Faculty Bibliography

PURPOSE: To evaluate optic disc drusen, extracellular protein deposits known to contain numerous aggregates of mitochondria, using multimodal modalities featuring optical coherence tomography (OCT) and autofluorescence imaging. DESIGN: Retrospective observational case series. METHODS: Eyes with optic nerve drusen were examined with enhanced depth imaging (EDI)-OCT, swept source OCT, and fundus autofluorescence using a fundus camera. RESULTS: Twenty-six eyes of 15 patients with optic disc drusen were evaluated. EDI-OCT and swept source OCT showed multiple optic disc drusen at different levels; most were located immediately anterior to the lamina cribrosa. The drusen were ovoid regions of lower reflectivity that were bordered by hyperreflective material, and in 12 eyes (46.2%) there were internal hyperreflective foci. The mean diameter of the optic disc drusen as measured in OCT images was 686.8 (standard deviation +/- 395.2) mum. There was a significant negative correlation between the diameter of the optic disc drusen and the global retinal nerve fiber layer thickness (r = -0.61, P = .001). There was a significant negative correlation between proportion of the optic disc drusen area occupied by optic nerve drusen as detected by autofluorescence imaging and the global retinal nerve fiber layer thickness (r = -0.63, P = .001). CONCLUSIONS: Deeper-penetration OCT imaging demonstrated the internal characteristics of optic disc drusen and their relationship with the lamina cribrosa in vivo. This study also showed that both the larger the drusen and the more area of the optic canal occupied by drusen, the greater the associated retinal nerve fiber layer abnormalities.

OBJECTIVE: The International Vitreomacular Traction Study (IVTS) Group was convened to develop an optical coherence tomography (OCT)-based anatomic classification system for diseases of the vitreomacular interface (VMI). DESIGN: The IVTS applied their clinical experience, after reviewing the relevant literature, to support the development of a strictly anatomic OCT-based classification system. PARTICIPANTS: A panel of vitreoretinal disease experts was the foundation of the International Classification System. METHODS: Before the meeting, panel participants were asked to review 11 articles and to complete 3 questionnaires. The articles were preselected based on searches for comprehensive reviews covering diseases of the VMI. Responses to questionnaires and the group's opinions on definitions specified in the literature were used to guide the discussion. MAIN OUTCOME MEASURES: Optical coherence tomography-based anatomic definitions and classification of vitreomacular adhesion, vitreomacular traction (VMT), and macular hole. RESULTS: Vitreomacular adhesion is defined as perifoveal vitreous separation with remaining vitreomacular attachment and unperturbed foveal morphologic features. It is an OCT finding that is almost always the result of normal vitreous aging, which may lead to pathologic conditions. Vitreomacular traction is characterized by anomalous posterior vitreous detachment accompanied by anatomic distortion of the fovea, which may include pseudocysts, macular schisis, cystoid macular edema, and subretinal fluid. Vitreomacular traction can be subclassified by the diameter of vitreous attachment to the macular surface as measured by OCT, with attachment of 1500 mum or less defined as focal and attachment of more than 1500 mum as broad. When associated with other macular disease, VMT is classified as concurrent. Full-thickness macular hole (FTMH) is defined as a foveal lesion with interruption of all retinal layers from the internal limiting membrane to the retinal pigment epithelium. Full-thickness macular hole is primary if caused by vitreous traction or secondary if directly the result of pathologic characteristics other than VMT. Full-thickness macular hole is subclassified by size of the hole as determined by OCT and the presence or absence of VMT. CONCLUSIONS: This classification system will support systematic diagnosis and management by creating a clinically applicable system that is predictive of therapeutic outcomes and is useful for the execution and analysis of clinical studies.

PURPOSE: To evaluate the characteristics of multifocal choroiditis and panuveitis (MCP) and punctate inner choroidopathy (PIC) using multimodal imaging. METHODS: This is a retrospective, consecutive, observational case series of 38 eyes of 22 patients. Each eye of patients with multiple yellow-white idiopathic inflammatory lesions in the fundus was classified as having MCP or PIC using standard diagnostic criteria in a masked fashion. The features of these eyes as determined from color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, and angiography were compared across diagnostic categories. The main outcome measures were the features of both MCP and PIC as evidenced by multimodal imaging. RESULTS: Of the 38 eyes, 23 eyes had MCP, 15 had PIC; and 7 patients had a discordant pairing of one diagnosis in 1 eye with the other diagnosis in the fellow eye. Acute lesions appeared as nodular collections under the retinal pigment epithelium. These solid retinal pigment epithelium detachments appeared to rupture leading to inflammatory infiltration of the subretinal space and outer retina, often with a widespread loss of the outer retinal architecture beyond the confines of the inflammatory exudate. Treatment with corticosteroids caused a rapid regression of this material with a slower resolution of the abnormalities of the outer retinal architecture. The pattern of inflammatory involvement seen by multimodal imaging did not vary between PIC and MCP. No consistent abnormalities were seen in the choroid in either condition, although there was slight thickening of the choroid underlying some acute lesions. CONCLUSION: Despite the names of these diseases, the principle sites involved appears to be the subretinal pigment epithelium and outer retinal spaces. Because both MCP and PIC target the same essential structures in the same phenotypic manner and, when active, are treated the same way, there seems to be limited clinical utility in trying to differentiate them. Based on multimodal imaging results, a reappraisal of pathogenic features and naming conventions of these diseases seems indicated.

PURPOSE: To investigate the effect that panretinal photocoagulation to peripheral areas of retinal vascular nonperfusion has on the visual acuity and injection frequency of ranibizumab in eyes with previous central retinal vein occlusion. METHODS: Patients enrolled in a prospective study of ranibizumab for central retinal vein occlusion were imaged with wide-field angiography using the Optos P200 system. Laser photocoagulation was carried out and the extent of laser photocoagulation was evaluated with repeat wide-field angiography. Injection of ranibizumab was based on an as needed strategy throughout the study. The injection frequency in the 6 months before laser was compared with a 6-month period starting 2 months after the laser photocoagulation. The visual acuity was measured by Early Treatment Diabetic Retinopathy Study protocol refraction at both the end of the 6-month follow-up period and at the time of laser photocoagulation. RESULTS: There were 10 patients treated in this study with a mean number of 1,757 spots of laser photocoagulation in the peripheral retina. The injection frequency in the 6-month lead-in period was 3.4 and in the 6-month follow-up period was 3.1, a difference that was not significant (P = 0.26). The visual acuity at the time of laser photocoagulation was 54.2 letters (approximate Snellen equivalent of 20/80) and at the end of the observation period was 51.4 letters, a difference that was not significant (P = 0.33). CONCLUSION: In this small study, laser photocoagulation to peripheral areas of nonperfusion as visualized by wide-field angiography did not result in either decreased injection frequency or improved visual acuity in eyes with central retinal vein occlusion treated with ranibizumab.

PURPOSE: To investigate the posterior segment in cases of clinically evident intraocular inflammation for punctate reflections consistent with that expected to arise from inflammatory cells. METHODS: Patients with ocular inflammatory diseases imaged with spectral-domain optical coherence tomography (SD-OCT) were retrospectively reviewed. RESULTS: There were 7 patients with mean age of 66.7 years, and the diagnosis was toxoplasmosis in 5 eyes, multiple evanescent white dot syndrome in 1 eye, and posttraumatic outer retinitis in 1 eye. At baseline, the SD-OCT showed vitreous cells as numerous punctate spots in the vitreous in all seven eyes. The SD-OCT also showed similar-sized hyperreflective dots in the retina in all seven eyes. During follow-up, reduced vitreous cellular infiltration was correlated with a decrease in the number of the punctate spots visible by SD-OCT. CONCLUSION: Eyes with intraocular inflammation had SD-OCT images of the vitreous containing punctate spots of a size consistent with that expected from inflammatory cells. Similarly sized punctate spots were seen within the retina in regions of retinitis. Additional characterization of the optical section should permit stereological estimations of actual cell counts per unit volume.

PURPOSE: To characterize the morphology, prevalence, and topography of subretinal drusenoid deposits, a candidate histological correlate of reticular pseudodrusen, with reference to basal linear deposit (BlinD), a specific lesion of age-related macular degeneration, and to propose a biogenesis model for both lesion. METHODS: Donor eyes with median death-to-preservation of 2:40 hours were postfixed in osmium tannic acid paraphenylenediamine and prepared for macula-wide high-resolution digital sections. Annotated thicknesses of 21 chorioretinal layers were determined at standard locations in sections through the fovea and the superior perifovea. RESULTS: In 22 eyes of 20 white donors (83.1 +/- 7.7 years), SDD appeared as isolated or confluent drusenoid dollops punctuated by tufts of retinal pigment epithelium apical processes and associated with photoreceptor perturbation. Subretinal drusenoid deposits and BlinD were detected in 85 and 90% of non-neovascular age-related macular degeneration donors, respectively. Subretinal drusenoid deposit was thick (median, 9.4 mum) and more abundant in the perifovea than in the fovea (P < 0.0001). BlinD was thin (median, 2.1 mum) and more abundant in the fovea than in the perifovea (P < 0.0001). CONCLUSION: Subretinal drusenoid deposits and BlinD prevalence in age-related macular degeneration eyes are high. Subretinal drusenoid deposits organized morphology, topography, and impact on surrounding photoreceptors imply specific processes of biogenesis. Contrasting topographies of subretinal drusenoid deposits and BlinD suggest relationships with differentiable aspects of rod and cone physiology, respectively. A 2-lesion 2-compartment biogenesis model incorporating outer retinal lipid homeostasis is presented.

PURPOSE: To demonstrate the mechanism by which retinal pigment epithelium (RPE) tears occur in eyes with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents using spectral-domain optical coherence tomography (OCT). DESIGN: Retrospective observational case series. METHODS: OCT images of 8 eyes that developed RPE tears following the administration of intravitreal anti-VEGF agents for neovascular AMD were evaluated. Pretear and posttear images were compared in order to elucidate the mechanism by which RPE tears occur in this setting. RESULTS: In all eyes, pretear images revealed a vascularized pigment epithelial detachment (PED) containing hyperreflective material consistent with choroidal neovascularization (CNV). This CNV was adherent to the undersurface of the RPE and created contractile folds in the RPE contour. In 6 eyes, contractile neovascular tissue spanned the PED, causing outward bowing of the Bruch membrane and a peaked appearance to the overlying RPE monolayer. RPE tears occurred after the first anti-VEGF injection in 6 of 8 eyes. The posttear OCT images showed a discontinuity in the RPE with the CNV adherent to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution and contraction of neovascular tissue adherent to the undersurface of the RPE may impart a substantial contractile force that tears this already-strained tissue layer.

PURPOSE: To investigate the association of fundus features with choroidal thickness in eyes with early age-related macular degeneration. METHODS: Consecutive patients with age-related macular degeneration were evaluated. Major exclusionary criteria included late age-related macular degeneration (central geographic atrophy or choroidal neovascularization), macular laser therapy, myopia greater than -6 diopters, past vitreoretinal surgery, or central serous chorioretinopathy. Charts and multimodal imaging were reviewed for refraction, cataract, hypertension, diabetes, open-angle glaucoma, beta-zone peripapillary atrophy, fundus tessellation, pigmentary changes, drusen, subretinal drusenoid deposits (also known as reticular pseudodrusen). Data measured from enhanced-depth imaging spectral-domain optical coherence tomography included subfoveal choroidal thickness, central foveal thickness, outer nuclear layer thickness, inner segment to retinal pigment epithelium aggregate thickness, presence of subretinal drusenoid deposit, and outer retinal hyperreflective layers (including the band corresponding to overlap between retinal pigment epithelium apical processes and outer segments). Correlations were calculated among the measured variables, fundus features, open-angle glaucoma, and visual acuity. RESULTS: In 90 eyes of 70 early age-related macular degeneration patients with mean visual acuity 20/31 (logarithm of the minimum angle of resolution 0.193), subfoveal choroidal thickness showed a significant inverse correlation with age (P = 0.004) and increasing myopic spherical equivalent refractive error (P = 0.023). Subfoveal choroidal thickness was thinner in eyes with fundus tessellation (P < 0.001), subretinal drusenoid deposit (P = 0.023), an absence of conventional drusen (P < 0.001), the presence of beta-zone peripapillary atrophy (P < 0.001), and in eyes with a diagnosis of open-angle glaucoma (P = 0.003) or an absent band on optical coherence tomography corresponding to overlap between outer segment and retinal pigment epithelium apical processes (P = 0.022). CONCLUSION: Major ocular manifestations in early age-related macular degeneration and open-angle glaucoma are associated with the choroid-the main blood supply in the eye. Theories concerning the pathogenesis of these two diseases should incorporate interactions involving the choroid.