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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
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Special thanks to Ana Carolina
Vieira, Citlali Gurrusquieta,
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for assistance in translation to
Spanish and Portuguese.
Prepress
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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.
Sírvase notar que si usted se inscribe como Miembro Titular PAAO sin serlo o no está al
día en sus cuotas, la PAAO le cargará la cuota de membresia como Miembro Titular (cuota
anual US$150) y la cuota reducida de inscripción al curso.
** Miembro Asociado: Miembro de Sociedades Nacionales afiliadas a la PAAO.
*** Se requiere una carta del director del programa que certifica su calidad de residente o
fellow. De no adjuntarla, se cobará como Asociado/No miembro.
Política de Cancelación: Peticiones de cancelación y reembolso deberán ser por escrito.
- entre el 15 de marzo de 2010 y el 1 de agosto de 2010, se reembolsará el 50% de la
cuota de inscripción.
- Después del 1 de agosto de 2010, reembolso de inscripción no es posible.
Cheque (solamente banco US) a nombre del PAAO
Check (US banks only) payable to: PAAO
USD $
Cargo a su tarjeta de crédito / Credit card charge:
USD $
Emisor de la tarjeta / Type of Credit Card:
Número de tarjeta / Card Number:
Visa
* PAAO Active member. Ophthalmologist who pays annual fees to the PAAO.
Please note that if you register as a PAAO Active Member but are not current on your membership dues, you will be charged the
Active Member registration fee and PAAO membership dues.
** Associate member: Member of national societies affiliated to the PAAO.
*** Must show letter from the training Hospital verifying your residence or fellowship. Otherwise non-member fee will be charged.
Cancellation Policy: Cancellations and reimbursement requests must be made in writing.
- If a cancellation is made between March 16 and August 1, a reimbursement of 50% of the Registration Fee(s) will be made.
- There is no refund for cancellations after August 1.
El cargo será hecho por la PAAO / Charge will be made by PAAO
Master Card
American Express
Discover
Válido hasta / Expiration Date: ____ / ____
Código de Seguridad / Security Code:
Visa and MasterCard los 3 dígitos al reverso en el espacio de la firma / Visa and MasterCard a 3 digit number found in the back of the card
American Express los 4 dígitos que aparecen a la derecha de la tarjeta / American Express a 4 digit number found in the center right front of your card
Nombre que aparece en la tarjeta /Name of Cardholder as it appers on the card:
Fecha / Date:
Llene este formulario, imprímalo y envíelo de inmediato a:
Fill in this form and email or fax it immediately to:
Firma del tarjetahabiente / Signature
Pan-American Association of Ophthalmology
1301 S Bowen Road #365, Arlington TX 76013 USA
Tel: (817) 275-7553 / Fax: (817) 275-3961 / E-mail: [email protected] / Web: www.paao.org
Course Web page: http://web.me.com/lihtehwu/PAAO_2010/Welcome.html
Alojamiento: Para hacer su reserva en el Hotel Marriott Los Sueños, sírvase llamar +888-236-2427 ó local +506-2360-9000,
y mencionar el Congreso de Oftalmología. Código Asocación Oftalmóloga.
Housing: to make your hotel reservation, please call the toll-free number +888-236-2427 or the local Marriott number +506-2630-9000
and mention the Ophthalmology Meeting.
O
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Organizan: Asoicana de Oftalmología.
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Asociación Panam
INFORMES:iacostarica.com
info@oftalmolog
otmail.com
joaqmartinez@h
[email protected]
18.
Tel: (506)2289-74
4 :
PAN-AMERICA