Faculty Bibliography

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

PURPOSE: To analyze the retinal structure underlying the hyperautofluorescent ring visible on fundus autofluorescence in patients with retinitis pigmentosa. METHODS: Twenty-four eyes of 13 patients with retinitis pigmentosa, aged 13 years to 67 years, were studied. The integrity of the photoreceptor cilia, also known as the inner/outer segment junction of the photoreceptors, the outer nuclear layer, and retinal pigment epithelium, was evaluated outside, across, and inside the ring with spectral-domain optical coherence tomography (OCT). RESULTS: Inside the foveal area, fundus autofluorescence did not detect abnormalities. Outside the ring, fundus autofluorescence revealed hypoautofluorescence compatible with the photoreceptor/retinal pigment epithelium degeneration. Spectral-domain OCT inside the ring, in the area of normal foveal fundus autofluorescence, revealed an intact retinal structure in all eyes and total retinal thickness values that were within normal limits. Across the ring, inner/outer segment junction disruption was observed and the outer nuclear layer was decreased in thickness in a centrifugal direction in all eyes. Outside the hyperautofluorescent ring, the inner/outer segment junction and the outer nuclear layer appeared to be absent and there were signs of retinal pigment epithelium degeneration. CONCLUSION: Disruption of the inner/outer segment junction and a decrease in outer retinal thickness were found across the central hyperautofluorescent ring seen in retinitis pigmentosa. Outer segment phagocytosis by retinal pigment epithelium is necessary for the formation of an hyperautofluorescent ring

PURPOSE: To evaluate intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity (VA) secondary to central retinal vein occlusion (CRVO). DESIGN: Prospective, interventional case series. METHODS: Patients with CRVO prospectively recruited from a practice were administered intravitreal ranibizumab 0.5 mg (Lucentis; Genentech Inc, South San Francisco, California, USA) at baseline and monthly for two additional doses. The patients were given additional ranibizumab if they had macular edema as determined by optical coherence tomography or any new intraretinal hemorrhage. Patients were evaluated for number of required injections, side effects, changes in VA, and macular thickness. RESULTS: There were 20 eyes of 20 patients who at baseline had a mean age of 72.1 years, a mean VA of 45.8 Early Treatment of Diabetic Retinopathy letters, and a mean central macular thickness of 574.6 microm. Of the 20 eyes, five previously had received intravitreal triamcinolone and 11 had received intravitreal bevacizumab (Avastin; Genentech Inc). At 12 months of follow-up, the mean VA improved to 64.3 letters and the central macular thickness decreased to 186 microm (both different than baseline values; P < .001) using a mean of 8.5 injections. The change in macular thickness was not correlated with the change in VA. In one patient with a history of transient ischemic attack, an ischemic stroke developed but no sequela resulted. In another patient, vitreomacular traction developed, but the patient had improved acuity as compared with baseline. There were no infections, retinal tears, or detachments. CONCLUSIONS: Intravitreal ranibizumab used over a period of one year improved mean VA, with low rates of adverse events, in patients with CRVO

BACKGROUND: Multifocal choroiditis (MFC) is an inflammatory condition, occasionally associated with choroidal neovascularization (CNV). Bevacizumab (Avastin) and ranibizumab (Lucentis) are therapies that target vascular endothelial growth factor. Bevacizumab and ranibizumab have been used successfully to treat CNV in age-related and myopic macular degeneration. PURPOSE:: To describe the treatment of MFC-associated CNV with intravitreal bevacizumab and/or ranibizumab. DESIGN: Retrospective interventional case series. PARTICIPANTS: Six eyes of five patients with MFC-associated CNV were treated with intravitreal bevacizumab and/or ranibizumab. MAIN OUTCOME MEASURES: Visual acuity at 1, 3, and 6 months after the initial injection. RESULTS: Previous therapies (number of eyes treated) included sub-Tenon's corticosteroids (2), intravitreal corticosteroids (1), photodynamic therapy (1), and thermal laser (1). The mean number (range) of antivascular endothelial growth factor injections per eye was 2.3 (1-6). The mean duration (range) of follow-up per patient was 41.5 (25-69) weeks. Five of six eyes improved to 20/30 acuity or better at 6 months. One eye suffered a subfoveal rip of the retinal pigment epithelium with 20/400 acuity. There was a qualitative decrease in clinical and angiographic evidence of CNV. CONCLUSIONS: Bevacizumab and ranibizumab were effective at improving visual acuity over 6 months in a small series of patients with MFC-associated CNV. Tears of the retinal pigment epithelium may occur after intravitreal antivascular endothelial growth factor therapy in MFC-associated CNV

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

OBJECTIVE: To describe cases of acute zonal occult outer retinopathy (AZOOR) in patients previously diagnosed as having multiple evanescent white dot syndrome (MEWDS). METHODS: In a retrospective case series, we studied fundus photographs, fundus autofluorescence images, optical coherence tomographic scans, fluorescein and indocyanine green angiograms, visual fields, and results of electroretinography. RESULTS: Three patients diagnosed as having MEWDS developed clinical, angiographic, autofluorescence, visual field, and/or electrophysiologic evidence of AZOOR. Spectral domain optical coherence tomographic findings disclosed attenuation of the photoreceptor inner segment-outer segment junction in areas of AZOOR involvement. In 1 patient, hyperautofluorescence on fundus autofluorescence images during the MEWDS episode coincided with the area of involvement of AZOOR. CONCLUSIONS: Development of AZOOR may occur in patients with MEWDS, suggesting that the conditions may share a common genetic susceptibility and/or pathogenetic factor. Although the typical visual prognosis after MEWDS is excellent, subsequent diagnosis of AZOOR may portend a worse outcome

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 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.

OBJECTIVE: To analyze the frequency of major age-related macular degeneration (AMD)-associated alleles in patients with multifocal choroiditis (MFC). METHODS: A cohort of 48 patients with MFC was compared with previously characterized cohorts of patients with advanced AMD (368 samples) and matched unaffected controls (368 samples). Allele and genotype frequencies of single nucleotide polymorphisms for the following AMD-associated alleles were evaluated: risk alleles in complement factor H (CFH) gene (Y402H and IVS14) and LOC387715/HTRA1 gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3) and complement factor B loci (H9L and R32Q). RESULTS: Frequencies of all major AMD-associated alleles in the CFH locus indicate a strong, statistically significant association of CFH gene single nucleotide polymorphisms and MFC. However, the same analysis for the single nucleotide polymorphisms in complement factor B and 10q26 loci matched the results in the control group. CONCLUSIONS: Like AMD, the MFC phenotype is strongly associated with the major alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling evidence of a strong association between CFH polymorphisms and MFC, which contributes to the understanding of MFC pathogenesis and suggests new potential therapeutic targets