- Email: [email protected]
Choroidal neovascular membrane associated with optic nerve coloboma in a patient with CHARGE association
associated with fundus albipunctatus with RDH5 gene mutation. Molecular genetic examination revealed a homozygous mutation, a G to C mutation at nucleotide 319 (Gly107Arg), in RDH5. No such base substitutions were recognized in 100 alleles from normal subjects. We are unaware of previous reports of fundus albipunctatus case with this Gly107Arg homozygous mutation. It was also not clear whether the phenotype variation resulted from different genotype of RDH5 gene mutation. Our cases suggest that different phenotypes may result from same genotype, but further data will be necessary to understand the clinical features and the genotype–phenotype correlation with the RDH5 gene mutations. REFERENCES
1. Heckenlively J. Congenital stationary night blindness. Genetic diseases of the eye. New York: Oxford University Press, 1998:389 –396. 2. Miyake Y, Shiroyama N, Sugita S, Horiguchi M, Yagasaki K. Fundus albipunctatus associated with cone dystrophy. Br J Ophthalmol 1992;76:375–379. 3. Yamamoto H, Simon A, Eriksson U, Harris E, Berson EL, Dryja TP. Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet 1999;22:188 –191. 4. Nakamura M, Hotta Y, Tanikawa A, Terasaki H, Miyake Y. A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci 2000;41:3925–3932. 5. Wada Y, Abe T, Sato H, Tamai M. A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy. Arch Ophthalmol 2001;119:1059 –1063.
Choroidal Neovascular Membrane Associated With Optic Nerve Coloboma in a Patient With CHARGE Association Medhat F. Guirgis, MD, and Gregg T. Lueder, MD PURPOSE: To report a patient with CHARGE association (coloboma, heart disease, choanal atresia, growth retardation, genital hypoplasia, and ear abnormalities) who developed a choroidal neovascular membrane in association with an optic nerve coloboma. Accepted for publication Dec 17, 2002. From the Departments of Ophthalmology (M.F.G., G.T.L.) and Visual Sciences and Pediatrics (G.T.L.), Washington University School of Medicine, St. Louis, Missouri, and Prevea Clinic (M.F.G.), Green Bay, Wisconsin. Inquiries to Gregg T. Lueder, MD, St. Louis Children’s Hospital, Division of Pediatric Ophthalmology, Suite 2 South 89, One Children’s Place, St. Louis, MO 63110; fax: (314) 454-2368; e-mail: [email protected]
VOL. 135, NO. 6
Interventional/observational case report. A 21-month-old boy with CHARGE association developed a grayish choroidal neovascular membrane associated with lipid exudation, subretinal fluid, and retinal hemorrhage at the temporal edge of his right optic nerve coloboma. RESULTS: The patient underwent transpupillary diode laser of the choroidal neovascular membrane. Five months later, it and the serous retinal detachment had resolved. CONCLUSIONS: Patients with CHARGE association may develop choroidal neovascular membrane with serous retinal detachments in association with optic nerve colobomas. These neovascular membranes may be treated successfully with transpupillary diode laser. (Am J Ophthalmol 2003;135:919 –920. © 2003 by Elsevier Inc. All rights reserved.) DESIGN:
METHODS:
T
HE CHARGE ASSOCIATION (COLOBOMA, HEART DIS-
ease, choanal atresia, growth retardation, genital hypoplasia, and ear abnormalities) is a nonrandom combination of congenital anomalies that is commonly associated with significant ophthalmic manifestations. Ocular colobomas represent the most common eye findings in CHARGE association and may involve the eyelids, iris, retina, choroid, and optic disk.1 Optic nerve colobomas are congenital defects caused by defective closure of the anterior end of the optic stalk during the first 5 to 6 weeks of embryogenesis.2 They may be associated with serous retinal detachments and other ocular abnormalities, including lenticonus, persistent hyaloid arteries, and optic disk pits.2,3 We present an interventional/observational case report of a child with CHARGE association who developed a choroidal neovascular membrane in association with an optic nerve coloboma. The association of optic nerve coloboma and choroidal neovascular membrane has rarely been reported.3 After conducting a MEDLINE search, we were unable to find any previous cases of choroidal neovascular membrane associated with the CHARGE. Internal review board approval was obtained for this report. A 7-day-old male infant with numerous malformations presented for ophthalmic evaluation. The child had a history of patent foramen ovale and choanal atresia, and CHARGE association was suspected. He was born at term with normal birth weight and had no family history of hereditary ocular or systemic disease. On examination, the infant responded to light in each eye. A mild relative afferent pupillary defect was found in the right eye. Adnexal and anterior segment examination were normal, with no eyelid, iris, or lens colobomas. Retinal examination revealed a large optic nerve coloboma of the right eye. A small retinochoroidal coloboma was noted inferior to the left optic disk. The left eye was otherwise normal.
BRIEF REPORTS
919
FIGURE 2. Postoperative fundus photograph of the right eye, showing resolution of the neovascular membrane and serous retinal detachment (arrow).
FIGURE 1. Fundus photograph of the right eye, showing grayish choroidal neovascular membrane associated with lipid exudation, subretinal fluid, and retinal hemorrhage at the temporal edge of the patient’s right optic nerve coloboma (arrow).
to the coloboma, resulting in choroidal neovascular membrane formation.4 Diode laser photocoagulation has been demonstrated to be effective in treating choroidal neovascular membrane associated with both age-related macular degeneration and angioid streaks.5 A number of advantages of diode over other laser systems include compactness of size, excellent transmission through media opacities (cataract, vitreous hemorrhage), and minimal macular luteal pigment absorption.5 A previously reported case of a choroidal neovascular membrane associated with an optic nerve coloboma was successfully treated with krypton laser photocoagulation.3 Our findings indicate that diode laser photocoagulation may also produce resolution of choroidal neovascular membrane and serous retinal detachment.
The patient was followed regularly, and at age 21 months he was noted to have a grayish choroidal neovascular membrane associated with lipid exudation, subretinal fluid, and retinal hemorrhage at the temporal edge of his right optic nerve coloboma (Figure 1). Under general anesthesia, the patient underwent transpupillary diode laser photocoagulation. A total of 183 burns (power, 200 to 700 mW; duration, 200 to 900 ms) were applied to the neovascular membrane, titrating power until whitish burns were produced. Two weeks later, the serous retinal detachment had diminished; 5 months later, the choroidal neovascular membrane had resolved (Figure 2). At age 7, the patient has visual acuity of 20/100 in the right eye and 20/20 in the left eye and no evidence of recurrence of the choroidal neovascular membrane. Choroidal neovascularization is a well-documented complication of ocular disorders associated with discontinuities in the Bruch membrane, including lacquer cracks, angioid streaks, choroidal rupture, and age-related macular degeneration. Histopathologically, retinochoroidal colobomas are circumscribed regions of nearly bare sclera that can be devoid of retinal pigment epithelium, neurosensory retina, and choroid.2 The margins of these defects feature an abrupt termination of the Bruch membrane. This discontinuity can allow aberrant growth and penetration of nearby choroidal vessels into the subretinal space adjacent
920
AMERICAN JOURNAL
REFERENCES
1. Russell-Eggitt IM, Blake KD, Taylor DSI, Wyse RKH. The eye in the CHARGE association. Br J Ophthalmol 1990;74:421– 426. 2. Onwochei BC, Simon JW, Bateman JB, Couture KC, Mir E. Ocular colobomata. Surv Ophthalmol 2000;45:175–194. 3. Dailey JR, Cantore WA, Gardner TW. Peripapillary choroidal neovascular membrane associated with an optic nerve coloboma. Arch Ophthalmol 1993;111:441–442. 4. Leff SR, Britton WA, Brown GC, Lucier AC, Brown JF. Retinochoroidal coloboma associated with subretinal neovascularization. Retina 1985;5:154 –156. 5. Ulbig MW, McHugh DA, Hamilton AMP. Photocoagulation of choroidal neovascular membranes with a diode laser. Br J Ophthalmol 1993;77:218 –221.
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OPHTHALMOLOGY
JUNE 2003
1. Heckenlively J. Congenital stationary night blindness. Genetic diseases of the eye. New York: Oxford University Press, 1998:389 –396. 2. Miyake Y, Shiroyama N, Sugita S, Horiguchi M, Yagasaki K. Fundus albipunctatus associated with cone dystrophy. Br J Ophthalmol 1992;76:375–379. 3. Yamamoto H, Simon A, Eriksson U, Harris E, Berson EL, Dryja TP. Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet 1999;22:188 –191. 4. Nakamura M, Hotta Y, Tanikawa A, Terasaki H, Miyake Y. A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci 2000;41:3925–3932. 5. Wada Y, Abe T, Sato H, Tamai M. A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy. Arch Ophthalmol 2001;119:1059 –1063.
Choroidal Neovascular Membrane Associated With Optic Nerve Coloboma in a Patient With CHARGE Association Medhat F. Guirgis, MD, and Gregg T. Lueder, MD PURPOSE: To report a patient with CHARGE association (coloboma, heart disease, choanal atresia, growth retardation, genital hypoplasia, and ear abnormalities) who developed a choroidal neovascular membrane in association with an optic nerve coloboma. Accepted for publication Dec 17, 2002. From the Departments of Ophthalmology (M.F.G., G.T.L.) and Visual Sciences and Pediatrics (G.T.L.), Washington University School of Medicine, St. Louis, Missouri, and Prevea Clinic (M.F.G.), Green Bay, Wisconsin. Inquiries to Gregg T. Lueder, MD, St. Louis Children’s Hospital, Division of Pediatric Ophthalmology, Suite 2 South 89, One Children’s Place, St. Louis, MO 63110; fax: (314) 454-2368; e-mail: [email protected]
VOL. 135, NO. 6
Interventional/observational case report. A 21-month-old boy with CHARGE association developed a grayish choroidal neovascular membrane associated with lipid exudation, subretinal fluid, and retinal hemorrhage at the temporal edge of his right optic nerve coloboma. RESULTS: The patient underwent transpupillary diode laser of the choroidal neovascular membrane. Five months later, it and the serous retinal detachment had resolved. CONCLUSIONS: Patients with CHARGE association may develop choroidal neovascular membrane with serous retinal detachments in association with optic nerve colobomas. These neovascular membranes may be treated successfully with transpupillary diode laser. (Am J Ophthalmol 2003;135:919 –920. © 2003 by Elsevier Inc. All rights reserved.) DESIGN:
METHODS:
T
HE CHARGE ASSOCIATION (COLOBOMA, HEART DIS-
ease, choanal atresia, growth retardation, genital hypoplasia, and ear abnormalities) is a nonrandom combination of congenital anomalies that is commonly associated with significant ophthalmic manifestations. Ocular colobomas represent the most common eye findings in CHARGE association and may involve the eyelids, iris, retina, choroid, and optic disk.1 Optic nerve colobomas are congenital defects caused by defective closure of the anterior end of the optic stalk during the first 5 to 6 weeks of embryogenesis.2 They may be associated with serous retinal detachments and other ocular abnormalities, including lenticonus, persistent hyaloid arteries, and optic disk pits.2,3 We present an interventional/observational case report of a child with CHARGE association who developed a choroidal neovascular membrane in association with an optic nerve coloboma. The association of optic nerve coloboma and choroidal neovascular membrane has rarely been reported.3 After conducting a MEDLINE search, we were unable to find any previous cases of choroidal neovascular membrane associated with the CHARGE. Internal review board approval was obtained for this report. A 7-day-old male infant with numerous malformations presented for ophthalmic evaluation. The child had a history of patent foramen ovale and choanal atresia, and CHARGE association was suspected. He was born at term with normal birth weight and had no family history of hereditary ocular or systemic disease. On examination, the infant responded to light in each eye. A mild relative afferent pupillary defect was found in the right eye. Adnexal and anterior segment examination were normal, with no eyelid, iris, or lens colobomas. Retinal examination revealed a large optic nerve coloboma of the right eye. A small retinochoroidal coloboma was noted inferior to the left optic disk. The left eye was otherwise normal.
BRIEF REPORTS
919
FIGURE 2. Postoperative fundus photograph of the right eye, showing resolution of the neovascular membrane and serous retinal detachment (arrow).
FIGURE 1. Fundus photograph of the right eye, showing grayish choroidal neovascular membrane associated with lipid exudation, subretinal fluid, and retinal hemorrhage at the temporal edge of the patient’s right optic nerve coloboma (arrow).
to the coloboma, resulting in choroidal neovascular membrane formation.4 Diode laser photocoagulation has been demonstrated to be effective in treating choroidal neovascular membrane associated with both age-related macular degeneration and angioid streaks.5 A number of advantages of diode over other laser systems include compactness of size, excellent transmission through media opacities (cataract, vitreous hemorrhage), and minimal macular luteal pigment absorption.5 A previously reported case of a choroidal neovascular membrane associated with an optic nerve coloboma was successfully treated with krypton laser photocoagulation.3 Our findings indicate that diode laser photocoagulation may also produce resolution of choroidal neovascular membrane and serous retinal detachment.
The patient was followed regularly, and at age 21 months he was noted to have a grayish choroidal neovascular membrane associated with lipid exudation, subretinal fluid, and retinal hemorrhage at the temporal edge of his right optic nerve coloboma (Figure 1). Under general anesthesia, the patient underwent transpupillary diode laser photocoagulation. A total of 183 burns (power, 200 to 700 mW; duration, 200 to 900 ms) were applied to the neovascular membrane, titrating power until whitish burns were produced. Two weeks later, the serous retinal detachment had diminished; 5 months later, the choroidal neovascular membrane had resolved (Figure 2). At age 7, the patient has visual acuity of 20/100 in the right eye and 20/20 in the left eye and no evidence of recurrence of the choroidal neovascular membrane. Choroidal neovascularization is a well-documented complication of ocular disorders associated with discontinuities in the Bruch membrane, including lacquer cracks, angioid streaks, choroidal rupture, and age-related macular degeneration. Histopathologically, retinochoroidal colobomas are circumscribed regions of nearly bare sclera that can be devoid of retinal pigment epithelium, neurosensory retina, and choroid.2 The margins of these defects feature an abrupt termination of the Bruch membrane. This discontinuity can allow aberrant growth and penetration of nearby choroidal vessels into the subretinal space adjacent
920
AMERICAN JOURNAL
REFERENCES
1. Russell-Eggitt IM, Blake KD, Taylor DSI, Wyse RKH. The eye in the CHARGE association. Br J Ophthalmol 1990;74:421– 426. 2. Onwochei BC, Simon JW, Bateman JB, Couture KC, Mir E. Ocular colobomata. Surv Ophthalmol 2000;45:175–194. 3. Dailey JR, Cantore WA, Gardner TW. Peripapillary choroidal neovascular membrane associated with an optic nerve coloboma. Arch Ophthalmol 1993;111:441–442. 4. Leff SR, Britton WA, Brown GC, Lucier AC, Brown JF. Retinochoroidal coloboma associated with subretinal neovascularization. Retina 1985;5:154 –156. 5. Ulbig MW, McHugh DA, Hamilton AMP. Photocoagulation of choroidal neovascular membranes with a diode laser. Br J Ophthalmol 1993;77:218 –221.
OF
OPHTHALMOLOGY
JUNE 2003