CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH GOLDMANN–FAVRE SYNDROME Rafael Navarro, MD,* Carlos Mateo, MD,* Borja Corco´stegui, MD,* Montserrat Baiget, PHD,† Sara Bernal, PHD†
A case of peripapillary choroidal neovascularization associated with Goldmann-Favre syndrome was successfully managed with subretinal surgery.
From *Vitreo-retinal Unit, Instituto de Microcirugı´a Ocular de Barcelona, Barcelona, Spain; Universidad Auto´noma de Barcelona (UAB), Barcelona, Spain; and †Servei de Gene`tica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
rous detachment on the right macula. Electroretinograms were not recordable bilaterally. DNA sequencing of the NR2E3 gene allowed identification of the R311Q mutation in a homozygous state. The patient underwent pars plana vitrectomy, posterior hyaloid dissection, neovascular membrane removal through a superior macular retinotomy, and fluid–air exchange. No histologic study of the membrane was performed. Six months after surgery, visual acuity improved to 20/80 in the right eye. Funduscopic examination revealed an area of reduced pigmentation where the membrane was localized, but no recurrence of CNV was detected (Fig. 2). Optical coherence tomography showed a decreased in the neurosensory detachment of the macula with the cystoid spaces remaining (Fig. 3).
G
oldmann–Favre syndrome (GFS) is a rare autosomal recessive vitreoretinal disorder. The clinical features of GFS are night blindness, visual impairment, atypical peripheral pigmentary degeneration, macular and peripheral retinoschisis, posterior subcapsular lens opacities, degenerative vitreous changes, and an extinguished electroretinogram. We describe a case of choroidal neovascularization (CNV) associated with GFS in a patient homozygous for the R311Q mutation in the NR2E3 gene who was treated with subretinal surgery.
Discussion GFS is a rare condition that exhibits a combination of the features seen in retinitis pigmentosa and Xlinked retinoschisis. GFS is allelic with the enhanced S cone syndrome, and both are caused by mutations in a nuclear receptor gene, NR2E3, located on chromosome 15q23.1 CNV infrequently occurs in patients affected by diffuse hereditary retinal dystrophies.2 This may occur due to an extensive degeneration of the outer retina and retinal pigment epithelium that curtails the process of angiogenesis. We are unaware of previous reports of peripapillary CNV associated with GFS and could not find reference to it in a computer search of the literature. Peripapillary CNV accounts for an estimated 10% of all CNV cases, and the most frequent causes in pediatric patients are idiopathic, presumed ocular histoplasmosis syndrome, and optic nerve anomalies. Peripapillary CNV can cause central visual loss in three ways: progressive subfoveal extension of CNV, serous macular detachment, and submacular hemorrhage. Management of peripapillary CNV includes thermal laser photoablation, photodynamic therapy, and submacular surgery. Although Cialdani et al3 de-
Case Report A 13-year-old boy presented with a complaint of night blindness and gradual decline in visual acuity in the right eye. His ocular history was significant for a diagnosis of GFS. Previous medical records obtained from his ophthalmologist disclosed previous visual acuity of 20/60 in the right eye and 20/200 in the left eye 3 years before. At presentation, best-corrected visual acuity was 20/200 in the right eye and 20/400 in the left eye. Dilated funduscopic examination revealed peripheral retinoschisis and macular cysts in either eye, atypical pigmentary retinopathy, and a peripapillary grayish subretinal membrane in the right eye. A fluorescein angiogram showed early hyperfluorescence of CNV and progressive dye leakage surrounding the membrane extending to the macular area without accumulation of dye in the cystic spaces (Fig. 1). Optical coherence tomography disclosed extensive cystoid spaces and seThe authors have no financial or proprietary interest in the subject matter or materials discussed in this article. Reprint requests: Rafael Navarro Alemany, Instituto de Microcirugı´a Ocular de Barcelona, calle Munner No. 10, 08022 Barcelona, Spain; e-mail: [email protected]
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Fig. 3. Postoperative horizontal optic coherence tomogram through the fovea of the right eye reveals thickening of the retina due to a wide hyporeflective space that split the neurosensory retina. There are large intraretinal cysts temporal to the fovea (big arrow). Note that a small neurosensory detachment of the fovea still remains (narrow arrow).
Fig. 1. Late-phase preoperative fluorescein angiogram of the right eye shows dye leakage of peripapillary choroidal neovascularization that extends to the macular area.
scribed stabilization or improvement of visual acuity in 80% of 27 symptomatic eyes with peripapillary CNV treated with argon laser photocoagulation, the recurrence rate after a mean follow-up of 37.7 months was 28%. Furthermore, risks of laser photocoagulation include thermal damage to the optic disk and
peripapillary retina. Photodynamic therapy is not recommended for CNV localized within 200 m of the optic disk, and its role in peripapillary CNV in no yet known. Uemura and Thomas4 described good recovery of vision after surgical removal of CNV in pediatric patients, postulating that the removal of these membranes may be a viable alternative to laser photocoagulation. Mateo et al5 also reported good visual outcomes after submacular surgery in four cases of peripapillary CNV secondary to optic disk drusen, with no recurrence during a mean follow-up of 26 months. In summary, peripapillary CNV is a rare complication of hereditary vitreoretinal disorders. Subretinal surgery can be a useful option in selected cases, even in the presence of underlying microcystic schisis cavities in the macular area. Key words: choroidal neovascularization, Goldmann–Favre syndrome, subretinal surgery. References 1.
2.
3.
4.
Fig. 2. Fundus photographs of the right eye 6 months after submacular surgery showing a partial peripapillary retinal pigment epithelial defect.
5.
Sharon D, Sandberg MA, Caruso RC, et al. Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldman-Favre syndrome, and many cases of clumped pigmentary retinal degeneration. Arch Ophthalmol 2003;121:1316–1323. Marano F, Deutman AF, Leys A, Aandekerk AL. Hereditary retinal dystrophies and choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 2000;238:760–764. Cialdani AP, Jalkh AE, Tremoe CL, et al. Argon green laser treatment of peripapillary choroidal neovascular membranes. Ophthalmic Surg 1989;20:93–99. Uemura A, Thomas M. Visual outcome after surgical removal of choroidal neovascularization in pediatric patients. Arch Ophthalmol 2000;118:1373–1378. Mateo C, Moreno J, Lechuga M, et al. Surgical removal of peripapillary choroidal neovascularization associated with optic nerve drusen. Retina 2004;24:739–745.
A case of peripapillary choroidal neovascularization associated with Goldmann-Favre syndrome was successfully managed with subretinal surgery.
From *Vitreo-retinal Unit, Instituto de Microcirugı´a Ocular de Barcelona, Barcelona, Spain; Universidad Auto´noma de Barcelona (UAB), Barcelona, Spain; and †Servei de Gene`tica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
rous detachment on the right macula. Electroretinograms were not recordable bilaterally. DNA sequencing of the NR2E3 gene allowed identification of the R311Q mutation in a homozygous state. The patient underwent pars plana vitrectomy, posterior hyaloid dissection, neovascular membrane removal through a superior macular retinotomy, and fluid–air exchange. No histologic study of the membrane was performed. Six months after surgery, visual acuity improved to 20/80 in the right eye. Funduscopic examination revealed an area of reduced pigmentation where the membrane was localized, but no recurrence of CNV was detected (Fig. 2). Optical coherence tomography showed a decreased in the neurosensory detachment of the macula with the cystoid spaces remaining (Fig. 3).
G
oldmann–Favre syndrome (GFS) is a rare autosomal recessive vitreoretinal disorder. The clinical features of GFS are night blindness, visual impairment, atypical peripheral pigmentary degeneration, macular and peripheral retinoschisis, posterior subcapsular lens opacities, degenerative vitreous changes, and an extinguished electroretinogram. We describe a case of choroidal neovascularization (CNV) associated with GFS in a patient homozygous for the R311Q mutation in the NR2E3 gene who was treated with subretinal surgery.
Discussion GFS is a rare condition that exhibits a combination of the features seen in retinitis pigmentosa and Xlinked retinoschisis. GFS is allelic with the enhanced S cone syndrome, and both are caused by mutations in a nuclear receptor gene, NR2E3, located on chromosome 15q23.1 CNV infrequently occurs in patients affected by diffuse hereditary retinal dystrophies.2 This may occur due to an extensive degeneration of the outer retina and retinal pigment epithelium that curtails the process of angiogenesis. We are unaware of previous reports of peripapillary CNV associated with GFS and could not find reference to it in a computer search of the literature. Peripapillary CNV accounts for an estimated 10% of all CNV cases, and the most frequent causes in pediatric patients are idiopathic, presumed ocular histoplasmosis syndrome, and optic nerve anomalies. Peripapillary CNV can cause central visual loss in three ways: progressive subfoveal extension of CNV, serous macular detachment, and submacular hemorrhage. Management of peripapillary CNV includes thermal laser photoablation, photodynamic therapy, and submacular surgery. Although Cialdani et al3 de-
Case Report A 13-year-old boy presented with a complaint of night blindness and gradual decline in visual acuity in the right eye. His ocular history was significant for a diagnosis of GFS. Previous medical records obtained from his ophthalmologist disclosed previous visual acuity of 20/60 in the right eye and 20/200 in the left eye 3 years before. At presentation, best-corrected visual acuity was 20/200 in the right eye and 20/400 in the left eye. Dilated funduscopic examination revealed peripheral retinoschisis and macular cysts in either eye, atypical pigmentary retinopathy, and a peripapillary grayish subretinal membrane in the right eye. A fluorescein angiogram showed early hyperfluorescence of CNV and progressive dye leakage surrounding the membrane extending to the macular area without accumulation of dye in the cystic spaces (Fig. 1). Optical coherence tomography disclosed extensive cystoid spaces and seThe authors have no financial or proprietary interest in the subject matter or materials discussed in this article. Reprint requests: Rafael Navarro Alemany, Instituto de Microcirugı´a Ocular de Barcelona, calle Munner No. 10, 08022 Barcelona, Spain; e-mail: [email protected]
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Fig. 3. Postoperative horizontal optic coherence tomogram through the fovea of the right eye reveals thickening of the retina due to a wide hyporeflective space that split the neurosensory retina. There are large intraretinal cysts temporal to the fovea (big arrow). Note that a small neurosensory detachment of the fovea still remains (narrow arrow).
Fig. 1. Late-phase preoperative fluorescein angiogram of the right eye shows dye leakage of peripapillary choroidal neovascularization that extends to the macular area.
scribed stabilization or improvement of visual acuity in 80% of 27 symptomatic eyes with peripapillary CNV treated with argon laser photocoagulation, the recurrence rate after a mean follow-up of 37.7 months was 28%. Furthermore, risks of laser photocoagulation include thermal damage to the optic disk and
peripapillary retina. Photodynamic therapy is not recommended for CNV localized within 200 m of the optic disk, and its role in peripapillary CNV in no yet known. Uemura and Thomas4 described good recovery of vision after surgical removal of CNV in pediatric patients, postulating that the removal of these membranes may be a viable alternative to laser photocoagulation. Mateo et al5 also reported good visual outcomes after submacular surgery in four cases of peripapillary CNV secondary to optic disk drusen, with no recurrence during a mean follow-up of 26 months. In summary, peripapillary CNV is a rare complication of hereditary vitreoretinal disorders. Subretinal surgery can be a useful option in selected cases, even in the presence of underlying microcystic schisis cavities in the macular area. Key words: choroidal neovascularization, Goldmann–Favre syndrome, subretinal surgery. References 1.
2.
3.
4.
Fig. 2. Fundus photographs of the right eye 6 months after submacular surgery showing a partial peripapillary retinal pigment epithelial defect.
5.
Sharon D, Sandberg MA, Caruso RC, et al. Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldman-Favre syndrome, and many cases of clumped pigmentary retinal degeneration. Arch Ophthalmol 2003;121:1316–1323. Marano F, Deutman AF, Leys A, Aandekerk AL. Hereditary retinal dystrophies and choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 2000;238:760–764. Cialdani AP, Jalkh AE, Tremoe CL, et al. Argon green laser treatment of peripapillary choroidal neovascular membranes. Ophthalmic Surg 1989;20:93–99. Uemura A, Thomas M. Visual outcome after surgical removal of choroidal neovascularization in pediatric patients. Arch Ophthalmol 2000;118:1373–1378. Mateo C, Moreno J, Lechuga M, et al. Surgical removal of peripapillary choroidal neovascularization associated with optic nerve drusen. Retina 2004;24:739–745.
