Volumen IX No.2 Junio 2010

ACUTE STEVENS-JOHNSON SYNDROME: OPHTHALMOLOGIC ACUTE STEVENS-JOHNSON SYNDROME: OPHTHALMOLOGIC EVALUATION AND MANAGEMENTEVALUATION AND MANAGEMENTDarren G. Gregory MD

EVOLUCIÓN DE LAS ALTERACIONES EN EL SEGMENTO ANTERIOR DEL GLOBO EVOLUCIÓN DE LAS ALTERACIONES EN EL SEGMENTO ANTERIOR DEL GLOBO OCULAR EN NIÑOS PORTADORES DE ENFERMEDADES REUMÁTICASOCULAR EN NIÑOS PORTADORES DE ENFERMEDADES REUMÁTICASElena Joa Miró MD PhD

CONJUNCTIVAL VERSUS LIMBAL-CONJUNCTIVAL AUTOGRAFT IN PRIMARY PTERYGIUM CONJUNCTIVAL VERSUS LIMBAL-CONJUNCTIVAL AUTOGRAFT IN PRIMARY PTERYGIUM SURGERY: DO LIMBAL CELLS MAKE A DIFFERENCE?SURGERY: DO LIMBAL CELLS MAKE A DIFFERENCE?Olga Alvarez-Bulnes MD; Josep Gracia-Martínez MD; María Teresa Sellares-Fabres PhD; Xavier Nuñez Pérez MD; Alfons Casale-Turu MD; Josep Visa-Nasarre MD; Manuel Alejandro Romera MD

SINGLE SUBRETINAL DOSE OF BEVACIZUMAB (AVASTIN) FOR THE TREATMENT OF CHOROIDAL SINGLE SUBRETINAL DOSE OF BEVACIZUMAB (AVASTIN) FOR THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION. ONE-YEAR FOLLOW-UP.NEOVASCULARIZATION IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION. ONE-YEAR FOLLOW-UP.Juan P. Pusterla MD; María A. Williams MD; Ana L. Gramajo MD; Gustavo A. Colombres MD; Aneesh Neekhra MD; Claudio P. Juárez MD PhD; José D. Luna MD

¿ES UN SIMPLE ORZUELO Ó ES ALGO MÁS?¿ES UN SIMPLE ORZUELO Ó ES ALGO MÁS?Chun Cheng Lin Yang MD MSc; Manuela Gongora Moraga RN; Carmen Maria González López PharmD; John D. McCann MD PhD

ORBITAL GRANULOCYTIC SARCOMA WITHOUT SYSTEMIC MANIFESTATIONORBITAL GRANULOCYTIC SARCOMA WITHOUT SYSTEMIC MANIFESTATIONAlexandre Nakao Odashiro MD, PhD; Patrícia Rusa Pereira Odashiro MD; Maçanori Odashiro MD; Lívio Viana O. Leite MD, PhD; Priscila Inácio Fernandes Zaupa MD; Atalla Mnayarji MD; Bruno F. Fernandes MD, PhD; Shawn C Maloney MSc; Miguel N. Burnier Jr MD PhD

AMANTADINE-INDUCED CORNEAL EDEMA IN A PATIENT WITH PARKINSON’S AMANTADINE-INDUCED CORNEAL EDEMA IN A PATIENT WITH PARKINSON’S DISEASE AND EARLY FUCHS’ ENDOTHELIAL DYSTROPHYDISEASE AND EARLY FUCHS’ ENDOTHELIAL DYSTROPHYJay C. Bradley MD; Brian S. Phelps MD

CATARACT SURGERY IN THE GLAUCOMA PATIENTCATARACT SURGERY IN THE GLAUCOMA PATIENTBrooks J Poley, MD, Richard L Lindstrom, MD, Thomas W Samuelson, MD, Richard R. Schulze, MD

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.

Febrero 2009

PAN-AMERICA : BPAN-AMERICA

Mark J. Mannis, MDUniversity of California, Davis

Sacramento, CaliforniaEditor-in-Chief

Cristian Luco, MDSantiago, ChileAssociate Editor

Teresa J. BradshawArlington, TexasManaging Editor

Terri L. GrassiArlington, TexasProduction Editor

EDITORIAL BOARD

Eduardo Alfonso, MDMiami, Florida USA

Eduardo Arenas, MDBogotá, Colombia

J. Fernando Arévalo, MDCaracas, Venezuela

José A. Roca Fernández, MDLima, Perú

Denise de Freitas, MDSão Paulo, Brazil

Marian Macsai, MDChicago, Illinois USA

David E. Pelayes, MD PhDBuenos Aires, Argentina

Alfredo Sadun, MDLos Angeles, California USA

Allan Slomovic, MDToronto, Ontario, Canada

Luciene Barbosa de Sousa, MDSão Paulo, Brazil

Lihteh Wu, MDSan José, Costa Rica

Paulo Dantas, MDSão Paulo, Brazil

Chun Cheng Lin Yang, MD MScSan José, Costa Rica

OFFICERS

Cristián Luco MDSantiago, Chile

President, Pan-American Association of Ophthalmology

Nelson R. MarquesSão Paulo, Brazil

Chairman of the Board,Pan-American Ophthalmological Foundation

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Special thanks to Ana Carolina Vieira, Citlali Gurrusquieta, Mapy Padilla, and Cristián Luco for assistance in translation to Spanish and Portuguese.

Junio 2010

Cristian Luco, MDPresidente PAAO 2009-2011President PAAO 2009-2011Presidente PAAO 2009-2011

34 PAN-AMERICA

MENSAJE DEL PRESIDENTE / MESSAGE FROM THE PRESIDENT

Editorial Editorial

La PAAO es la unión de las sociedades oftalmológicas naciona-les desde el Ártico a la Antártica, incluyendo Portugal y España.

Ellos son nuestros mandantes y nosotros somos el equipo que debe ejecutar este mandamiento. Pero… ¿Cómo es posible aunar las necesidades de sociedades tan diferentes como por ejemplo Ca-nadá y Haití? La PAAO es una entidad supranacional que actúa como un paraguas bajo el cual se juntan todas las sociedades nacionales. Debe tratar de conocer las necesidades nacionales y regionales y ver si dentro de sus posibilidades puede resolverlas. Debe conocer los hechos político-económicos oftalmológicos de cada región o de cada área o país y tratar que nuestros tres pilares, educación, prevención de ceguera y amistad y entendimiento entre los oftalmólogos, se utilicen para solucionar los problemas actuales y a futuro. Debemos interac-tuar con la fuerza activa de la oftalmología de cada país, desde los más antiguos con su experiencia a los más nuevos con sus sueños, su modernidad, actualidad y poder de acción. La PAAO debe tener una idea global de los problemas locales, pero las soluciones deben ser regionales. Pero conocer los problemas sólo es posible con una comunicación fluida entre la PAAO y las sociedades nacionales.

No será la primera ni la última vez que exprese que es funda-mental la comunicación entre sociedades nacionales y la PAAO, y con esta información empezar a movernos en el camino correcto.

Un gran saludo,Cristián Luco

Presidente

The PAAO is the union of national ophthalmological societies from the Arctic to the Antarctic, including Portugal and Spain.

These are our constituents, and we are charged with carrying out their mandate. But… how it is possible to fulfill the needs of societies from countries as different as, for example, Canada and Haiti? The PAAO is a supranational organization that serves as an umbrella under which all the national societies are joined. It must understand national and regional needs and determine if it is within the organization’s ability to help address them. It must clearly understand the ophtalmo-politico-economic facts of each region or country and to apply the three pillars of our mission--education, prevention of blindness and collegiality between oph-thalmologists -- to solve present and future problems. We must respond to the strengths of ophthalmology in each country, from the oldest and most experienced to the newest with its dreams for the future and its potential for development. The PAAO must have a global concept of local problems, but the specific solutions must be regional. This will only be possible with fluid communication between the PAAO and the national societies.

It is neither the first nor last time that we emphasize how fun-damental is open communication between the national societies and the PAAO, and with this information we can begin to move in the right direction.

Warmest greetings,Cristian Luco

President

PAN-AMERICA : 35PAN-AMERICA

Junio 2010

Acute Stevens-Johnson Syndrome:Ophthalmologic Evaluation and Management

Darren G. Gregory MDAssociate Professor of OphthalmologyRocky Mountain Lions Eye InstituteUniversity of Colorado, DenverAurora, Colorado, USA

Abstract: Stevens-Johnson syndrome (SJS) and toxic epidermal necrol-

ysis (TEN) can cause significant damage to the ocular surface and eyelids. The intense inflammation during the acute phase may lead to scarring sequelae and vision loss. Treatment of the chronic manifestations is challenging and only partially effective in many cases. Ophthalmologic evaluation and management during the acute phase is crucial in avoiding these problems. The evaluation and management of patients with SJS and TEN is described, with an emphasis on amniotic membrane transplantation as an effective means of limiting the acute phase damage.

IntroductionStevens-Johnson Syndrome (SJS) is a rare, acute blistering

disease involving the skin and mucous membranes. The inci-dence of SJS is approximately 6 cases per million persons per year.1,2 The most severe form, toxic epidermal necrolysis (TEN), involves >30% of the body surface and can be life-threatening. TEN is less common, with an incidence of approximately 1-2 cases per million persons per year.1,2 These diseases are most commonly drug-induced and produce extensive blistering and sloughing of the epidermis, similar to a second degree burn. Their effects on the ocular surface can be devastating, leaving some survivors with severe dry eye problems, debilitating pho-tophobia and decreased vision. This article will review recent developments in the evaluation and management of the acute ocular manifestations of these diseases.

EvaluationA significant majority of patients with acute SJS/TEN will have

ophthalmic pathology.3-5 Damage to the ocular surface is caused by widespread cell death and necrosis in the deep epidermal lay-ers, as well the intense inflammation that can follow. The ophthal-mic pathology mainly involves the bulbar and palpebral conjunc-tiva, but can also involve the cornea, lid margins, eyelashes and eyelid skin.

Milder cases are characterized by a conjunctivitis that may yield localized conjunctival epithelial defects. Fluorescein stain-ing is crucial in the evaluation of disease severity and can be easily done at the bedside. The fornices must be inspected to look for hidden areas of sloughing (Figure 1). The mouth can also give insight into the state of affairs on the ocular surface. It is rare to have significant ocular inflammation without the mouth and lips

being similarly affected (Figure 2). Daily inspection and rinsing of the ocular surface with saline should be performed. The buildup of mucus and debris on the cornea not only makes evaluation dif-ficult, but also increases the risk of infectious keratitis. The daily exam must include fluorescein staining to assess for progression of epithelial sloughing. The fornices should be swept using a muscle hook or scleral depressor. The formation of necrotic membranes indicates an intense level of inflammation that will likely require more significant ophthalmologic treatments. A cotton-tipped swab can be used to clean debris from the fornices. The swab can also be used to assess whether areas of fluorescein staining are ne-crotic membranes or simply debris. Membranes will bleed with

Address correspondence, proof, and reprint requests to:Darren G. Gregory MDRocky Mountain Lions Eye Institute, 1675 Aurora Ct, Mailstop F.731, Aurora, CO 80045-0510Tel: (720) 848-2500Fax: (720) 848-5014Email: darren.gregory@ucdenver.eduProprietary interest: None

Figure 1

Figure 2

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attempted removal and should prompt a higher level of concern.

More severe cases yield diffuse, de-structive conjunctival inflammation with pseudomembranous and membranous conjunctivitis. Fluorescein staining is ex-tensive, involving much of the ocular sur-face (Figure 3). Skin loss on other parts of the body can vary, however, and should not be used to judge the situation on the eye (i.e. mucous membrane involvement may be severe despite limited external skin involvement). Discomfort and pho-tophobia tend to be more pronounced in severe cases, but these patients may be intubated and unable to communicate their symptoms. The raw surfaces can lead to adhesion formation between the palpebral and bulbar conjunctiva, known as symblepharon. Although the formation of the symblepharon is concerning, the larger problem is the underlying intense inflammation that has actually produced the symblepharon. Such inflammation can destroy goblet cells and accessory lacrimal glands, as well as the secretory ductules of the main lacrimal gland.4 The normal mucosal structure of the conjunc-tiva may eventually be replaced by a cica-tricial epithelium.6 More recent treatments using amniotic membrane transplantation (AMT) or pulsed, high-dose systemic cor-ticosteroids have focused on suppressing this destructive inflammation in the acute phase. AMT will be covered in more de-tail and should be considered for all cases with extensive fluorescein staining of the conjunctiva and lid margins.

The eyelids may also suffer significant

damage and can be a major source of long term morbidity. Lid margin inflamma-tion can yield widespread destruction of meibomian gland orifices and the glands themselves.6 Scarring can affect both eye-lid and eyelash architecture, resulting in entropion, trichiasis and distichiasis. The abnormally directed lashes can abrade the compromised ocular surface and lead to discomfort, corneal abrasions, and cor-neal ulceration. Keratinization of the lid margins and palpebral conjunctiva further contributes to discomfort and corneal damage via blink-related microtrauma to the corneal epithelium.6 Scarring of the tarsal conjunctiva has been associated with more severe chronic problems,6 so any sloughing of the tarsal conjunctiva is particularly concerning. Daily examination must include careful inspection of the for-nices and tarsal conjunctiva.

Severe cases can also cause limbal stem cell failure, probably from injury during the acute phase combined with ongoing damage from the abnormal tear film and mucosal surfaces. The resultant opacification and “conjunctivalization” of the cornea can lead to significantly de-creased vision. The prognosis for corneal transplantation in such cases is poor.

ManagementA. Medical Management

The widespread loss of skin and mu-cous membranes in SJS/TEN can lead to sepsis and pneumonia, with mortality rates approaching 40% in some series.7 Early referral to a facility experienced in the care of burn patients significantly

decreases mortality rates.8-10 The life-threatening problems, however, can ini-tially cause the eye situation to be less of a priority. It is important for the ophthal-mologist to educate the appropriate staff in these facilities regarding the need for urgent ophthalmologic evaluation of all SJS/TEN patients. Patients with milder skin involvement may still have severe ophthalmic inflammation and need prompt and persistent ophthalmologic evaluation during the acute phase.

The ophthalmologic management of acute SJS/TEN should focus on infection prophylaxis, symblepharon prevention, and minimization of destructive inflammation. A recent report has suggested that high dose systemic and topical corticosteroids initiated within 4 days of the onset of ill-ness may significantly decrease ocular surface damage.11 The authors concluded that to minimize the potential adverse ef-fects of systemic corticosteroid treatment it was crucial to begin the pulse of ste-roids before any significant skin slough-ing had occurred. The use of systemic corticosteroids has been controversial, however, with some studies suggesting an increased risk of mortality with such treat-ment.12 Additionally, many patients may not receive ophthalmologic evaluation until after significant skin sloughing has actually begun, putting them beyond the safe timeframe for initiation of systemic corticosteroid therapy.

Milder cases with nonmembranous conjunctivitis and no lid margin or corneal involvement may be managed with daily inspection. Many will not progress to more

Figure 3 Figure 4

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Junio 2010

severe involvement, but close monitor-ing is still required until it is clear that no progression is occurring. Topical antibiot-ics and anti-inflammatory agents such as cyclosporine or corticosteroid drops may be used. Such cases have a low risk of yielding long term sequelae. If membra-nous conjunctivitis, symblepharon or lid margin sloughing develop, however, then urgent AMT should be considered. Sym-blepharon formation indicates an intense level of ocular surface inflammation. Sym-blepharon lysis and the placement of sym-blepharon rings may prevent further sym-blepharon formation, but they do nothing to address the destructive inflammation

that has caused the symblepharon to form in the first place.

B. Surgical managementCryopreserved amniotic membrane

grafting to the ocular surfaces during the acute phase of SJS and TEN has been described in multiple case reports and 1 small case series.6,13-17 Its use in this set-ting has also been summarized in 2 differ-ent reviews.18,19 No reports exist describing the use of freeze-dried amniotic membrane in the treatment SJS or TEN. AMT ap-pears beneficial if applied during the first 2 weeks of illness, the earlier the better.

The membranes degrade within 7-10 days, though, and may need to be reapplied in more severe cases with persistent mucosal sloughing. Although the application pro-cedure can be performed under local an-esthesia at the bedside, it is preferable to do it under an operating microscope in a surgical suite whenever possible.

The AMT should completely cover the lid margins, palpebral conjunctiva and ocular surface, including the cornea. To achieve this, one half of a 3.5 cm2 sheet of cryopreserved AM (Amniograft®, Bio-Tis-sue, Miami, FL) is used on each eyelid and a full 3.5 cm2 sheet is used on the ocular surface. For the eyelids, the eyelashes are trimmed and a long edge of the AM is laid along the eyelid margin with the stromal surface against the skin. It is fixated along the eyelid margin using a running 8-0 ny-lon suture with suture bites placed along the external eyelid skin approximately 2mm from the lid margin. The remainder of this AM sheet is then wrapped over the lid margin and tucked into the fornix using a muscle hook. Both ends of a double-armed 6-0 polypropylene suture are then passed through the AM in the fornix and full thick-ness through the eyelid to be tied over bol-sters on the external eyelid skin surface. The twin suture passes are placed about 1cm apart. Two such sutures and bolsters are used on each eyelid (Figure 4).

Following the application of AM to each eyelid, a full 3.5 cm2 piece is cen-tered over the cornea and sutured to the conjunctiva using a 10-0 nylon suture run-ning circumferentially around the cornea 1-2mm posterior to the limbus. Prior to removing the AM from the nitrocellulose filter paper, a mark is placed on the cen-ter point of the AM sheet to ensure that it stays properly centered during positioning and suturing. To limit bleeding, drops of 1:1000 epinephrine are applied to the ocu-lar surface prior to suturing. After place-ment of the perilimbal running suture, a muscle hook is used to rotate the eye so that single interrupted 10-0 nylon sutures can placed in each oblique quadrant and at the medial and lateral canthi. The tails of all the sutures are left long enough to lay flat on the ocular surface.

A symblepharon ring is placed over the eye at the end of the case to help maintain the fornices and to improve the contact between the amniotic membrane and the

Figure 5

Figure 6

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REFERENCES1. Roujeau JC, Guillaume JC, Fabre JP, et al. Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981-1985. Arch Dermatol 1990;126:37-42

2. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epi-dermal necrolysis. N Engl J Med 1995;333:1600-7

3. Power WJ, Ghoraishi M, Merayo-Lloves J, et al. Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum. Ophthalmol-ogy 1995;102:1669-76

4. Chang Y, Huang F, Tseng S, et al. Erythema mul-tiforme, Stevens-Johnson syndrome, and toxic epider-mal necrolysis: acute ocular manifestations, causes, and management. Cornea 2007;26:123-9

5. De Rojas MV, Dart JKG, Saw VPJ. The natural his-tory of Stevens-Johnson syndrome: patterns of chronic ocular disease and the role systemic immunosuppres-sive therapy. Br J Ophthalmol 2007;91:1048-53

6. Di Pascuale MA, Espana EM, Liu DT, et al. Cor-relation of corneal complications with eyelid cicatricial pathologies in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome. Ophthalmol-ogy 2005;112:904-12

7. Haber J, Hopman W, Gomez M, Cartotto R. Late outcomes in adult survivors of toxic epidermal necroly-sis after treatment in a burn center. J Burn Care Reha-bil 2005;26:33-41

8. Kelemen JJ, Cioffi WG, McManus WF, et al. Burn center care for patients with toxic epidermal necroly-sis. J Am Coll Surg 1995;180:273-8

9. Murphy JT, Purdue GF, Hunt JL. Toxic epidermal necrolysis. J Burn Care Rehabil 1997;18:417-20

10. McGee T, Munster A. Toxic epidermal necroly-sis syndrome; mortality rate reduced with early re-ferral to regional burn center. Plast Reconstr Surg 1998;102:1018-22

11. Araki Y, Sotozono C, Inatomi T, et al. Success-ful treatment of Stevens-Johnson syndrome with steroid pulse at disease onset. Am J Ophthalmol 2009;147:1004-11

12. Halebian PH, Shires GT. Burn unit treatment of acute, severe exfoliating disorders. Ann Rev Med 1989;40:137-47

13. Shammas MC, Lai EC, Sarkar JS, et al. Manage-ment of acute Stevens-Johnson syndrome and toxic epidermal necrolysis utilizing amniotic membrane and topical steroids. Am J Ophthalmol 2010;149:203-13

14. John T, Foulks GN, John ME, et al. Amniotic membrane in the surgical management of acute toxic epidermal necrolysis. Ophthalmology 2002;109:351-60

15. Kobayashi A, Yoshita T, Sugiyama K, et al. Amni-otic membrane transplantation in acute phase of toxic epidermal necrolysis with severe corneal involvement. Ophthalmology 2006;113:126-132

16. Muquit M, Ellingham R, Daniel C. Technique of amniotic membrane transplant dressing in the man-agement of acute Stevens-Johnson syndrome. Br J Ophthalmol 2007;91:1536

17. Tandon A, Cackett P, Mulvihill A, Fleck B. Amni-otic membrane grafting for conjunctival and lid surface disease in the acute phase of toxic epidermal necroly-sis. J AAPOS 2007;11:612-3

18. Gregory DG. The ophthalmologic manage-ment of acute Stevens-Johnson syndrome. Ocul Surf 2008;2:87-93

19. Shay E, Kheirkhah A, Liang L, et al. Amniotic membrane as a new therapy for the acute ocular mani-festations of Stevens-Johnson syndrome and toxic epi-dermal necrolysis. Surv Ophthalmol 2009;54:686-96

20. Meller D, Pires RT, Mack RJ, et al. Amniotic membrane transplantation for acute chemical or ther-mal burns. Ophthalmology 2000;107:980-90

mucosal surfaces. A Prokera® (Bio-Tissue, Miami, FL) should be used on the ocular surface only in cases with corneal involve-ment and very limited sloughing of the bulbar conjunctiva. It is not an adequate substitute for covering the entire ocular surface with a sheet of AM. A Prokera® is basically a 16mm diameter symblepharon ring with a sheet of AM stretched across the ring like a drum. It can be placed di-rectly on the eye like a contact lens, but its small diameter only covers the cornea and perilimbal areas. Significant damage may still occur in the large areas of conjunctiva that the Prokera® does not cover.

C. Postoperative carePostoperatively, the eyes are inspect-

ed daily and rinsed with sterile saline. The buildup of ointment and serosan-guinous debris can be significant (Figure 5). The corneas are evaluated carefully for the presence of infiltrates under the AM. Any persistent lagophthalmos must also be addressed as it can yield drying of the AM and increase the risk for infec-tious keratitis. A plastic wrap moisture chamber or a partial temporary tarsor-rhaphy may be applied, depending on the severity of exposure. Topical quinolone antibiotics are applied 4 times per day. Topical corticosteroid and cyclosporine drops cyclosporine 0.5% (Restasis®, Allergan, Irvine, CA) are also applied 2 times per day. Combination tobramycin/dexamethasone ointment (Tobradex®, Alcon, Fort Worth, TX) is applied to the eyelid margins and eyelashes 4 times per day to minimize inflammation and prevent desiccation of the lid margin AM. It is important to educate the nursing staff in the proper application of the medications. The membranes will degrade in 1-2 weeks and can be reapplied to areas of persis-tent, severe inflammation if needed.

ConclusionsSJS and TEN are among the worst dis-

eases of the ocular surface. In severe cas-es, topical medical treatments during the acute phase do not effectively prevent the permanent, serious problems of profound dry eye and photophobia. Late attempts to repair the long term cicatricial sequelae are difficult and prone to failure. Recently, the application of cryopreserved amniotic

membrane to the eyes and eyelids during the acute phase of the disease has shown great promise in preventing both the cica-tricial sequelae and the dry eye problems (Figure 6). In severe cases, prompt inter-vention with amniotic membrane grafting during the acute phase is crucial, as the window of opportunity is short and the potential consequences of the disease are dire.

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AbstractThe current study illustrates the evolution

of the active uveitis found in 15 children two years after initiating treatment; the number of patients in whom the uveitis was treated and controlled; and the duration and the manner of treatment

The evolution of other alterations found is also shown including synechiae, capsular opacities, band keratopathy and pathologic cataract, in the same time period.

Resumen:En el presente trabajo se muestra la

evolución de las uveítis en actividad halla-da en estos 15 niños dos años después de iniciado el tratamiento; en cuántos pacientes se logró controlar y hacer desaparecer, en cuánto tiempo y cómo. Se muestra también la evolución de las otras alteraciones que se hallaron tales como sinequias, opacidades capsulares, queratopatía en banda y catarata patológica, en el mismo lapso.

IntroducciónDesde 1967 en el Hospital Infantil Uni-

versitario “Pedro Borrás” de La Habana tra-baja un equipo formado por pediatras, reu-matólogos y oftalmólogos para el tratamiento

de enfermedades reumatológicas en el niño. Desde su constitución, formo parte de ese equipo como oftalmóloga.

Los oftalmólogos tienen a su cargo el examen oftalmológico de todos los pacien-tes que presenten enfermedades reumatoló-gicas y, en caso de que presenten alteracio-nes oftalmológicas, imponer el tratamiento necesario. Todos los pacientes son vistos de forma integral y después de realizarles los exámenes pertinentes de cada espe-cialidad, se discute el tratamiento que lle-varán por cada una de las especialidades. Periódicamente se revisa la evolución y se decide si se deben realizar cambios en el tratamiento o no.

En el tratamiento sistémico los medica-mentos son impuestos y controlados por los reumatólogos y los pediatras. En caso de que el paciente presente alteraciones oculares, el oftalmólogo sigue la evolución conjun-tamente con ellos para decidir si hace falta hacer cambios en el tratamiento. Los medi-camentos sistémicos más utilizados son Me-trotexate, Inmuran, Azulfidina, Prednisolona y Ciclosporina A.

Hace muchos años existía un proverbio médico que decía: “que la fiebre reumática lamía las articulaciones y mordía el corazón” y en relación con las alteraciones sistémicas

y la uveítis anterior podemos parafrasear lo mismo. Cuando coexisten ambas, las alte-raciones sistémicas, en general, responden rápidamente al tratamiento, mientras que las oftalmológicas, que a veces se encuentran en actividad sin que haya manifestaciones sistémicas, demoran mucho tiempo en ser controladas. De esto se desprende que el paciente deba ser examinado periódicamen-te por el oftalmólogo aunque no se presente alteración sistémica.

Por la parte oftalmológica, todos los pa-cientes que no presentan alteraciones activas son examinados como mínimo tres veces por año. Si se presenta una uveítis anterior activa o cualquier otra alteración, se impone trata-miento local y se monitorea la evolución del tratamiento mediante consultas al paciente con una frecuencia de dos veces por sema-na hasta que sea necesario. Si al cabo de un mes la uveítis no ha comenzado a disminuir, se valora el tratamiento sistémico con el fin de cambiar o añadir medicamentos, según la evolución de la uveítis.

Tratamiento OftalmológicoEn los 15 niños portadores de enfer-

medades reumáticas en quienes se com-probó la presencia de uveítis anterior y, en algunos casos, de otras alteraciones se

Evolución de las alteraciones en el segmento anterior del globo ocular en niños portadores de enfermedades reumáticas

Elena Joa Miró MD PhD

Profesora TitularHospital Infantil Universitario “Pedro Borrás”, La Habana, CubaEmail: elena.joa@infomed.sld.cu

(1) Joa Miró, Elena. Manifestaciones oculares en algunas enfermedades reumáticas en el niño. Vision Pan-America. Volumen VII No.1 Febrero 2008. pp. 9-11

Palabras claves: enfermedades reumáticas, uveítis anterior, queratopatía en banda, sinequias

Fig.2 Uveítis anterior recurrente, Sinequia posterior soldada, opacidad capsular posterior desaparecida, esta fi gura corresponde a la paciente anterior.

Fig.1 Uveítis Anterior con sinequias posterior y opacidad capsular posterior.

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comenzó el tratamiento después de haber obtenido el consentimien-to de los padres. De estos 15 niños, 9 eran portadores de artritis juvenil idiomática (60%), 4 eran portadores de espóndilo artropa-tía indiferenciada (27%), 1 de artritis reactiva (6.5%) y 1 de artritis psoriásica (6.5 %).

En general, para las uveítis anteriores comenzamos con inmuno-supresores esteroideos, como Prednisolona en colirio, Diclofenaco en colirio u otro semejante, acompañado por midriático ciclopégico como Atropina al 1% en colirio, haya presencia de sinequias o no. Si la uveítis no responde a los tratamientos anteriores, se utiliza la Ciclosporina A en colirio.

Si hay sinequias y logramos romperlas con la Atropina, cambia-mos a la Homatropina al 2%. Si al cabo de 2 semanas no se ha logrado romper las sinequias con el colirio, se administra Atropina por vía subconjutival.

Cuando el niño presenta opacidades capsulares y/o queratopatía en banda, indico además vitamina C oral (1000 mg diarios). Para la queratopatía en banda prescribo, además de la vitamina C oral, Clo-ruro de Sodio hipertónico en colirio.

Para indicar vitamina C oral, me baso en los conocimientos de bioquímica que dicen que el humor acuoso es el fluido del cuerpo humano que presenta la mayor cantidad de vitamina C, un 20% más que los demás. Tomando en cuenta que conjuntamente con el iris, se inflama el cuerpo ciliar por ser parte de la úvea anterior, y que una de las funciones del mismo es la producción del humor acuoso, deduzco que la calidad del humor acuoso no debe ser óptima. Puesto que tanto el cristalino como la córnea son nutridos por este humor acuoso, las opacidades del cristalino y la queratopatía en banda, son producto de un humor acuoso defectuoso. Es por ello que, tratando de mejorar la calidad del acuoso, indico la vitamina C. De igual manera, considero que la cantidad de humor acuoso no es la que se produce normalmente; de ahí que en estos pacientes con uveítis anterior, cuyo tratamiento conlleva medicamentos locales y sistémicos que normal-mente son capaces de producir hipertensión ocular, esta se presenta en estos pacientes con uveítis solo en muy contadas ocasiones.

EvoluciónDe los 15 pacientes que presentaron uveítis anteriores, sólo en 1

paciente se controló la uveítis y desapareció en dos meses (uveítis subaguda); en 10 pacientes, el control y la desaparición de la misma tomó más de cinco meses (uveítis anterior crónica); otros 3 evolucio-naron de forma recurrente, es decir, después de desaparecer, al cabo de algún tiempo volvieron a aparecer; y en 1 paciente no se ha podido controlar la uveítis y continúa activa.

Es de señalar que el paciente en el cual la uveítis desapareció en dos meses era portador de artritis psoriásica. De los 10 pacientes en los cuales la uveítis desapareció en más de cinco meses, 1 era portador de artritis reactiva; 4 eran portadores de artritis reactiva y 5, de AJI. Los 3 casos de uveítis recurrente y el caso no controlado, eran portadores de AJI.

En 5 de las uveítis se encontró la presencia de sinequias: 4 con sinequias posteriores y 1 con sinequia anterior y posterior. En 2 pa-cientes se mantienen las sinequias posteriores; uno de ellos era tam-bién portador de sinequia anterior, la cual sí se logró desprender, en la foto se ven claramente los restos de iris en la cara posterior de la córnea y el iris atrofiado en este sector. Los 2 pacientes que man-

Fig.3 Uveítis Anterior con sinequias anterior y posterior.

Fig.5 Uveítis Anterior con opacidades capsulares posterior.

Fig.4 Sinequia anterior rota. Sinequia posterior continúa, a partir de ella Uveítis Recurrente Activa. Opacidad capsular posterior desapareció. Atrofi a Iridiana a partir de la Sinequia. Es la paciente de la fi gura anterior.

Fig.6 Uveítis Anterior. Opacidad capsular anterior y posterior. Esta foto corresponde a la paciente de la fi gura anterior en la cual la uveítis nunca ha podido ser controlada totalmente y después de haber desaparecido la opacidad capsular posterior, ha vuelto a aparecer.

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tienen las sinequias posteriores presentan uveítis recurrente y siempre es a partir de estas sinequias, donde va a comenzar la nueva uveítis.

Las opacidades capsulares del cristalino se presentaron en los 3 pacientes que evo-lucionaron de forma recurrente y también en el que no se ha logrado controlar. En los pa-cientes con uveítis recurrente, la opacidad era capsular posterior y desapareció. No sucedió lo mismo con el otro paciente cuyas opacida-des eran anteriores y posteriores. Debo hacer notar que este paciente que no logra controlar la uveítis, a diferencia del resto de los niños, no concurre regularmente a consulta, ni cum-ple el tratamiento indicado.

La agudeza visual de los pacientes re-gistrada al inicio y al final de los dos años, no muestra grandes diferencias. Tanto la

fibrina y los pigmentos, así como las opa-cidades capsulares, se inician en la peri-feria, por lo que el paciente tiene toda el área pupilar libre y, como casi siempre el humor acuoso está transparente, práctica-mente nunca se presenta disminución de la agudeza visual. Todos los casos que tra-tamos con uveítis, incluidos aquellos con opacidades capsulares y queratopatía en banda, finalizaron con 1.0 de visión, excep-to el paciente que no ha logrado controlar la uveítis ni la opacidades capsulares, cuya visión comenzó a disminuir y, por no haber vuelto a la consulta, no sabemos cuál es su agudeza visual.

La tensión ocular, a pesar del largo tiempo que duraron los tratamientos loca-les con medicamentos que normalmente pueden producir hipertensión ocular, sólo se vio alterada en 2 pacientes en los cua-les se logró controlar la hipertensión con hipotensores oculares locales, y la misma nunca sobrepasó los 7 días.

La queratopatía en banda se presentó en 1 paciente. Se logró detener su avance, pero no se ha logrado hacerla desaparecer.

La catarata total no fue tributaria de ci-rugía, pues desde que el paciente llegó a consulta ya presentaba desprendimiento de retina y coroide total.

Uno de los pacientes portadores de uveí-tis recurrente sufrió durante un mes en 2009 la influenza A (H1N1), cuya positividad fue determinada por el departamento de virolo-gía del Instituto de Medicina Tropical Pedro Kourí. Se le mantuvo tratamiento local y un mínimo del sistémico, con una dosis mínima diaria de 20 mg de Prednisona oral; se revisó al paciente durante la influenza y después de la misma y no presentó uveítis, ni opacida-des capsulares.

ConclusionesEste estudio demuestra que un examen

oftalmológico preventivo y un tratamiento médico impuesto por un equipo compues-to por pediatras, reumatólogos y oftalmólo-gos, es indispensable para detectar y tratar las posibles alteraciones activas del seg-mento anterior del globo ocular de estos pacientes y así, contribuir a reducir la alta incidencia de ceguera en estos niños.

El tratamiento oportuno de las uveítis anteriores que presentaron los pacientes incluidos en este estudio, logró hacerlas desaparecer en 11 (73%) de los 15 pa-cientes que presentaban uveítis anterior en actividad en un período comprendido entre 2 y 6 meses. Los 3 pacientes con uveítis recurrente se mantienen bajo tratamiento (20%) y 1 paciente mantiene la uveítis en actividad y es necesario destacar que es el único que no concurre regularmente a la consulta, ni cumple el tratamiento indica-do. Lo que revela la necesidad de cumplir un programa de consultas y de seguimiento del tratamiento para controlar las alteracio-nes en el segmento anterior del globo ocu-lar en estos pacientes.

El hecho de que en muchas ocasio-nes la uveítis se presenta antes de que se manifiesten los primeros síntomas de en-fermedad reumática en el niño, indica que el chequeo médico al que se le somete sistemáticamente, siempre debe incluir un examen oftalmológico preventivo.

BIBLIOGRAFÍA1.García de Vicuña Muñoz de la Nava, C: Manifestaciones oculares en las enfermedades re-umáticas pediátricas. En González E. Manual de Reumatología Pediátrica. Cap. XXXI (753-765) Edit. Laboratorios Menarini, Barcelona España, 1999.

2.García Serrano, JL; Cisternas Maggi, M: Manifestaciones oculares de las enfermedades re-umáticas en el niño. En Muñoz A. Reumatología Infantil. Vol.8 Cap.25 (477-500).Edit. For-mación Alcalá. España, 2004

3.Pras E, Neuman R, Zandman-Goddard G: Intraocular infl ammation in autoimmune diseases. Semin Arthritis Rheum 2004 Dec; 34(3):602-9

4.O’day, DM; Horn, JD: El ojo y la enfermedad reumática. En Ruddy S. Kelley ‘s Texbook of Rheumatology. 6th ed. Cap 29 (393-400) Edit W.B.Saunders Company. E.U.A. 2003

5.Kadayifcilar S, Eldem B, Tumer B: Uveitis in chilhood. J Pediatr Ophthalmol Strabismus 2003 Nov-Dec; 40(6):335-40

6.Chen CS, Roberton D, Hammerton ME. Juvenile arthritis associated uveitis: visual outcomes and prognosis. Can J Ophthalmol 2004 Oct; 39(6):614-20

7.García-Consuegra MJ, Tapia R, Abelairas J: Uveitis and Juvenile Idiopathic Artritis. An Esp Pediatr 2001 Mar; 54(3):255-9

8.Petty RE, Smith JR, Rosenbaun JT: Arthritis and uveitis in children. A pediatric rheumatology perspective. Am J Ophthalmol 2003 Jun; 135(6):879-84

9.Cannel CA, Holland GN, Helm CJ: Causes of uveitis in the general practice of aphthalmology.UCLA Community-Based Uveitis Study Group. Am J Ophthalmol 1996 Jan; 121(1):35-6

10.Paivonsalo-Hietanen T, Tuominen J, Saari KM. Uveitis in children: population-based study.

Acta Ophthalmol Scand 2000 Feb; 78(1):84-8

11.Baldassano VF Jr: Ocular manifestations of rheumatic diseases. Curr Opin Ophthalmol 1998 Dec; 9(6):85-8

12.Kotanieni K, Aho K, Kotanieni A: Uveitis as a cause of visual loss in arthritides and compa-rable conditions. J Rheumatol 2001 Feb; 28(2):309-12

13.Murphy CC, Duncan L, Forrester JV: Systemic CD4 (+) Tcell phenotype and activation status in intermediate uveitis. Br J Ophthalmol 2004 Mar; 88(3):412-6

14.Klok AM, Luyendijk L, Zaal MJ: Elevated serum IL-8 levels are associated with disease activity in idiopathic intermediate uveitis. Br J Ophthalmol 1998 Aug; 82(8):871-4

15.Frassamto MA, Dammacco R, Fusaro T: Combined Cyclosporin-A/Prednisone therapy of pa-tients with active uveitis suppresses INF-gamma production and the function of dendritic cells. Clin Exp Immunol 2003 Aug; 133(2):233-9

16.Kiss S, Letko E, Qamruddin S: Long-term progression, prognosis and treatment of patients with recurrent ocular manifestations of Reiter’s syndrome.Ophthalmology 2003 Sep: 110(9):1764-9

17.Weiss AH, Wallace CA, Sherry DD: Methotrexate for resistant chronic uveitis in children with juvenile rheumatoid arthritis. The Journal of Pediatrics 1998; 133:266-8

18.A. Muñoz Hoyos, E. Raya Álvarez. “Reumatología Infantil”. Formación Continuada en Pe-diatría. Editorial: Formación Alcalá España 2004.

19.Joa Miró, Elena . Manifestaciones Oculares en algunas Enfermedades Reumáticas en el Niño. Vision Pan-America Volumen VII No.1 Febrero 2008 9-11

Fig.7 Uveítis Activa con Sinequia postrriores rotas.

Fig.8 Sinequias posteriores rotas, con pigmentos uveales en área pupilar.

CLINICAL SCIENCES

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Conjunctival versus Limbal-Conjunctival Autograft in Primary Pterygium Surgery: Do Limbal Cells Make a Difference?Olga Alvarez-Bulnes MD; Josep Gracia-Martínez MD; María Teresa Sellares-Fabres PhD; Xavier Nuñez-Pérez MD; Alfons Casale-Turu MD; Josep Visa-Nasarre MD; Manuel Alejandro Romera MD

Hospital Parc Taulí. Universitat Autònoma de Barcelona

ResumenObjetivo: Determinar si las células límbicas tienen un papel en la prevención de las recidivas tras cirugía del pterigio primario.

Diseño: Serie de casos clínicos.

Participantes: 36 ojos con pterigio primario sometidos a exéresis asociada a autoinjerto conjuntival o limboconjuntival.

Métodos: 18 ojos se sometieron a exéresis con plastia conjun-tival, mientras que los restantes se sometieron a exéresis con autoinjerto limboconjuntival. Todos ellos fueron seguidos durante un año.

Principal Resultado Medido: Recidiva.

Resultados: 2 pacientes en el grupo de plastia conjuntival (11%) presentaban recidiva a los 12 meses, por el contrario ninguno de los pacientes en el otro grupo presentó recidivas. A pesar de esto, no se encontraron diferencias estadísticamente significativas entre ambos tipos de injerto. (P=0.2).

Conclusión: Los resultados sugieren que es el efecto barrera del in-jerto, y no las propias células límbicas, las que tienen un papel en la reducción de las recidivas tras la cirugía del pterigio primario.

AbstractPurpose: To determine whether limbal cells have a role in the prevention of recurrence after primary pterygium surgery.

Design: Case report series.

Participants: 36 eyes with primary pterygium undergoing exci-sion with conjunctival or limbal-conjunctival autograft.

Methods: 18 eyes underwent excision with conjunctival autograft, whereas the rest underwent excision with limbal-conjuntival au-tograft. All of them were followed up for one year.

Main Outcome Measure: Recurrence.

Results: Two patients in the conjunctival graft group (11%) pre-sented recurrence after 12 months, while none of the patients in the other group had recurrence. However, no statistical difference was found between the two types of autograft. (P=0.2).

Conclusion: The results suggest that the barrier effect of the graft, and not the limbal cells themselves, plays a role in reducing recur-rences after primary pterygium surgery.

Despite all the advances in ophthalmology, pterygium is still a challenge for ocular surface specialists. There are many surgical

techniques, single or combined, but there is a variable recurrence percentage1-6. After a revision of the literature, it is interesting to notice that conjunctival and limbal-conjunctival autografts seem to have the lowest recurrence rate but there are few clinical tri-als comparing them7-8. Damage of limbal stem cells by ultraviolet radiation seems to be the starting point of pterygium, although it is a multifactorial disease9. So, apparently, limbal-conjunctival graft should have better results than conjunctival autograft. We de-signed this case series report to attempt to approach this idea.

Materials And MethodsThirty-six consecutive patients undergoing primary pterygium

surgery at our hospital were included in this case series report. Eighteen eyes underwent excision with conjunctival autograft whereas the rest underwent excision with limbal-conjunctival graft. Inclusion criteria were primary nasal pterygium in patients over 18 years-old, grades II to IV or grade I symptomatic. Exclusion criteria were patients under 18 years-old, grade I asymptomatic, atrophic or recurrent pterygium or any previous conjunctival surgery. We looked for recurrence after the surgery, considering recurrence when observing a regrowth higher than 0.5mm over the cornea.

Surgical TechniqueUnder topical or retrobulbar anesthesia, depending on the sur-

geon preference, the pterygium head is removed using forceps. The body and the remaining Tenon’s capsule were excised with West-cott scissors. Hemostasis of the scleral bed was performed with a cautery when needed. The conjunctival defect was measured using a caliper and a same-size area was marked in bulbar conjunctiva under the upper lid. This is the only difference in the procedure for both groups. Using Westcott scissors and conjunctival forceps we dissect the conjunctiva leaving all Tenon’s tissue behind. To obtain a conjunctival graft, we stop the dissection before reach-ing the limbus. In the limbal-conjunctival graft group, dissection continued until entering clear cornea to ensure limbal cells where included (figure 1). The graft was moved over the scleral bed. This procedure must be done very carefully to keep the right orientation. Once the graft is correctly placed, it is secured using continuous 10-0 nylon suture in both groups.

Postoperative treatment and follow-upAll patients in both groups followed the same postoperative

treatment for one month. They used a chloramphenicol and dex-

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amethasone ointment every 8 hours. Following this treatment, they used fluorometholone drops twice a day for one month. At the end of the treatment, patients were encouraged to used artificial tears on demand. Patients attended seven follow-up appointments: days one, seven, fifteen and thirty and months three, six and twelve after surgery. All sutures were removed in the two week follow-up examination.

ResultsThirty-six eyes were included, eighteen in each group. The

average age of our patients was forty-nine years-old (28-79). Regarding patient’s origin, 53% were Hispanic, 44% Caucasians and 3% Chinese. In this series, most of the pterygia were grade II (78%), followed by grade III (14%) and I (8%). We found similar discomfort levels in both groups, which improved substantially after suture removal. The donor area epitelization was completed in twenty-four hours and there was no evidence of limbal insuf-ficience. We found a higher graft edema after twenty-four hours in the conjunctival graft group (50%) rather than in the limbal graft group (11%). Finally, Dellen was described in 17% of the patients, although it improved in the next two weeks. Regarding recurrences (0.5mm regrowth over the cornea) we only found two cases (11%), being 1mm and 0.8mm respectively. Both cases were Hispanic-origin patients who underwent excision associated with conjunctival autograft. They were registered three months af-ter surgery and showed no changes in the month six and month twelve examinations.

DiscussionIn our series, we found a similar recurrence rate in both the

conjunctival and the limbal-conjunctival autograft groups. Pa-tients origin and pterygium grade were found not to be relevant in recurrences in which there is an association of a graft to the excision. Besides, one year after surgery recurrences turned out to be less aggressive than the original pterygium. We also found no limbal insufficience in the limbal conjunctival graft group after one year. Other complications were similar in both groups and not outstanding.

We had two recurrences registered. Both patients were His-panic with grade II primary pterygium who underwent excision associated with conjunctival autograft. However, this recurrence rate was not statistically significant (p=0.2).

In conclusion, the results of our study suggest that the barrier effect of the graft, not the limbal cells themselves, plays a signifi-cant role in the reduction of recurrences after primary pterygium surgery.

REFERENCES

1.Sánchez-Thorin JC, Rocha G, Yelin JB. Meta-analysis on the recurrence rates after bare sclera resection with and without mitomycin C use and conjunctival autograft placement in surgery for primary pterygium. Br J Ophthalmol 1998; 82: 661-665

2.Oguz H, Kilitcioglu A, Yasar M. Limbal conjunctival mini-autografting for preventing recurrence after pterygium surgery. Eur J Ophthalmol 2006; 16: 209-213

3.Dekaris I, Gabric N, Karaman Z, Mravicic I, Kastelan S. Limbal-conjunctival autograft transplantation for recurrent pterygium. Eur J Ophthalmol 2002; 12: 177-182

4.Tananuvat N, Martin T. The results of amniotic membrane transplantation for primary pterygium compared with conjunctival autograft. Cornea 2004; 23: 458-463

5.Prabhasawat P, Barton K, Burkett G, Tseng SC. Comparison of conjunctival autografts, amniotic membrane grafts, and primary closure for pterygium exci-sion. Ophthalmology 1997; 104: 974-985

6.Marticorena J, Rodríguez-Ares MT, Touriño R, Mera P, Valladares MJ, Mar-tínez de la Casa JM, Benítez del Castillo JM. Pterygium surgery: conjunctival autograft using a fibrin adhesive. Cornea 2006; 25: 34-36

7.Al Fayez MF. Limbal versus conjuntival autograft transplantation for ad-vanced and recurrent pterygium. Ophthalmology 2002; 109:1752-1755

8.Mutlu MF, Sobaci G, Tatar T, Yildirim E. A comparative study of recurrent pterygium surgery: Limbal conjunctival autograft transplantation versus mito-mycin C with conjunctival flap. Ophthalmology April 1999; 106: 817-820

9.Reid TW, Dushku N. Pterygia and limbal epithelial cells: relationship and-molecular mechanisms. Prog Retin Eye Res 1996; 15: 297-325

Figure 1: Draft of the donor area for: 1A: Conjunctival autograft. 1B: Limbal-conjunctival autograft.

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ResumenPropósito: Evaluar los resultados visuales y de tomografía de coherencia óptica (OCT) luego de tratamiento con una única dosis de bevacizumab subretinal en pacientes con neovascularización coroidea (CNV) secun-daria a degeneración macular relacionada con la edad (AMD).Métodos: Se trataron 4 ojos de cuatro pa-cientes con CNV subfoveal unilateral avanza-da secundaria a AMD, que rechazaron dosis múltiples de bevacizumab intravítreo. Todos los pacientes presentaban una agudeza visual (VA) de 20/400 o peor en el ojo afectado y 20/30 o más en el ojo contralateral. Cada paciente fue sometido a vitrectomía con una única inyección subretinal de bevacizumab (750μg / 0.3ml) y fueron seguidos por un año con exámenes oftalmológicos completos, in-cluyendo retinofluoresceinografía (FA) y OCT.Resultados: Luego de un año de segui-miento, la VA se mantuvo estable o mejoró en el 100% de los ojos. El grosor macular central (CMT) también disminuyó significa-tivamente y la FA demostró una reducción considerable en el tamaño de las membra-nas neovasculares subretinales.Conclusiones: Nuestros resultados sugie-ren que una única dosis de bevacizumab subretinal es segura, efectiva y bien tole-rada, y mejora significativamente la VA y el CMT en pacientes con AMD neovascular. Sin embargo, una evaluación a más largo plazo con un seguimiento más extenso y una población mayor es deseable.

AbstractPurpose: To evaluate visual results and optical coherence tomography (OCT) fin-dings after treatment with a single subre-tinal dose of bevacizumab in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular dege-neration (AMD).Methods: Four eyes of 4 patients with unilateral advanced subfoveal CNV due to AMD, who refused multiple doses of intravitreal bevacizumab, were recluted. All patients had 20/400 or worse visual acuity (VA) in the affected eye and 20/30 or better in the fellow eye. Each patient underwent vitrectomy with a single subre-tinal injection of bevacizumab (750μg / 0.3ml) and was followed up for one year with complete eye examinations, inclu-ding fluorescein angiography (FA) and OCT.Results: At the one year follow-up, VA was stable or improved in 100% of eyes. The central macular thickness (CMT) also decreased significantly, with FA demons-trating a considerable reduction in the size of the subretinal neovascular mem-branes.Conclusions: Our results suggest that a single dose of subretinal bevacizumab is safe, effective and well tolerated, and significantly improved VA and CMT in patients with neovascular AMD. However, further evaluation with longer follow-up and a bigger population is desirable.

IntroductionThe expensive cost of treatment with

ranibizumab (Lucentis) has led to many AMD patients to be treated with off-la-bel intravitreal bevacizumab (IVB),1-3 an antibody approved by FDA only for the treatment of malignant tumors.4

Indeed, for economically disadvanta-ged patients with AMD, bevacizumab may represent the only valid treatment option. For this reason, IVB is currently widely used in private practice and is starting to become available at National Hospital Services around the world. Nevertheless, there is no long-term information on the safety or efficacy associated with the use of IVB. Moreover, the optimum amount and dose frequency are still not determined. In most patients, the short-term effect of IVB results in recurrence of leakage, leading to the requirement for additional intravitreal injections at intervals of 4 to 18 weeks (median 8 weeks).2,5 Repeated administrations represent an issue of concern among retinal specialists due to local adverse reactions, such uveitis,6 endophthalmitis,7 retinal pigment epithe-lial tears, retinal detachment and acute vision loss.8

The purpose of this study was to eva-luate the safety and efficacy of a single subretinal dose of bevacizumab in pa-tients with advanced subfoveal CNV due to AMD, in an attempt to provide an alter-native treatment to wet AMD.

Single Subretinal Dose of Bevacizumab (Avastin) for the Treatment of Choroidal Neovascularization in Patients with Age-Related Macular Degeneration. One-year Follow-upJuan P. Pusterla MD1*; María A. Williams MD1*; Ana L. Gramajo MD1; Gustavo A. Colombres MD1; Aneesh Neekhra MD2; Claudio P. Juárez MD PhD1; José D. Luna MD1

1 Departamento de Oftalmología, Centro de Ojos Romagosa-Fundación VER, Córdoba, Argentina2 Department of Ophthalmology, University of Wisconsin, Madison, WI

* These authors contributed equally to this project and should be considered co-fi rst authors.

Corresponding author: José D. Luna MDDepartamento de Oftalmología, Centro de Ojos Romagosa-Fundación VER, Deán Funes 432, (5000) Córdoba, ArgentinaTel: 54-0351-4211333 Fax: 54-0351-4234848. E-mail: fundacionver@gmail.com

The authors do not have any confl icts of interest or commercial involvement associated with this work.

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Materials And MethodsThe study was conducted according to

the tenets of the Declaration of Helsinki, with informed consent being obtained from all patients. Patients older than 55 years with a subfoveal CNV secondary to AMD and a best-corrected visual acuity (BCVA) ≤20/400 in the worst eye and≥20/40 in the fellow eye were included. Active leaka-ge was confirmed by fluorescein angiogra-phy (FA) and optical coherence tomogra-phy (OCT), with subretinal hemorrhages being <25% of the neovascular complex and subretinal fibrosis <30%. Patients with previous treatment for AMD, history of previous ocular disease or eye surgery were excluded.

All patients included in this study had declined recommended standard treatment with re-injections every 4 wee-ks according to standard protocols for ranibizumab.9

At baseline and on each following visit (postoperative days 1, 3, 15 and months 1, 3, 6 and 12), all patients underwent a complete ophthalmological examination which included BCVA, intraocular pressu-re (IOP) measurement, indirect ophthal-moscopy and slit-lamp evaluation of the posterior pole. FA and OCT images were obtained before surgery and on months 1, 6 and 12 after surgery.

BCVA was recorded using modified ETDRS charts. All visual acuities were con-verted to logMAR scale before been avera-ged. Counting finger (CF) and hand motion (HM) visual acuity (VA) were converted to a decimal equivalent of 1.8 and 3 respecti-vely, as suggested by Holladay.10 OCT data were obtained using the Status OCT. Central macular thickness (CMT) was measured, and the presence or absence of cystic in-traretinal fluid, subretinal fluid, or pigment epithelial detachment (PED) was verified as well. Unpaired t-test was performed bet-ween baseline and the last follow-up visit measurements.

All eyes underwent a conventional 20-gauge pars plana vitrectomy performed by the same author (JDL). First, conventional core vitrectomy was completed. Subse-quently, the cortical vitreous was separated in block, and a 39-gauge micro cannula (Synergetics USA, Inc) was inserted in the subretinal space slightly temporal and su-perior to the neovascular membrane. Then,

0.3 ml of reconstituted bevacizumab (0.1ml -2500μg- reconstituted with 0.9 ml of lac-tated ringer’s solution) was injected under the retina (Figure 1). Afterwards, fluid-gas exchange was performed and an injection of gas (SF6) ended the procedures.

ResultsFour eyes of four patients were selec-

ted for the procedure.The preoperative findings are shown in

Table I. The mean BCVA was logMAR 2.4 ± 0.35, with the mean greatest linear dimen-sion (GLD) being 2.7mm (range, 1.5-3.5). The lesion composition was predominantly classic in all patients. The mean baseline

CMT was 359.00 ± 53.65μm.

Following each injection, a localized re-tinal detachment was created in the macular area, which resolved itself completely within 7 days. Two of the four patients developed a rise in IOP during the first postoperative days, which was well controlled by topical medication, with no patient receiving glau-coma drops by day 7. Two of the four pa-tients developed progression of lens opacity by the 4 and 6 month follow-up, and surgery was performed at those times with no com-plications. None of the patients developed endophthalmitis or retinal detachment, as has been reported elsewhere in the context of vitrectomy.11

Table II. LogMAR Visual Acuity Changes

Patient No.Patient No. VA* at baselineVA* at baseline VA at 1 month VA at 1 month post-oppost-op

VA at 6 months VA at 6 months post-oppost-op

VA at 12 months VA at 12 months post-oppost-op

1 3 1.3 1.8 1.8

2 3 1.3 1.8 1.83 1.8 1.8 1.8 1.84 1.8 1.8 1.3 1.3

* VA: Visual Acuity

Table I. Preoperative fi ndings.

Patient No.Patient No. VA* in the VA* in the treated eyetreated eye

Size of CNV† Size of CNV† lesion (mm)lesion (mm)

Subtype of Subtype of CNVCNV

Presence of Presence of SRH‡SRH‡ CMT** ( m)CMT** ( m)

1 HM†† 3.5 PC‡ ‡ Yes 3402 HM 2.8 PC Yes 2503 CF£ 3.0 PC Yes 5074 CF 1.5 PC No 339

* VA: Visual Acuity† CNV: Choroidal Neovascularization. ‡ SRH: Subretinal Hemorrhage**CMT: Central Macular Thickness.

†† HM: Hand Motion.‡‡: PC: Predominantly classic£ CF: Counting fi ngers

Figure 1: Subretinal Avastin injection technique.

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Table III. OCT ChangesPatient No.Patient No. OCT* at OCT* at

baseline (µm)baseline (µm)OCT 1 month OCT 1 month post-op (µm)post-op (µm)

OCT 6 months OCT 6 months post-op (µm)post-op (µm)

OCT 1 year OCT 1 year post-op (µm)post-op (µm)

1 340 254 233 2802 250 283 359 2953 507 170 259 2634 339 181 187 180

* OCT: Optical Coherence Tomography

Pre- and post-operative logMAR visual acuities are stated in Table II. After surgery, baseline BCVA ranged from LogMAR 2.40 ± 0.35 to 1.67 ± 0.12 (p= 0.096). None of the patients experienced a decline in their postoperative VA. Moreover, 3 pa-tients (75% of the sample) showed a better BCVA postoperatively.

CNV lesion showed a dramatic result after treatment, with practically a complete disappearance of the CNV complex in 75 % of the patients, reduction maintained throughout the study (Figure 2). In the other 25% of patients, a new neovascular lesion was observed at month 12.

The mean CMT was 359 ± 53.65 µm at the baseline, which was reduced to 254.5 ± 25.7 (p=0.129) after surgery (Table III). Subretinal fluid and cystic macular changes decreased in all cases. By the end of fo-llow-up period, 3 of the 4 patients showed a mean reduction of 37.6% when compared to the baseline, with the remaining patient continuing to be stable. No progression in the CMT was observed in any case. Never-theless, no correlation was found between CMT and BCVA (Figure 3).

DiscussionAlthough pilot studies of IVB for AMD

suggest efficacy and infrequent serious side effects, these studies all have limited size and follow-up.12 Recently, it has been reported that more than one intravitreal application is

needed to control AMD.13 However, as a minor dose and less frequent applications could re-duce the possibility of local or systemic side effects, we decided to study the efficacy and tolerability of a single dose of 750 µg of SRB in patients with CNV due to AMD.

The recommended intravitreal dose of bevacizumab is 1.25 to 2.5 mg (0.05 to 0.1 ml) of the commercially available Avastin. This injected drug is presumed to diffuse uniformly into the entire vitreous. The ave-rage normal vitreous volume is about 4 ml, and therefore, the dose to which the retinal cells are expected to be exposed after intra-vitreal injection of bevacizumab is 0.3125 -0.625 mg/ml. Thus, in our study we tes-ted the highest dose to which retinal cells are theoretically exposed (750ug or 0.3 ml of reconstituted bevacizumab). Although bevacizumab immunoreactivity has been found in the choroid and the inner layers of the retina as early as 1 day after intravitreal injection,14 the exact concentration of the drug is unknown. By applying bevacizumab under the retina, we are not only reducing the necessary dose of this drug, but also the whole concentration of bevacizumab is directly applied to the neovascular lesion.

In our study, SRB resulted in a rapid decrease in CMT in the majority of cases. BCVA also improved, suggesting a potential corresponding visual benefit. Even though after 3 months most of the patients had a regression from the initial results, all of

them had the same or better BCVA after a one-year follow-up with no additional anti-angiogenic treatment. Regrowth of the CNV was seen in only one case.

After surgery, we observed changes on the retinal pigment epithelial (RPE) la-yer. RPE atrophy was noted at the location of the application, but also at the area of retinal detachment due to the SRB injec-tion. The reason for this phenomenon is not clear. One explanation could be a direct toxic effect by bevacizumab on the RPE, but this does not correlate well with previous

Figure 2: Representative FA image showing pre- and postoperative changes.

Figure 3c: Post-operative OCT. One year post-injection

Figure 3. Representative OCT image showing pre- and postoperative changes

Figure 3b. Post-operative OCT. One month post-injection

Figure 3a. Pre-operative OCT

FA at Baseline 1 month post-injection 1 year post-injection

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in-vitro studies where direct exposition of the cells to higher concentrations of beva-cizumab were shown to be safe.15 A diffe-rent explanation could be that, as we were dealing with advanced cases, the functional alterations between the photoreceptor and RPE around the lesion were irreversible, but only after some time the morphological changes become evident. A third hypothe-sis is that a mechanical injury was made not only with the cannula but also by the fluid entering the subretinal space. Last, but not least, some reports stated that VEGF can protect RPE and photoreceptors from undergoing cell death.16 One of the above theories, or a combination of these, could probably explain the RPE defects seen over time in our study.

Although these results suggest that be-vacizumab directly applied over the neovas-cular lesion is very effective in controlling vessel growth, the number of patients used in the trial is small. Another limitation of this pilot study is that it was performed with advanced AMD eyes. It has been previously shown that the efficiency of bevacizumab depends mainly on initial lesion size and the initial reading ability, being indepen-dent of the amount of intraretinal and/or subretinal fluid.17 Consequently, there is a possibility that in patients with better rea-ding ability and smaller lesions, SRB could have better VA outcomes.

Although this technique is not devoid of risks and complications, it had a tolerable side-effect profile and it is a treatment mo-dality that warrants further investigation. It delivers a widely available anti-angiogenic agent directly at the site of the pathology, reducing even more the risks of systemic toxicity. Moreover, it only requires a single procedure rather than a treatment course over a period of months or years.

After on year, the mean reduction on CMT is comparable with studies develo-ped over recent years where multiple IVB applications were used.13, 18

In conclusion, although further stu-dies are necessary, SRB may provide a new therapeutic alternative for selected patients with exudative AMD.

AcknowledgmentsWe are grateful to Dr. Paul David Hob-

son, native speaker, for the language co-rrection of this manuscript.

REFERENCES1. Mitka M. Study aims to clarify efficacy, safety of eye drug treatments. Jama 2007;297(14):1538-9.

2. Aisenbrey S, Ziemssen F, Volker M, et al. In-travitreal bevacizumab (Avastin) for occult chor-oidal neovascularization in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2007;245(7):941-8.

3. Bashshur ZF, Bazarbachi A, Schakal A, et al. Intravitreal bevacizumab for the manage-ment of choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol 2006;142(1):1-9.

4. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335-42.

5. Aggio FB, Farah ME, Silva WC, Melo GB. Intravitreal bevacizumab for exudative age-related macular degeneration after multiple treatments. Graefes Arch Clin Exp Ophthalmol 2007;245(2):215-20.

6. Bakri SJ, Larson TA, Edwards AO. Intraocular inflammation following intravitreal injection of bevacizumab. Graefes Arch Clin Exp Ophthalmol 2008;246(5):779-81.

7. Jonas JB, Spandau UH, Rensch F, et al. In-fectious and noninfectious endophthalmitis after intravitreal bevacizumab. J Ocul Pharmacol Ther 2007;23(3):240-2.

8. Fung AE, Rosenfeld PJ, Reichel E. The Inter-national Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 2006;90(11):1344-9.

9. Rosenfeld PJ, Brown DM, Heier JS, et al. Ra-nibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1419-31.

10. Holladay JT. Proper method for calcu-lating average visual acuity. J Refract Surg 1997;13(4):388-91.

11. Pieramici DJ, De Juan E, Jr., Fujii GY, et al. Limited inferior macular translocation for the treatment of subfoveal choroidal neovasculariza-tion secondary to age-related macular degenera-tion. Am J Ophthalmol 2000;130(4):419-28.

12. Costa RA, Jorge R, Calucci D, et al. Intrav-itreal bevacizumab for choroidal neovasculariza-tion caused by AMD (IBeNA Study): results of a phase 1 dose-escalation study. Invest Ophthalmol Vis Sci 2006;47(10):4569-78.

13. Melamud A, Stinnett S, Fekrat S. Treatment of neovascular age-related macular degeneration with intravitreal bevacizumab: efficacy of three consecutive monthly injections. Am J Ophthalmol 2008;146(1):91-5.

14. Heiduschka P, Fietz H, Hofmeister S, et al. Penetration of bevacizumab through the retina after intravitreal injection in the monkey. Invest Ophthalmol Vis Sci 2007;48(6):2814-23.

15. Luthra S, Narayanan R, Marques LE, et al. Evaluation of in vitro effects of bevacizumab (Avastin) on retinal pigment epithelial, neurosen-sory retinal, and microvascular endothelial cells. Retina 2006;26(5):512-8.

16. Saint-Geniez M, Maharaj AS, Walshe TE, et al. Endogenous VEGF is required for visual function: evidence for a survival role on muller cells and photoreceptors. PLoS One 2008;3(11):e3554.

17. Lux A, Llacer H, Heussen FM, Joussen AM. Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions. Br J Ophthalmol 2007;91(10):1318-22.

18. Yoganathan P, Deramo VA, Lai JC, et al. Vi-sual improvement following intravitreal bevaci-zumab (Avastin) in exudative age-related macular degeneration. Retina 2006;26(9):994-8.

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AbstractOur studies published in 2008 and

2009 found: Phaco/IOL alone provides an effective treatment for patients with cataract coexistent with ocular hypertension or glau-coma when glaucoma drops are no longer adequate. Phaco/IOL alone may provide an effective treatment for patients with ocular hypertension or glaucoma who do not have cataracts when glaucoma drops are no lon-ger adequate. We postulate as to why phaco/IOL alone lowers IOP in eyes with elevated IOP: The natural lens, as it ages, com-presses the trabecular meshwork and canal of Schlemm, and becomes a major cause of ocular hypertension, a precursor to adult glaucoma. Replacing the enlarged natural lens with a thin artificial lens expands the compressed trabecular meshwork and ca-nal of Schlemm, improves their function, and thereby lowers the once elevated IOP.

According to Research to Prevent Blind-ness, 20.5 million Americans have cataract, and 2.0 million Americans are visually im-paired from glaucoma. Today, we do ap-proximately 3.0 million cataracts per year in the USA. By 2015 we will do 4.0 million cataract operations per year. So, 300,000 to 400,000 times a year an American surgeon must decide how to treat the patient with combined cataract and glaucoma.

Cataract extraction alone may be the most appropriate procedure for patients with controlled or modestly uncontrolled glaucoma1. An exception would be very far advanced disease. Two factors most influ-encing strategy would be incredible ad-vances in surgical management of cataract and equally impressive advances in medical management of glaucoma. Cataract surgery has distanced itself from the comparatively primitive approach to glaucoma surgery,

and the patient’s experience is vastly differ-ent for the two operations. Cataract surgery entails purely topical anesthesia, no con-junctival manipulation, and a comfortable quite eye after surgery. Astigmatism can be reduced with cataract surgery rather than increased, and visual rehabilitation is within a week versus three months with glaucoma surgery. Cataract surgery lowers IOP more than previously realized1,and may be the most common “glaucoma operation” per-formed today.

We have published two studies, Poley, Lindstrom, Samuelson, Schulze1,12, of IOP reduction following phaco/IOL surgery for cataract removal that found greater IOP reduction than previously recognized. We retrospectively studied the IOP reduction following phaco/IOL of 588 non-glaucoma eyes and 124 glaucoma eyes. Frequency of glaucomatous and non-glaucomatous eyes in each postoperative year is shown in table one. We recorded their IOP before surgery, one year after surgery and at the final measurement (1 to 10 years postop, av. 4.5 years).

Eyes were stratified according to their presurgical IOP and divided into five groups. Table two shows results of the non-glaucomatous eye study, and table three shows results of the glaucomatous eye study. When the non-glaucomatous and glaucomatous eyes were stratified according to their presurgical IOP as de-picted in these charts, we found eyes with the highest presurgical IOPs which needed the greatest IOP reduction had the greatest IOP reduction. Non-glaucomatous eyes with presurgical IOPs ranging from 23 to 31mm Hg had mean - 6.5mm Hg/27% reduction to final mean 18.0mm Hg for the 10 years of the study. Similarly, table three shows glaucomatous eyes with pre-surgical IOPs ranging from 29 to 23mm Hg. had mean -8.4mm Hg/34% reduction to mean 16.3mm Hg for the 10 years of the study. Presurgical IOPs of glaucoma eyes were as low as glaucoma drops could achieve. However, significant IOP reductions followed phaco/IOL surgery. Surgeons operating cataractous eyes with IOPs ≥ 20mmHg would like to know if

Table 1. Frequency of glaucomatous (N=124)and non-glaucomatous (N =588) eyes in each postoperative year

PO YearsPO Years FrequencyFrequency PercentPercent Cumulative PercentCumulative Percent

GlaucGlauc Non-GlaucNon-Glauc Glauc Glauc Non-GlaucNon-Glauc GlaucGlauc Non-GlaucNon-Glauc

0 1 19 0.8 3.2 0.8 3.2

1 9 66 7.2 11.2 8.0 14.5

2 12 99 9.6 16.8 17.6 31.1

3 32 68 25.8 11.6 43.4 42.9

4 19 51 15.3 8.7 58.7 51.5

5 17 58 13.7 9.9 72.4 61.4

6 10 55 8.0 9.4 80.4 70.7

7 5 68 4.0 11.6 84.4 82.3

8 3 58 2.4 9.9 86.8 92.3

9 14 42 11.2 7.7 98.4 99.3

10 2 3 1.6 0.7 100.0 100.0

All eyesAll eyes 124 124 588588 100100 100100 100100 100100

Cataract Surgery in the Glaucoma PatientBrooks J Poley, MD (1), Richard L Lindstrom, MD (2), Thomas W Samuelson, MD (3), Richard R. Schulze, MD (4)

1 Retired Brooks Poley Eye Assoc. Retired Associate Professor, University of Minnesota department of Ophthalmology.

2 Founder and attending surgeon Minnesota Eye Consultants. AdjunctProfessor Emeritus , University of Minnesota department of Ophthalmology.

3 Attending surgeon Minnesota Eye Consultants. Associate Professor, University of Minnesota department of Ophthalmology.

4 Schulze Eye & Surgery Center

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Table 2. Characteristics and IOP results by presurgical IOP group of non-glaucoma eyes when operated with phaco/IOL

IOP (mm Hg)IOP (mm Hg) Mean IOP (mm Hg)Mean IOP (mm Hg)

GroupGroup Eyes (n) Age (Y) Postop FU (Y)

At Surgery

1 Y Postop

Change at 1 Y Final Final

Change(%)

31-23 19 69 2.4 24.5 17.8 -6.7 18.0 -6.5 (27)

22-20 62 70.9 4.6 20.9 15.8 -5.1 16.1 -4.8 (22)

19-18 86 67.4 4.9 18.3 15.5 -2.8 15.8 -2.5 (14)

17-15 223 71.2 4.7 15.9 14.6 -1.4 14.3 -1.6 (10)

14-9 198 70.5 4.2 12.7 13.1 +0.4 12.9 +0.2 (0)

P value --- .57 .002 <.001 <.001 <.001 <.001 <’001

All eyes 588 70.3 4.5 16.0 14.5 -1.5 14.4 -1.6 (10)

FU = follow up; IOP = intraocular pressure

Table 3. Characteristics and IOP results by presurgical IOP group of glaucomatous eyes when operated with phaco/IOL

IOP (mm Hg)IOP (mm Hg) Mean IOP (mm Hg)Mean IOP (mm Hg)

Group Eyes (n) Age (Y) Postop FU (Y)

At Surgery

1 Y Postop

Change at 1 Y Final Final

Change(%)

29-23 17 73 5.8 24.7 18.7 -6.0 16.3 -8.4 (34)

22-20 23 72.8 5.0 20.7 17.0 -3.7 16.1 -4.6 (22)

19-18 28 75.4 4.6 18.5 15.8 -2.7 15.2 -3.3 (18)

17-15 33 78.0 3.2 16.0 14.4 -1.6 14.9 -1.1 (7)

14-5 23 76.3 4.6 11.6 12.9 +1.3 13.5 +1.9 (16)

P value --- .57 .210 .002 <.001 <.001 .007 <’001

All eyes 124 75.5 4.5 17.8 15.4 -2.4 15.1 -2.7 (15)

FU = follow-up; IOP = intraocular pressure

IOPs after phaco/IOL surgery would be elevated or reduced. Our study found all eyes with presurgical IOPs ≥ 20mmmHg had IOP reductions following surgery from - 2 to - 12mm Hg. None elevated.

Figures one and two are bar graphs of non-glaucoma and glaucoma eyes com-paring mean IOP changes one year after surgery with IOP changes at the final mea-surement (1 – 10 yrs, av. 4.5 yrs). Mean IOP reductions at final measurement were the same or greater than reductions one year after surgery. Hence, IOP reductions achieved one year after surgery of both non-glaucomatous and glaucomatous eyes were sustained for the duration of the study (1 – 10 yrs, av. 4.5 yrs).

Table four shows 81 eyes of the Poley et al study were ocular hypertensive (IOPs ≥ 20mm Hg) before lens exchange with an IOP range of 20 - 31mm Hg. At the final measurement only 21 OHT eyes remained (IOPs ≥20mm Hg) with their IOP range re-duced to 20 - 24mm Hg. 60 of the 81 OHT eyes (74%) had reverted to normotensive eyes (IOPs <20mm Hg) for the 10 years of the study.

Table five compares the OHTS study11 conversion rates of OHT eyes to glauco-ma or normal-tension when treated with glaucoma drops to conversion rates of OHT eyes to glaucoma or normal-tension when treated with phaco/IOL12. The OHTS study conversion factor was development of visual field changes associated with glaucoma. The Poley et al conversion fac-tor was the physician’s starting glaucoma drops to treat development of elevated pressure. The OHTS study concluded: “Treating OHT eyes with glaucoma drops was effective in preventing the onset of primary open angle glaucoma (POAG)”. Their study showed the conversion rate of OHT eyes to glaucoma was 9.5% over 5 years with no treatment (controls), and was 4.4% over 5 years when eyes were treated with glaucoma drops. Our 2008 study of non-glaucoma eyes12 showed the conversion rate of OHT eyes to glaucoma was 1.1% over 4.1 years when eyes were treated with phaco/IOL surgery. Our study also found 74% of OHT eyes (IOP ≥20mm Hg) converted to normal-tension eyes (IOPs <20mm Hg) for the duration of

our study (1-10yrs, av. 4.5 yrs); whereas, no OHT eyes in the OHTS study that were treated with glaucoma drops converted to normal-tension because whenever the drops are stopped, the IOP elevates to prior or higher levels. Because of the foregoing studies, we suggest phaco/IOL appears at least as effective as glaucoma drops in preventing OHT eyes from de-veloping glaucoma. It would seem adult glaucoma can become a mostly prevent-

able disease if OHT eyes that have signifi-cant risk factors are treated with Phaco/IOL surgery.

Table six shows mean IOP reductions after phaco/IOL from earlier studies, and from our glaucoma study (by group) ac-cording to presurgical IOP. Eyes with high mean presurgical IOPs had great mean IOP reductions after surgery. Studies with low mean presurgical IOPs had less mean IOP reductions or mean elevation in IOP

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The Strenk’s MRI images also show “The uveal tract returns to the anterior/posterior position of relative youth after lens exchange.” The anterior lens cap-sule surrounding the artificial lens be-comes positioned well rearward of the canal of Schlemmafter phaco/IOL surgery. This rearward re-positioning of the lens capsule creates rearward traction by the zonules on the TM, and expansion of the TM and CS. This expansion is associated with the reduction of the elevated IOPs we found with our two studies1,12. We have found1,12 : phaco/IOL significantly lowers elevated IOP of eyes with ocular hyper-tension and adult glaucoma. The term adult glaucoma would include eyes with primary open angle glaucoma, narrow angle glaucoma, chronic narrow angle glaucoma, and angle closure glaucoma. We have suggested1 that adult glaucoma is actually a continuum of a progressive disease. As the lens enlarges with age, some eyes first develop POAG, then NAG, then CNAG, then ACG, and eventually some develop phacomorphic glaucoma.Strenk’s MRI images provide an anatomic rational together with our two studies that support our proposition that phaco/IOL is a treatment that lowers IOP of ocular hy-pertensive and glaucomatous eyes. Glau-coma is defined as an optic neuropathy with IOP as a risk factor for progression. Elevated IOP is one of several risk fac-tors for adult glaucoma. Since it is the only risk factor for adult glaucoma that can be changed, lowering this risk fac-tor with phaco/IOL becomes a method to forestall or prevent the development of adult glaucoma, and will improve the IOP control of most eyes that have developed adult glaucoma.

SummaryOur studies showed stratifying eyes

according to their presurgical IOP re-vealed higher IOP reduction after phaco/IOL surgery than previously recognized. We found IOP reduction after phaco/IOL surgery is proportional to the presurgical IOP. Eyes with the highest IOP that need the greatest IOP reduction get the greatest IOP reduction. Eyes with lowest presurgi-cal IOP gain minimal to no IOP reduction.

Table 4. Frequency of OHT eyes (≥20mm Hg) before surgery, 1 yr after surgery, and at the fi nal measurement

Initial Preop IOP mm HgInitial Preop IOP mm HgIOP Frequency, Eyes (n)IOP Frequency, Eyes (n)

Preop 1 Y Postop Final Exam

20 25 12 12

21 19 5 5

22 18 3 1

23 9 2 2

24 4 2 1

25 2 _ _

27 3 _ _

31 1 _ _

# of OHT eyes 81/100% 24/30% 21/26%

# of OHT eyes become normotensive 57/70% 60/74%

after surgery. Ge’s2 study of angle closure glaucoma eyes had the greatest presurgi-cal mean IOP, 25.5mm Hg, and the great-est mean IOP reduction, 13.5mm Hg, after surgery. Information from table six sug-gests eyes with the shallowest anterior chambers have the greatest presurgical IOPs, and achieve the greatest IOP reduc-tions after phaco/IOL surgery.

Figure three shows SA and LM Strenk’s10

published MRI images of “Anterior displace-ment of the uveal tract with age resulting from lens growth”. Observe, the anterior surface of the 24 year old lens is rearward of the ca-nal of Schlemm; whereas, lens growth with

age positions the anterior lens surface of the 74 year old eye well forward of the canal of Schlemm (CS) which causes displacement of the anterior uveal tract which compresses the trabecular meshwork (TM) and CS. As the lens enlarges with each passing year, more eyes develop shallow anterior chambers, compressed outflow channels and elevated IOP. Several theories exist as to why the eye’s outflow channels fail. We have proposed1,12: Lens enlargement with age becomes one pos-siblecause of outflow channel failure leading to increased IOP. The Strenk’s MRI images of lens growth with age would appear to support our proposition.

Table 5. Conversion Rates of OHT to Adult Glaucoma OHTS Study-2002 & P/L/S Study-2007

Study Treatment "n" Follow Up Yrs Initial IOP Range IOP Reduction Conversion Factor Conversion %

OHTS Untreated 750 5,0 32-21mm 9,9% VF Change 9,5%

OHTS Glau Gtts. 750 5,0 32-21mm 22,5% VF Change 4,4%

P/L/S Phaco/IOL 81 4,1 31-20mm 23,8% Glau Gtts. Started 1,1%

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REFERENCES1. Poley B, Lindstrom R, Samuelson T. In-traocular pressure reduction after phacoemul-sification with intraocular lens implantation in glaucomatous and non-glaucomatous eyes. Evaluation of a causal relationship between the natural lens and open-angle glaucoma. J Cata-ract and Refract Surg 2009; 35: 1946-1955.

2. Ge J, Guo Y, Liu Y. Preliminary clinical study on the management of angle closure glau-coma by phacoemulsification with foldable pos-terior chamber intraocular lens implantation. ZhonghuaYan Ke Za Zhi 2001; 37: 355-358.

3. Euswas A, Warrasak S. Intraocular pres-sure control following phacoemulsification in patients with chronic angle closure glaucoma. J Med Assoc Thai 2005: 88: S121-S125.

4. Hayashi K, Hayashi H, Nakao F, Hayashi F. Changes in anterior chamber angle width and depth after intraocular lens implantation in eyes with glaucoma. Ophthalmology 2000: 107:698-703.

5. Lai JS, Tham CC, Chan JC. The clinical outcomes of cataract extraction by phacoemul-sification in eyes with primary angle-closure glaucoma (PACG) and coexisting cataract: a prospective case series. J Glaucoma 2006; 15: 47-52.

6. Mathalone N, Hymas M, Neiman S, Buck-man G, Yair H Geyer O. Long-term intraocular pressure control after clear corneal phacoemul-sification in glaucoma patients. J Cataract Re-fract Surg; 31: 479-483.

7. Shingleton BJ, Gamell LS, O’Donoghue MW, Baylus SL, King R. Long-term changes in intraocular pressure after clear corneal pha-coemulsification: normal patients versus glau-coma suspect and glaucoma patients. J Cataract Refract Surg 1999; 25: 885-890.

8. Shingleton BJ, Pasternack JJ, Hung JW, O’Donoghue MW. Three and five year changes in intraocular pressures after clear corneal pha-coemulsification in open angle glaucoma pa-tients, glaucoma suspects, and normal patients. J Glaucoma 2006; 15: 494-497.

9. Tham CY, Kwong YY, et al. Phacoemulsi-fication versus combined Phacotrabeculectomy in medically controlled chronic angle closure glaucoma with cataract. Ophthalmology 2008; 115: 2167-2173.

10. Strenk SA, Strenk LM, In vivo MRI…vi-sualizing the haptics. Eye World 2007; Sept: 49-52.

11. Kass M, Heuer D, Higginbotham E, et al, A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma; the Oc-ular The Hypertension Treatment Study. Arch Ophthalmol 2002; 120:701-713.

12. Poley, BJ, Lindstrom RL, Samuelson, TW. Long-term effects of phacoemulsification with intraocular lens implantation in normotensive and ocular hypertensive eyes. J Cataract Re-fract Surg 2008; 34:735-742.

Pressure reduction achieved at one year is sustained for ten years, and is essentially the same for patients of all ages.

We postulate: The lens, as it ages, becomes one possible cause of ocular hypertension, a precursor to adult glau-coma. When glaucoma drops are no lon-ger adequate, phaco/IOL alone provides an effective treatment for patients with cataract coexistent with ocular hyperten-sion or glaucoma when the target IOP of 16mm Hg. is adequate. If a lesser target IOP is needed, an alternative treatment such as an ab interno surgical procedure

(i.e.Trabetome surgery [NeoMedix Corp]) or trabeculectomy would be advised. Phaco/IOL alone may provide an effec-tive treatment for patients with ocular hy-pertension or glaucoma who do not have cataracts when glaucoma drops are no longer adequate.

Table 6. Mean IOP reductions after phaco/IOL surgery sorted by presurgical IOP.

IOP (mm Hg)IOP (mm Hg)

Study Glaucoma Type Eyes (n) Preop Final Change

Ge J. et al2 ACG 47 25.5 12.0 -13.5/53%

Poley et al 1 Adult 17 24.4 16.3 -8.4/34%

Euswas A. et al3 CACG 48 22.0 17.1 -4.9/22%

Hayashi K. et al4 ACG 73 21.4 15.0 -6.4/30%

Poley et al 1 Adult 23 20.7 18.0 -4.6/22%

Hayashi K. et al4 OAG 73 20.5 16.4 -4.4/21%

Lai JS. et al5 PACG 21 19.7 15.5 -4.2/20%

Poley et al 1 Adult 28 18.5 15.2 -3.3/18%

Shingleton B.et al7,8 OAG 55 18.4 16.6 -1.8/10%

Mathalone N. et al6 OAG 58 17.0 15.1 -1.9/11%

Tham CCY. et al9 ACG 25 16.3 14.5 -1.8/11%

Poley et al 1 Adult 33 16.0 14.9 -1.1/7%

Poley et al 1 Adult 23 11.6 13.5 +1.9/16%ACG = angle-closure glaucoma ; CACG = chronic angle-closure glaucoma; IOP = intraocular pressureOAG = open-angle glaucoma; PACG = primary angle-closure glaucomaP/L/S = Poley/ Lindstrom/ Samuelson.2009 glaucoma study

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oped as a drug for the treatment of the influenza A virus in 19591. Today, it is widely used in the management of ex-trapyramidal symptoms associated with neurologic disorders such as Parkinson’s disease, multiple sclerosis, chorea, and tardive dykinesia. Although rare, many ocular side effects have been reported in the literature including vision loss, my-driasis, oculogyric crises, visual hallu-cinations, superficial punctuate keratitis, subepithelial deposits, and corneal ede-ma2-6. The onset of corneal side effects varies widely from weeks to years after the initiation of amantadine therapy2,7.

Amantadine-associated corneal edema appears to have the greatest impact on quality of vision and is most often rap-idly reversible with the discontinuation of therapy. We report a case of revers-ible amantadine-induced corneal edema in a patient with Parkinson’s disease and early Fuchs’ endothelial dystrophy.

Case ReportA 53 year old Caucasian gentleman

was referred to our clinic for evaluation of unexplained bilateral corneal edema. He presented with a chief complaint of

Jay C. Bradley MD1; Brian S. Phelps MD1

1 Department of Ophthalmology & Visual Sciences, Texas Tech University, Lubbock, TX, USA

The authors do not have fi nancial confl icts of interest in the subject matter of the manuscript.

Corresponding Author/Reprint requests:Jay C. Bradley MDDepartment of Ophthalmology & Visual Sciences, Texas Tech University HSC, 3601 4th St., STOP 7217, Lubbock, TX 79430-7217Phone: (806)743-2020, Fax: (806) 743-2471Email: jay.bradley@ttuhsc.edu

Amantadine-Induced Corneal Edema in a Patient with Parkinson’s Disease and Early Fuchs’ Endothelial Dystrophy

Abstract

Purpose: We report a case of reversible amantadine-induced corneal edema in a patient with Parkinson’s disease and early Fuchs’ endothelial dystrophy.

Methods: Case report of patient man-aged by the Cornea & External Disease service at Texas Tech University Health Sciences Center.

Results: Clinical findings during the course of treatment including visual acuity, slit lamp examination, specular microsco-py, and pachymetry are described.

Conclusion: Amantadine is known to cause the onset of endothelial dysfunc-tion and visual impairment even after years of treatment. Fortunately, its ef-fects on the cornea have been shown to be mostly reversible in patients with a near normal endothelial count and func-tion. However, more recent evidence suggests the possibility of irreversible edema despite discontinuation of the drug. Therefore, amantadine-induced endothelial dysfunction in a patient with a significantly reduced endothelial count and/or functionality may also lead to irre-versible corneal edema and vision loss. For this reason, we suggest a screening examination for endothelial disease prior to initiating amantadine therapy.

Key words: amantadine, corneal edema, Parkinson’s disease, Fuchs’ endothelial dystrophy

IntroductionAmantadine was originally devel-

Figure 1:

Slit lamp photography of the right eye (top, left: slit beam; bottom, left: diffuse illumination) and the left eye (top, right: slit beam; bottom, right: diffuse illumination) demonstrating marked inferior paracentral and central corneal edema.

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“foggy vision” in both eyes for approxi-mately one month in duration. A gross physical evaluation revealed a resting tremor, bradykinesia, and postural insta-bility that became even more apparent when attempting slit lamp biomicros-copy. These findings initiated a review of the patient’s medical history that re-vealed the diagnosis of Parkinson’s dis-ease treated with 100 mg of amantadine three times daily for the past 4 years. His best-corrected visual acuity (BCVA) was 20/40, right eye and 20/70, left eye. The intraocular pressures, motility exam, confrontational fields, and pupillary exam were all within normal limits. Slit lamp biomicroscopy and photography of the cornea revealed bilateral stromal edema centrally, more prominent in the left eye (Figure 1). Mild central guttae were also noted in both eyes. Specu-lar microscopy was performed which showed an endothelial cell density of 2200/mm2 with few scattered guttae in both eyes. Central corneal pachymetric measurements were 870 microns and 960 microns, in the right and left eye respectively. No visually significant pa-thology of the eyelids, conjunctiva, ante-rior chamber, iris, or lens was identified. The dilated fundus exam was also within normal limits.

Amantadine-induced corneal edema was highly suspected. With the consent of the patient’s neurologist, amantadine was permanently discontinued. The pa-tient was unable to follow-up until 3 months later, though he later reported a complete restoration of vision 3 weeks after cessation of amantadine. His 3 month appointment revealed a BCVA of 20/20 in both eyes. Central cornea pachymetry measurements were 580 microns in both eyes. Repeat slit lamp biomicroscopy and photography of the cornea confirmed complete resolution of stromal edema (Figure 2).

DiscussionAmantadine-induced corneal edema

should be highly suspected in patients with unexplained corneal edema and signs of neurologic disease. To the best of our knowledge, corneal edema

Figure 2: Slit lamp photography of the right eye (top, left: slit beam; bottom, left: diffuse illumination) and the left eye (top, right: slit beam; bottom, right: diffuse illumination) demonstrating complete resolution of the corneal edema and mild endothelial guttae.

has only been reported in cases where amantadine was used in this subgroup of patients. More specifically, the majority of reports of amantidine-induced corneal edema were from patients being treated for Parkinson’s disease2,8-11. Patients with Parkinson’s disease frequently pres-ent with easily recognized clinical fea-tures such as resting tremor, cogwheel rigidity, bradykinesia, and postural instability1,8. In this case, the recogni-tion of such clinical features served as a reminder to review the patient’s medi-cation history. Therefore, physical exam skills and knowledge of extrapyramidal signs may provide assistance in mak-ing the diagnosis of amantadine-induced corneal edema.

It is believed that amantadine-induced corneal toxicity often goes unreported in the treatment of other indications such as influenza. This is likely explained by a shorter course of treatment and the rapid reversibility of any corneal side ef-fects experienced during the treatment of non-chronic indications. In 2006, the Centers for Disease Control and Preven-tion recommended discontinuing the use of amantadine to treat influenza due

to high levels of resistance12. However, a recent article shows co-circulation of amantadine-resistant and -sensitive strains that has led to the creation of a predominantly amantadine-sensitive re-assortant H1N1 influenza A virus during the 2007-2008 season in Japan13. Due to this, amantadine use for the treatment of H1N1 influenza A may increase.

To date, there has been no study to elucidate the pathogenesis of amanta-dine-induced corneal edema. The ma-jority of reports in the literature demon-strate rapid reversibility after cessation of amantadine. However, a more recent report suggests the possibility of irre-versible edema following discontinuation of the drug as evidenced by permanent endothelial damage shown on scanning electron microscopy7. A 2-year retro-spective study looked at patients pre-scribed amantadine within the Veterans Health Administration and found that 36 (0.27%) of 13,137 patients studied were diagnosed with corneal edema or Fuchs’ endothelial dystrophy. The authors dis-close that their decision to include Fuchs dystrophy as an outcome mea-surement was based on the assumption

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that the “diagnosis of Fuchs dystrophy may at times be based on nothing more objective than the presence of corneal edema.”14 Because diagnostic criteria for Fuchs’ endothelial dystrophy in this study could not be verified, it remains unknown whether endothelial compro-mise predisposes to the development amantadine-induced corneal edema. Additionally, the degree of reversibil-ity could not be demonstrated after the discontinuation of the medication due to study design limitations.

Amantadine is known to cause the onset of endothelial dysfunction and vi-sual impairment even after years of treat-ment. Late onset corneal edema may be explained by a decline in endothelial cell count and/or functionality that falls below a critical threshold. Corneal endothelial cell loss and dysfunction are character-istic features of Fuchs’ endothelial dys-trophy. Fuchs’ endothelial dystrophy and Parkinson’s disease often affect people within the same age group with clinical presentation primarily after age 501,8.

In summary, amantadine has been shown to be reversible in most patients, but irreversible corneal edema requiring surgical intervention can occur. Although anecdotal, this case report suggests that patients with a significantly reduced en-dothelial count or functionality may be at higher risk for the development of cor-neal edema. In addition, it is anticipated that the number of amantadine prescrip-tions for the treatment of H1N1 influenza A will begin to rise. For these reasons, we suggest screening examinations for endothelial disease prior to initiating amantadine therapy.

REFERENCES

1. Schwab RS, England AC Jr, Poskanzer DC, Young RR. Amantadine in the treatment of Parkinson’s disease. JAMA, 1969; 208 (7): 1168-1170.

2. Chang KC, Kim MK, Wee WR, Lee JH. Corneal Endothelial Dysfunction Associated With Amanta-dine Toxicity. Cornea, 2008; 27 (10): 1182-1185.

3. Nogaki H, Morimatsu M. Superficial punctuate keratitis and corneal abrasion due to amantadine hydrochloride. J Neurology, 1993; 240: 388-389.

4. Fraunfelder FT, Meyer SM. Amantadine and corneal deposits. Am J Ophthalmol, 1990; 110: 96-97.

5. Blanchard DL. Amantadine caused corneal edema. Cornea, 1990; 9 (2): 181.

6. Pearlman JT, Kadish AH, Ramseyer JC. Vision loss associated with amantadine hydrochloride use. JAMA, 1977; 237:1200.

7. Jeng BH, Galor A, Lee MS, et al. Amantadine-Associated Corneal Edema; Potentially Irreversible Even after Cessation of the Medication. Ophthalmology, 2008; 115 (9):1540-1544.

8. Kubo SI, Iwatake A, Ebihara N, et al. Visual impairment in Parkinson’s disease treated with aman-tadine: case report and review of the literature. Parkinsonism Relat Disord, 2007; 14: 166-169.

9. Naumann GO, Schlotzer-Schrehardt U. Amanatadine-associated Corneal Edema. Ophthalmology, 2009; 116 (6): 1230-1231.

10. Dubow JS, Rezak M, Berman AA. Reversible Corneal Edema Associated with Amantadine Use: An Unrecognized Problem. Movement Disorders, 2008; 23 (14): 2096-2097.

11. Pond A, Lee MS, Hardten DR, et al. Toxic corneal oedema associated with amantadine use. Br J Ophthalmology, 2009; 93 (3): 281.

12. Hersh AL, Maselli JH, Cabana MD. Changes in Prescribing of Antiviral Medications for Influenza Associated With New Treatment Guidelines. Am J Public Health, 2009; 99 (S2): S362-S364.

13. Furuse Y, Suzuki A, Shimizu M, et al. Reassortment between Amantadine-Resistant and –Sen-sitive H1N1 Influenza A Viruses Generated an Amantadine-Sensitive Virus during the 2007-2008 Season. J Infect Dis, 2009; 200 (11): 1766-1773.

14. French DD, Margo CE. Postmarketing Surveillance of Corneal Edema, Fuchs Dystrophy, and Amantadine use in the Veterans Health Administration. Cornea, 2007; 26: 1087-1089.

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Chun Cheng Lin Yang MD MSc1, 2; Manuela Gongora Moraga RN1; Carmen Maria González López PharmD2; John D. McCann MD PhD3

1 Oculoplastic and Orbital Surgery Division, Ophthalmology Service, Hospital San Rafael de Alajuela, Alajuela, Costa Rica

2 Costa Rica Oculoplastics Inc., Hospital Cima San José, San José, Costa Rica

3 Center for Facial Appearances, Salt Lake City, Utah, United States

Autor para Correspondencia:Chun Cheng Lin Yang MD MScCosta Rica Oculoplastics Inc., Hospital CIMA San José, Torre 3, Cons. 322, Escazú, Costa RicaPhone: (506) 2208-8322 Fax: (506) 2208-8372Email: ccluislin@gmail.com

¿Es un Simple Orzuelo ó es Algo más?

Declaración de Interés Financiero: Ninguno de los autores tiene interés fi nanciero en el material presentado

AbstractBecause eyelid ophthalmomyiasis exter-

na is uncommon, it can be confused easily with a hordeolum or chalazion. We report a case of a 28-year-old patient with lower eyelid myiasis simulating a hordeolum. The patient underwent extraction using a simple surgical technique. The extracted worm was a Dermatobia hominis larva.

ResumenPorque la oftalmomiasis externa es in-

usual, esta entidad puede ser confundida fácilmente con un orzuelo ó chalazión. Re-portamos un caso de un paciente de 28 años con una miasis del párpado inferior simulan-do un orzuelo. Utilizando una simple técnica quirúrgica, una larva de Dermatobia hominis fue extraída en este paciente.

IntroducciónLa infestación del ojo y/o anexos por larva

del orden Diptera se denomina oftalmomiasis, y esta representa el 5% de la miasis en los hu-manos. Dependiendo de la localización de la larva, oftalmomiasis externa se refiere al invo-

lucro de la larva en la conjuntiva, párpados, y órbita. Cuando la larva penetra el globo ocular, una entidad que compromete la visión, esta se conoce como oftalmomiasis interna.1-3 Las lar-vas de Oestrus ovis y Dermatobia hominis se han asociado con oftalmomiasis. En Centro-américa y Sur América, la Dermatobia hominis es el agente causal más frecuente de la miasis cutánea.3 El tratamiento de estos casos varía desde la remoción directa de la larva con for-ceps, oclusión del orificio de entrada forzando la expulsión, ivermectina oral y extracción qui-rúrgica. Reportamos un caso de oftalmomiasis externa causada por Dermatobia hominis simu-lando un orzuelo, la cual fue extraída utilizando una simple técnica quirúrgica.

Reporte de CasoUn agricultor de 28 años de edad con

cuadro de enrojecimiento, dolor, prurito y edema en su párpado inferior del ojo dere-cho fue referido del servicio de emergencias al servicio de oftalmología del Hospital de Alajuela con diagnóstico presuntivo de or-zuelo en el párpado inferior. El paciente no presentaba historia de trauma ó cirugía pre-via del párpado; sin embargo, el paciente

recuerda que 5 días previos al inicio de los síntomas se había quedado dormido en la finca durante su descanso de almuerzo. Pos-teriormente a la sintomatología, el paciente sentía que algo se movía en su párpado infe-rior conforme el edema incrementaba.

Al examen oftalmológico, la agudeza visual era 20/20 OU, presión intraocular y los movi-mientos oculares dentro de límites normales. Tanto el segmento anterior como el posterior de ambos ojos dentro de límites normales. El único hallazgo era una lesión eritematosa con aspectos de un orzuelo en el tercio interno del párpado inferior del ojo derecho (Figura 1A). A la microscopía, se observa una costra sobre el punto en la zona central de la masa (Figura 1B). Al remover la costra, se evidenció burbujas de aire y a la presión de la masa con un aplica-dor hubo drenaje de líquido sero-purulento. Se diagnostica al paciente con una presunta oftalmomiasis externa del párpado inferior del ojo derecho y el paciente fue programado para exploración quirúrgica.

Bajo anestesia local se realizó la extrac-ción quirúrgica de la sospechosa larva. Se colocó una pinza de chalazión, con el anillo sobre la superficie cutánea de la masa pal-

Figura 1: Presentación clínica del paciente con una masa en el párpado inferior derecho. (A) Masa subcutánea en párpado inferior derecho con aspecto clínico de un chalazión a simple vista. (B) La masa con una costar sobre el centro del punto, vista por lámpara de hendidura.

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pequeñas espículas en la larva se anclan al tejido subcutáneo y segundo, el movimiento de la larva asociado al estímulo directo de la larva. Por ende, la intervención quirúrgica facilita la extracción de la larva y esta es la mejor opción de manejo.1-6

Aunque la remoción quirúrgica es el método de preferencia para el manejo de la oftalmomiasis externa, no existen reportes en la literatura describiendo técnicas quirúrgicas sobre estas extracciones. Nosotros describi-mos una técnica quirúrgica muy sencilla y útil, usando una pinza de chalazión y su cu-reta. La técnica que utilizamos es como cual-quier técnica de extirpación simple. Uno de los pasos de importancia en esta técnica es la infiltración de la anestesia. En este paso, es importante hacer recalcar que la infiltración no sólo tiene el propósito de anestesiar el tejido subcutáneo del campo quirúrgico, pero a la vez, se puede aprovechar a inmovilizar la larva en la infiltración. El otro aspecto beneficioso de nuestra técnica es el uso de la pinza de chalazión. Esta pinza tiene la ventaja de que el anillo contribuye con la delimitación y el atra-pamiento de la larva. La placa de la pinza tam-bién tiene función de proteger el globo ocular. Además de estas funcionalidades, la pinza tiene función hemostática, ya que esta ejerce presión directa sobre los tejidos adyacentes. La cureta de chalazión también tiene una fun-ción muy particular para el debridamiento del tracto dejado por la larva, ya que encaja bien este tracto. Consideramos que esta técnica utilizando estos dos instrumentos puede ser útil para los oftalmólogos que se enfrentan a esta inusual entidad. Más importante aún, el oftalmólogo debe considerar la oftalmomiasis como un diagnóstico diferencial cuando abor-da un caso de una masa palpebral.

pebral, delimitándola. Una incisión horizon-tal de espesor completa atravesando el punto central de la masa fue construida. Una vez hecha la incisión, una larva móvil con sus espículos fue evidente. La larva fue extraída cuidadosamente con firmeza moderada con una pinza con diente, evitando la fragmen-tación de ésta. Una vez removida la larva, se debridó el trayecto que esta dejó con la cureta de chalazión y se lavó el campo qui-rúrgico con gentamicina y solución salina. La incisión se cerró con suturas interrumpidas. Al paciente se le recetó cefalexina oral por una semana asociada a ungüento oftálmico en la incisión y acetaminofen oral. La larva fue enviada al departamento de microbiolo-gía del hospital, la cual fue identificada por el microbiólogo como larva de Dermatobia hominis. El paciente tuvo una evolución sa-tisfactoria, auque sólo regresó a la consulta control a la semana para retiro de puntos en su párpado.

DiscusiónLa invasión de los párpados, conjuntiva,

córnea y órbita ó el ojo de los mamíferos por la larva de las moscas (órden Diptera) se de-fine como oftalmomiasis. Aunque la causa más común de oftalmomiasis en el mundo corresponde a la larva de la oveja (Oestrus ovis), el tórsalo ó larva de la mosca D ho-

minis es la causa más común de la miasis cutánea en Centro y Sur América.1-4

La infestación en el humano inicia con la mosca femenina adhiriendo los huevecillos en el abdomen de otra mosca. Cuando esta mosca vectora aterriza en un ser humano, la larva incubada sale del huevo con el calor de la piel humana. La larva entonces cons-truye un tracto en la piel a través del sitio de la mordedura del insecto ó del folículo piloso. Una vez dentro, la larva se posiciona con la cabeza hacia abajo para alimentarse, respirando por los espiráculos respiratorios caudales.1,5 La presencia de la larva dentro de la piel insita una reacción inflamatoria local,6 y el paciente infestado con la larva frecuen-temente aqueja de prurito y dolor localizado. El paciente también puede sentir los movi-mientos de la larva. Ambos síntomas fueron aquejados por nuestro paciente.

El manejo de la oftalmomiasis externa varía desde la extracción bajo visualiza-ción directa; remoción de la larva posterior a oclusión del agujero de ingreso con un-güento, ó cera, ó goma de mascar, ó grasa porcina1,5; remoción de larva post tratamien-to con ivermectina oral7; y extracción qui-rúrgica. Cuando la intención de remover la larva es la extracción directa con pinzas, esta maniobra se torna súmamente difícil debi-do a dos factores: primero, las filas de las

BIBLIOGRAFÍA

1.Goodman RL, Montalvo MA, Reed JB, et al. Anterior orbital myiasis caused by human botfl y (Dermatobia hominis). Arch Ophthalmol. 2000;118 (7): 1002-3.

2.Savino DF, Margo CE, McCoy ED, Friedl FE. Dermal myiasis of the eyelid. Ophthalmology.1986;93:1225-1227.

3.Wilhelmus KR. Myiasis palpebrarum. Am J Oph-thalmol. 1986;101:496-498.

4.Lane RP, Lowell CR, Griffi ths WA, Sonnex TS. Hu-man cutaneous myiasis: a review and report of three cases due to Dermatobia hominis. Clin Exp Derma-tol. 1987;12:40-45.

5.Elgart ML. Flies and myiasis. Dermatol Clin. 1990;8:237-244.

6.Emborsky ME, Faden H. Ophthalmomyiasis in a child. Pediatr Infect Dis J. 2002;21:82-83.

7.Wakamatsu TH, Pierre-Filho PT. Ophthalmomyiasis externa caused by Dermatobia hominis: a successful treatment with oral ivermectin. Eye. 2006; 20:1088-90.

Extracción quirúrgica de la larva en el párpado inferior derecho. (A) Posterior a la colocación de la pinza de chalazión en el párpado inferior, el anillo de la pinza delimita la larva, la placa de la pinza protege el globo ocular y también tiene función hemostática. (B) Exposición de la larva previo a extracción en pieza completa. (C) El tracto que dejó la larva en su travesía. La cureta de chalazión calza bien en este tracto para el debridamiento apropiado. (D) Aspecto de la larva extraida, identifi cada como larva de Dermatobia hominis.

Figura 2:

PAN-AMERICA : 57

Junio 2010

Alexandre Nakao Odashiro MD, PhD1,3; Patrícia Rusa Pereira Odashiro MD2; Maçanori Odashiro MD1,3; Lívio Viana O. Leite MD, PhD2; Priscila Inácio Fernandes Zaupa MD2; Atalla Mnayarji MD4; Bruno F. Fernandes MD PhD5; Shawn C Maloney MSc5; Miguel N. Burnier Jr MD PhD5

1 Department of Pathology – Federal University of Mato Grosso do Sul - Brazil2 Department of Ophthalmology – Associação Benefi cente de Campo Grande – Brazil3 LAC – Pathology and Cytopathology Laboratory - Campo Grande – Brazil4 Oncology – Hospital Regional de Mato Grosso do Sul – Campo Grande -Brazil5 Henry C. Witelson Ocular Pathology Laboratory - Department of Ophthalmology, McGill University - Montreal - Canada

Corresponding Author:Alexandre Nakao OdashiroLAC – Pathology and Cytopathology LaboratoryRua Rui Barbosa, 371679002-362 Campo Grande, MS, Brazil Fax: (55-67) 3083-7325E-mail: alexandrenakao@yahoo.com.br

Orbital Granulocytic Sarcoma without Systemic Manifestation

The authors declare that they have no competing interests Authors declare no fi nancial interest

AbstractGranulocytic Sarcoma is an uncom-

mon manifestation of AML that can affect the orbit. A 10 year-old girl presented with a history of 1 day old proptosis (OS). The patient also presented with diplopia in the inferior quadrants OS. No other significant alterations were seen during her ophthal-mological exam, with the exception of proptosis (OS). A CT scan displayed an extraconal mass to the left orbit. The mass had a molding contour with minimal bone destruction. A lateral orbitotomy was later performed. Subsequent histopathological examination and immunohistochemistry confirmed the diagnosis of granulocytic sarcoma. The systemic work-up was normal. The patient later underwent che-motherapy plus radiotherapy, and is now free of systemic disease after a 18-month follow-up.

ResumoSarcoma Granulocítico é uma forma

incomum da Leucemia Mielóide Aguda e pode acometer a órbita. Apresentamos uma criança de 10 anos, feminina, que apresentou uma história de proptose no olho esquerdo há 1 dia. A paciente tam-bém apresentava diplopia on quadrante in-ferior do olho esquerdo. Não havia outras alterações ao exame clínico. Tomografia Computadorizada da órbita mostrou uma massa extraconal na órbita esquerda, com contornos em “moldura” sem destruição óssea. Foi realizada uma orbitotomia la-teral com biópsia do tumor. O exame histopatológico confirmou o diagnóstico de Sarcoma Granulocítico. Exame clínico-radiológico não mostrou doença sistêmi-

ca. A paciente foi submetida a tratamento com quimioterapia e radioterapia e está livre de doença sistêmica após 1 ano e meio de seguimento.

IntroductionLeukemia is the most common form

of childhood cancer. Acute lymphoblastic leukemia accounts for 80% of all childho-od leukemias, while acute myeloid leuke-mia (AML) accounts for only 15% of cases diagnosed1. Granulocytic Sarcoma (GS) is an uncommon manifestation of AML, ac-counting for 3-8% of all AML cases. GS may also be referred to as Chloroma, due to the green color present on gross patho-logical examination. However, up to 30% of GS are not green on gross examination. GS is a localized tumor, usually located in the extramedullary tissue, and compo-sed of immature myeloid cells originating from granulocytic precursors2. In fact, GS is an extramedullary leukemic deposit and is also known as myeloid extramedullary sarcoma3.

GS can manifest together with syste-mic AML or can precede systemic blood and/or bone marrow disease4. Diagnosing GS can be difficult, especially if the tumor does not occur in the presence of AML5. This tumor can appear in a variety of sites including skin, bone, orbit and medias-tinum6 and is more common in children less than 10 years of age7. Here we report one case of GS with clinical-pathological manifestations.

Case ReportA 10 year-old girl presented at our de-

partment with discrete proptosis of the left

eye (OS), which was previously noticed by her parents only one day before coming into the clinic (Figure A). The patient had no pain or history of trauma. Her visual acuity was 20/20 bilaterally and also had diplopia in her inferior quadrants OS. On examination, she had irreducible proptosis (20 mm) (Figure A), with OS downward and outward displacement. The biomi-croscopy examination further exposed discrete conjunctival hyperemia OS. The fundus examination and intraocular pres-sure were normal in both eyes. She had no systemic (signs or symptoms. Results of the physical examination were normal wi-thout evidence of lymphadenopathy or or-ganomegaly. Computed Tomography (CT) imaging of the orbit (Figure B) revealed a large extraconal mass in the left orbit. The mass was located along the lateral wall, and had a molding contour with minimal bone destruction.

A lateral orbitotomy was performed for removal of the tumor. Histopathological examination (Figures C and D) showed a tumor composed of diffuse monotonous infiltrate of medium-sized cells with in-terspersed eosinophilic myelocytes. The neoplastic cells had round nuclei, fine chromatin, and distinct nucleoli. A mo-derate amount of basophilic cytoplasm, with fine azurophilic granulation, was also observed in some of the cells. Scattered eosinophilic myelocytes were further ob-served.

Immunostaining of the neoplastic cells revealed positive staining for LCA (leuko-cyte common antigen) and Myeloperoxida-se, while CD3, CD20 and CD10 were nega-tive (Figures E and F). Muscular markers (desmin and myoD1) were also negative.

CASE REPORT

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The diagnosis of GS was made based on these results.

Systemic work-up included comple-te hemogram and bone marrow biopsy, which came back normal. The patient subsequently underwent chemotherapy according to the protocol AML-BMF 98. First induction cycle was performed with Cytarabine, Etoposide, Idarubicin and in-trathecal Cytarabine. One month later a se-

cond induction cycle was performed with high dose Cytarabine, Mitoxantrone and intrathecal Cytarabine. One month later a consolidation cycle was done with Pred-nisone, Tioguanin, Vincristin, Idarubicin, Cytarabine and intrathecal Cytarabine. Four months later, a 4th cycle was perfor-med with high doses of Cytarabine, Eto-poside and intrathecal cytarabine. A final cycle was performed one month later with

Figure 1: A. Picture showing patient with proptosis OS. B. Computed Tomography showing a large mass located on the orbit OS, with displacement of the globe. The mass presented a molding pattern on the bone and showed minimal bone destruction. C. Histopathological picture showing tumor composed of uniform round to oval cells with hyperchromatic nuclei and minimal cytoplasm (Hematoxilin-Eosin, 100x). D. Detail of the pleomorphic cells. Some interspersed tumoral cells present eosinophilic granular cytoplasm (arrows) resembling myeloid origin (Hematoxilin-Eosin, 400x). E. Immunohistochemistry for Myeloperoxidase showing positive reaction in the tumoral cells. F. Immunohistochemistry for Leucocyte Common Antigen (LCA) showing positive membrane reaction in some tumoral cells.

radiation therapy with Tioguanin, Cytarabi-ne and intrathecal Cytarabine. A follow-up with images exams showed no recurrence or systemic disease post 18 months of follow-up. Moreover, a complete reduction of the proptosis was seen.

DiscussionLeukemic cells can infiltrate any extra-

medullary site. When it occurs within soft tissues or bone it is referred to as GS8. This can be further defined as a localized tumor derived from primitive myeloid cells. GS may present in association with different types of myeloid leukemia that include AML, with or without blast crisis. Other types of myeloproliferative disorders2 may also be associated with GS.

In cases showing no evidence of syste-mic disease with thorough work-up, leuke-mia almost always develops after an inter-val of weeks to years if systemic treatment is not administered9. On the other hand, the presence of orbital involvement is a sign of poor prognosis for AML10. Orbital locali-zation of GS is unusual in western coun-tries. However, it is considered common in African and Asian countries and can be correlated with low socio-economic status and poor T-cell mediated immunity11. Our patient was of low socio-economic status but showed no signs of being immuno-compromised.

GS can occur at any age but most fre-quently affects children, with 75% of cases presenting by age 108. Boys are traditio-nally more affected than girls. Presentation can be in a variety of locations such as bone, soft tissues, lymph nodes, skin and kidney12. However, the orbit is one of the most classic sites of disease prevalence. The clinical features of orbital GS can vary considerably, but proptosis is the most common presenting clinical sign2. Other signs include iris and eyelid tumors, uvei-tis, a conjunctival mass or scleral mass7. Our patient presented with classic clinical signs, with the sole exception of gender. Orbital GS simulating inflammatory condi-tions or thyroid ophthalmopathy is parti-cularly important because it delays correct diagnosis, as previously reported by Fon-seca Júnior et al 4.

Classically, GS arises in the bone ma-rrow and traverses the Haversian canals to reach the periosteum, and subsequently spreads to soft tissues8. Interestingly, our

PAN-AMERICA : 59

Junio 2010

patient did not have massive bone des-truction on CT exam. The lesion showed a molding pattern on the bone surface, a classical sign for lymphoid tumors. In fact, imaging studies alone cannot confidently distinguish GS from other orbital malig-nant tumors. This also includes distinguis-hing lymphomas, rhabdomyosarcoma and neuroblastoma2 through imaging alone. Therefore, a definitive diagnosis relies pri-marily on histopathological examination of the tumor.

Histopathologically, the tumor is com-posed of immature myeloid cells. Immuno-histochemistry was essential in rendering this particular diagnosis. The diagnosis can be missed in 50% of cases when im-munohistochemistry is not used. As lym-phomas are the main differential diagnosis considered on histopathology, an antibody panel of CD43, lysozyme, myeloperoxida-se, CD68, CD3 and CD20 can successfully identify the majority of GS13. GS are clas-sically positive for myeloperoxidadase and CD43. Other antibodies such as lysozyme, CD15 and CD68 have been reported to be positive in GS but are less specific. GS is usually negative for T-cell (CD3) and B-cell (CD20) markers14. MAC387 can also be helpful, but is less sensitive15 and is po-sitive in mature granulocytes16. Rhabdom-yosarcoma is the most common malignant orbital tumor in children. It is composed of small, round cells with scanty cytoplasm,

and is another differential diagnosis to be considered. Muscular markers such as desmin and MyoD1 are positive in rhab-domyosarcoma but negative in GS4.

In the past, Leder stain (chloroacetate esterase) was widely used to diagnose GS. The stain would produce a characteristic diffuse pattern of argyrophilic granules14. However, the present widespread use of immunohistochemistry has led to a more confident and specific method for diagno-sing GS while differentiating it from other neoplastic lesions. In the present case, the strong and diffuse reaction to myelo-peroxidase confirmed the diagnosis. This is important because early diagnosis and treatment provides the best prognosis for patients with GS8. As previously observed in a Turkish oncology center, orbital in-volvement of GS represented a very poor prognosis compared to GS in general11. Our patient received systemic chemothe-rapy and remains disease free post 18 months of follow-up.

ConclusionGS is an uncommon malignant tumor

of which ophthalmologists, general clini-cians and pathologists should be aware. Making an early and accurate diagnosis when possible systemic disease is not involved can drastically improve patient outcome.

REFERENCES

1.Porto L, Kieslich M, Schwabe D, et al. Granulo-cytic sarcoma in children. Neuroradiology 2004; 46(5):374-7.

2.Stockl FA, Dolmetsch AM, Saornil MA, et al. Or-bital granulocytic sarcoma. Br J Ophthalmol 1997; 81(12):1084-8.

3.Azim HA, Jr., Gigli F, Pruneri G, et al. Extramedul-lary myeloid sarcoma of the breast. J Clin Oncol 2008; 26(24):4041-3.

4.Fonseca Junior NL, Paves L, Nakanami DM, et al. [Orbital granulocytic sarcoma: case report]. Arq Bras Oftalmol 2005; 68(4):557-60.

5.Manabe Y, Hamakawa Y, Sunami K, et al. Granu-locytic sarcoma with orbit, cauda equina, muscle and peripheral nerve extension but without bone marrow involvement. Intern Med 2007; 46(9):633-5.

6.Bhattacharjee K, Bhattacharjee H, Das D, et al. Chloroma of the orbit in a non-leukemic adult: A case report. Orbit 2003; 22(4):293-7.

7.Hmidi K, Zaouali S, Messaoud R, et al. Bilateral orbital myeloid sarcoma as initial manifestation of acute myeloid leukemia. Int Ophthalmol 2007; 27(6):373-7.

8.Uyesugi WY, Watabe J, Petermann G. Orbital and facial granulocytic sarcoma (chloroma): a case report. Pediatr Radiol 2000; 30(4):276-8.

9.Neiman RS, Barcos M, Berard C, et al. Granulocytic

sarcoma: a clinicopathologic study of 61 biopsied cas-es. Cancer 1981; 48(6):1426-37.

10.Fisgin T, Yarali N, Duru F, Kara A. Parvovirus-B19 infection preceding acute myeloid leukemia with orbital granulocytic sarcoma. Leuk Lymphoma 2002; 43(10):2059-61.

11.Gozdasoglu S, Yavuz G, Unal E, et al. Orbital granu-locytic sarcoma and AML with poor prognosis in Turk-ish children. Leukemia 2002; 16(5):962; author reply 3.

12.Bhat VK, Naseeruddin K, Narayanaswamy GN. Sino-orbital chloroma presenting as unilateral prop-tosis in a boy. Int J Pediatr Otorhinolaryngol 2005; 69(11):1595-8.

13.Alexiev BA, Wang W, Ning Y, et al. Myeloid sarco-mas: a histologic, immunohistochemical, and cytoge-netic study. Diagn Pathol 2007; 2:42.

14.Fletcher CDM. Diagnostic histopathology of tumors, 3rd ed. Edinburgh; Philadelphia: Churchill Living-stone Elsevier, 2007; 2 v. (x, 1883, 41).

15.Menasce LP, Banerjee SS, Beckett E, Harris M. Ex-tra-medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases. Histopathol-ogy 1999; 34(5):391-8.

16.Liu YH, Zhuang HG, Liao XB, et al. [Diagnosis and differential diagnosis of granulocytic sarcomas]. Zhon-ghua Xue Ye Xue Za Zhi 2003; 24(11):568-71.

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DR. MANNIS IS INTERNATIONALLY RECOGNIZED

Mark J. Mannis, Professor and Chair of the UC Davis Health System Eye Center and President Elect of the PAAO, has received the Moacyr Alvaro Gold Medal from the Federal University of São Paulo for his contributions to Latin American ophthalmic educa-tion and eye banking.

The award is the highest honor given to an ophthalmolo-gist in Latin America and is designated for outstanding contri-butions to the field in teaching, research and service. Mannis received the award at the International Symposium sponsored by

the Federal University of São Paulo. Mannis and other faculty in the Department of Ophthalmology & Vision Science at UC Davis have trained 10 fellows from Latin America, many of whom have achieved prominence in academic ophthalmology.

The Eye Center also sponsors semi-annual telemedicine grand rounds with colleagues at several Brazilian academic cen-ters. Mannis is currently the president of the Pan-American As-sociation of Eye Banks (APABO) and is the President Elect of the Pan-American Association of Ophthalmology (PAAO).

Dr. Mannis was also recently awarded the title of Doctor Honoris Causa by the National University of San Marcos (Uni-versidad Nacional Mayor de San Marcos) in Lima, Peru.

The University of San Marcos, founded in 1551, is the oldest continuously running university in the Americas. It is the largest and most prestigious university in Peru. Mannis joined an illustrious cadre of previous awardees that include, among others, the president of Spain in 2009 and Nobel Lau-reate Peter Agre in 2008.

Mannis received the award in recognition of his contributions to clinical ophthalmic science, eye banking and Latin American ophthalmology. He received the medallion given to recipients of the honorary doctorate and addressed the convocation in Span-ish, citing the intrinsic role that universities and, specifically, medical schools have played in modern civilization.

Dr. Mannis is presented the Moacyr Alvaro Gold Medal by his former fellow and Chief of the Cornea Service at Escola Paulista, Dr. Luciene Barbosa de Sousa

Rector of the National University of San Marcos and prominent Peruvian ophthalmologist Dr. Luis Izquierdo, presents the certificate of Doctor Honoris Causa to Dr. Mannis

PAN-AMERICA : 61

LATIN AMERICAN / PAAO PEDIATRICOPHTHALMOLOGY FELLOWSHIP

Junio 2010

APPLICANT QUALIFICATIONS:

The following qualifications for a successful candidate are as follows:

1. General ophthalmologist, age 35 years or younger, from Mexi-co, Central or South America or the Caribbean.

2. Fluent in both written and spoken English. Candidates must have take the TOEFL exam and submit their results with their ap-plication. Mandatory: Candidates will be interviewed by telephone to gauge their English abilities.

3. Willing to commit for one or two years of training.

4. Completion of a recognized ophthalmology residency in Latin America.

5. Applicants with additional training in or those currently practicing pediatric ophthalmology and/or strabismus will be given preference.

6. Established medical and surgical competence and good depth perception.

7. Highly recommended by chairperson and training program di-rector.

8. Commitment to return to Latin America at conclusion of fellow-ship training program.

9. The candidate must be a member of the PAAO.

MEDICAL LICENSURE DURING PROGRAM:Either (1) a physician in training license, if all necessary parts of USMLE has been passed, or (2) an Assistant Visiting Professor’s license if USMLE not taken and passed.

COMPENSATION:Salary of approximately $54,000 per year plus fringe benefits will be provided. Salary and the fringe benefits come from the Univer-sity of Texas Southwestern Medical Center (UTSWMC) and Chil-dren’s Medical Center (CMC) and include health insurance along with an accrual of vacation and sick leave hours. The fellow will be an employee of UTSWMC, working at Children’s Medical Center.

METHOD OF APPLICATIONAll applications and materials must be submitted electronically, by email to info@paao.org. Failure to submit all requested materials can result in a delay in review of the application.1. Completed application form.2. English language proficiency (such as the TOEFL exam or the former ECFMG English Test).3. CV (two to three pages) including training information and re-cent publications.4. Letter of recommendation from department chair and/or train-ing program director.

application deadline: August 10, 2010

PROGRAM DESCRIPTION:A one or two year hands-on pediatric ophthalmology fellowship is available for one (1) qualified Latin

American ophthalmologist through the PAAO in the Department of Ophthalmology at the University of Texas Southwestern Medical Center in Dallas and its affiliated Children’s Medical Center. The position will include the opportunity for direct patient medical and surgical interactions as well as the opportunity to participate in significant clinical research activities.

The 2011 Troutman-Véronneau Prize of US $10,000.00, funded by a perma-nent endowment from the Microsurgical Research Foundation to the Pan-American Ophthalmological Foundation for the most original, previously unpublished paper on the subject of Pediatric Ophthalmology, emphasizing Strabismus, and Strabismus microsurgery will be awarded at the opening session of the 29th Pan-American Congress of Ophthalmology in Buenos Aires, Argentina on July 7, 2011. The selected paper will be a featured part of the 29th Pan-American Congress.

The awardee (first author) must be:

* 45 years of age or younger at the time of submission of his/her paper

* Be a PAAO Active Member (Miembro Titular) at the time of submission

* Be certified by the American Board of Ophthalmology or by the Oph-thalmology Board of his/her respective country, or be Board eligible. If no Board exists, he/she must be a member in good standing with the national ophthalmological society affiliated with the PAAO.

The candidate must submit the complete manuscript ELECTRONICALLY, in-cluding illustrations and tables. The manuscript may be submitted in any of the three official languages of the PAAO, English, Spanish or Portuguese.

If selected for the award, the winning author is required to attend the 29th Congress in Buenos Aires to receive the prize at the Opening Ceremony and to present the paper on the scheduled day. The winning author is responsible for his/her own travel, housing arrangements and expenses.

Manuscript Preparation

Manuscripts should be prepared in accordance with the American Medical Association Manual of Style and/or the Uniform Requirements for Manu-scripts Submitted to Biomedical Journals (www.icmje.org).

Manuscripts should begin each component on a new page and be in the following order:(1) title page; (2) structured abstract; (3) text; (4) refer-ences; (5) figure legends; (6) tables; and (7) figures.

1. Title Page: Specify the full title; each author’s name, highest academic degree or degrees, and affiliation. Indicate the name, mailing address, tele-phone, fax, and email address of the corresponding author, who will be responsible for all questions about the manuscript.

2. Structured abstract: Provide a structured abstract of 250 words or less with the following four headings: Purpose, Methods, Results, Conclusions.

3. Text: Number the pages of the manuscript consecutively, begin-ning with the title page 1. Place the manuscript title on each page. DO NOT indicate the authors’ names on the pages of the manuscript.

4.References: References should be numbered consecutively in the order in which they are first mentioned in the text. Identify references in text, tables, and legends by Arabic numerals in parentheses. Refer-ences cited only in tables or figure legends should be numbered in accordance with the sequence established by the first identification in the text of the particular table or figure. The titles of journals should be abbreviated according to the style used in Index Medicus.

5. Figure Legends: Type or print out legends for illustrations using double spacing, starting on a separate page, with Arabic numerals corresponding to the illustrations. When symbols, arrows, numbers, or letters are used to identify parts of the illustrations, identify and explain each one clearly in the legend. Explain the internal scale and identify the method of staining in photomicrographs.

6. Tables: Type or print each table with double spacing on a separate sheet of paper. Number tables consecutively in the order of their first citation in the text and supply a brief title for each. Do not use internal horizontal or vertical lines. Give each column a short or abbreviated heading. Authors should place explanatory matter in footnotes, not in the heading. Explain in footnotes all nonstandard abbreviations

7. Figures: Figures should be numbered consecutively according to the order in which they have been first cited in the text. If a figure has been published, acknowledge the original source and submit writ-ten permission from the copyright holder to reproduce the material. Permission is required irrespective of authorship or publisher except for documents in the public domain.

Troutman-Véronneau Prize winning paper authors:

2007 – Vanessa Macedo Batista Fiorelli MD (Brazil)

2005 – Rocio Carolina Gutiérrez Colina MD (Venezuela)

2003 – Maria Estela Arroyo Yllanes, MD (Mexico)

2001 – José A.P. Gomez, MD (Brazil)

1999 – Jonathan C. Horton, MD (USA)

1997 – Peter J. McDonnell, MD (USA)

1995 – William Lavin, MD (USA)

1993 – John D. Gottsch, MD (USA)

** Subject matter for submissions for the Troutman-Véronneau Prize alternates between Pediatric Ophthalmology, emphasizing Strabis-mus, and Strabismus microsurgery and Cornea and/or Corneal Re-fractive Surgery.

Deadline for Submission: Tuesday, January 18, 2011

PAN-AMERICA

The 2011 Troutman-Véronneau Prize

62

29th Pan-American Congressof Ophthalmology

Buenos Aires, Argentina

Mayor Información:Lina María López

apabo.hispanoamerica@gmail.comTel. (57-4) 230 22 88

XII Curso Internacional Certifi cado de Entrenamiento

Técnico y Científi co en Bancos de Ojos

Asociación Panamericana de Bancos de Ojos - APABO Agosto 20 al 28 de 2010

Medellín – Colombia

Objetivo: Formar Técnicos y Directores Médicos idóneos, dando las herramientas conceptuales y prácticas que permitan comprender los aspectos

necesarios para desempeñarse en las actividades de los Bancos de Ojos, cumpliendo las normas técnicas internacionales y estableciendo controles de la

más alta calidad en los tejidos oculares donados.

A

Pan-American Association of Eye BanksAsociación Pan Americana de Bancos de OjosAssociaçâo Pan Americana de Bancos de Olhos

XI CURSO INTERNACIONAL

Nombre completo / Full Name:

Domicilio / Mailing address:

Nombre / First Name & Middle initial

Dirección de correo aéreo / Street (include suite or apartment)

Código Postal / Zip

Teléfono / Telephone

( ) ( )

Nombre de Acompañante(s) / Accompanying Person(s) name:

Ciudad / City Estado / State

Fax

País / Country

E-mail

Apellido(s) en letra MAYUSCULA / Last Name(s) in CAPITAL LETTERS

INSCRIPCIÓN AL CURSO Marque en el espacio correspondiente con una X

COURSE REGISTRATION Mark the corresponding box with an X

Categoría / Category1 abril 2010 hasta 1 agosto 2010 /

April 1, 2010 - August 1, 2010Después del 1 agosto 2010 /

After August 1, 2010 and onsite

Miembro Titular PAAO/Miembro Vitalicio / PAAO Active Member $ 175 USD $ 200 USD

Miembro Asociado/No-Socio / Associate/Non-Member $ 350 USD $ 375 USD

Residentes*** y Fellows*** / Residents*** and Fellows*** $ 100 USD $ 125 USD

Acompañante(s) / Accompanying Person(s) $ 75 USD $ 75 USD* Miembro Titular: Oftalmólogo que paga cuotas anuales a la PAAO.Sírvase notar que si usted se inscribe como Miembro Titular PAAO sin serlo o no está al día en sus cuotas, la PAAO le cargará la cuota de membresia como Miembro Titular (cuota anual US$150) y la cuota reducida de inscripción al curso.** Miembro Asociado: Miembro de Sociedades Nacionales afiliadas a la PAAO.*** Se requiere una carta del director del programa que certifica su calidad de residente o fellow. De no adjuntarla, se cobará como Asociado/No miembro.Política de Cancelación: Peticiones de cancelación y reembolso deberán ser por escrito. - entre el 15 de marzo de 2010 y el 1 de agosto de 2010, se reembolsará el 50% de la cuota de inscripción.- Después del 1 de agosto de 2010, reembolso de inscripción no es posible.

* PAAO Active member. Ophthalmologist who pays annual fees to the PAAO. Please note that if you register as a PAAO Active Member but are not current on your membership dues, you will be charged the Active Member registration fee and PAAO membership dues.** Associate member: Member of national societies affiliated to the PAAO.*** Must show letter from the training Hospital verifying your residence or fellowship. Otherwise non-member fee will be char-ged.Cancellation Policy: Cancellations and reimbursement requests must be made in writing. - If a cancellation is made between March 16 and August 1, a reimbursement of 50% of the Registration Fee(s) will be made. - There is no refund for cancellations after August 1.

Cheque (solamente banco US) a nombre del PAAO USD $ Check (US banks only) payable to: PAAO

Cargo a su tarjeta de crédito / Credit card charge: USD $ El cargo será hecho por la PAAO / Charge will be made by PAAO

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Llene este formulario, imprímalo y envíelo de inmediato a:Fill in this form and email or fax it immediately to:

Pan-American Association of Ophthalmology1301 S Bowen Road #365, Arlington TX 76013 USATel: (817) 275-7553 / Fax: (817) 275-3961 / E-mail: info@paao.org / Web: www.paao.orgCourse Web page: http://web.me.com/lihtehwu/PAAO_2010/Welcome.html

Alojamiento: Para hacer su reserva en el Hotel Marriott Los Sueños, sírvase llamar +888-236-2427 ó local +506-2360-9000, y mencionar el Congreso de Oftalmología. Código Asocación Oftalmóloga.

Housing: to make your hotel reservation, please call the toll-free number +888-236-2427 or the local Marriott number +506-2630-9000 and mention the Ophthalmology Meeting.

XVII Curso Regional PanamericanoXVII Pan-American Regional CourseHotel Marriott Los Sueños, Playa Herradura, Costa Rica 19 – 21 Agosto 2010 / August 19 – 21, 2010

Organizan: Asociación Oftalmológica de Costa Rica y

Asociación Panamericana de Oftalmología.

INFORMES: info@oftalmologiacostarica.com

joaqmartinez@hotmail.com

lihteh@gmail.com

Tel: (506)2289-7418.

19 al 21 de AGOSTO del 2010.

LUGAR:FECHA:

XVII CURSO

REGIONAL PANAMERICANO

DE OFTALMOLOGIA

COSTA RICA

Resort de Playa Marriott Los Sueños

Costa del Oceáno Pacífico, Costa Rica.

PAN-AMERICA4 :