group has identified as essential http://www.consort-statement.org.

Vision Pan-America is a multilingual journal, publishing papers in English, Portuguese, Spanish and French; however, for indexing purposes and better diffusion of the scientific information, Structured Abstracts must also be provided in English along with one in the original idiom, when other than English.

Provide five key words associated with your paper. The key words must be cited as listed in the MESH-Medical Subject Headings from the National Library of Medicine.

C. Introduction Provide a brief context or background for the study (that is, the nature of the problem and its significance).

State the specific purpose or research objective of, or hypothesis tested by, the study or observation; the research objective is often more sharply focused when stated as a question.

D. Methods The Methods section should include only information that was available at the time the plan or protocol for the study was being written; all information obtained during the study belongs in the Results section.

Selection and Description of Participants Describe the selection of the observational or experimental participants (patients or laboratory animals, including controls) clearly, including eligibility and exclusion criteria and a description of the source population.

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Technical Information Identify the methods, apparatus (give the manufacturerâ&#x20AC;&#x2122;s name and address in parentheses), and procedures in sufficient detail to allow others to reproduce the results.

Cite references to established methods, including statistical methods (see below); provide references and brief descriptions for methods that have been published but are not well-known; describe new or substantially modified methods, give the reasons for using them, and evaluate their limitations. Identify precisely all drugs and chemicals used, including generic name(s), dose(s), and route(s) of administration.

Authors submitting review manuscripts should include a section describing the methods used for locating, selecting, extracting, and synthesizing data. These methods should also be summarized in the abstract.

Statistics Describe statistical methods with enough detail to enable a knowledgeable reader with access to the original data to verify the reported results. When possible, quantify findings and present them with appropriate indicators of measurement error or uncertainty (such as confidence intervals). References for the design of the study and statistical methods should be to standard works when possible (with pages stated). Specify the computer software used.

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When data are summarized in the Results section, give numeric results not only as derivatives (for example, percentages) but also as the absolute numbers from which the derivatives were calculated, and specify the statistical methods used to analyze them. Restrict tables and figures to those needed to explain the argument of the paper and to assess supporting data.

F. Discussion Emphasize the new and important aspects of the study and the conclusions that follow from them in the context of the totality of the best available evidence. Do not repeat in detail data or other information given in the Introduction or the Results section. For experimental studies, it is useful to begin the discussion by briefly summarizing the main findings, then explore possible mechanisms or explanations for these findings, com-

Vision Pan-America - Instructions to Authors

pare and contrast the results with other relevant studies, state the limitations of the study, and explore the implications of the findings for future research and for clinical practice.

Link the conclusions with the goals of the study but avoid unqualified statements and conclusions not adequately supported by the data.

Avoid claiming priority or alluding to work that has not been completed. State new hypotheses when warranted, but label them clearly as such.

G. References General Considerations Related to References Readers should be provided with direct references to original research sources whenever possible..

Avoid using abstracts as references. References to papers accepted but not yet published should be designated as “in press” or “forthcoming”; authors should obtain written permission to cite such papers as well as verification that they have been accepted for publication.

Information from manuscripts submitted but not accepted should be cited in the text as “unpublished observations” with written permission from the source.

Avoid citing a “personal communication” unless it provides essential information not available from a public source, in which case the name of the person and date of communication should be cited in parentheses in the text.

Editors will check the accuracy of all reference citations; thus, citation errors sometimes appear in the published version of articles. To minimize such errors, references should be verified using either an electronic bibliographic source, such as PubMed or print copies from original sources. Authors are responsible for checking that none of the references cite retracted articles except in the context of referring to the retraction. For articles published in journals indexed in MEDLINE, the ICMJE and Vision Pan-America consider PubMed the authoritative source for information about retractions.

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INSTRUCTIONS FOR AUTHORS / Vis. Pan-Am. 2012;11(1):28-32

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PAN-AMERICA

Preserva la visión alcanzando las menores presiones-objetivo en más pacientes Investigadores de diversos estudios, (AGIS, Shirakashi, Shields) han comprobado que alcanzar y mantener la PIO entre 14 y 15 mmHg reduce la progresión de pérdida del campo visual1,2,3.

Lumigan® alcanza la PIO-objetivo de 14/15 mmHg en un mayor número de pacientes: ®

vs. timolol 4

®

vs.

dorzolamida/ timolol 5

®

vs. latanoprost 6

Porcentaje de Pacientes que alcanzaron la PIO-Objetivo ≤14

21%

9%

17%

2%

19%

9%

Porcentaje de Pacientes que alcanzaron la PIO-Objetivo ≤15

31%

16%

24%

9%

29%

14%

Lumigan ® (bimatoprost) Forma farmacéutica y pr esentación.

Composición. Cada ml contiene: 0,3 mg de bimatoprost. Vehículo: cloreto de sódio, fosfato de sódio presentación. esentación.Frascos cuenta-gotas conteniendo 5 ml de solución oftalmológica estéril de bimatoprost a 0,03%. USO ADULTO.Composición. hepta-hidratado, ácido cítrico mono-hidratado, ácido clorídrico y/o hidróxido de sódio, cloruro de benzalconio y agua purificada qsp. Indicaciones. LUMIGAN® (bimatoprost) es indicado para la reducción de la presión intra-ocular elevada en pacientes con glaucona o hipertensión ecauciones y Adver tencias. Advertencias. Fueron relatados aumento gradual del crescimiento Contraindicaciones. LUMIGAN® (bimatoprost) está contraindicado en pacientes con hipersensibilidad al bimatoprost o cualquier otro componente de la fórmula del producto. Pr Precauciones Advertencias. ocular.Contraindicaciones. de las pestañas en el largo y espesura, y oscurecimiento de las pestañas (en 22% de los pacientes después 3 meses, y 36% después 6 meses de tratamiento), y, oscurecimiento de los párpados (en 1 a <3% de los pacientes después 3 meses y 3 a 10% de los pacientes después 6 meses de tratamiento). También fue relatado oscurecimiento del íris en 0,2% de los pacientes tratados durante 3 meses y en 1,1% de los pacientes tratados durante 6 meses. Algunas de esas alteraciones pueden ser permanentes. Pacientes que deben recibir el tratamiento ecauciones LUMIGAN® (bimatoprost) no fue estudiado en pacientes con insuficiencia renal o hepática y por lo tanto debe ser utilizado con cautela en tales pacientes.Las lentes de contacto deben Precauciones de apenas uno de los ojos, deben ser informados a respecto de esas reacciones. Pr 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.