Faculty Bibliography

PURPOSE: To investigate the association of the rs2301995 haplotype-tagging single nucleotide polymorphism (htSNP) in the elastin gene (ELN) with polypoidal choroidal vasculopathy (PCV) in European-American patients. METHODS: Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the rs2301995 haplotype-tagging single nucleotide polymorphism (htSNP) in the ELN locus in fifty-six patients with PCV, 368 patients with advanced age-related macular degeneration (AMD) and 368 age- and ethnically-matched unaffected controls. RESULTS: The ELN rs2301995 SNP was not statistically significantly associated with the PCV phenotype (P = 0.9). The frequency of the minor allele of the rs2301995 SNP was practically identical in the PCV, AMD and control groups (6.3% vs. 5.4% vs. 7.1%). CONCLUSION: The PCV phenotype in European-American patients is not associated with rs2301995 SNP in the ELN locus.

PURPOSE: To describe the retinal imaging findings in the index patient with Heimler syndrome (OMIM #234580). DESIGN: Non-interventional case report. METHODS: A 29-year-old woman with Heimler syndrome developed bilateral vision loss. Fluorescein angiography (FA), fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) were performed to assess the retinal anatomy and function. RESULTS: FA showed mottling of the retinal pigment epithelium (RPE) in the posterior pole and periphery of the retina. FAF revealed hyper and hypoautofluorescent dots corresponding to the RPE mottling observed on FA. SD-OCT documented loss of the inner/outer segments boundary, and RPE thinning. ERG testing excluded generalized rod-cone dysfunction. CONCLUSION: We report an adult-onset macular dystrophy in one of the previously reported patients with Heimler syndrome and hypothesize that this syndrome is probably an expression of a ciliopathy.

PURPOSE: To develop a method of imaging the retina using wide-field fluorescein angiography and use this method to investigate the areas of perfusion abnormalities in patients treated with ranibizumab for central retinal vein occlusion. METHODS: Cross-sectional analysis of patients recruited to a prospective study. Patients in a prospective study of ranibizumab for central retinal vein occlusion were imaged with wide-field angiography. Fluorescein angiograms taken with the Optos P200 Scanning Laser Ophthalmoscope were obtained of the posterior portion of the eye and of the periphery through ocular steering. Resultant images of the periphery were registered to the posterior image using thin-plate spline warping. A transformation was used to measure the retinal surface area. Perfusion characteristics were compared with injection frequencies and protocol refraction visual acuity measurements. RESULTS: Of 22 patients imaged, 7 would be classified as nonperfused by the Central Retinal Vein Occlusion Study (CVOS) angiographic criteria. However, all patients showed confluent areas of nonperfusion in the retinal periphery ranging in size from 16 disk areas to 242 disk areas. The areas of peripheral nonperfusion were not significantly different in the Central Retinal Vein Occlusion Study-perfused group versus nonperfused group. The area of peripheral nonperfusion was not correlated with the number of injections (r = -0.13, P = 0.58), but was inversely correlated with visual acuity (r = -0.52, P = 0.013). Blood vessels at the border of the peripheral nonperfusion did not show signs of neovascular growth or profuse leakage. CONCLUSION: Angiographic mapping of the retina is possible using image-processing techniques with wide-field images. Eyes with central retinal vein occlusion develop widespread peripheral vascular obliteration in regions that are difficult to image with conventional fundus cameras. These nonperfused areas may have important implications for visual function.

PURPOSE: To evaluate long-term effectiveness and safety of intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity secondary to central retinal vein occlusion. METHODS: In this prospective interventional case series, patients with central retinal vein occlusion were administered intravitreal ranibizumab 0.5 mg at baseline and monthly for 2 additional doses. Thereafter, the patients were given additional ranibizumab if they had macular edema by optical coherence tomography, leakage during fluorescein angiography, or any intraretinal hemorrhage. RESULTS: There were 35 eyes of 35 patients who at baseline had a mean visual acuity of 44.2 Early Treatment Diabetic Retinopathy Study letters and a mean central macular thickness of 638 mum. At 12 months, mean visual acuity of 32 eyes improved by 16.5 letters and macular thickness decreased to 164 mum (P < 0.001 vs. baseline for each). At 24 months, mean visual acuity of 24 eyes improved by 17.8 letters and macular thickness was 263 mum (P < 0.001 vs. baseline for each). Patients received an average of 10.2 injections during the first year and 6.6 injections during the second year. No cases of endophthalmitis, retinal detachment, or neovascularization were observed. CONCLUSION: Intravitreal ranibizumab caused a significant improvement in visual acuity and central retinal thickness, which persisted for up to 2 years with minimal side effects

PURPOSE: To investigate the fundus autofluorescence (FAF) abnormalities in central serous chorioretinopathy (CSC) and evaluate potential correlations with visual acuity. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four hundred seventy-five eyes of 238 patients with CSC. METHODS: Consecutive patients with CSC underwent FAF imaging, as well as routine ophthalmologic examinations. Confluent hypoautofluorescence was defined as a region of absent autofluorescence greater than one fourth of a disk diameter. Granular hypoautofluorescence was defined if there was a grainy or coarse region of decreased fluorescence as compared with normal surrounding areas greater than one fourth of a disc diameter in size. A descending tract was a downward leading swathe of decreased autofluorescence originating from the posterior pole to extend below the inferior arcade. MAIN OUTCOME MEASURES: The pattern and frequency of FAF abnormalities and their correlations with corrected visual acuity. RESULTS: The mean age of the subjects was 57.1 years (standard deviation, 13.3), and 181 (76.1%) were male. Confluent and granular hypoautofluorescence was detected in the macula of 54 (11.4%) and 300 (63.2%) of 475 eyes, respectively. Descending tracts from the macula were observed in 43 (9.1%) eyes and from the optic disc in 43 (9.1%) eyes. Multiple regression analysis revealed that confluent hypoautofluorescence of the macula, granular hypoautofluorescence of the macula, and increasing age all were independent predictors of decreased visual acuity. CONCLUSIONS: The FAF abnormalities in CSC show multiple distinct patterns and seem to provide functional information.

PURPOSE: To investigate the spectral-domain optical coherence tomography findings in four cases of acute macular neuroretinopathy and identify features that may differentiate acute macular neuroretinopathy from similar conditions in the acute zonal occult outer retinopathy complex. METHODS: Patients with acute macular neuroretinopathy underwent complete periodic examinations, including ophthalmoscopy, color photography and autofluorescence photography, visual field testing, and spectral-domain optical coherence tomography. Abnormalities as seen by multimodal imaging were documented and evaluated during follow-up. RESULTS: The average age of the 4 patients was 32 years (range, 28-34 years), and 2 had bilateral involvement. The follow-up ranged from 1 month to 5 months. In each patient, dark lobular areas seen by ophthalmoscopy corresponded to the measured visual field defect and what appeared to be a regional loss of outer segments of the photoreceptors. The outer segment defect resolved in two patients and improved in the other two during follow-up. All patients showed a colocalizing regional thinning of the outer nuclear layer, which did not change during the follow-up period. There were no associated abnormalities in the fundus appearance. CONCLUSION: Acute macular neuroretinopathy causes reddish brown patches that are because of outer retinal damage as documented by spectral-domain optical coherence tomography. Unlike other entities in the acute zonal occult outer retinopathy complex, acute macular neuroretinopathy has no other synchronic ophthalmoscopically visible fundus abnormalities. These lesions may resolve over time, with restoration of the outermost retinal architecture, but persistent thinning of the overlying outer nuclear layer remained.

PURPOSE: To evaluate the subfoveal choroidal thickness in Vogt-Koyanagi-Harada (VKH) disease using enhanced depth imaging optical coherence tomography. METHODS: Retrospective observational study. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography, in which the optical coherence tomography instrument was placed close enough to the eye to obtain an inverted image, which was averaged for 100 scans. All patients were diagnosed as having the ocular findings of VKH disease with or without extraocular disorders. The patients were followed during their initial treatment with corticosteroids. RESULTS: All 8 patients (16 eyes) with acute phase VKH disease presented with thickening of the choroid. The serous retinal detachment disappeared in 1 month after corticosteroid treatment. The mean choroidal thickness in 16 eyes decreased from 805 +/- 173 mum at the first visit to 524 +/- 151 mum at 3 days (P < 0.001) and 341 +/- 70 mum by 2 weeks (P < 0.001). CONCLUSION: Patients with active VKH disease have markedly thickened choroids, possibly related not only to inflammatory infiltration but also to increased exudation. Both the choroidal thickness and the exudative retinal detachment decreased quickly with corticosteroid treatment. Enhanced depth imaging optical coherence tomography can be used to evaluate the choroidal involvement in VKH disease in the acute stages and may prove useful in the diagnosis and management of this disease noninvasively.

PURPOSE: To investigate spectral domain optical coherence tomography and autofluorescence findings in eyes with pseudoxanthoma elasticum. METHODS: A retrospective analysis of visual acuity, spectral domain optical coherence tomography, and autofluorescence findings of consecutive patients with pseudoxanthoma elasticum was performed. The spectral domain optical coherence tomography was evaluated for retinal architecture, subretinal accumulations, and photoreceptor layer thickness. Autofluorescence and near-infrared reflectance images were reviewed for correlative findings. RESULTS: There were 21 patients (42 eyes) with pseudoxanthoma elasticum with a mean age of 56.1 +/- 12.4 years. Subretinal fluid was found in 14 eyes, 7 of which had no signs of choroidal neovascularization. In six of the seven eyes with a history of choroidal neovascularization controlled with antivascular endothelial growth factor injections, there were areas of subretinal fluid that were not contiguous with the choroidal neovascularization and did not seem responsive to antivascular endothelial growth factor injections. Two types of formed material were observed in the subretinal space and outer retina. The first was hypoautofluorescent deposits above the retinal pigment epithelium resembling subretinal drusenoid deposits (reticular pseudodrusen). The second was yellow to brown hyperautofluorescent aggregates in the subretinal space and outer retina similar to those seen in pattern dystrophies and was found in 19 eyes. There was an apparent association between the presence of subretinal fluid and pattern dystrophy-like findings. CONCLUSION: Subretinal fluid in patients with pseudoxanthoma elasticum is not always indicative of active leakage from underlying choroidal neovascularization and can be resistant to antivascular endothelial growth factor injections. This fluid is associated with pattern dystrophy-like findings and may indicate abnormal retinal pigment epithelial function.

PURPOSE: To examine the posterior anatomic structure of eyes with dome-shaped macula using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT). DESIGN: Retrospective observational case series. METHODS: Patients with dome-shaped macula, a condition defined as convex elevation of the macula as compared with the surrounding staphylomatous region in a highly myopic eye, were identified through routine examinations using optical coherence tomography (OCT). EDI-OCT was used to examine their posterior anatomic changes. The scleral thickness was measured from the outer border of the choroid to the outer scleral border under the fovea and 3000 mum temporal to the fovea. RESULTS: The mean age of the 15 patients (23 eyes) was 59.3 (+/- 12.2) years, and the mean refractive error was -13.6 (+/- 5.0) diopters. The best-corrected visual acuity ranged from 20/15 to 20/800 (median: 20/30). Eight patients (53%) had dome-shaped macula bilaterally. The mean subfoveal scleral thickness in 23 eyes with dome-shaped macula was 570 (+/- 221) mum, and that in 25 eyes of 15 myopic patients with staphyloma but without dome-shaped macula was 281 (+/- 85) mum (P < .001) even though both groups had similar myopic refractive error. The scleral thickness 3000 mum temporal to the fovea was not different in the 2 groups. CONCLUSIONS: Dome-shaped macula is the result of a relative localized thickness variation of the sclera under the macula in highly myopic patients, and it cannot be categorized into any of the known types of staphyloma. This finding suggests the ocular expansion in myopia may be more complex than previously thought.

PURPOSE: To report a recently observed association of macular vitelliform detachment and subretinal drusenoid deposits (reticular pseudodrusen). METHODS: Clinical and multimodal imaging data of patients with acquired vitelliform lesions in association with subretinal drusenoid deposits were reviewed. Acquired vitelliform lesions were defined as subretinal accumulations of yellow material that developed in adulthood. Subretinal drusenoid deposits were diagnosed as being present if there were drusen-like accumulations that colocalized with aggregates of subretinal material as seen by multimodal imaging including spectral-domain optical coherence tomography, autofluorescence, and near-infrared imaging. RESULTS: Seven eyes of 6 patients with a mean age of 85 years, all of whom were white, were found to have vitelliform material in association with subretinal drusenoid deposits. The median visual acuity was 20/30. The vitelliform material was hyperautofluorescent and was in all eyes located in the subretinal space between the inner segment/outer segment junction and the retinal pigment epithelium. This material had the same color, autofluorescence, and optical coherence tomographic characteristics as the vitelliform material seen in association with cuticular drusen. CONCLUSION: Acquired vitelliform lesions can occur in association with subretinal drusenoid deposits. Subretinal drusenoid deposits might be mistaken for cuticular drusen because of their similar appearance in color fundus photography but can be easily distinguished with multimodal imaging because they lie above the retinal pigment epithelium. Subretinal drusenoid deposits may reflect abnormalities in the function of the retinal pigment epithelium and their presence may interfere with photoreceptor outer segment turnover, leading to an accumulation of vitelliform material.