Faculty Bibliography

PURPOSE: To report additional data on a pattern of the fundus described in 2002 as unilateral, idiopathic leopard-spot lesion of the retinal pigment epithelium (RPE). DESIGN: Observational, consecutive case series. METHODS: The fundus characteristics, natural history, and prognosis of 9 patients are described after examining them by means of diagnostic adjuncts not previously available, including optical coherence tomography (OCT) and fundus autofluorescence (FAF) photographs. RESULTS: Nine patients, 6 male and 3 female, aged 14 to 42, presented with a large area, usually contiguous to the optic nerve, characterized by a distinct scalloped margin of reticular RPE hyperplasia, mid-lesion lacunae of RPE hyperplasia, and central thinning and atrophy of the RPE. FAF of the lesion showed a pattern that is inverted relative to fluorescein hyperfluorescence with a distinctive dark reticular pattern. OCT revealed fibroglial changes of the above retina in some cases. Two cases that have been documented up to 10 years showed enlargement of the affected area, one slightly and one significantly. Associated lesions included retinal folds (4 cases), retinal vascular tortuosity (4 cases), and progressive localized hyperplasia of the RPE (1 case). Related complications included choroidal neovascularization (2 cases) and localized retinal detachment (1 case). CONCLUSION: The inverted scalloped patterns of hyperfluorescence and hypofluorescence on fluorescein angiography and FAF with the newly described OCT features may help in the diagnosis of this rare condition of the RPE. Vision-threatening complications may be observed. Based on the present updated review of this condition, we suggest changing the name of this entity to 'unilateral RPE dysgenesis.'

PURPOSE: To describe a neovascular pattern associated with treatment-refractory neovascular age-related macular degeneration (AMD). DESIGN: A retrospective observational case series. METHODS: SETTING: Clinical practice. PATIENT POPULATION: Twelve eyes of 12 patients with neovascular AMD in which a poor anatomic response to anti-vascular endothelial growth factor (VEGF) therapy was related to polypoidal choroidal vasculopathy (PCV). OBSERVATION PROCEDURE: Slit-lamp biomicroscopy, optical coherence tomography, fluorescein and indocyanine green angiography. MAIN OUTCOME MEASURES: Snellen visual acuity (VA), anatomic response to therapy including presence or absence of retinal edema, hemorrhage, and lipid exudates. RESULTS: New or persistent PCV was identified in a cohort of patients demonstrating increasing macular exudation despite regular intravitreal ranibizumab (Lucentis; Genentech Inc, South San Francisco, California, USA) or bevacizumab (Avastin; Genentech Inc) injections for a minimum of 6 months. Treatment with verteporfin photodynamic therapy (PDT), PDT/anti-VEGF combination therapy, or continued anti-VEGF monotherapy resulted in complete resolution of exudation in 9 of 12 patients and partial resolution of exudation in the remaining 3 patients. CONCLUSION: Treatment-refractory neovascular AMD may harbor vascular abnormalities such as PCV. Modifications in therapeutic protocols may be indicated in order to improve visual and anatomic outcomes in this population

PURPOSE: To evaluate vitreomacular relations in different stages of age-related macular degeneration (AMD) without the influence of genetics and environmental factors. DESIGN: Retrospective, observational case series. METHODS: This was a multicenter study consisting of 29 previously untreated subjects with active exudative (wet) AMD in one eye and active nonexudative (dry) AMD in the fellow eye who were compared with 10 previously untreated subjects with end-stage geographic atrophy in one eye and an end-stage fibrotic (disciform) scar in the fellow eye. All subjects were studied with ultrasonography to identify the presence of posterior vitreous detachment (PVD) and by optical coherence tomography to detect vitreomacular adhesion (VMA). RESULTS: The incidence of PVD in eyes with nonexudative AMD was 20 (69%) of 29, compared with 6 (21%) of 29 with active exudative AMD (P = .002). VMA was present in 11 (38%) of 29 of eyes with exudative AMD and in only 3 (10%) of 29 eyes with nonexudative AMD (P = .008). The incidence of PVD in geographic atrophy was 7 (70%) of 10, compared with 4 (40%) of 10 with disciform scar (P = .44). VMA was present in 2 (20%) of 10 eyes with disciform scars and in 0 (0%) of 10 eyes with geographic atrophy (P = .48). CONCLUSIONS: PVD may protect against exudative AMD, whereas VMA may promote exudative AMD. This phenomenon is not evident in end-stage disease because of an increased incidence of PVD and a decreased incidence of VMA in eyes with disciform scars. Genetic and environmental factors do not seem to influence these observations

OBJECTIVE: To describe the phenotypes of 5 patients with NR2E3 mutations. METHODS: Two patients with familial and 3 with sporadic early-onset nyctalopia and retinal pigment abnormalities were screened for mutations in the NR2E3 gene (OMIM 604485). The clinical course, fundus features, visual field test results, and fluorescein angiographic and electrophysiologic findings were compared. RESULTS: Three different mutations in NR2E3 were identified: R311Q and 2 novel mutations--missense change Q350R and an in-frame deletion of phenylalanine at position 71 (delF71) in exon 2. Three patients who were homozygous for R311Q had posterior subcapsular cataracts and a concentric ring of round pigment clumps. Electroretinograms were extinguished. A fourth patient, a 24-year-old man who was heterozygotic for R311Q and Q350R, had Goldmann-Favre syndrome. A fifth patient, a 10-year-old boy with heterozygotic mutations R311Q and delF71, had diminished foveal reflexes and subtle pigmentary changes, perhaps a forme fruste of Goldmann-Favre syndrome. Both of these patients had an identical spectral electroretinographic pattern characteristic of enhanced S-cone syndrome. CONCLUSIONS: Molecular genetic testing is essential for establishing the correct diagnosis in patients with NR2E3 mutations because of the variable phenotype associated with these degenerations. Two novel NR2E3 mutations are described that are associated with Goldmann-Favre syndrome and enhanced S-cone syndrome

PURPOSE: To report the long-term follow-up of a case of enhanced S-cone syndrome (ESCS). METHODS: Retrospective chart review. RESULTS: The patient was misdiagnosed with atypical retinitis pigmentosa at 17 years of age. Twenty-seven years of follow-up showed slow deterioration but relative preservation of vision. The most striking clinical feature was the formation of a ring of heavy round pigment clumping around the vascular arcades. Electroretinogram was reported as extinguished in advanced stages of the condition. Genetic testing revealed the most common mutation of the NR2E3 gene reported in the Goldmann-Favre syndrome/ESCS entity. CONCLUSION: Visual acuity can be relatively preserved over the course of ESCS. In advanced stages, genetic testing can be a valuable diagnostic tool.

PURPOSE: To report a case of bullous retinal detachment complicated by peripheral retinal ischemia and neovascularization in a patient with chronic central serous chorioretinopathy (CSC). RESULTS: Focal laser photocoagulation to the active retinal pigment epithelial leaks in the posterior pole resulted in resolution of the bullous detachment and regression of the retinal neovascularization. CONCLUSIONS: Patients with chronic CSC and a large, dependent serous detachment with peripheral retinal ischemia and neovascularization may be managed by focal treatment to active pigment epithelial leaks alone. This could spare patients of the adverse effects associated with widespread laser treatment and reduce the risk of visual loss due to vitreous hemorrhage and/or more severe complications resulting from progressive retinal ischemia.

PURPOSE: To investigate the prevalence of sequence variants in the ATM gene and to determine the frequency of major age-related macular degeneration (AMD)-associated variants in CFH, CFB, and 10q26 loci in patients with idiopathic perifoveal telangiectasia (IPT). METHODS: Thirty patients with diagnoses of IPT underwent standard ophthalmologic evaluation that included visual acuity testing, fundus photography, and fluorescein angiography. DNA was screened for variations in the ATM gene by a combination of denaturing high-performance liquid chromatography and direct sequencing. Major AMD-associated alleles in CFH, CFB, and 10q loci were screened by PCR-restriction fragment-length polymorphism. RESULTS: Nineteen female and 11 male patients (average age, 59 years) with a median visual acuity of 20/50 were evaluated. Six patients were of Asian-Indian origin, one was Hispanic, and 23 were of European-American ancestry. Nine of 30 (30%) patients had diabetes mellitus, 18 of 30 (60%) patients had hypertension, and 12 of 30 (40%) patients had a history of smoking. Screening of the ATM gene revealed a null allele in 2 of 23 (8.7%) patients of European ancestry, previously disease-associated missense alleles in 4 of 23 (17.4%) patients, and common missense alleles in 7 of 23 (30.4%) patients. No variants were identified in the ATM gene in patients of Asian or Hispanic origin. Frequencies of major AMD-associated alleles in CFH, CFB, and 10q loci in the IPT cohort were similar to those in the ethnically matched general population. CONCLUSIONS: At least 26%, and maybe up to 57%, of IPT patients of European-American descent carried possibly disease-associated ATM alleles. Vascular risk factors such as hypertension, diabetes, and smoking may be associated with the pathogenesis of the disease

PURPOSE: The presence or absence of functional changes associated with solitary, congenital, hypopigmented lesions of the retinal pigment epithelium (RPE) have been a matter of controversy. This case report describes retinal and functional findings in a young patient with such a lesion. METHODS: A 10-year-old Hispanic female with a solitary congential hypopigmented spot of the RPE was examined using fundus photography, fluorescein angiography, autofluorescence imaging (AF) and optical coherence tomography (OCT). Functional analyses were performed using the Humphrey 24 - 2 visual field, Goldmann perimetry and the multifocal ERG (mfERG). RESULTS: A small visual field defect was demonstrated on both Goldmann perimetry (I/ 2e test object) and on Humphrey 24 - 2 visual field testing (significant at the 0.5 % level for pattern deviation). The multifocal ERG response amplitudes were decreased in the corresponding area and increased in implicit time. Autofluorescence imaging showed an absence of fluorescence corresponding to the area of the lesion. OCT findings were indicative of a small amount of subretinal fluid or schisis-like changes overlying the RPE anomaly. CONCLUSION: The results indicate that solitary, albinotic spots of the RPE can be associated with visual field defects and outer retinal deficits; these may be related to impaired RPE function and/or chronic exudative changes

BACKGROUND: Retinal angiomatous proliferation (RAP) is a distinct form of neovascularization in patients with age-related macular degeneration. Lacking definitive sequential histopathologic evidence of its intraretinal versus choroidal origin, the clinical observations of early stages of RAP lesions may provide clues to help further expand our understanding of this entity. METHODS: Five eyes of four patients with early Stage 1 RAP were examined. Fundus photography, fluorescein and indocyanine green angiography as well as time-domain and spectral-domain optical coherence tomography were performed. Images were assessed to determine the characteristics of neovascularization in early stage RAP lesions and the response of the lesions to treatment or observation. RESULTS: The analysis of the selected cases suggests a choroidal origin of the neovascular complex with the early formation of a retinal choroidal anastomosis without evidence of underlying occult Type 1 neovascularization. Three eyes responded to a single treatment with intravitreal ranibizumab (0.5 mg) and 2 eyes (1 patient) resolved spontaneously without treatment. CONCLUSION: The neovascularization in RAP may originate not only from deep retinal capillaries but also from the choroid. We therefore propose the more descriptive term 'Type 3 neovascularization' for this entity to emphasize the intraretinal location of the vascular complex and distinguish this type from the two types of neovascularization previously described by J. Donald Gass in his classic text