Volumen IV No.4 Diciembre 2005

Sindrome de Sjögren: Análise e comparação dosdiferentes critérios diagnósticos.SSeerrggiioo FFeellbbeerrgg,, PPaauulloo EElliiaass CCoorrrreeaa DDaannttaass,, EEllcciioo HH.. SSaattoo..

Queratoprotesis (Corneas Artificiales)EEdduuaarrddoo CC.. AAllffoonnssoo MMDD,, JJoosseeff SSttooiibbeerr,, MMDD,, VViivviiaannaa FFeerrnnaannddeezz MMDD,, PPeeggggyy DD.. LLaammaarr BBSS,, JJeeaann--MMaarriiee PPaarreell PPhhDD

Metastatic sclerochoroidal calcification:Case ReportIIvvaann GG.. CCaassttiilllloo MMDD,, CCaannddiiccee CC.. HHuuaanngg MMDD,, SStteepphheenn GG.. SScchhwwaarrttzz MMDD..

Long Term Follow-Up of Intraocular Pressure Elevation inPatients Post Intravitreal Triamcinolone Acetonide InjectionMMaalliikk YY.. KKaahhooookk,, MMDD,, JJeeffffeerryy LL.. OOllssoonn,, MMDD,, NNaarreesshh MMaannddaavvaa,, MMDD

VISIONPAN-AMERICA 1: :

Diciembre 2005

a Junta Directiva de la Asociación Panamericana de Oftalmología,como es tradicional, se reunió en el mes de octubre durante la

reunión de la Academia Americana de Oftalmología. En dicha reunión seanalizaron temas de importancia para la oftalmología Panamericana. Sediscutió la posición que deben guardar las sociedades oftalmológicasnacionales en relación con dos temas centrales: Las cirugías de cataratay el programa Visión 20/20 y la relación que debe guardar la oftalmologíaen relación con la optometría.

En relación con el programa Visión 20/20 se discutió y aprobó ladeterminación de la oftalmología latinoamericana de colaborar inten-samente en la erradicación de la ceguera prevenible provocada porcatarata. Para tal efecto, se concluyó que los programas de erradicacióndeben de ser aprobados y de alguna forma normados, por cada una de

las Sociedades Nacionales represen-tantes de los oftalmólogos de cadapaís. Cada nación le dará a sus pro-gramas las características propiaspara su mejor funcionamiento. De talmanera, que instamos a las organi-zaciones representadas en nuestraasociación, a que de manera conjuntacon las autoridades gubernamentalesy no gubernamentales se integren encomités nacionales a cumplir con estecometido. Es importante que la oftal-

mología organizada se ponga a la cabeza de estas organizaciones, hagasuyo los programas y evite, de esta manera, que un fin noble con el quetodos estamos de acuerdo, se convierta en un tema político, sujeto declientelismo popular y desvirtúe la finalidad de dar una mejor salud visuala los pacientes que así lo necesitan. La Asociación Panamericana deOftalmología, insiste en que las políticas sobre salud ocular sonresponsabilidad de la oftalmología organizada de cada una denuestras naciones.

La relación que la oftalmología debe guardar hacia la optometría esdistinta entre nuestras naciones, por lo que la Asociación Panamericanade Oftalmología, distribuyó entre los representantes de los distintospaíses que acudieron a la reunión de Chicago, una declaración generalde principios que debe ser discutida internamente por cada sociedadnacional para adaptarse a sus necesidades específicas e individualizarla posición que debe guardar nuestra Asociación en relación con estetema. Insistimos en que esto sea discutido internamente por cada nacióny sea esta una declaración a ser aprobada en la próxima reunión en SãoPaulo, Brasil.

La Oftalmología Latinoamericana los espera a todos en elCongreso Mundial en febrero del año próximo.

he Board of Directors of the Pan-American Association ofOphthalmology, as is customary, met in October during the Annual

Meeting of the American Academy of Ophthalmology. During the meeting,the Board reviewed important topics impacting Pan-Americanophthalmology. The delegates of Board of Directors discussed theposition that the national ophthalmological societies should have withregard to two important topics: Cataract surgery and the Vision 20/20program, and the viewpoint that ophthalmology should hold with regard tooptometry.

In regard to the Vision 20/20 program, the Board discussed andapproved the motion that Latin American ophthalmology shouldcollaborate intensely with the eradication of preventable blindnessprograms. Toward this end, it was concluded that the eradicationprograms must be approved and governed by each of the nationalsocieties representing the ophthalmologists in each country. Each of thedifferent nations will forward its rules and guidelines for its optimaloperation. In this way, we urge the national societies affiliated to the Pan-American Association, that together with the national governmental andnon-governmental organizations to create national committees to carryout this task. It is important that the ophthalmological society is the headof this committee, who organizes these programs and directs theseactivities to toward a nobler end, with which we are all in agreement, toturn away from politics, subject to popular clientelism, and toward agenuine concern for patient eye health care, which is what they need. ThePan-American Association of Ophthalmology insists that the policies ofocular health are the responsibility of the national ophthalmologicalsociety in each of our affiliated countries.

Regarding the relationship that ophthalmology should have towardoptometry, this situation is different in each of our affiliated countries. Therepresentatives that sit on the Pan-American Association of Ophthal-mology’s Board of Directors, during the meeting in Chicago, agreed thatthese policies need to be discussed internally by each national society. Aseach country is distinct and has specific needs, each society should definethe position that it should hold with optometry in its country, and the Pan-American Association should be informed of this national position. Wewould like this to be discussed internally in each country and eachdeclaration be read and approved at our next Board meeting in SãoPaulo, Brazil.

Latin American ophthalmology looks forward to your participation inthe World Congress in February 2006.

MENSAJE DEL PRESIDENTE

L T

Enrique GrauePresidente de la Asociación Panamericanade Oftalmología.

PRESIDENT’S MESSAGE

Sincerely,Enrique Graue MDPresident, Pan-American Association of Ophthalmology

AtentamenteEnrique Graue MDPresidente de la Asociación Panamericana de Oftalmología

Diciembre 2005

VISIONPAN-AMERICA2: :

Queratoprótesis (Córneas Artificiales)

EEdduuaarrddoo CC.. AAllffoonnssoo MMDD,, JJoosseeff SSttooiibbeerr,, MMDD,, VViivviiaannaa FFeerrnnaannddeezz MMDD,, PPeeggggyy DD.. LLaammaarr BBSS,, JJeeaann--MMaarriiee PPaarreell PPhhDDBascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine

n los últimos 25 años varios investigadoreshan estado trabajando para desarrollar

una queratoprótesis como una córnea artificialpara pacientes quienes no son buenos candi-datos para las técnicas actuales de querato-plástia aloinjerto. Debido a los problemas derechazo en pacientes de alto riesgo y la faltade tejido donante, el desarrollo de una quera-toprótesis se ha intensificado en los últimosdiez años. La Organización mundial de lasalud (OMS) estima que el número de ciegospor enfermedad corneal asciende a los 10millones. Al menos un millón corresponde apacientes en quienes un transplante aloinjertoseguramente fallaría y en quienes una corneaartificial o queratoprótesis sería una mejoralternativa.

En el pasado, se han tratado muchosmateriales para este propósito, tales como eluso de vídrio o cuarzo para implantes lame-lares o de espesor total. Polimetílmetacrilato(PMMA) ha sido utilizado en diferentes quera-toprótesis tales como en el diseño en botónde collar de la queratoprótesis de Dolhman-Doane Boston, en la óptica con faldasconstruidas de un polímero poroso de la que-ratoprótesis de Cardona, Girard y Pintucci yen la óptica con faldas biológicas de lasqueratoprótesis de Strampelli, Falcinelli yTemprano. Biomateriales, tales como poli (2hidroximetilmetacrilato) (pHEMA) ha sidousado en la Queratoprótesis de Alphacor(Argus Biomedical Pty Ltd.) y PHEMA-MMA34en la queratoprótesis de Keralia (Universidadde Miami). La bioingeniería es una posibili-dad, produciendo una córnea de células vivaslo cuál ha sido recientemente alcanzado(Griffith)1.

Además la colocación de la queratoprótesisha sido modificada, tal como un implantelamelar anterior de la odontoqueratoprótesisde Strampelli. Implantes intraestromales comolos de Dolhman-Doane Boston y el de Alpha-cor. Un implante pre-descemet en el caso dela más reciente queratoprótesis (Keralia).

La queratoprótesis ideal debería tener lassiguiente características: ser aceptada por eltejido, tener una buena óptica, ser accequible,ser fácil de implantar, proveer un fácil segui-miento y estabilidad al largo término, y serreversible si el implante no cumple su objetivo.

La queratoprótesis de Dolhman-Doane-Boston es un implante de PMMA que sepuede colocar directamente en la cornea (tipoI) o a través de los parpados (tipo II). Elimplante tipo I consiste de un plato frontal de7 mm de diámetro, un plato posterior entre 7 y11 mm de diámetro y el tallo de unión entre losdos platos de 3.35mm de diámetro. Un anillode seguridad de titanium previene que sedestornille el plato posterior. Los platos tienenun espesor de 0.9mm. El implante tipo IItambién tiene una parte adicional de 2mm. Elpoder óptico es calculado basándose en elestado del cristalino del paciente y su longitudaxial (Fig 1).

Esta queratoprótesis ha dado buenosresultados hasta la fecha con un porcentajede retención del 90%. De esos pacientes lamitad han mantenido buena agudeza visualen el rango de 20/20 a 20/200 a 5 años post-operatorio.

Todos los pacientes requirieron de implantesde glaucoma. Otras de las complicaciones re-versibles fue la formación de membranasretroprostésicas, las cuales pueden tratarsecon el láser de YAG. Pacientes con el síndro-me de Stevens Johnson son más propensos adesarrollar endoftalmítis. Estos pacientes sontratados con vancomicina tópica para prevenirla infección. El problema con este tratamientocrónico es el riesgo de desarrollar infeccionescon organismos resistentes. Nosotros preferi-mos un ciclo de antibióticos tópicos usandodiferentes clases de antibióticos cada 3 meses.

El porcentaje de supervivencia de estaprótesis ha sido promisoria cuando secompara con otros estudios de pacientes con

Stevens Johnson bajo queratoplástia pene-trante, transplante de células madres limbal ytratamiento con ciclosporina. Pacientes usan-do vancomicina tópica tuvieron un porcentajede supervivencia de sus implantes por encimadel 75% a 1 año, sin embargo en el grupo bajoqueratoplástia penetrante y transplante decélulas madre limbal fue mucho mas bajo. Elporcentaje de retención en pacientes con fallamúltiple de injertos y sin ninguna condicióninflamatoria fue de 95% a 8 meses (Repor-tado en el Congreso Mundial de Cornea, 2005)2.

Otra queratoprótesis, la Osteo-odonto que-ratoprótesis de Falcinelli-Strampelli (OOKP)3-5,es usado principalmente en Europa y másrecientemente en Asia. El implante fue desa-rrollado hace mas de 30 años por el DoctorStrampelli, y luego modificado por el DoctorGiancarlo Falcinelli, en Roma. La OOKPconsiste de una falda construida de la raíz deldiente del paciente y el hueso alveolar, lo cualsoporta un cilindro óptico hecho de PMMA(figura 2). La prótesis es implantada en elpaciente después de reconstrucción de lasuperficie ocular.

En un estudio en el 2002, el Dr Falcinellireportó un porcentaje de retención de 93% deOOKP en 181 pacientes quienes han recibidoeste implante. En este grupo, 70 pacientestuvieron alguna forma de ojo seco, 68 tuvieronquemadura ocular, 15 tuvieron queratopatía y13 tuvieron queratopatía bulosa. A los 8 añospost-operatorios, 90% retuvieron su quera-toprótesis. A los 9 años, 70% retuvieron lamejor agudeza visual alcanzada post-operatoriamente. En el congreso mundial deCornea 2005, se reportó un grupo de 102

E

Figura 1: Boston Keratoprosthesis.

Figura 2:

Falcinelli Osteo-odonto-keratoprosthesis OOKP)

VISIONPAN-AMERICA 3: :

Diciembre 2005

pacientes con ojos secos y OOKPs con unseguimiento de 6 meses a 31 años. Noventa yseis por ciento de estos pacientes hanmantenido o mejorado la visión de su estadopre-operatorio4. Liu también presentó un 72%de mejoría en la agudeza visual con unseguimiento en promedio de 2.5 años. Lacomplicación mas común con este tipo de deimplante es la reabsorción de la lamina dental.

Una modificación de esta técnica ha sidohecha por el Doctor Pintucci quien usa unafalda de Dacrón, por el Doctor Tempranoquien usa una falda de fascia y por el DoctorLeón quien usa una falda de Coralina.

El implante de Alphacor, previamenteconocido como la queratoprótesis de Chirilia,fue desarrollado en Australia y actualmente haganado popularidad. El implante de 7mm dediámetro consiste de un disco central transpa-rente hecho de gel de pHEMA y una faldaopaca construida de una esponja porosa depHEMA. La falda porosa permite que el propiotejido del paciente crezca dentro de ésta. Elimplante tiene un espesor de 0.5mm. Existenmodelos disponibles para ojos fáquicos yáfacos (Figura 3).

La técnica quirúrgica es concreta y constade 2 pasos. En el primero, la falda delimplante es colocada en un bolsillo corneallamelar con un trepanación de espesor centralcompleto para la porción óptica y puede sercubierto con un flap conjuntival. Después dealgunas semanas, la trepanación es realizadaen el flap conjuntival anterior.

En el estudio del 2002 publicado enOphthalmology, 13 pacientes (93%) retuvie-ron el implante de Alphacor más de 2.5 añospost-operatoriamente. En un caso, el implantetuvo que ser removido regresando a sucondición preoperatoria. La visión preope-ratoria fue retenida o mejorada.

Esta queratoprótesis de pHEMA no esrecomendada para pacientes con condicionesinflamatorias, ojos secos o fumadores.

Algunos medicamentos tópicos pueden serdepositados en la prótesis o incluso deco-lorearla6.

En Europa se ha implantado recientementeuna queratoprótesis desarrollada en elBascom Palmer Eye Institute de la Univer-sidad de Miami (figura 4). Su implantación es

supra-descemet y es conocida como Keralia.El implante es hecho de pHEMA-MMA34.Tiene un diámetro de 7mm, con una ópticacentral de 4.5mm y una falda anular de1.25mm. El espesor central es de 350 micrasy en la periféria de 100 micras. Presentaagujeros en la háptica externa para cre-cimento interno tisular. Esto permite laimplantación de la prótesis sobre una mem-brana de Descemet intacta.

Esta queratoprótesis ha sido implantadaexperimentalmente en conejos, gatos y ojosdonantes7-9. Recientemente ha sido aprobadapor el gobierno Europeo, y ha sido implantadaen 10 personas hasta el momento. Los ensa-yos clínicos se están realizando en Francia,Bélgica, Austria e Italia.

La selección de cuál queratoprótesis usardepende de la condición del paciente y laexperiencia del cirujano. Actualmente noso-tros recomendamos la OOKP para pacientescon síndrome de Stevens Johnson. Parapacientes con menos inflamación, nosotrossugerimos el Alphacor o la queratoprótesis deBostón y Keralia.

La evaluación preoperatoria es importantee incluye una historia detallada y éxamenfísico oftalmológico completo. Ecografíadebería ser hecha si la retina y el nervio ópticono pueden ser visualizados.

Experiencia es necesaria en el seguimientode estos pacientes. La cirugía para implan-tación de estos implantes es bien específica,pero el seguimiento toma bastante tiempo ypuede llevar a gran diferencia en el resultado.

Frecuentes exámenes son necesarios ydeben programarse cada 3 meses en pro-medio. Los problemas que se presentendeben ser identificados a tiempo y resolverlostempranamente. Antibióticos deben serusados en forma crónica y cambiar a diferen-tes clases cada 3 meses. Anti-inflamatoriosson usados e incluyen tetraciclinas, medroxi-progesterona y corticoesteroides. El glauco-ma es monitorizado con campos visuales yestudios del nervio óptico.

Se ha creado el grupo de estudio dequeratoprótesis y puede accederse a élatravéz de la pagina web, www.KPro.org

Figura 3: AlphaCor

Figura 4: Keralia.

1. Carlsson DJ, Li F, Shimmura S, Griffith M: Bio-engineered corneas: how close are we? Curr OpinOphthalmol 2003; 14(4):192-7.2.Dohlman CH, Waller SG, Netland PA. Kerato-prosthesis surgery. In: Lindquist TD, Lindstrom RL,eds. Ophthalmic Surgery; Looseleaf and UpdateService.Chicago,Mosby Year Book;1996:V-L-1-32.3.Falcinelli G, Barogi G, Taloni M. Osteoodonto-keratoprosthesis: Present experience and futureprospects. Refract Corneal Surg 1993; 9: 193-194.4.Falcinelli G, Falsini B, Taloni M, et al. ModifiedOsteo-odonto-keratoprosthesis for Treatment ofCorneal Blindness: Long-term Anatomical andFunctional Outcomes in 181 Cases. Arch Ophthal-mol 2005; 123:1319-29.5.Hille K, Grabner G, Liu C, et al. Standards forModified Osteoodontokeratoprosthesis (OOKP)Surgery According to Strampelli and Falcinelli:TheRome-Vienna Protocol. Cornea 2005; 24:895-9086.Crawford GJ, Hicks CR, Lou X, et al.The Chirilakeratoprosthesis: Phase I human clinical trial.Ophthalmology 2002; 109: 883-889.7.Stoiber J, Fernandez V, Kaminski S, Lamar PD,Dubovy S, Alfonso E, Parel JM. BiologicalResponse to a SupraDescemetic Synthetic Cornea(sDSC) in Rabbits. Arch Ophthalmol 2004;122:1850-1855.8.Stoiber J, Fernandez V, Lamar PD, Kaminski S ,Acosta AC, Dubovy S, Alfonso E, Parel J-M.Biocompatibility of a non-penetrating syntheticcornea in vascularized rabbit corneas. CORNEA2005; 24:467-473.9.Stoiber J, Fernandez V, Lamar PD, Kaminski S,Lacombe E, Duchesne B, Alfonso E, Parel J-M.SupraDescemetic Synthetic Cornea (sDSC): Ex-Vivo Feasibility Study in Human Eye Bank Eyes. AnInstituto Barraquer (Barc.). 2003; 32(3-4):252-256.

REFERENCES:

Diciembre 2005

VISIONPAN-AMERICA4: :

Sindrome de Sjögren: Análise e comparação dos diferentes critérios diagnósticos.

AAuuttoorreess::SSeerrggiioo FFeellbbeerrggOftalmologista. Pós graduando nível Doutorado na Universidade Federal de São Paulo - Escola Paulista de Medicina.Endereço para correspondência:Avenida Brigadeiro Faria Lima, 1597 - 4º andar, conjunto 408. Jd Paulistano. CEP 01452-001. São Paulo/SP. Brasil. e-mail: sergio@oftalmosantacasa.com.br

PPaauulloo EElliiaass CCoorrrreeaa DDaannttaassOftalmologista. Doutor em Medicina pela Universidade de São Paulo.

EEllcciioo HH.. SSaattooOftalmologista. Professor Afiliado da Universidade Federal de São Paulo - Escola Paulista de Medicina.

RESUMO:Atualmente diversos critérios diagnósticos

propostos por diferentes autores são utiliza-dos para estabelecer o diagnóstico da sín-drome de Sjögren. Este estudo analisou ecomparou alguns dos critérios mais utilizadoscomo os de Copenhagen, San Francisco, SanDiego e os do Consenso Americano-Europeu,dentre outros. Não há, até o momento, critérioaceito universalmente para definir síndromede Sjögren. Portanto, devemos proceder comcautela ao comparar estudos clínicos de sín-drome de Sjögren, principalmente quandocritérios de inclusão diferentes foram nelesutilizados.

Olho seco representa uma das doençasoculares mais freqüentemente diagnosticadasna prática oftalmológica diária. Como apre-senta espectro clínico variado e inúmerascondições implicadas na sua gênese, classifi-cações foram propostas por diversos autorescom os objetivos de facilitar seu diagnóstico epropor o tratamento mais adequado. Deacordo com a classificação do olho seco,proposta em 1995 por um grupo de pesqui-sadores e patrocinada pelo NATIONAL EYEINSTITUTE (NEI), as diversas doençasresponsáveis pela gênese do quadro de olhoseco foram separadas em dois grandesgrupos: olho seco causado pela deficiênciaaquosa do filme lacrimal e olho seco causadopelo excesso de evaporação do filmelacrimal1. Embora a classificação propostaseja de grande utilidade e facilite o raciocínioclínico, muitas doenças, durante o curso dasua história natural, causarão olho seco pormecanismos associado.

Na Síndrome de Sjögren, doença deprovável etiologia auto-imune e exemploclássico de olho seco causado por deficiênciada produção lacrimal, na qual a produção deauto-anticorpos contra os ácinos das glân-dulas lacrimais e a infiltração celular sãoresponsáveis diretamente pela redução na

produção do componente aquoso da lágrima,os pacientes podem apresentar na suaevolução, alteração do tempo de ruptura dofilme lacrimal e excesso de evaporação,caracterizando mecanismo misto no estabele-cimento do olho seco. Ainda são incertos osmotivos que levam ao quadro evaporativonestes pacientes, mas suspeita-se que a hi-perosmolaridade do filme lacrimal possa lesaras glândulas de Meibomius ou ainda queauto-anticorpos sejam produzidos tambémcontra as células caliciformes da conjuntiva ea própria glândula de Meibomius2,3.

Na síndrome de Sjogren descrita comoprimária, há comprometimento das glândulasexócrinas, desencadeando quadro clássicode xeroftalmia (olho seco) e xerostomia (bocaseca). Outras mucosas podem estar envolvi-das como as do trato respiratório, do sistemagenito-urinário e do tubo gastrintestinal.Quando o paciente apresenta doença dotecido conectivo associada (artrite reuma-tóide, lúpus eritematoso sistêmico, poliarteritenodosa, dentre outras) a síndrome passa aser classificada como secundária4.

Os auto-anticorpos circulantes freqüente-mente associados à síndrome de Sjogren sãoo SS-A (anti Ro) e o SS-B (anti La) na sín-drome primária e fator reumatóide e fatorantinúcleo na síndrome secundária. A des-truição das glândulas exócrinas por infiltradocelular linfo-plasmocitário pode ser evidencia-da através de biópsia realizada em sítiosdiversos como diretamente na glândulalacrimal principal, nas glândulas salivaresmenores ou ainda, de mais fácil acesso, namucosa labial. Já as conseqüências dadoença, como os quadros de olho seco eboca seca, são diagnosticados com auxílio detestes clínicos como o teste de Schirmer-I e aprova de quantificação fluxo salivar2,3.

Pesquisas na literatura com intenção dedeterminar a incidência desta síndrome napopulação mundial ou em grupos popula-

cionais, poderão fornecer números extrema-mente distintos, mesmo quando uma mesmapopulação seja o objeto do estudo. De acordocom Fox e colaboradores, a incidência dasíndrome pode variar de 0,5% a 3,5% entre asmulheres de um mesmo grupo estudado5.

Este fato é comum a quase todas asdoenças auto-imunes e ocorre quando doisconceitos diferentes são tratados como sendosinônimos: diagnóstico de uma doença Xcritérios diagnósticos de uma doença6. Oprocesso de diagnóstico de uma doença écomplexo e exige raciocínio no qual oconhecimento prévio da história natural destadoença, associado à experiência clínica doobservador e eventualmente aos examessubsidiários permite que se chegue àconclusão da sua entidade causadora. Jácritérios diagnósticos compreendem ferra-mentas ou chaves cujos objetivos são apadronização e a normatização de informa-ções. Tem por objetivo principal facilitar acomunicação e tornar possível a comparaçãode dados, principalmente entre ensaiosclínicos. Desta forma, há sempre a possibi-lidade, quando critérios diagnósticos sãoutilizados, que pacientes realmente portado-res da doença não preencham os critérios(falso-negativos) ou ainda, que pacientes nãoportadores da doença preencham estescritérios (falso-positivos). Critérios diagnós-ticos só poderiam ser utilizados comosinônimos de diagnóstico para uma determi-nada doença, quando apresentarem 100% desensibilidade e 100% de especificidade.

Como no caso da síndrome de Sjögrenexistem inúmeros critérios descritos na lite-ratura (Tabela I) e utilizados para definir estadoença, a incidência dela numa determinadapopulação poderá variar de acordo com ocritério escolhido.

Os critérios podem ser considerados maisconservadores, ou seja, exigem grandequantidade de requisitos para seu preenchimento,

VISIONPAN-AMERICA 5: :

Diciembre 2005

ou ainda, liberais, quando poucos achadossão necessários para definir a doença.Quando critérios conservadores são utiliza-dos, a incidência de determinada doençanuma população tende a ser menor do quequando critérios liberais são utilizados paraeste mesmo grupo.

No caso da síndrome de Sjögren, os critériosde Copenhagen são tidos como liberais ,pois,apenas requisitos clínicos são necessários paraque se estabeleça o diagnóstico da doença7. Jáos chamados critérios Grego8, de San Fran-cisco9 e o de San Diego10 exigem a detecçãode auto-anticorpos circulantes e também debiópsia compatível para que o diagnósticoseja considerado. Dois dos critérios mais utili-zados nos trabalhos que estudam pacientescom síndrome de Sjögren publicados nosúltimos anos (os critérios da ComunidadeEuropéia definidos em 199611 e os critériosestabelecidos pelo Consenso Americano-Europeu em 200212) quando relacionam ossintomas apresentados pelos pacientes,exigem dos pacientes apenas um sintoma deolho seco dentre três apresentados e tambémum sintoma de boca seca, dentre trêsapresentados. De forma distinta, o chamadoCritério Japonês13, amplamente utilizado nostrabalhos publicados por pesquisadores depaíses orientais, exige que o paciente apresen-te dois sintomas que sugiram olho seco etambém dois sintomas que sugiram bocaseca, dentre os mesmos três apresentadosnos critérios anteriormente descritos14.

A tabela II detalha os critérios deCopenhagen, de San Francisco, de SanDiego e do Consenso Americano-Europeu. Ocritério de San Francisco não inclui os doisprincipais sintomas da síndrome: boca seca eolhos secos. O critério de San Diego exigepara o diagnóstico sintomas e sinais de olhoseco, além dos auto-anticorpos e também dabiópsia compatível.

O critério definido pelo Consenso Ameri-cano-Europeu em 2002 representa umarevisão do critério definido por países dacomunidade européia em 1996, no qual foramincluídos diagnósticos de exclusão, quequando presentes, inviabilizam a utilizaçãodeste critério para o estabelecimento dodiagnóstico da síndrome de Sjögren. Alémdisto, este Consenso possibilita ao pesquisa-dor que sejam selecionados pacientessuspeitos de terem a síndrome. A Tabela III compara requisitos exigidos por

três diferentes critérios utiliza-dos para definir síndrome deSjögren.

Como conclusão, é impor-tante observar que não há, atéo momento, critério para de-finir síndrome de Sjögren queseja aceito universalmente.Portanto, devemos procedercom cautela ao compararestudos clínicos de síndromede Sjögren, principalmentequando critérios de inclusãodiferentes foram neles utilizados.

TABELA IIOs critérios de Copenhagen, San Francisco, San Diego e do Consenso

Americano-Europeu

Critérios de Copenhagen:a) XEROFTALMIA: pelo menos 2 das seguintes provas

- Schirmer basal inferior a 10mm- BUT < 10 segundos- Rosa Bengala ? 4 (escala de Van Bijesterveld)

b) XEROSTOMIA: pelo menos 2 das seguintes provas- Sialometria não estimulada inferior a 1,5mL em 15 minutos- Sialocintilografia evidenciando disfunção da glândula salivar- Biópsia glândulo-labial

Critérios de San Francisco para o diagnóstico de SS primária e SSsecundária:- SS primária

a) Biópsia de glândula salivar menor evidenciando sialoadenite focal com infiltração linfocitáriacom mais de 1 "focus"/4mm2 ou lesão beningna linfo-epitelial localizada em glândula salivar maior.b) Diagnóstico de cérato-conjuntivite seca- uso de Rosa Bengala demonstrando comprometimento córneo-conjuntival e- redução do menisco lacrimal ou do tempo de ruptura do filme lacrimal ou- teste de Schirmer I (sem anestésico) menor ou igual a 5mm em 5 minutos

- SS secundáriaa) Presença de artite reumatóide ou outra doença do tecido conectivob) Pelo menos um dos ítens descritos para o diagnóstico da SS primária

- Possível SS: pelo menos um dos ítens descritos para o diagnóstico da SS primária e umadas doenças a seguir: infiltrado linfocítico pulmonar, nefrite intersticial, púrpura, hepatite crônica(sem cirrose ou infecção), neuropatia periférica e hiper-gamaglobulinemia.

Critérios de San Diego para o diagnóstico de SS:a) evidência objetiva de cérato-conjuntivite seca, documentada com coloração por Rosa Bengala ou fluoresceína.b) evidência objetiva da diminuição do fluxo salivar.c) biópsia de glândula salivar menor, contendo pelo menos 4 lóbulos e com presença de pelo menos 2 foci/4mm2.d) Presença de doença auto-imune sistêmica comprovada por auto-anticorpos séricos como FR, FAN, SS-A e SS-B.SS: quando os quatro ítens são encontradosPossível SS: quando três ítens estão presentesExclusão: doenças existentes como linfoma, infecção pelo HIV, uso de medicações que sabidamente causam olho seco, sarcoidose, doença enxerto x hospedeiro.

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Critérios europeus revisados pelo Grupo de Consenso Americano-Europeu:1. Sintomas ocularesPelo menos uma resposta afirmativa para uma das três questões formuladas abaixo:a. Tem problemas oculares diários e persistentes, relacionados a quadro de olho seco há mais de três meses?b. Tem sensação de areia ou queimação ocular?c. Usa colírios lubrificantes mais de três vezes ao dia?2. Sintomas oraisPelo menos uma resposta afirmativa para uma das três questões formuladas abaixo:a. Tem sensação de boca seca há mais de três meses?b. Tem inchaço recorrente ou persistente das glândulas salivares, na idade adulta?c. Sente necessidade de ingerir líquidos para ajudar na deglutição de alimentos sólidos?3. Sinais ocularesEvidencia de modo objetivo o comprometimento ocular, quando pelo menos um dos dois testes abaixo é positivo.a. Teste de Schirmer I (< 5 mm em 5 minutos)b. Rosa Bengala (> 4 pontos na escala de Bijsterveld)4. Achados histopatológicosAglomeração de pelo menos 50 células mononucleares numa biópsia de 4mm2 da glândula salivar.5. Comprometimento da glândula salivarEvidencia de modo objetivo o comprometimento das glândulas salivares, com pelo menos um dos três métodos abaixo.a. Cintilografia da glândula salivarb. Sialografia da glândula parótidac. Fluxo salivar sem estimulo reflexo (<1.5 mL in 15 minutes)6. Auto-anticorposPresença de pelo menos um dos seguintes auto-anticorpos séricos:a. Anticorpos contra os antígenos Ro/SS-A ou La/SS-Bb. Anticorpos anti-nuclearc. Fator reumatóideCritérios de exclusão: Linfoma pré-existente, AIDS, sarcoidose ou doença do enxerto x hospedeiro.Provável SS primária: Presença de pelo menos 3 dos 6 ítens.SS primária: Presença de pelo menos 4 dos 6 ítens (aceitando como padrão sorológico positivo apenas SS-A ou SS-B)Provável SS secundária: Combinação da resposta positiva para os ítens 1 ou 2 com pelo menos 1 ítem positivos entre as questões 3,4 ou 5.SS secundária: Combinação da resposta positiva para os ítens 1 ou 2 com pelo menos 2 ítens positivos entre as questões 3, 4 ou 5.

TABELA III:Comparação dos requisitos exigidos entre três critérios diferentes

NOME do CRITÉRIO Consenso Americano-Europeu Critérios Japoneses Critérios de CopenhagenNecessidade de sintomas oculares subjetivos sim não nãoNecessidade de sintomas orais objetivos sim não nãoNúmero mínimo de testes que comprovemxerostomia 1 2 2

Número mínimo de testes que comprovemxeroftalmia 1 2 2

Número de focus necessário na biópsia demucosa labial > 1 focus/4mm2 > 1 focus/4mm2 > 1 focus/4mm2

Presença de SS-A e SS-B e/ou biópsiacompatível Totalmente necessário Não necessário Não necessário

1. Lemp M. Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. CLAO J1995;21(4):221-32.2. Jonsson R, Moen K, Vestrheim D, Szodoray P. Current issues in Sjögren´s syndrome. Oral Dis2002;8(3):130-40.3. Rehman H. Sjögren syndrome.Yonsei Med J 2003;44(6):947-54.4. Ramos-Casals M,Tzioufas AG, Font J. Sjogren syndrome. New therapeutic approaches. Med Clin (Barc)2005;124(3):111-5.5. Fox RI,Tornwall J, Michelson P. Current issues in the diagnosis and treatment of Sjögren´s syndrome.Curr Opin Rheumatol 1999;11(5):364-71.6. Vitali C. Classification criteria for Sjögren´s syndrome. Ann Rheum Dis 2003;62(1):94-96.7. Manthorpe R, Oxholm P, Prause JU, Schiödt M.The Copenhagen criteria for Sjögren´s syndrome. ScandJ Rheumatol 1986;61:19-21.8. Skopouli FN, Drosos AA, Papaioannou T, Moutsopoulos HM. Preliminary diagnostic criteria forSjogren's syndrome.Scand J Rheumatol 1986;61:22-5.9. Fox RI, SaitoI. Criteria for diagnosis of Sjogren's syndrome. Rheum Dis Clin North Am1994;20(2):391-407.10. Fox RI, Robinson C, Curd JC, Michelson P, Kozin F, Howell FV. Sjögren´s syndrome: proposed criteriafor classification. Arthitis Rheum 1986;29(5):577-85.11. Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, Bjerrum KB,

Braga S, Coll J, de Vita S, et al. Preliminary classification criteria for Sjögren´s syndrome. Results of aprospective concerted action supported by the European Community. Arthitis Rheum 1993;36(3):340-7.12. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, FoxPC, Fox RI, Kassan SS, Pillemer SR,Talal N,Weisman MH. Classification criteria for Sjögren´s syndrome:a revised version of the European criteria proposed by the American-European Consensus Group. AnnRheum Dis 2002;61(6):554-8.13. Fujibayashi T, Sugai S, Miyasaka S, Ichikawa Y, et al. Criteria for the diagnosis of Sjögren´s syndrome(Japanese criteria III). Supported by the Ministry of Health and Welfare of Japan. In:1999 Annual reportsof research group of autoimmune disease 1999;135-8.14. Manthorpe R. Sjögren´s syndrome criteria: American-European and Japanese Group´s criteriacompared and contrasted. Ann Rheum Dis 2002;61(6):482-484.15. Vitali C, Bombardieri S, Moutsopoulos HM, Coll J, Gerli R, Hatron PY, Kater L, et al. Assessment ofthe European classification criteria for Sjogren's syndrome in a series of clinically defined cases: results ofa prospective multicentre study.The European Study Group on Diagnostic Criteria for Sjogren's Syndrome.Ann Rheum Dis. 1996;55(2):116-21.16. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, LiangMH, Luthra HS, et al.The American Rheumatism Association 1987 revised criteria for the classificationof rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315-24.

REFERÊNCIAS BIBLIOGRÁFICAS

focus = presença de mais de 50 linfócitos em 4mm2 de tecido biopsiadoFonte: Manthorpe R. Sjögren´s syndrome criteria: American-European and Japanese Group´s criteria compared and contrasted. Ann Rheum Dis 2002;61:482-484.

ABSTRACTPurpose: to report a case of metastaticsclerochoroidal calcification is a rare ocularentity characterized by yellow-white irregularsubretinal lesions. These lesions are causedby the deposition of calcium salts at the levelof the sclera and choroid, in patients withabnormal calcium and phosphate metabolism.

METHODS: CASE REPORTA 52 year-old asymptomatic woman under-went a routine ophthalmic examination. Pastmedical history was remarkable for end-stagerenal insufficiency on haemodialysis asso-ciated with secondary hyperparathyroidism.Visual acuities, anterior segment examinationand intraocular pressures were within normallimits. Fundoscopic examination revealedbilateral symmetric subretinal yellow whitecluster-like lesions located above the superiorvascular arcades. Fluorescein angiography,ultrasonographic and computerized tomogra-phy studies were obtained; their resultsconfirmed our clinical diagnosis of metastaticsclerochoroidal calcification.

CONCLUSIONSclerochoroidal calcification, a rare and poorlyrecognized disease with a characteristicpattern, should be included in the differentialdiagnosis of yellow-white lesions in the retina.A complete anamnesis to rule out possiblecalcium homeostasis abnormalities can behelpful.

BACKGROUNDSclerochoroidal calcification is a rare andoften misdiagnosed entity1,2 characterized byyellow-white irregular subretinal lesions.These lesions are caused by the deposition ofcalcium salts at the level of the sclera andchoroid, and can occur in three varietiesaccording to its origin: metastatic, dystrophicand idiopathic. Even though several casesand series have been reported in theliterature,1-5 it remains poorly recognized andis often misdiagnosed.2-5 Thus, increa-sedawareness of this diagnosis is warranted.

IIvvaann GG.. CCaassttiilllloo MMDDDepartment of Ophthalmology, Virginia Commonwealth University School of Medicine,Medical College of Virginia Campus, Richmond, VA 23298, USA

CCaannddiiccee CC.. HHuuaanngg MMDDDepartment of Ophthalmology, Virginia Commonwealth University School of Medicine, MedicalCollege of Virginia Campus, Richmond, VA 23298, USA

SStteepphheenn GG.. SScchhwwaarrttzz MMDDAssociate Professor of Ophthalmology Department of Ophthalmology, University of Miami School of Medicine, Bascom Palmer EyeInstitute, 311 9th Street North, Naples FL 34102, USAE-mail: sschwartz2@med.miami.edu

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Metastatic sclerochoroidal calcification: Case Report

Case report:

A 52 year-old asymptomatic white female presented for a routine eye examination. Pastmedical history was remarkable for end-stage renal insufficiency with secondary hyperpara-thyroidism. Family history was non-contributory. Her medications included anti-hypertensiveagents, as well as doxercalciferol, a synthetic vitamin D analogue used for the management ofsecondary hyperparathyroidism.

Best-corrected visual acuity was 20/20 OU. External examination, pupillary responses andanterior segment biomicroscopy were unremarkable. Goldman applanation tonometries were 12mm Hg OD and 14 mm Hg OS. Fundoscopic examination revealed normal discs, macula andvessels. Bilateral clustered yellow-white placoid lesions were noted in the temporal mid-peripherynear the superior temporal vascular arcades. The lesions had a central area of loss of the retinalpigment epithelium surrounded by a yellowish halo.(Figure 1)

The lesions demonstrated autofluores-cence with the red-free filter.Fluorescein angiography revealed mild to moderate hypofluorescence in the arterial phase

with patchy hyperfluo-rescence in the venous phase and late staining.(Figure 2) B-scanultrasonography showed dense lesions with high internal reflectivity and orbital shadowing com-

Figure 1: (Left and Right)

Clinical fundus photographs showing bilateral yellow-white lesions along the superotemporal arcades and macula

left eye.

Figure 2:

Left: Red free fundus photograph showing autoflurescence of the plaques. Center: Venous phase of the fluorescein

angiogram showing patchy hyperfluorescence of the lesions. Right: Late phase of the fluorescein angiogram

showing diffuse staining.

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compatible with calcification.(Figure 3) Compu-ted tomography of the head and orbitsdemonstrated the presence of bilateralsymmetric calcific scleral lesions.(Figure 4)Ionized calcium level was between 4.9 and 6.0(normal 4.4-5.3). Parathyroid hormone levelwas 329 pg/ml (Normal 75-150 pg/ml).

Discussion

In general, pathologic calcification in the eyecan be dystrophic, metastatic or idiopathic.Sclerochoroidal calcification can occur in allthree clinical settings. Metastatic calcificationis defined as extraskeletal tissue deposition ofcalcium salts in patients with abnormal cal-cium metabolism6,7. This type of calcificationcan occur in conditions like vitamin D intoxi-cation8, sarcoidosis9, hypophosphatemia10,pseudohypoparathyroidism11, chronic renalfailure12, pseudogout13 and hyperparathy-roidism14. Dystrophic calcification usuallyoccurs in areas of cell injury or necrosis6,7 andis associated with chronic inflammation,scleritis15, trauma, phthisis bulbi, retino-blastoma, Coats disease5, Cogan's senilescleral plaques16 and band keratopathy. Thethird type of calcification, of idiopathic orunknown etiology presents in asymptomaticpatients without calcium and phosphorusmetabolism abnormalities1,3,5.

Clinical FeaturesTypically sclerochoroidal calcification presents

as clusters of bilateral and symmetrical,multifocal flat (plaque-like) to raised (tumor-like) creamy white to yellow-orange lesions1,4,located in the midperiphery mainly near thesuperotemporal arcade in visually asympto-matic patients1,3,17 but can be locatedinferiorly or elsewhere in the eye18 includingthe foveal region.14 Lesions are bilateral in 40

to 80 percent of cases.4,18 Choroidal neovas-cularization can complicate sclerochoroidalcalcification2,19-21 and can cause visual loss. 19

The pathogenesis of sclerochoroidalcalcification is uncertain. Some authors be-lieve that the characteristic pattern of thislesion is caused by calcium deposition in oraround the lobules of the choroidalcirculation22. Other authors have theorizedthat the calcification originates in the scleraand only involves the choroid secondarily.18.

Clinically and histopathologically, sclerocho-roidal calcification has been compared toCogan's scleral plaques.5

Ancillary testingFundus photography typically reveals

autofluorescence. Fluorescein angiographynormally demonstrates central hypofluo-rescence in the arterial phase, due to atrophyof the choriocapillaris and overlying retinalpigment epithelium. There is moderate hyper-fluorescence in the venous phase, and latehomogeneous hyperfluorescence2,18. Themost important ancillary tests are ultrasono-graphy and computed tomography18. B-scanultrasonography shows a highly reflectiveplaque in the choroid with marked shadowingbehind the lesion. A-scan ultrasonographydemonstrates high reflectivity and posteriororbital shadowing.5,17 Computed tomographyof the orbits typically reveals a calcifiedplaque-like lesion at the level of the sclera andchoroid.1,17

Associated diseasesSclerochoroidal calcification may occur with

various ocular inflammatory diseases, such asscleritis. Associated systemic diseasesinclude primary and secondary hyperpara-

thyroidism, pseudohypoparathyroidism, Bartterand Gitelman syndromes, pseudogout, andglomerulonephritis. Primary hyperparathy-roidism represents an autonomous, sponta-neous overproduction of parathyroid hormone.

The traditional constellation of symptomsincludes "painful bones, renal stones,abdominal groans, and psychic moans." Thedisease is more common in adults thanchildren, typically occurs in women, and isoften caused by a parathyroid adenoma. Themost common laboratory abnormalities arehypercalcemia, hypophosphatemia and in-creased urinary excretion of both calcium andphosphate.

Secondary hyperparathyroidism is mainlycaused by chronic renal failure. It is morecommon in children than adults. The renalinsufficiency leads to decreased phosphateexcretion and serum hyperphosphatemia. Theelevated serum phosphate levels depressserum calcium levels and thereby stimulateparathyroid gland activity. Therefore, untrea-ted secondary hyperparathyroidism is asso-ciated with hypocalcemia and hyperphospha-temia.23

Bartter and Gitelman syndromes are thetwo major variants of familial hypokalemic,hypochloremic alkalosis. Patients with Barttersyndrome demonstrate polyuria and polydip-sia. They have hypertrophy and hyperplasia ofthe juxtaglomerular apparatus of the kidneyswith elevation of serum angiotensin II,aldosterone, and renin. They may have anincrease in urinary calcium excretion, andsome exhibit hypomagnesemia. Prostaglandinsynthesis and excretion is significantly in-creased and may account for much of thesystemic symptoms.24 Gitelman syndrome ismore common and less severe than Barttersyndrome. Morbidity relates to muscularsymptoms and fatigue. Patients with Gitelmansyndrome demonstrate hypocalciuria andhypomagnesemia. Although plasma reninactivity may be increased, renal prostaglandinexcretion is not elevated.25 Finally, pseu-dogout is a clinical manifestation of a crystal-induced synovitis resulting from the depositionof calcium pyrophosphate dehydrate (CPPD)crystals in joint hyaline and fibrocartilage. Thecartilage deposition, chrondrocalcinosis, ispresent in more than 20% of the population inthe eighth decade, but is usually asympto-matic. Symptoms are similar to those of goutyarthritis with acute attacks and chronicinflammation. The knees and wrists arecommonly affected. The etiology is unknown,and is often associated with various medical

Figure 3:

Combined A and B-scan ultrasonography of the

right eye showing dense lesions with high internal

reflectivity and orbital shadowing compatible with

calcification.

Figure 4:

Computed tomography of the head and orbits

demonstrated the presence of bilateral symmetric

calcific scleral lesions.

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Diciembre 2005

conditions, including hyperparathyroidism,hypothyroidism, hemochromatosis, hypomag-nesemia and amyloidosis. Therefore, newlydiagnosed CPPD should be followed up withserum measurements of calcium, magnesium,phosphorus, thyroid-stimulating hormone,ferritin, and alkaline phosphatase. Therapyincludes non steroidal anti-inflammatoryagents, joint immobilization, and intraarticularsteroids.26,27

ConclusionMetastatic sclerochoroidal calcification is

associated with abnormalities in calciumhomeostasis. Usually presents as a plaquelike, white-yellowish cluster of lesions, thatappear to follow the choroidal vasculaturepattern. They can be located more frequentlyin the mid- periphery along the superotem-poral arcades but can seen in other locationsincluding the foveal region. It is a unique entitywith typical clinical, fluorescein angiography,ultrasonographic and computerized tomogra-phy characteristics. Differential diagnosis include: choroidalosteoma, choroidal metastasis, amelanoticchoroidal nevus, and choroidal granuloma.

Abstract

AIM: To assess the long term effect ofintravitreal triamcinolone acetonide (IVTA) onintraocular pressure (IOP) in patients withmacular edema.

METHODS: A retrospective case review wasperformed to identify all patients treated withIVTA at a university based retina practicebetween March 2003 and January 2004.Baseline IOP was calculated using the meanmeasurement from three previous visits andchanges in IOP were followed after IVTAinjection.

RESULTS: A total of 35 eyes of 23 patientswere identified. Each patient was injectedwith 0.1ml (4mg) of 40mg/ml triamcinoloneacetonide. Responders were defined as mild(elevation 5-10mm Hg), moderate (11-15mmHg), and severe (over 15mm Hg elevation)elevation in IOP from baseline. 23 of the 35eyes (66%) were classified as IVTA respon-ders. Mean time to IOP elevation was 42 days.Of those patients with elevated IOP, 15 (65%)required topical hypotensive treatment andone patient required trabeculectomy. Eleven(48%) patients remain on topical therapy andmean time of therapy for all IOP responderswas 352 days at last follow up. Nine of ten

central retina vein occlusion (CRVO) patientshad an elevation in IOP classified as moderateor severe. Mean IOP elevation in the CRVOgroup was 12.3 mm Hg.

CONCLUSIONS: Elevated intraocular pre-ssure is a frequently observed sequela ofIVTA treatment and may require long termhypotensive topical medication. Preoperativediagnosis of CRVO has a strong correlationwith IOP spikes requiring treatment, anincreased number of antiglaucoma medica-tions once therapy is initiated, and in somecases, filtering surgery.

1. Munier F, Zografos L, Schnyder P. Idiopathic sclerochoroidalcalcification: new observations. Eur J Ophthalmol 1991; 1 (4): 167-172.2. Honavar SG, Shields CL, Demirci H, Shields JA. Sclerochoroidalcalcification: clinical manifestations and systemic associations. ArchOphthalmol 2001; 119 (6): 833-840.3. Lim JI, Goldberg MF. Idiopathic sclerochoroidal calcification. Casereport. Arch Ophthalmol 1989; 107 (8): 1122-1123.4. Schachat AP, Robertson DM, Mieler WF, et al. Sclerochoroidalcalcification. Arch Ophthalmol 1992; 110 (2): 196-199.5. Sivalingam A, Shields CL, Shields JA, et al. Idiopathicsclerochoroidal calcification. Ophthalmology 1991; 98 (5): 720-724.6. Howes EL, Rao NA. Basic Mechanisms in pathology. Calcifications,in: Spencer WH ed. Ophthalmic Pathology: An Atlas and Textbook.Chap 13. p. 2948-2949. W.B. Saunders Co., Philadephia, 19967. Suzuki J, Takeda M, Sekine N, et al. Bilateral metastaticsclerochoroidal calcification in a patient with hyperparathyroidism.Ophthalmologica 1992; 205 (1): 10-14.8. Gartner S, Rubner K. Calcified sceral nodules and hypervitaminosis.Am J Ophthalmol 1955; 39 : 658-663.9. Hassenstein A, Bialasiewicz AA, Knospe V, Richard G. [Incidence ofocular manifestations in patients with histologically confirmedsystemic sarcoidosis]. Klin Monatsbl Augenheilkd 2003; 220 (6): 414-417.10. Caldemeyer KS, Smith RR, Edwards-Brown MK. Familialhypophosphatemic rickets causing ocular calcification and optic canalnarrowing. AJNR Am J Neuroradiol 1995; 16 (6): 1252-1254.11. Wong S, Zakov ZN, Albert DM. Scleral and choroidalcalcifications in a patient with pseudohypoparathyroidism. Br JOphthalmol 1979; 63 (3): 177-180.12. Harris LS, Cohn K, Toyofuku H, et al. Conjunctival and cornealcalcific deposits in uremic patients. Am J Ophthalmol 1971; 72 (1):130-133.13. Shields JA. Sclerochoroidal calcification in calcium pyrophosphatedihydrate deposition disease (pseudogout). Arch Ophthalmol 1997;115 (8): 1077-1079.14. Floegel I, Klein A, Langmann G. Metastatic sclerochoroidalcalcification involving the fovea. Retina 2002; 22 (4): 503-505.

15. Saatci AO, Kaynak S, Kazanci L, et al. Calcification at theposterior pole in scleritis. A case report. Int Ophthalmol 1996; 20 (5):285-287.16. Cogan DG, Kuwabara T. Focal senile translucency of the sclera.Arch Ophthalmol 1959; 62 : 604-610.17. Goldstein BG, Miller J. Metastatic calcification of the choroid in apatient with primary hyperparathyroidism. Retina 1982; 2 (2): 76-79.18. Shields JA, Shields CL. CME review: sclerochoroidal calcification:the 2001 Harold Gifford Lecture. Retina 2002; 22 (3): 251-261.19. Cohen SY, Guyot-Sionnest M, Puech M. Choroidalneovascularization as a late complication of hyperparathyroidism. AmJ Ophthalmol 1998; 126 (2): 320-322.20. Leys A, Stalmans P, Blanckaert J. Sclerochoroidal calcificationwith choroidal neovascularization. Arch Ophthalmol 2000; 118 (6):854-857.21. Zaheen M, Sellar W, Mucci B. Idiopathic sclerochoroidalcalcification. Eye 2000; 14 ( Pt 4) : 681-684.22. O'Driscoll AM, Quraishy MM, Andrew NC. Choroidal calcificationin primary hyperparathyroidism. Eye 1995; 9 ( Pt 6) : 804-806.23. Cotran RS, Kumar V, Collins T. The Endocrine System, RobbinsPathologic Basis of Disease. Chap 26. p. 1121-1169. W.B. SaundersCompany, Philadephia, 199924. Bartter FC, Pronove P, Gill JR, Jr., MacCardle RC. Hyperplasia ofthe juxtaglomerular complex with hyperaldosteronism andhypokalemic alkalosis. A new syndrome. Am J Med 1962; 33 : 811-828.25. Gitelman HJ, Graham JB, Welt LG. A new familial disordercharacterized by hypokalemia and hypomagnesemia.Trans Assoc AmPhysicians 1966; 79 : 221-235.26. Mercier LJ. Pseudogout, in: Ferri FF ed. Ferri's Clinical Advisor:Instant Diagnosis and Treatment. p. 709. Mosby, Philadephia, 200427. Gravel JW, Jr., Pastan RS. Rheumatology and MusculoskeletalProblems, in: Rakel RE ed. Rakel:Textbook of Family Practice. Chap40. p. 950-991. W.B. Saunders Company, Philadephia, 2002

Reference List

MMaalliikk YY.. KKaahhooookk,, MMDDCorresponding AuthorThe University of Colorado Health Sciences CenterRocky Mountain Lions Eye InstituteP.O. BOX 65101675 N. Ursula St.Campus Box F731Aurora, CO 80045USAOffice (330) 414-4897Fax (720) 848-5014Malik.kahook@gmail.com

JJeeffffeerryy LL.. OOllssoonn,, MMDDThe University of Colorado Health Sciences CenterRocky Mountain Lions Eye Institute

NNaarreesshh MMaannddaavvaa,, MMDDThe University of Colorado Health Sciences CenterRocky Mountain Lions Eye Institute

Long Term Follow-Up of Intraocular Pressure Elevation in Patients Post Intravitreal Triamcinolone Acetonide Injection

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VISIONPAN-AMERICA10: :

Introduction

Secondary chronic open angle glaucomahas become an increasingly recognized sideeffect of intravitreal triamcinolone acetonide(IVTA) injections. The frequency and level ofintraocular pressure (IOP) elevation havebeen reported at various doses and for manyvariable diseases. It has also become increa-singly apparent that the level and frequency ofIOP elevation may depend on the originaldiagnosis for which IVTA is being used. Weseek to report our long term follow up data forpatients receiving IVTA for different diseaseprocesses and shed light on the cost-benefitratio for treating macular edema in patientsmore likely to suffer from dangerous eleva-tions of IOP.

Patients and MethodsA retrospective case review was performed

to identify all patients treated with IVTA at auniversity based retina practice betweenMarch 2003 and January 2004. The study wasapproved by the institutional review board atthe University of Colorado Health SciencesCenter. A total of 35 eyes of 23 patients wereidentified. Any patient who had undergonepars plana vitrectomy was excluded. Afterobtaining informed consent, each patient wasinjected with 0.1ml (4mg) of 40mg/mltriamcinolone acetonide. Clinical work upincluded visual acuity, slit lamp examination,Goldmann applanation and dilated fundus-copic exam. Data points were followedthrough April 2005 unless cataract surgery,trabeculectomy, or pars plana vitrectomy wasdone during the follow up period beingreviewed, in which case final data points weretaken prior to the surgery. Responders weredefined as mild (elevation 5-10mm Hg),moderate (11-15mm Hg), and severe (over15mm Hg elevation) elevation in IOP frombaseline. Baseline IOP was calculated byaveraging results from three previouspressure measurements taken at our eyeinstitute. Mean follow up time was 451.2 daysfor all eyes studied.

Results

Of the 35 eyes studied, one carried thediagnosis of cystoid macular edema (CME)post phacoemulsification, five were diagnosedwith age related macular degeneration, tenwith central retinal vein occlusion (CRVO),one with branch retinal vein occlusion(BRVO), 16 with diabetic macular edema(DME), and two with macular edemaassociated with posterior uveitis (Figure 1).

23 of the 35 eyes (66%) were classified asIVTA responders using our criteria to defineIOP elevation (Figure 2). Mean time to IOPelevation was 42 days. Fifteen patients hadmild IOP increase, five patients had moderatespikes, and three patients had severe spikesgreater than 15mm Hg. Mean follow up timefor steroid responders was 497.3 days. Ofthose patients with elevated IOP, 15 (65%)required topical hypotensive treatment. Onepatient required trabeculectomy after failingmaximum medical therapy. For thosesuccessfully treated with topical therapy, anaverage of 1.8 medications was necessary fortreatment. Patients with elevated IOP whowere diagnosed with CRVO required a meanof 2.5 medications to control their pressure.Eleven (48%) patients remain on topicaltherapy and mean time of medication therapyfor all IOP responders was 352 days at lastfollow up.

A closer look at the IVTA responders revealsan interesting breakdown of frequency by pre-injection diagnosis. Of concern was that nineof ten CRVO (six nonischemic and threeischemic) patients had an elevation in IOPclassified as moderate or severe. Mean IOPelevation in the CRVO group was 12.3 mmHg. One patient in this group requiredtrabeculectomy and remains on two topicalmedications for IOP control. The remainingseven of eight other CRVO responder patientsremain on topical medications for pressurecontrol at last follow up.

Also of note, 13 of the 35 (37%) eyesstudied developed posterior subcapsularcataracts (PSC) when none existed prior toinjection. Of these 13 patients, eight (61.5%)were among the steroid responder group.

Four of the eight patients who developed

PSC had cataract extraction and have shownimprovement in visual acuity following surgery.

Discussion

IVTA has been used to treat retinal diseasesassociated with macular edema includingDME, edema secondary to CRVO, and CMEpost phacoemulsification. The efficacy of IVTAin decreasing macular thickness is well docu-mented and in many cases leads to improvedvisual function. The success of this treatmentmust be viewed in terms of possible sideeffects of steroids on the eye. It is well knowthat topical steroids can lead to extremeelevations in intraocular pressure.1 What hasbecome increasingly clear is that IVTA leads tosimilar, if not more extreme, increases withoutthe benefit of being able to discontinue thesteroid effect by merely stopping the topicaldrop regimen.

Many studies have been published toelucidate the level of IOP increase in postIVTA patient populations.2,3,4 A study by Jonasand colleagues reviewed the IOP response in75 eyes of patients diagnosed with age relatedexudative macular degeneration or diabeticmacular edema.2 They noted a pressure riseto a level greater than 21mm Hg in 52% of thestudy population at a mean of 2 months. Ofthese, all but one eye was controlled on to-pical medication. The remaining case was in apatient with known preoperative glaucoma,which required filtering surgery for control. Allpatients had normalized their IOP by sixmonths and were taken off of topical medi-cation. This study used 25mg of IVTA fortreatment and concluded that IVTA was a safeand efficacious treatment for macular edemain their study population. A second study byJonas et al looked at IOP response after 20mg

Figure 2:

Percent IVTA responders

CME

60.00%

2.8%

14.3%

28.6%

2.8%

45.7%

5.7%

40.00%

20.00%

0.00%

AMD

CRVO

BRVO

DME

Uveitis

VISIONPAN-AMERICA 11: :

Diciembre 2005

IVTA injections and noted an IOP rise in 41.2%of patients at a mean follow up of 10.4+/-6.7months.3 IOP began to rise at one week andreturned to base line at approximately ninemonths post injections.

A more recent study by Smithen andcolleagues reported the incidence of IOPelevation in 89 patients post IVTA injection.4

Thirty six patients (40.4%) experienced IOPelevation over 24mm Hg at a mean of 100.6days post injection. Follow up time was 280.5days and the dose used was also 4mg in0.1ml. They noted a relationship betweenpreoperative pressure and likelihood of steroidresponse. Those patients with baseline IOPless than 15mm Hg who were not diagnosedwith glaucoma previously were less likely toexperience pressure spikes above 24mm Hg.Twelve of the 89 (13.5%) patients carried thediagnosis of glaucoma prior to IVTA injectionand most patients (80.9%) were diagnosedwith age related macular degeneration.

Our study includes a cross section ofpatients currently being treated with IVTA formacular edema. We noted a larger IOPincrease in patients diagnosed with CRVO.These patients were more likely to respond toIVTA with pressure spikes and ultimately morelikely to reach higher pressures requiring moreintensive topical medication treatment and, inone case, filtering surgery.

Previous studies looking at CRVO and IVTAtreatment have shown variable percentages ofpatients showing IOP response.5, 6, 7 In a studyby Bashshur, et al. looking at 20 nonischemicCRVO patients post IVTA, three had IOPspikes from baseline.5 The IOP level did notgo higher than 25mm Hg and was treated withtimolol 0.5% with discontinuation of treatmentby three months.

A second study looking at both ischemicand nonischemic CRVO post IVTA by Ip andcolleagues revealed only one of thirteenpatients with elevated IOP post injection.6The dose used in this study was 4mg and thesingle responder had the nonischemic form ofCRVO. There was no statistically significantdifference in intraocular pressure responsebetween ischemic and nonischemic eyes.Finally, a third study looking at CRVO and postIVTA IOP response looked at nine patientspost 4mg/0.1ml triamcinolone acetonideinjection and noted that seven of the ninepatients experienced pressure spikes of atleast 6mm Hg.7 One patient required parsplana vitrectomy to remove the steroid depotfor pressure control after IOP spiked to 56mmHg and failed medical treatment. We are

unable to explain the disparity in the rate ofIOP rise post IVTA injection in CRVO patientsnoted in this study and those noted above. Inour practice, however, it is clear that CRVOpatients carry an increased risk of intraocularpressure post IVTA and should be followedclosely post treatment to intervene at theearliest possible time.

Limitations of this study include smallpopulation size and the retrospective studydesign. We also include both eyes of patientstreated for bilateral disease, which could havean influence on the high percentage ofresponders. Strengths include the calculationof baseline IOP by reviewing three visits priorto IVTA injection. Most studies have calculatedbaseline IOP measurement based solely onIOP at the time of injection. We also have alonger period of follow up which is, to ourknowledge, the longest in patients injectedwith 4mg of triamcinolone acetonide.

In conclusion, the use of IVTA injections forthe treatment of macular edema is increasing.Elevated intraocular pressure is a frequentlyobserved sequela of this treatment modalityand may require long term hypotensive topicalmedication administration. The preoperativediagnosis of central retinal vein occlusion hasa strong correlation with intraocular pressurespikes requiring treatment with increasednumber of antiglaucoma medications, and insome cases, filtering surgery. Also, patientsundergoing IVTA, and especially those whohave pressure spikes, are at increased risk ofdeveloping PSC cataracts as has beenpreviously reported.8 It is important thatpatients are informed about the long termimplications of side effects involved with IVTAtreatment.

1. Becker B, Ballin N. Glaucoma and corticosteroidprovocative testing. Arch Ophthalmol 1965;74:621-4.2. Jonas JB, Kreissig I, Degenring R. Intraocularpressure after intravitreal injection of triamcinoloneacetonide. Br J Ophthalmol 2003;87 (1):24-7.3. Jonas JB, Degenring RF, Kreissig I, et al. Intraocularpressure elevation after intravitreal triamcinoloneacetonide injection. Ophthalmology 2005; 112 (4):593-8.4. Smithen LM, Ober MD, Maranan L, et al. Intravitrealtriamcinolone acetonide and intraocular pressure. Am JOphthalmol 2004;138 (5):740-3.5. Bashshur ZF, Ma'luf RN, Allam S, et al. Intravitrealtriamcinolone for the management of macular edemadue to nonischemic central retinal vein occlusion. ArchOphthalmol 2004;122 (8):1137-40.6. Ip MS, Gottlieb JL, Kahana A, et al. Intravitrealtriamcinolone for the treatment of macular edemaassociated with central retinal vein occlusion. ArchOphthalmol 2004;122 (8):1131-6.7. Kaushik S, Gupta V, Gupta A, Dogra MR, Singh R.Intractable glaucoma following intravitrealtriamcinolone in central retinal vein occlusion. Am JOphthalmol 2004;137 (4):758-60.8. Gillies MC, Kuzniarz M, Craig J, et al. Intravitrealtriamcinolone-induced elevated intraocular pressure isassociated with the development of posteriorsubcapsular cataract. Ophthalmology 2005;112(1):139-43.

Reference

Sponsors/acknowledgements and a

competing interest

The authors have no sponsors or

competing interests related to this

manuscript

Diciembre 2005

VISIONPAN-AMERICA12: :

Gillingham Pan-American Fellowship. Two (2) six-month fellowships in the amount of $10,000 each are offered per year to qualified Latin Americancandidates in a variety of subspecialty interests at various institutions in the United States and Canada. Funding provided by Retina ResearchFoundation of Houston, Texas. The applicant should be a general ophthalmologist, no more than 2 to 3 years out of his/her residency program, andfrom the Caribbean, Mexico, Central, or South America and have been already accepted into an accredited fellowship program in the United Statesor Canada.

Vinicius Saraiva, MD (Retina) from São Paulo, BrazilReceiving Institution: Capital Health Institute of Halifax, Canada

David & Julianna Pyott Fellowship in Retina. One (1) scholarship in the amount of $20,000 is offered per annum for two years to a fully-qualifiedOphthalmologist from a Latin American country (outside of Brazil and Mexico), to spend 2 years at the University of California, Irvine, Department ofOphthalmology as an international retina fellow participating in research and clinical work under the supervision of Dr. Baruch Kuppermann, AssociateProfessor Ophthalmology. Funding provided by David & Julianna Pyott for the advancement of education in ophthalmology throughout the world.Applicants should have completed a residency in Ophthalmology, speak fluent conversational English, and be interested in a career in Retina annuallyto Pan-American members for advanced training.

Ana Laura Gramajo, MD (Retina) from Córdoba, ArgentinaReceiving Institution: University of California in Irvine

Paul Kayser International Scholar Program. Up to eight (8) two-week scholarships are offered to North American (US and Canadian) candidatesfor the purpose of introducing exceptional North American ophthalmologists to the best practice and research approaches in Latin America andCanada. The stipend is $3,000 and funding provided by Retina Research Foundation of Houston, Texas.

Tim & Judith Sear Scholarship for the Advancement of Ophthalmology. One (1) scholarship in the amount of $4,000 is offered annually to Pan-American members. Funding is provided by the Tim & Judith Sear Foundation. This scholarship recognizes potential future professors and leaderswithin the organization and is for the advancement of education in ophthalmology throughout the world. The applicant should be a generalophthalmologist, no more than 2 to 3 years out of his/her residency program, and from the Caribbean, Mexico, Central, or South America.

Reinaldo A. García Arismendi, MD (Retina) from Caracas, VenezuelaReceiving Institution: Retina Consultants of Charleston, SC

Tyson ARVO/PAAO Travel Scholarship. Up to five (5) travel scholarships are awarded to Latin American candidates yearly, in the amount of $2,500,to attend the ARVO (Association for Research in Vision and Ophthalmology) annual meeting. The candidate must be recommended to the PAAO bythe ophthalmology department chairman or national ophthalmological society affiliated with the PAAO. Funding provided by Retina ResearchFoundation of Houston, Texas. These awards are given in February prior to the ARVO meeting.

William C. Conner Scholarship One (1) scholarship in the amount of $4,000 is offered biennially to Latin American candidates. Candidates must beoutstanding students who have presented papers or published during their training period. Funding provided by the Pan-American OphthalmologicalFoundation. The applicant should be a general ophthalmologist, no more than 2 to 3 years out of his/her residency program, and from the Caribbean,Mexico, Central, or South America.

Carmen Elena de la Paz Lizana-Henriquez, MD (Retina) from Rancagua, ChileReceiving Institution: Conde de Valenciana, MexicoCity, Mexico

1. Robison Chan, MD (Retina/Vitreous)Massachussettes Eye & Ear, Boston, USA

2. Howard Chen, MD (Retina/Vitreous)University of Toronto, Toronto, Canada

3. Emma L. Clay, MD (Uveitis)Jules Stein Eye Institute, Los Angeles, USA

4. Gary R. Fishman, MD (Cornea/Refractive)New York Eye & Ear Infirmary, NYC, USA

5. David A. Goldman, MD (Cornea)Bascom Palmer Eye Institute, Miami, USA

6. Srilakshmi Maguluri, MD (ROP)Vanderbilt Eye Institute, Nashville, USA

7. William Porfilio, MD (Oculoplastics/General)St Louis Univ. Eye Institute, St. Louis, USA

8. Homayoun Tabandeh, MD (General/Retina)Wilmer Eye Institute, Baltimore, USA

Pan-American Ophthalmological Foundation2006 Fellowships & Scholarship Awards Report*

*Additional scholarships are available but were not awarded for 2006. Please contact the PAAO Administrative Office for complete details at 1301 South Bowen Road, Suite 365, Arlington,Texas 76013 USA. Tel.: 817.275.7553; Fax 817.275.3961 or email: info@paao.org.

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 VisualField 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 Bimatoprostand 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 ofOphthalmol, New Orleans, La, 2001.

Preserva la visión alcanzando las menorespresiones-objetivo en más pacientes

Mejor comodidad posológica:

1 vez al día.

No requiere refrigeración.

Presentación conteniendo 3 ml.

LLLLLumiganumiganumiganumiganumigan® ® ® ® ® (bimatoprost) Forma farmacéutica y prForma farmacéutica y prForma farmacéutica y prForma farmacéutica y prForma farmacéutica y presentación.esentación.esentación.esentación.esentación.Frascos cuenta-gotas conteniendo 5 ml de solución oftalmológica estéril de bimatoprost a 0,03%. USO ADULTO.Composición. Composición. Composición. Composición. Composición. Cada ml contiene: 0,3 mg de bimatoprost. Vehículo: cloreto de sódio, fosfato de sódiohepta-hidratado, ácido cítrico mono-hidratado, ácido clorídrico y/o hidróxido de sódio, cloruro de benzalconio y agua purificada qsp. Indicaciones.Indicaciones.Indicaciones.Indicaciones.Indicaciones. LUMIGAN®®®®® (bimatoprost) es indicado para la reducción de la presión intra-ocular elevada en pacientes con glaucona o hipertensiónocular.Contraindicaciones.Contraindicaciones.Contraindicaciones.Contraindicaciones.Contraindicaciones. LUMIGAN®®®®® (bimatoprost) está contraindicado en pacientes con hipersensibilidad al bimatoprost o cualquier otro componente de la fórmula del producto. Pr Pr Pr Pr Precauciones y Adverecauciones y Adverecauciones y Adverecauciones y Adverecauciones y Advertencias.tencias.tencias.tencias.tencias. Advertencias. Fueron relatados aumento gradual del crescimientode 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 después6 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 tratamientode apenas uno de los ojos, deben ser informados a respecto de esas reacciones. PrPrPrPrPrecaucionesecaucionesecaucionesecaucionesecauciones 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 debenser 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 medicamentode 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.Interacciones medicamentosas.Interacciones medicamentosas.Interacciones medicamentosas.Interacciones medicamentosas.Considerando que las concentracionescirculantes 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.No son conocidas incompatibilidades. R R R R Reacciones adversas.eacciones adversas.eacciones adversas.eacciones adversas.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, durante3 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 infeccionesde 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,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 y Administración.Posología y Administración.Posología y Administración.Posología y Administración.Posología y 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 oftálmicostópicos 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 HAYANINDICADO 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.

vs. timolol 4 vs. latanoprost6

Porcentaje de Pacientes quealcanzaron la PIO-Objetivo ≤≤≤≤≤14 21% 9% 17% 2% 19% 9%

Porcentaje de Pacientes quealcanzaron la PIO-Objetivo ≤≤≤≤≤15 31% 16% 24% 9% 29% 14%

dorzolamida/ timolol 5vs.

®®®

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

Investigadores de diversos estudios, (AGIS, Shirakashi, Shields)han comprobado que alcanzar y mantener la PIO entre 14 y 15 mmHgreduce la progresión de pérdida del campo visual1,2,3.