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Volumen IX No.2 Junio 2010 ACUTE STEVENS-JOHNSON SYNDROME: OPHTHALMOLOGIC EVALUATION AND MANAGEMENT Darren G. Gregory MD EVOLUCIÓN DE LAS ALTERACIONES EN EL SEGMENTO ANTERIOR DEL GLOBO OCULAR EN NIÑOS PORTADORES DE ENFERMEDADES REUMÁTICAS Elena Joa Miró MD PhD 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 SINGLE SUBRETINAL DOSE OF BEVACIZUMAB (AVASTIN) FOR THE TREATMENT OF CHOROIDAL 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 CATARACT SURGERY IN THE GLAUCOMA PATIENT Brooks J Poley, MD, Richard L Lindstrom, MD, Thomas W Samuelson, MD, Richard R. Schulze, MD AMANTADINE-INDUCED CORNEAL EDEMA IN A PATIENT WITH PARKINSON’S DISEASE AND EARLY FUCHS’ ENDOTHELIAL DYSTROPHY Jay C. Bradley MD; Brian S. Phelps MD ¿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 MANIFESTATION Alexandre 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 Preserva la visión alcanzando las menores presiones-objetivo en más pacientes Investigadores de diversos estudios, (AGIS, Shirakashi, Shields) han comprobado que alcanzar y mantener la PIO entre 14 y 15 mmHg reduce la progresión de pérdida del campo visual1,2,3. Lumigan® alcanza la PIO-objetivo de 14/15 mmHg en un mayor número de pacientes: ® vs. timolol 4 ® vs. dorzolamida/ timolol 5 ® vs. latanoprost 6 Porcentaje de Pacientes que alcanzaron la PIO-Objetivo ≤14 21% 9% 17% 2% 19% 9% Porcentaje de Pacientes que alcanzaron la PIO-Objetivo ≤15 31% 16% 24% 9% 29% 14% Lumigan ® (bimatoprost) Forma farmacéutica y pr esentación. Composición. Cada ml contiene: 0,3 mg de bimatoprost. Vehículo: cloreto de sódio, fosfato de sódio presentación. esentación.Frascos cuenta-gotas conteniendo 5 ml de solución oftalmológica estéril de bimatoprost a 0,03%. USO ADULTO.Composición. hepta-hidratado, ácido cítrico mono-hidratado, ácido clorídrico y/o hidróxido de sódio, cloruro de benzalconio y agua purificada qsp. Indicaciones. LUMIGAN® (bimatoprost) es indicado para la reducción de la presión intra-ocular elevada en pacientes con glaucona o hipertensión ecauciones y Adver tencias. Advertencias. Fueron relatados aumento gradual del crescimiento Contraindicaciones. LUMIGAN® (bimatoprost) está contraindicado en pacientes con hipersensibilidad al bimatoprost o cualquier otro componente de la fórmula del producto. Pr Precauciones Advertencias. ocular.Contraindicaciones. de las pestañas en el largo y espesura, y oscurecimiento de las pestañas (en 22% de los pacientes después 3 meses, y 36% después 6 meses de tratamiento), y, oscurecimiento de los párpados (en 1 a <3% de los pacientes después 3 meses y 3 a 10% de los pacientes después 6 meses de tratamiento). También fue relatado oscurecimiento del íris en 0,2% de los pacientes tratados durante 3 meses y en 1,1% de los pacientes tratados durante 6 meses. Algunas de esas alteraciones pueden ser permanentes. Pacientes que deben recibir el tratamiento ecauciones LUMIGAN® (bimatoprost) no fue estudiado en pacientes con insuficiencia renal o hepática y por lo tanto debe ser utilizado con cautela en tales pacientes.Las lentes de contacto deben Precauciones de apenas uno de los ojos, deben ser informados a respecto de esas reacciones. Pr ser retiradas antes de la instilación de LUMIGAN® (bimatoprost) y pueden ser recolocadas 15 minutos después. Los pacientes deben ser advertidos de que el producto contiene cloruro de benzalconio, que es absorvido por las lentes hidrofílicas.Si más que un medicamento de uso tópico ocular estuviera siendo utilizado, se debe respetar un intervalo de por lo menos 5 minutos entre las aplicaciones.No está previsto que LUMIGAN® (bimatoprost) presente influencia sobre la capacidad del paciente conducir vehículos u operar máquinas, sin embargo, así como para cualquier colírio, puede ocurrir visión borrosa transitoria después de la instilación; en estos casos el paciente debe aguardar que la visión se normalice antes de conducir u operar máquinas. Interacciones medicamentosas. medicamentosas.Considerando que las concentraciones circulantes sistemicas de bimatoprost son extremadamente bajas después múltiplas instilaciones oculares (menos de 0,2 ng/ml), y, que hay varias vías encimáticas envueltas en la biotransformación de bimatoprost, no son previstas interacciones medicamentosas en humanos. eacciones adversas. LUMIGAN® (bimatoprost) es bien tolerado, pudiendo causar eventos adversos oculares leves a moderados y no graves.Eventos adversos ocurriendo en 10-40% de los pacientes que recibieron doses únicas diarias, durante No son conocidas incompatibilidades. RReacciones 3 meses, en orden decreciente de incidencia fueron: hiperenia conjuntival, crecimento de las pestañas y prurito ocular.Eventos adversos ocurriendo en aproximadamente 3 a < 10% de los pacientes, en orden decreciente de incidencia, incluyeron: sequedad ocular, ardor ocular, sensación de cuerpo estraño en el ojo, dolor ocular y distúrbios de la visión.Eventos adversos ocurriendo en 1 a <3% de los pacientes fueron: cefalea, eritema de los párpados, pigmentación de la piel periocular, irritación ocular, secreción ocular, astenopia, conjuntivitis alérgica, lagrimeo, y fotofobia.En menos de 1% de los pacientes fueron relatadas: inflamación intra-ocular, mencionada como iritis y pigmentación del íris, ceratitis puntiforme superficial, alteración de las pruebas de función hepática e infecciones (principalmente resfriados e infecciones de las vías respiratorias).Con tratamientos de 6 meses de duración fueron observados, además de los eventos adversos relatados más arriba, en aproximadamente 1 a <3% de los pacientes, edema conjuntival, blefaritis y astenia. En tratamientos de asociación con betabloqueador, durante 6 meses, además de los eventos de más arriba, fueron observados en aproximadamente 1 a <3% de los pacientes, erosión de la córnea, y empeoramiento de la acuidad visual. En menos de 1% de los pacientes, blefarospasmo, depresión, retracción de los párpados, Posología y Administración. hemorragia retiniana y vértigo.La frecuencia y gravedad de los eventos adversos fueron relacionados a la dosis, y, en general, ocurrieron cuando la dosis recomendada no fue seguida.Posología Administración.Aplicar una gota en el ojo afectado, una vez al día, a la noche. La dosis no debe exceder a una dosis única diaria, pues fue demostrado que la administración más frecuente puede disminuir el efecto hipotensor sobre la hipertensión ocular.LUMIGAN® (bimatoprost) puede ser administrado concomitantemente con otros productos oftálmicos tópicos para reducir la hipertensión intra-ocular, respetándose el intervalo de por lo menos 5 minutos entre la administración de los medicamentos. VENTA BAJO PRESCRIPCIÓN MÉDICA.“ESTE PRODUCTO ES UM MEDICAMENTO NUEVO AUNQUE LAS INVESTIGACIONES HAYAN INDICADO EFICACIA Y SEGURIDAD, CUANDO CORRECTAMENTE INDICADO, PUEDEN SURGIR REACCIONES ADVERSAS NO PREVISTAS, AÚN NO DESCRIPTAS O CONOCIDAS, EN CASO DE SOSPECHA DE REACCIÓN ADVERSA, EL MÉDICO RESPONSABLE DEBE SER NOTIFICADO. 1. The AGIS Investigators: The Advanced Glaucoma Intervetion Study - The Relationship Between Control of Intraocular Pressure and Visual Field Deterioration. Am. J. Ophthalmol, 130 (4): 429-40, 2000. 2. Shirakashi, M. et al: Intraocular Pressure-Dependent Progression of Visual Field Loss in Advanced Primary Open-Angle Glaucoma: A 15-Year Follow-Up. Ophthalmologica, 207: 1-5, 1993. 3. Mao, LK; Stewart, WC; Shields, MB: Correlation Between Intraocular Pressure Control and Progressive Glaucomatous Damage in Primary Open-Angle Glaucoma. Am. J. Ophthalmol, 111: 51-55, 1991. 4. Higginbotham, EJ et al. One-Year Comparison of Bimatoprost with Timolol in Patients with Glaucoma or Ocular Hypertension. Presented at American Academy Ophthalmology, Nov 11-14, 2001. 5. Gandolfi, S et al. Three-Month Comparison of Bimatoprost and Latanoprost in Patients with Glaucoma and Ocular Hypertension. Adv. Ther, 18 (3): 110-121, 2001. 6. Coleman, AL et al: A 3-Month Comparison of Bimatoprost with Timolol/Dorzolamide in Patients with Glaucoma or Ocular Hypertension. Presented at American Acedemy of Ophthalmol, New Orleans, La, 2001. Mejor comodidad posológica: 1 vez al día. No requiere refrigeración. Presentación conteniendo 3 ml. Febrero Junio 2010 2009 Mark J. Mannis, MD University of California, Davis Sacramento, California Editor-in-Chief Cristian Luco, MD Santiago, Chile Associate Editor Teresa J. Bradshaw Arlington, Texas Managing Editor Terri L. Grassi Arlington, Texas Production Editor EDITORIAL BOARD Eduardo Alfonso, MD Miami, Florida USA Alfredo Sadun, MD Los Angeles, California USA Eduardo Arenas, MD Bogotá, Colombia Allan Slomovic, MD Toronto, Ontario, Canada J. Fernando Arévalo, MD Caracas, Venezuela Luciene Barbosa de Sousa, MD São Paulo, Brazil José A. Roca Fernández, MD Lima, Perú Lihteh Wu, MD San José, Costa Rica Denise de Freitas, MD São Paulo, Brazil Paulo Dantas, MD São Paulo, Brazil Marian Macsai, MD Chicago, Illinois USA Chun Cheng Lin Yang, MD MSc San José, Costa Rica David E. Pelayes, MD PhD Buenos Aires, Argentina OFFICERS Cristián Luco MD Santiago, Chile President, Pan-American Association of Ophthalmology Nelson R. Marques São Paulo, Brazil Chairman of the Board, Pan-American Ophthalmological Foundation PRODUCTION STAFF Director of Printed Matters CLM Eliana Barbosa Graphic Design CLM Juan David Medina Camilo Ballesteros Databases and Distribution CLM Catalina Lozano [email protected] Copyediting Isabel Pradilla Piedad Camacho Special thanks to Ana Carolina Vieira, Citlali Gurrusquieta, Mapy Padilla, and Cristián Luco for assistance in translation to Spanish and Portuguese. Prepress Alejandro Bernal PAOF INDUSTRY SPONSORS Advanced Medical Optics Inc. • Alcon Inc. • Allergan Inc. • Bausch & Lomb Inc. • Carl Zeiss Meditec Inc. • Johnson & Johnson Vision Care Latin America • Merck & Co Inc. • Novartis International AG. • Santen Inc. • Prepress Creative Latin Media. Printed in Printer Colombiana - Colombia CREATIVE LATIN MEDIA, LLC. P.M.B 117 2901 Clint Moore, Boca Raton, FL 33496 Tel.: (561) 495 4728 Fax: (561) 865 1934 E-mail: [email protected] [email protected] : B PAN-AMERICA PAN-AMERICA MENSAJE DEL PRESIDENTE / MESSAGE FROM THE PRESIDENT Cristian Luco, MD Presidente PAAO 2009-2011 President PAAO 2009-2011 Presidente PAAO 2009-2011 Editorial Editorial La PAAO es la unión de las sociedades oftalmológicas nacionales 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 Canadá 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 interactuar 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 fundamental 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 34 PAN-AMERICA 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 ophthalmologists -- 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 fundamental 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 Junio 2010 REVIEW Acute Stevens-Johnson Syndrome: Ophthalmologic Evaluation and Management Darren G. Gregory MD Associate Professor of Ophthalmology Rocky Mountain Lions Eye Institute University of Colorado, Denver Aurora, Colorado, USA Proprietary interest: None Address correspondence, proof, and reprint requests to: Darren G. Gregory MD Rocky Mountain Lions Eye Institute, 1675 Aurora Ct, Mailstop F.731, Aurora, CO 80045-0510 Tel: (720) 848-2500 Fax: (720) 848-5014 Email: [email protected] Abstract: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (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. Introduction Stevens-Johnson Syndrome (SJS) is a rare, acute blistering disease involving the skin and mucous membranes. The incidence 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 photophobia and decreased vision. This article will review recent developments in the evaluation and management of the acute ocular manifestations of these diseases. Figure 1 Evaluation A 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 layers, as well the intense inflammation that can follow. The ophthalmic pathology mainly involves the bulbar and palpebral conjunctiva, 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 staining 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 Figure 2 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 difficult, 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 necrotic membranes or simply debris. Membranes will bleed with PAN-AMERICA : 35 REVIEW Figure 3 Figure 4 attempted removal and should prompt a higher level of concern. More severe cases yield diffuse, destructive conjunctival inflammation with pseudomembranous and membranous conjunctivitis. Fluorescein staining is extensive, involving much of the ocular surface (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 photophobia 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 conjunctiva may eventually be replaced by a cicatricial epithelium.6 More recent treatments using amniotic membrane transplantation (AMT) or pulsed, high-dose systemic corticosteroids have focused on suppressing this destructive inflammation in the acute phase. AMT will be covered in more detail and should be considered for all cases with extensive fluorescein staining of the conjunctiva and lid margins. The eyelids may also suffer significant 36 PAN-AMERICA damage and can be a major source of long term morbidity. Lid margin inflammation can yield widespread destruction of meibomian gland orifices and the glands themselves.6 Scarring can affect both eyelid 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 corneal 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 fornices 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 decreased vision. The prognosis for corneal transplantation in such cases is poor. Management A. Medical Management The widespread loss of skin and mucous 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 lifethreatening problems, however, can initially cause the eye situation to be less of a priority. It is important for the ophthalmologist 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 illness may significantly decrease ocular surface damage.11 The authors concluded that to minimize the potential adverse effects of systemic corticosteroid treatment it was crucial to begin the pulse of steroids before any significant skin sloughing had occurred. The use of systemic corticosteroids has been controversial, however, with some studies suggesting an increased risk of mortality with such treatment.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 Junio 2010 Figure 5 Figure 6 severe involvement, but close monitoring is still required until it is clear that no progression is occurring. Topical antibiotics 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 membranous conjunctivitis, symblepharon or lid margin sloughing develop, however, then urgent AMT should be considered. Symblepharon formation indicates an intense level of ocular surface inflammation. Symblepharon lysis and the placement of symblepharon rings may prevent further symblepharon formation, but they do nothing to address the destructive inflammation that has caused the symblepharon to form in the first place. B. Surgical management Cryopreserved 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 setting has also been summarized in 2 different reviews.18,19 No reports exist describing the use of freeze-dried amniotic membrane in the treatment SJS or TEN. AMT appears 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 procedure can be performed under local anesthesia 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-Tissue, 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 nylon 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 thickness through the eyelid to be tied over bolsters 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 centered over the cornea and sutured to the conjunctiva using a 10-0 nylon suture running 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 center 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 ocular surface prior to suturing. After placement 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 PAN-AMERICA : 37 REVIEW mucosal surfaces. A Prokera® (Bio-Tissue, Miami, FL) should be used on the ocular surface only in cases with corneal involvement 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 directly 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 care Postoperatively, the eyes are inspected daily and rinsed with sterile saline. The buildup of ointment and serosanguinous 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 infectious keratitis. A plastic wrap moisture chamber or a partial temporary tarsorrhaphy 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 persistent, severe inflammation if needed. Conclusions SJS and TEN are among the worst diseases of the ocular surface. In severe cases, 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 38 PAN-AMERICA membrane to the eyes and eyelids during the acute phase of the disease has shown great promise in preventing both the cicatricial sequelae and the dry eye problems (Figure 6). In severe cases, prompt intervention 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. REFERENCES 1. 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 epidermal 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. Ophthalmology 1995;102:1669-76 4. Chang Y, Huang F, Tseng S, et al. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management. Cornea 2007;26:123-9 5. De Rojas MV, Dart JKG, Saw VPJ. The natural history of Stevens-Johnson syndrome: patterns of chronic ocular disease and the role systemic immunosuppressive therapy. Br J Ophthalmol 2007;91:1048-53 6. Di Pascuale MA, Espana EM, Liu DT, et al. Correlation of corneal complications with eyelid cicatricial pathologies in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome. Ophthalmology 2005;112:904-12 7. Haber J, Hopman W, Gomez M, Cartotto R. Late outcomes in adult survivors of toxic epidermal necrolysis after treatment in a burn center. J Burn Care Rehabil 2005;26:33-41 8. Kelemen JJ, Cioffi WG, McManus WF, et al. Burn center care for patients with toxic epidermal necrolysis. 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 necrolysis syndrome; mortality rate reduced with early referral to regional burn center. Plast Reconstr Surg 1998;102:1018-22 11. Araki Y, Sotozono C, Inatomi T, et al. Successful 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. Management 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;109:35160 15. Kobayashi A, Yoshita T, Sugiyama K, et al. Amniotic 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 management of acute Stevens-Johnson syndrome. Br J Ophthalmol 2007;91:1536 17. Tandon A, Cackett P, Mulvihill A, Fleck B. Amniotic membrane grafting for conjunctival and lid surface disease in the acute phase of toxic epidermal necrolysis. J AAPOS 2007;11:612-3 18. Gregory DG. The ophthalmologic management 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 manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis. Surv Ophthalmol 2009;54:686-96 20. Meller D, Pires RT, Mack RJ, et al. Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology 2000;107:980-90 Junio 2010 Evolución de las alteraciones en el segmento anterior del globo ocular en niños portadores de enfermedades reumáticas Elena Joa Miró MD PhD (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 Profesora Titular Hospital Infantil Universitario “Pedro Borrás”, La Habana, Cuba Email: [email protected] Fig.1 Palabras claves: enfermedades reumáticas, uveítis anterior, queratopatía en banda, sinequias Uveítis Anterior con sinequias posterior y opacidad capsular posterior. Abstract The 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 hallada 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. Introducción Desde 1967 en el Hospital Infantil Universitario “Pedro Borrás” de La Habana trabaja un equipo formado por pediatras, reumatólogos y oftalmólogos para el tratamiento Fig.2 Uveítis anterior recurrente, Sinequia posterior soldada, opacidad capsular posterior desaparecida, esta figura corresponde a la paciente anterior. 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 pacientes que presenten enfermedades reumatológicas y, en caso de que presenten alteraciones oftalmológicas, imponer el tratamiento necesario. Todos los pacientes son vistos de forma integral y después de realizarles los exámenes pertinentes de cada especialidad, se discute el tratamiento que llevarán 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 medicamentos son impuestos y controlados por los reumatólogos y los pediatras. En caso de que el paciente presente alteraciones oculares, el oftalmólogo sigue la evolución conjuntamente con ellos para decidir si hace falta hacer cambios en el tratamiento. Los medicamentos sistémicos más utilizados son Metrotexate, 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 alteraciones 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 periódicamente por el oftalmólogo aunque no se presente alteración sistémica. Por la parte oftalmológica, todos los pacientes 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 tratamiento local y se monitorea la evolución del tratamiento mediante consultas al paciente con una frecuencia de dos veces por semana 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 Oftalmológico En los 15 niños portadores de enfermedades reumáticas en quienes se comprobó la presencia de uveítis anterior y, en algunos casos, de otras alteraciones se PAN-AMERICA : 39 REVIEW comenzó el tratamiento después de haber obtenido el consentimiento de los padres. De estos 15 niños, 9 eran portadores de artritis juvenil idiomática (60%), 4 eran portadores de espóndilo artropatía indiferenciada (27%), 1 de artritis reactiva (6.5%) y 1 de artritis psoriásica (6.5 %). En general, para las uveítis anteriores comenzamos con inmunosupresores 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, cambiamos 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, Cloruro 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 normalmente son capaces de producir hipertensión ocular, esta se presenta en estos pacientes con uveítis solo en muy contadas ocasiones. Fig.3 Uveítis Anterior con sinequias anterior y posterior. Fig.4 Sinequia anterior rota. Sinequia posterior continúa, a partir de ella Uveítis Recurrente Activa. Opacidad capsular posterior desapareció. Atrofia Iridiana a partir de la Sinequia. Es la paciente de la figura anterior. Evolución De 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 evolucionaron 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 pacientes se mantienen las sinequias posteriores; uno de ellos era también 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 man40 PAN-AMERICA Fig.5 Uveítis Anterior con opacidades capsulares posterior. Fig.6 Uveítis Anterior. Opacidad capsular anterior y posterior. Esta foto corresponde a la paciente de la figura 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. Junio 2010 Fig.7 Uveítis Activa con Sinequia postrriores rotas. Fig.8 Sinequias posteriores rotas, con pigmentos uveales en área pupilar. 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 evolucionaron de forma recurrente y también en el que no se ha logrado controlar. En los pacientes con uveítis recurrente, la opacidad era capsular posterior y desapareció. No sucedió lo mismo con el otro paciente cuyas opacidades 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 cumple el tratamiento indicado. La agudeza visual de los pacientes registrada al inicio y al final de los dos años, no muestra grandes diferencias. Tanto la fibrina y los pigmentos, así como las opacidades capsulares, se inician en la periferia, por lo que el paciente tiene toda el área pupilar libre y, como casi siempre el humor acuoso está transparente, prácticamente nunca se presenta disminución de la agudeza visual. Todos los casos que tratamos con uveítis, incluidos aquellos con opacidades capsulares y queratopatía en banda, finalizaron con 1.0 de visión, excepto 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 locales con medicamentos que normalmente pueden producir hipertensión ocular, sólo se vio alterada en 2 pacientes en los cuales 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 cirugía, pues desde que el paciente llegó a consulta ya presentaba desprendimiento de retina y coroide total. Uno de los pacientes portadores de uveítis recurrente sufrió durante un mes en 2009 la influenza A (H1N1), cuya positividad fue determinada por el departamento de virología 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 opacidades capsulares. Conclusiones Este estudio demuestra que un examen oftalmológico preventivo y un tratamiento médico impuesto por un equipo compuesto por pediatras, reumatólogos y oftalmólogos, es indispensable para detectar y tratar las posibles alteraciones activas del segmento 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 pacientes 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 indicado. Lo que revela la necesidad de cumplir un programa de consultas y de seguimiento del tratamiento para controlar las alteraciones en el segmento anterior del globo ocular en estos pacientes. El hecho de que en muchas ocasiones la uveítis se presenta antes de que se manifiesten los primeros síntomas de enfermedad reumática en el niño, indica que el chequeo médico al que se le somete sistemáticamente, siempre debe incluir un examen oftalmológico preventivo. BIBLIOGRAFÍA 1.García de Vicuña Muñoz de la Nava, C: Manifestaciones oculares en las enfermedades reumáticas pediátricas. En González E. Manual de Reumatología Pediátrica. Cap. XXXI (753765) Edit. Laboratorios Menarini, Barcelona España, 1999. 2.García Serrano, JL; Cisternas Maggi, M: Manifestaciones oculares de las enfermedades reumáticas en el niño. En Muñoz A. Reumatología Infantil. Vol.8 Cap.25 (477-500).Edit. Formación Alcalá. España, 2004 3.Pras E, Neuman R, Zandman-Goddard G: Intraocular inflammation 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 comparable 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 patients 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 Pediatría. 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 PAN-AMERICA : 41 CLINICAL SCIENCES 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 Resumen Objetivo: 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 conjuntival, 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 injerto, y no las propias células límbicas, las que tienen un papel en la reducción de las recidivas tras la cirugía del pterigio primario. Abstract Purpose: 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 excision with conjunctival or limbal-conjunctival autograft. Methods: 18 eyes underwent excision with conjunctival autograft, whereas the rest underwent excision with limbal-conjuntival autograft. All of them were followed up for one year. Main Outcome Measure: Recurrence. Results: Two patients in the conjunctival graft group (11%) presented 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 recurrences after primary pterygium surgery. 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 trials 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 designed this case series report to attempt to approach this idea. Materials And Methods Thirty-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 Technique Under topical or retrobulbar anesthesia, depending on the surgeon preference, the pterygium head is removed using forceps. The body and the remaining Tenon’s capsule were excised with Westcott 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 reaching 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-up Despite all the advances in ophthalmology, pterygium is still a challenge for ocular surface specialists. There are many surgical 42 PAN-AMERICA All patients in both groups followed the same postoperative treatment for one month. They used a chloramphenicol and dex- Junio 2010 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. Results Thirty-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 insufficience. 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 after surgery and showed no changes in the month six and month twelve examinations. Discussion In our series, we found a similar recurrence rate in both the conjunctival and the limbal-conjunctival autograft groups. Patients 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 Hispanic 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 significant role in the reduction of recurrences after primary pterygium surgery. Figure 1: Draft of the donor area for: 1A: Conjunctival autograft. 1B: Limbal-conjunctival autograft. 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 excision. Ophthalmology 1997; 104: 974-985 6.Marticorena J, Rodríguez-Ares MT, Touriño R, Mera P, Valladares MJ, Martínez 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 advanced 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 mitomycin C with conjunctival flap. Ophthalmology April 1999; 106: 817-820 9.Reid TW, Dushku N. Pterygia and limbal epithelial cells: relationship andmolecular mechanisms. Prog Retin Eye Res 1996; 15: 297-325 PAN-AMERICA : 43 CLINICAL SCIENCES Single Subretinal Dose of Bevacizumab (Avastin) for the Treatment of Choroidal Neovascularization in Patients with Age-Related Macular Degeneration. One-year Follow-up Juan 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 2 Departamento de Oftalmología, Centro de Ojos Romagosa-Fundación VER, Córdoba, Argentina Department of Ophthalmology, University of Wisconsin, Madison, WI * These authors contributed equally to this project and should be considered co-first authors. The authors do not have any conflicts of interest or commercial involvement associated with this work. Corresponding author: José D. Luna MD Departamento de Oftalmología, Centro de Ojos Romagosa-Fundación VER, Deán Funes 432, (5000) Córdoba, Argentina Tel: 54-0351-4211333 Fax: 54-0351-4234848. E-mail: [email protected] Resumen Abstract Introduction Propósito: 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) secundaria a degeneración macular relacionada con la edad (AMD). Métodos: Se trataron 4 ojos de cuatro pacientes con CNV subfoveal unilateral avanzada 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, incluyendo retinofluoresceinografía (FA) y OCT. Resultados: Luego de un año de seguimiento, la VA se mantuvo estable o mejoró en el 100% de los ojos. El grosor macular central (CMT) también disminuyó significativamente y la FA demostró una reducción considerable en el tamaño de las membranas neovasculares subretinales. Conclusiones: Nuestros resultados sugieren que una única dosis de bevacizumab subretinal es segura, efectiva y bien tolerada, 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. Purpose: To evaluate visual results and optical coherence tomography (OCT) findings after treatment with a single subretinal dose of bevacizumab in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (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 subretinal injection of bevacizumab (750μg / 0.3ml) and was followed up for one year with complete eye examinations, including 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 demonstrating a considerable reduction in the size of the subretinal neovascular membranes. 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. The expensive cost of treatment with ranibizumab (Lucentis) has led to many AMD patients to be treated with off-label intravitreal bevacizumab (IVB),1-3 an antibody approved by FDA only for the treatment of malignant tumors.4 Indeed, for economically disadvantaged 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 epithelial tears, retinal detachment and acute vision loss.8 The purpose of this study was to evaluate the safety and efficacy of a single subretinal dose of bevacizumab in patients with advanced subfoveal CNV due to AMD, in an attempt to provide an alternative treatment to wet AMD. 44 PAN-AMERICA Junio 2010 Materials And Methods The 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 leakage was confirmed by fluorescein angiography (FA) and optical coherence tomography (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 weeks 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 pressure (IOP) measurement, indirect ophthalmoscopy 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 converted to logMAR scale before been averaged. Counting finger (CF) and hand motion (HM) visual acuity (VA) were converted to a decimal equivalent of 1.8 and 3 respectively, 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 intraretinal fluid, subretinal fluid, or pigment epithelial detachment (PED) was verified as well. Unpaired t-test was performed between baseline and the last follow-up visit measurements. All eyes underwent a conventional 20gauge pars plana vitrectomy performed by the same author (JDL). First, conventional core vitrectomy was completed. Subsequently, 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 superior to the neovascular membrane. Then, Figure 1: Subretinal Avastin injection technique. Table I. Preoperative findings. Patient No. 1 2 3 4 VA* in the treated eye Size of CNV† Subtype of lesion (mm) CNV HM†† HM CF£ CF 3.5 2.8 3.0 1.5 * VA: Visual Acuity † CNV: Choroidal Neovascularization. ‡ SRH: Subretinal Hemorrhage **CMT: Central Macular Thickness. Presence of SRH‡ PC‡ ‡ PC PC PC CMT** ( m) Yes Yes Yes No 340 250 507 339 †† HM: Hand Motion. ‡‡: PC: Predominantly classic £ CF: Counting fingers Table II. LogMAR Visual Acuity Changes Patient No. 1 2 3 4 VA* at baseline VA at 1 month post-op 3 3 1.8 1.8 1.3 1.3 1.8 1.8 VA at 6 months post-op VA at 12 months post-op 1.8 1.8 1.8 1.3 1.8 1.8 1.8 1.3 * VA: Visual Acuity 0.3 ml of reconstituted bevacizumab (0.1ml -2500μg- reconstituted with 0.9 ml of lactated 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. Results Four eyes of four patients were selected 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 dimension (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 retinal 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 glaucoma drops by day 7. Two of the four patients developed progression of lens opacity by the 4 and 6 month follow-up, and surgery was performed at those times with no complications. None of the patients developed endophthalmitis or retinal detachment, as has been reported elsewhere in the context of vitrectomy.11 PAN-AMERICA : 45 CLINICAL SCIENCES FA at Baseline 1 month post-injection 1 year post-injection Figure 2: Representative FA image showing pre- and postoperative changes. Table III. OCT Changes Patient No. OCT* at baseline (µm) OCT 1 month post-op (µm) OCT 6 months post-op (µm) OCT 1 year post-op (µm) 1 2 3 4 340 250 507 339 254 283 170 181 233 359 259 187 280 295 263 180 * 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 patients (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 follow-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. Nevertheless, no correlation was found between CMT and BCVA (Figure 3). Discussion Although 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 46 PAN-AMERICA needed to control AMD.13 However, as a minor dose and less frequent applications could reduce 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 average normal vitreous volume is about 4 ml, and therefore, the dose to which the retinal cells are expected to be exposed after intravitreal injection of bevacizumab is 0.3125 -0.625 mg/ml. Thus, in our study we tested 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 Figure 3a. Pre-operative OCT Figure 3b. Post-operative OCT. One month post-injection Figure 3c: Post-operative OCT. One year post-injection Figure 3. Representative OCT image showing pre- and postoperative changes them had the same or better BCVA after a one-year follow-up with no additional antiangiogenic treatment. Regrowth of the CNV was seen in only one case. After surgery, we observed changes on the retinal pigment epithelial (RPE) layer. RPE atrophy was noted at the location of the application, but also at the area of retinal detachment due to the SRB injection. 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 Junio 2010 in-vitro studies where direct exposition of the cells to higher concentrations of bevacizumab were shown to be safe.15 A different 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 hypothesis 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 bevacizumab directly applied over the neovascular 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 independent of the amount of intraretinal and/or subretinal fluid.17 Consequently, there is a possibility that in patients with better reading 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 modality 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 developed over recent years where multiple IVB applications were used.13, 18 In conclusion, although further studies are necessary, SRB may provide a new therapeutic alternative for selected patients with exudative AMD. Acknowledgments We are grateful to Dr. Paul David Hobson, native speaker, for the language correction of this manuscript. REFERENCES 1. 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. Intravitreal bevacizumab (Avastin) for occult choroidal 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 management of choroidal neovascularization in agerelated 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 agerelated 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. Infectious and noninfectious endophthalmitis after intravitreal bevacizumab. J Ocul Pharmacol Ther 2007;23(3):240-2. 8. Fung AE, Rosenfeld PJ, Reichel E. The International 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. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):141931. 10. Holladay JT. Proper method for calculating 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 neovascularization secondary to age-related macular degeneration. Am J Ophthalmol 2000;130(4):419-28. 12. Costa RA, Jorge R, Calucci D, et al. Intravitreal bevacizumab for choroidal neovascularization 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, neurosensory 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. Visual improvement following intravitreal bevacizumab (Avastin) in exudative age-related macular degeneration. Retina 2006;26(9):994-8. PAN-AMERICA : 47 CLINICAL SCIENCES Cataract Surgery in the Glaucoma Patient Brooks 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. 3 2 Founder and attending surgeon Minnesota Eye Consultants. Adjunct Professor Emeritus , University of Minnesota department of Ophthalmology. 4 Attending surgeon Minnesota Eye Consultants. Associate Professor, University of Minnesota department of Ophthalmology. Abstract Our studies published in 2008 and 2009 found: Phaco/IOL alone provides an effective treatment for patients with cataract coexistent with ocular hypertension or glaucoma 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 longer adequate. We postulate as to why phaco/ IOL alone lowers IOP in eyes with elevated IOP: The natural lens, as it ages, compresses 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 canal of Schlemm, improves their function, and thereby lowers the once elevated IOP. According to Research to Prevent Blindness, 20.5 million Americans have cataract, and 2.0 million Americans are visually impaired from glaucoma. Today, we do approximately 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 influencing strategy would be incredible advances 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, 48 PAN-AMERICA Schulze Eye & Surgery Center Table 1. Frequency of glaucomatous (N=124)and nonglaucomatous (N =588) eyes in each postoperative year PO Years Frequency Glauc Percent Non-Glauc Glauc Cumulative Percent Non-Glauc Glauc Non-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 All eyes 2 124 3 588 1.6 100 and the patient’s experience is vastly different for the two operations. Cataract surgery entails purely topical anesthesia, no conjunctival 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” performed 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). 0.7 100 100.0 100 100.0 100 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 depicted 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 presurgical 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 Junio 2010 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 comparing mean IOP changes one year after surgery with IOP changes at the final measurement (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 reduced 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 glaucoma 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 factor 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 Table 2. Characteristics and IOP results by presurgical IOP group of non-glaucoma eyes when operated with phaco/IOL IOP (mm Hg) Group Eyes (n) Age (Y) Mean IOP (mm Hg) Postop FU (Y) At Surgery 1Y 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) Mean IOP (mm Hg) Group Eyes (n) Age (Y) Postop FU (Y) At Surgery 1Y 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 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 developing glaucoma. It would seem adult glaucoma can become a mostly prevent- able disease if OHT eyes that have significant 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) according 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 PAN-AMERICA : 49 CLINICAL SCIENCES Table 4. Frequency of OHT eyes (≥20mm Hg) before surgery, 1 yr after surgery, and at the final measurement IOP Frequency, Eyes (n) Initial Preop IOP mm Hg 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% 57/70% 60/74% # of OHT eyes become normotensive 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% after surgery. Ge’s2 study of angle closure glaucoma eyes had the greatest presurgical mean IOP, 25.5mm Hg, and the greatest mean IOP reduction, 13.5mm Hg, after surgery. Information from table six suggests eyes with the shallowest anterior chambers have the greatest presurgical IOPs, and achieve the greatest IOP reductions after phaco/IOL surgery. Figure three shows SA and LM Strenk’s10 published MRI images of “Anterior displacement of the uveal tract with age resulting from lens growth”. Observe, the anterior surface of the 24 year old lens is rearward of the canal of Schlemm; whereas, lens growth with 50 PAN-AMERICA 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 possiblecause of outflow channel failure leading to increased IOP. The Strenk’s MRI images of lens growth with age would appear to support our proposition. 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 capsule surrounding the artificial lens becomes 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 hypertension 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 hypertensive and glaucomatous eyes. Glaucoma is defined as an optic neuropathy with IOP as a risk factor for progression. Elevated IOP is one of several risk factors for adult glaucoma. Since it is the only risk factor for adult glaucoma that can be changed, lowering this risk factor 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. Summary Our studies showed stratifying eyes according to their presurgical IOP revealed 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 presurgical IOP gain minimal to no IOP reduction. Junio 2010 Table 6. Mean IOP reductions after phaco/IOL surgery sorted by presurgical IOP. 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 pressure OAG = open-angle glaucoma; PACG = primary angle-closure glaucoma P/L/S = Poley/ Lindstrom/ Samuelson.2009 glaucoma study 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 glaucoma. When glaucoma drops are no longer adequate, phaco/IOL alone provides an effective treatment for patients with cataract coexistent with ocular hypertension 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 effective treatment for patients with ocular hypertension or glaucoma who do not have cataracts when glaucoma drops are no longer adequate. REFERENCES 1. Poley B, Lindstrom R, Samuelson T. Intraocular pressure reduction after phacoemulsification with intraocular lens implantation in glaucomatous and non-glaucomatous eyes. Evaluation of a causal relationship between the natural lens and open-angle glaucoma. J Cataract and Refract Surg 2009; 35: 1946-1955. 2. Ge J, Guo Y, Liu Y. Preliminary clinical study on the management of angle closure glaucoma by phacoemulsification with foldable posterior chamber intraocular lens implantation. ZhonghuaYan Ke Za Zhi 2001; 37: 355-358. 3. Euswas A, Warrasak S. Intraocular pressure 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 phacoemulsification 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, Buckman G, Yair H Geyer O. Long-term intraocular pressure control after clear corneal phacoemulsification in glaucoma patients. J Cataract Refract 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 phacoemulsification: normal patients versus glaucoma 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 phacoemulsification in open angle glaucoma patients, glaucoma suspects, and normal patients. J Glaucoma 2006; 15: 494-497. 9. Tham CY, Kwong YY, et al. Phacoemulsification 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…visualizing 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 Ocular 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 Refract Surg 2008; 34:735-742. PAN-AMERICA : 51 CLINICAL CASE REPORT SCIENCES Amantadine-Induced Corneal Edema in a Patient with Parkinson’s Disease and Early Fuchs’ Endothelial Dystrophy 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 financial conflicts of interest in the subject matter of the manuscript. Corresponding Author/Reprint requests: Jay C. Bradley MD Department of Ophthalmology & Visual Sciences, Texas Tech University HSC, 3601 4th St., STOP 7217, Lubbock, TX 79430-7217 Phone: (806)743-2020, Fax: (806) 743-2471 Email: [email protected] 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 managed 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 microscopy, and pachymetry are described. Conclusion: Amantadine is known to cause the onset of endothelial dysfunction and visual impairment even after years of treatment. Fortunately, its effects on the cornea have been shown to be mostly reversible in patients with a near normal endothelial count and function. 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 irreversible 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 Introduction Amantadine was originally devel52 PAN-AMERICA 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. oped as a drug for the treatment of the influenza A virus in 19591. Today, it is widely used in the management of extrapyramidal 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, mydriasis, oculogyric crises, visual hallucinations, superficial punctuate keratitis, subepithelial deposits, and corneal edema 2-6. 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 rapidly reversible with the discontinuation of therapy. We report a case of reversible amantadine-induced corneal edema in a patient with Parkinson’s disease and early Fuchs’ endothelial dystrophy. Case Report A 53 year old Caucasian gentleman was referred to our clinic for evaluation of unexplained bilateral corneal edema. He presented with a chief complaint of Junio 2010 “foggy vision” in both eyes for approximately one month in duration. A gross physical evaluation revealed a resting tremor, bradykinesia, and postural instability that became even more apparent when attempting slit lamp biomicroscopy. These findings initiated a review of the patient’s medical history that revealed the diagnosis of Parkinson’s disease 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. Specular 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 pathology of the eyelids, conjunctiva, anterior 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 patient 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). Discussion Amantadine-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 disease 2,8-11. Patients with Parkinson’s disease frequently present with easily recognized clinical features such as resting tremor, cogwheel rigidity, bradykinesia, and postural instability 1,8. In this case, the recognition of such clinical features served as a reminder to review the patient’s medication history. Therefore, physical exam skills and knowledge of extrapyramidal signs may provide assistance in making 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 effects experienced during the treatment of non-chronic indications. In 2006, the Centers for Disease Control and Prevention 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 reassortant 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 amantadine-induced corneal edema. The majority of reports in the literature demonstrate rapid reversibility after cessation of amantadine. However, a more recent report suggests the possibility of irreversible edema following discontinuation of the drug as evidenced by permanent endothelial damage shown on scanning electron microscopy7. A 2-year retrospective study looked at patients prescribed 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 disclose that their decision to include Fuchs dystrophy as an outcome measurement was based on the assumption PAN-AMERICA : 53 CASE REPORT 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 compromise predisposes to the development amantadine-induced corneal edema. Additionally, the degree of reversibility 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 visual impairment even after years of treatment. 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 characteristic features of Fuchs’ endothelial dystrophy. 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 endothelial count or functionality may be at higher risk for the development of corneal edema. In addition, it is anticipated that the number of amantadine prescriptions 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 Amantadine 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: 9697. 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 amantadine: 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 –Sensitive 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. 54 PAN-AMERICA Junio 2010 ¿Es un Simple Orzuelo ó es Algo más? 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 MSc Costa Rica Oculoplastics Inc., Hospital CIMA San José, Torre 3, Cons. 322, Escazú, Costa Rica Phone: (506) 2208-8322 Fax: (506) 2208-8372 Email: [email protected] Declaración de Interés Financiero: Ninguno de los autores tiene interés financiero en el material presentado 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. Abstract Because eyelid ophthalmomyiasis externa 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. Resumen Porque la oftalmomiasis externa es inusual, esta entidad puede ser confundida fácilmente con un orzuelo ó chalazión. Reportamos un caso de un paciente de 28 años con una miasis del párpado inferior simulando un orzuelo. Utilizando una simple técnica quirúrgica, una larva de Dermatobia hominis fue extraída en este paciente. Introducción La infestación del ojo y/o anexos por larva del orden Diptera se denomina oftalmomiasis, y esta representa el 5% de la miasis en los humanos. 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 larvas de Oestrus ovis y Dermatobia hominis se han asociado con oftalmomiasis. En Centroamérica 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 forceps, oclusión del orificio de entrada forzando la expulsión, ivermectina oral y extracción quirúrgica. Reportamos un caso de oftalmomiasis externa causada por Dermatobia hominis simulando un orzuelo, la cual fue extraída utilizando una simple técnica quirúrgica. Reporte de Caso Un agricultor de 28 años de edad con cuadro de enrojecimiento, dolor, prurito y edema en su párpado inferior del ojo derecho fue referido del servicio de emergencias al servicio de oftalmología del Hospital de Alajuela con diagnóstico presuntivo de orzuelo en el párpado inferior. El paciente no presentaba historia de trauma ó cirugía previa 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. Posteriormente a la sintomatología, el paciente sentía que algo se movía en su párpado inferior conforme el edema incrementaba. Al examen oftalmológico, la agudeza visual era 20/20 OU, presión intraocular y los movimientos 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 aplicador 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 extracción quirúrgica de la sospechosa larva. Se colocó una pinza de chalazión, con el anillo sobre la superficie cutánea de la masa palPAN-AMERICA : 55 CASE REPORT Figura 2: 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, identificada como larva de Dermatobia hominis. pebral, delimitándola. Una incisión horizontal 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 fragmentación de ésta. Una vez removida la larva, se debridó el trayecto que esta dejó con la cureta de chalazión y se lavó el campo quirúrgico 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 microbiología del hospital, la cual fue identificada por el microbiólogo como larva de Dermatobia hominis. El paciente tuvo una evolución satisfactoria, auque sólo regresó a la consulta control a la semana para retiro de puntos en su párpado. Discusión La invasión de los párpados, conjuntiva, córnea y órbita ó el ojo de los mamíferos por la larva de las moscas (órden Diptera) se define 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 ho56 PAN-AMERICA 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 construye 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 frecuentemente aqueja de prurito y dolor localizado. El paciente también puede sentir los movimientos de la larva. Ambos síntomas fueron aquejados por nuestro paciente. El manejo de la oftalmomiasis externa varía desde la extracción bajo visualización directa; remoción de la larva posterior a oclusión del agujero de ingreso con ungüento, ó cera, ó goma de mascar, ó grasa porcina1,5; remoción de larva post tratamiento con ivermectina oral7; y extracción quirúrgica. Cuando la intención de remover la larva es la extracción directa con pinzas, esta maniobra se torna súmamente difícil debido a dos factores: primero, las filas de las 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 describimos una técnica quirúrgica muy sencilla y útil, usando una pinza de chalazión y su cureta. La técnica que utilizamos es como cualquier 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 atrapamiento de la larva. La placa de la pinza también 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 función 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 aborda un caso de una masa palpebral. BIBLIOGRAFÍA 1.Goodman RL, Montalvo MA, Reed JB, et al. Anterior orbital myiasis caused by human botfly (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;93:12251227. 3.Wilhelmus KR. Myiasis palpebrarum. Am J Ophthalmol. 1986;101:496-498. 4.Lane RP, Lowell CR, Griffiths WA, Sonnex TS. Human cutaneous myiasis: a review and report of three cases due to Dermatobia hominis. Clin Exp Dermatol. 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. Junio 2010 Orbital Granulocytic Sarcoma without Systemic Manifestation 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 - Brazil 2 Department of Ophthalmology – Associação Beneficente de Campo Grande – Brazil 3 LAC – Pathology and Cytopathology Laboratory - Campo Grande – Brazil 4 Oncology – Hospital Regional de Mato Grosso do Sul – Campo Grande -Brazil 5 Henry C. Witelson Ocular Pathology Laboratory - Department of Ophthalmology, McGill University - Montreal - Canada Corresponding Author: Alexandre Nakao Odashiro LAC – Pathology and Cytopathology Laboratory Rua Rui Barbosa, 3716 79002-362 Campo Grande, MS, Brazil Fax: (55-67) 3083-7325 E-mail: [email protected] The authors declare that they have no competing interests Authors declare no financial interest Abstract Granulocytic Sarcoma is an uncommon 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 ophthalmological 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 chemotherapy plus radiotherapy, and is now free of systemic disease after a 18-month follow-up. Resumo Sarcoma 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 também apresentava diplopia on quadrante inferior 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 lateral com biópsia do tumor. O exame histopatológico confirmou o diagnóstico de Sarcoma Granulocítico. Exame clínicoradiológico 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. Introduction Leukemia is the most common form of childhood cancer. Acute lymphoblastic leukemia accounts for 80% of all childhood leukemias, while acute myeloid leukemia (AML) accounts for only 15% of cases diagnosed1. Granulocytic Sarcoma (GS) is an uncommon manifestation of AML, accounting for 3-8% of all AML cases. GS may also be referred to as Chloroma, due to the green color present on gross pathological 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 composed 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 systemic 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 mediastinum6 and is more common in children less than 10 years of age7. Here we report one case of GS with clinical-pathological manifestations. Case Report A 10 year-old girl presented at our department 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 biomicroscopy examination further exposed discrete conjunctival hyperemia OS. The fundus examination and intraocular pressure were normal in both eyes. She had no systemic (signs or symptoms. Results of the physical examination were normal without evidence of lymphadenopathy or organomegaly. 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 interspersed eosinophilic myelocytes. The neoplastic cells had round nuclei, fine chromatin, and distinct nucleoli. A moderate amount of basophilic cytoplasm, with fine azurophilic granulation, was also observed in some of the cells. Scattered eosinophilic myelocytes were further observed. Immunostaining of the neoplastic cells revealed positive staining for LCA (leukocyte common antigen) and Myeloperoxidase, while CD3, CD20 and CD10 were negative (Figures E and F). Muscular markers (desmin and myoD1) were also negative. PAN-AMERICA : 57 CASE REPORT The diagnosis of GS was made based on these results. Systemic work-up included complete 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 intrathecal 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 Prednisone, Tioguanin, Vincristin, Idarubicin, Cytarabine and intrathecal Cytarabine. Four months later, a 4th cycle was performed with high doses of Cytarabine, Etoposide 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. 58 PAN-AMERICA radiation therapy with Tioguanin, Cytarabine 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. Discussion Leukemic cells can infiltrate any extramedullary 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 systemic disease with thorough work-up, leukemia almost always develops after an interval 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 localization of GS is unusual in western countries. 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 immunocompromised. GS can occur at any age but most frequently affects children, with 75% of cases presenting by age 108. Boys are traditionally 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, uveitis, a conjunctival mass or scleral mass7. Our patient presented with classic clinical signs, with the sole exception of gender. Orbital GS simulating inflammatory conditions or thyroid ophthalmopathy is particularly important because it delays correct diagnosis, as previously reported by Fonseca Júnior et al 4. Classically, GS arises in the bone marrow and traverses the Haversian canals to reach the periosteum, and subsequently spreads to soft tissues8. Interestingly, our Junio 2010 patient did not have massive bone destruction 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 malignant tumors. This also includes distinguishing lymphomas, rhabdomyosarcoma and neuroblastoma2 through imaging alone. Therefore, a definitive diagnosis relies primarily on histopathological examination of the tumor. Histopathologically, the tumor is composed of immature myeloid cells. Immunohistochemistry was essential in rendering this particular diagnosis. The diagnosis can be missed in 50% of cases when immunohistochemistry is not used. As lymphomas are the main differential diagnosis considered on histopathology, an antibody panel of CD43, lysozyme, myeloperoxidase, CD68, CD3 and CD20 can successfully identify the majority of GS13. GS are classically 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 Bcell (CD20) markers14. MAC387 can also be helpful, but is less sensitive15 and is positive in mature granulocytes16. Rhabdomyosarcoma 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 rhabdomyosarcoma 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 diagnosing GS while differentiating it from other neoplastic lesions. In the present case, the strong and diffuse reaction to myeloperoxidase 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 involvement of GS represented a very poor prognosis compared to GS in general11. Our patient received systemic chemotherapy and remains disease free post 18 months of follow-up. Conclusion GS is an uncommon malignant tumor of which ophthalmologists, general clinicians 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. Granulocytic sarcoma in children. Neuroradiology 2004; 46(5):374-7. 2.Stockl FA, Dolmetsch AM, Saornil MA, et al. Orbital granulocytic sarcoma. Br J Ophthalmol 1997; 81(12):1084-8. 3.Azim HA, Jr., Gigli F, Pruneri G, et al. Extramedullary 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. Granulocytic 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 cases. Cancer 1981; 48(6):1426-37. 10.Fisgin T, Yarali N, Duru F, Kara A. ParvovirusB19 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 granulocytic sarcoma and AML with poor prognosis in Turkish children. Leukemia 2002; 16(5):962; author reply 3. 12.Bhat VK, Naseeruddin K, Narayanaswamy GN. Sino-orbital chloroma presenting as unilateral proptosis in a boy. Int J Pediatr Otorhinolaryngol 2005; 69(11):1595-8. 13.Alexiev BA, Wang W, Ning Y, et al. Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study. Diagn Pathol 2007; 2:42. 14.Fletcher CDM. Diagnostic histopathology of tumors, 3rd ed. Edinburgh; Philadelphia: Churchill Livingstone Elsevier, 2007; 2 v. (x, 1883, 41). 15.Menasce LP, Banerjee SS, Beckett E, Harris M. Extra-medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases. Histopathology 1999; 34(5):391-8. 16.Liu YH, Zhuang HG, Liao XB, et al. [Diagnosis and differential diagnosis of granulocytic sarcomas]. Zhonghua Xue Ye Xue Za Zhi 2003; 24(11):568-71. PAN-AMERICA : 59 DR. MANNIS IS INTERNATIONALLY RECOGNIZED 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 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 education and eye banking. The award is the highest honor given to an ophthalmologist in Latin America and is designated for outstanding contributions 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 centers. Mannis is currently the president of the Pan-American Association 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 (Universidad 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 Laureate Peter Agre in 2008. 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 60 PAN-AMERICA 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 Spanish, citing the intrinsic role that universities and, specifically, medical schools have played in modern civilization. Junio 2010 LATIN AMERICAN / PAAO PEDIATRIC OPHTHALMOLOGY FELLOWSHIP 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. APPLICANT QUALIFICATIONS: The following qualifications for a successful candidate are as follows: 1. General ophthalmologist, age 35 years or younger, from Mexico, 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 application. 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 director. 8. Commitment to return to Latin America at conclusion of fellowship 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 University of Texas Southwestern Medical Center (UTSWMC) and Children’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 APPLICATION All applications and materials must be submitted electronically, by email to [email protected]. 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 recent publications. 4. Letter of recommendation from department chair and/or training program director. PAN-AMERICA : 61 The 2011 Troutman-Véronneau Prize 3. Text: Number the pages of the manuscript consecutively, beginning with the title page 1. Place the manuscript title on each page. DO NOT indicate the authors’ names on the pages of the manuscript. 29th Pan-American Congress of Ophthalmology Buenos Aires, Argentina The 2011 Troutman-Véronneau Prize of US $10,000.00, funded by a permanent endowment from the Microsurgical Research Foundation to the PanAmerican 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 Ophthalmology 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, including 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. 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. References 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 written 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) Manuscript Preparation 2001 – José A.P. Gomez, MD (Brazil) Manuscripts should be prepared in accordance with the American Medical Association Manual of Style and/or the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (www.icmje.org). 1999 – Jonathan C. Horton, MD (USA) Manuscripts should begin each component on a new page and be in the following order:(1) title page; (2) structured abstract; (3) text; (4) references; (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, telephone, 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. 62 PAN-AMERICA 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 Strabismus, and Strabismus microsurgery and Cornea and/or Corneal Refractive Surgery. Deadline for Submission: Tuesday, January 18, 2011 XII Curso Internacional Certificado de Entrenamiento Técnico y Científico en Bancos de Ojos A Asociación Panamericana de Bancos de Ojos - APABO Agosto 20 al 28 de 2010 Medellín – Colombia XI CURSO INTERNAC 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. Mayor Información: Lina María López [email protected] Tel. (57-4) 230 22 88 Pan-American Association of Eye Banks Asociación Pan Americana de Bancos de Ojos Associaçâo Pan Americana de Bancos de Olhos XVII Curso Regional Panamericano XVII Pan-American Regional Course Hotel Marriott Los Sueños, Playa Herradura, Costa Rica 19 – 21 Agosto 2010 / August 19 – 21, 2010 Nombre completo / Full Name: Apellido(s) en letra MAYUSCULA / Last Name(s) in CAPITAL LETTERS Nombre / First Name & Middle initial Domicilio / Mailing address: Dirección de correo aéreo / Street (include suite or apartment) Ciudad / City Código Postal / Zip ( ) Estado / State ( País / Country ) Fax Teléfono / Telephone E-mail Nombre de Acompañante(s) / Accompanying Person(s) name: COURSE REGISTRATION Mark the corresponding box with an X INSCRIPCIÓN AL CURSO Marque en el espacio correspondiente con una X Categoría / Category 1 abril 2010 hasta 1 agosto 2010 / April 1, 2010 - August 1, 2010 Después 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 $ 75 USD $ 75 USD Acompañante(s) / Accompanying Person(s) * Miembro Titular: Oftalmólogo que paga cuotas anuales a la PAAO. 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