Faculty Bibliography

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

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

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

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.

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

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