Faculty Bibliography

PURPOSE: To investigate the cone photoreceptor mosaic in eyes with pseudodrusen as evidenced by the presence of subretinal drusenoid deposits (SDD) and conventional drusen using adaptive optics (AO) imaging integrated into a multimodal imaging approach. DESIGN: Observational case series. PARTICIPANTS: Eleven patients (11 eyes) with pseudodrusen and 6 patients (11 eyes) with conventional drusen. METHODS: Consecutive patients were examined using near-infrared reflectance (IR) confocal scanning laser ophthalmoscopy (SLO) and eye-tracked spectral-domain optical coherence tomography (SD-OCT) and flood-illuminated retinal AO camera of nonconfluent pseudodrusen or conventional drusen. Correlations were made between the IR-SLO, SD-OCT, and AO images. Cone density analysis was performed on AO images within 50 x 50-mum windows in 5 regions of interest overlying and in 5 located between SDD or conventional drusen with the same retinal eccentricity. MAIN OUTCOME MEASURES: Cone densities in the regions of interest. RESULTS: The pseudodrusen correlated with subretinal accumulations of material in SD-OCT imaging and this was confirmed in the AO images. Defects in the overlying ellipsoid zone band as seen by SD-OCT were associated with SDD but not conventional drusen. The mean +/- standard deviation cone density was 8964+/-2793 cones/mm(2) between the SDD and 863+/-388 cones/mm(2) over the SDD, a 90.4% numerical reduction. By comparison the mean cone packing density was 9838+/-3723 cones/mm(2) on conventional drusen and 12 595+/-3323) cones/mm(2) between them, a 21.9% numerical reduction. The difference in cone density reduction between the two lesion types was highly significant (P <0.001). CONCLUSIONS: The pseudodrusen in these eyes correlated with subretinal deposition of material in multiple imaging modalities. Reduced visibility of cones overlying SDD in the AO images can be because of several possible causes, including a change in their orientation, an alteration of their cellular architecture, or absence of the cones themselves. All of these explanations imply that decreased cone photoreceptor function is possible, suggesting that eyes with pseudodrusen appearance may experience decreased retinal function in age-related macular degeneration independent of choroidal neovascularization or retinal pigment epithelial atrophy.

The authors report the in vivo visualization through multimodal imaging of silicone oil in the vitreous cavity, optic nerve, and retina of a patient 11 years after surgical removal of the main tamponade. Contact B-scan ultrasonography revealed countless small echogenic particles in the vitreous cavity and a hyperreflective structure within the optic nerve head. Swept-source optical coherence tomography showed multiple round hyporeflective spaces within the substance of the prelaminar optic nerve head. Adaptive optics imaging revealed numerous particles in the optic nerve head and within the retina in the same plane as the photoreceptors, with similar size and shape to the silicone oil droplets in the vitreous cavity. The authors hypothesize that in this case, the silicone oil droplets in the retina and optic nerve head may be associated with the patient's otherwise unexplained progressive visual loss.

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 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 analyze the outer retinal layers using spectral domain optical coherence tomography (SD-OCT) in patients with cone-rod dystrophy. METHODS: The diagnosis of cone-rod dystrophy was determined by primary cone involvement or concomitant loss of both cones and rods. Electroretinography showed implicit time shift at 30-Hz flicker response and prevalent decrease of photopic over scotopic responses. Using SD-OCT, the outer retina was retrospectively evaluated in 24 eyes of 12 patients with cone-rod dystrophy. From the innermost to the outermost, the four studied hyperreflective outer retinal bands were labeled Band 1, the external limiting membrane; Band 2, the ellipsoid zone; Band 3, the interdigitation zone between the cone outer segments and the apical processes of the retinal pigment epithelium; and Band 4, the retinal pigment epithelium complex. RESULTS: The mean age of study patients was 30 years, and the median visual acuity was 20/30. A ring maculopathy appearance involving the fovea area was observed in all study eyes. There was an absence of interdigitation zone in the entire length of SD-OCT scan, including the foveal area, in all 24 study eyes. Outside the foveal area, the external limiting membrane and ellipsoid zone were intact in all study eyes. The intensity of the ellipsoid zone was decreased in the entire length of SD-OCT scan in all study eyes. Within the foveal area, there was loss of the external limiting membrane and ellipsoid zone in 20 (83%) and 22 eyes (92%), respectively. The retinal pigment epithelium complex was identified in all study eyes. None of the study eyes revealed cystoid macular edema. CONCLUSION: SD-OCT scans demonstrated complete absence of the interdigitation zone in patients with cone-rod dystrophy. Consistent with the known histology of animal models of cone dystrophy, this finding may represent abnormal outer retinal morphology, including an absence of the outer segments themselves or a defective or absent interdigitation between the apical processes of the retinal pigment epithelium with the cone outer segments.

PURPOSE: To investigate the long-term clinical course of eyes with pseudodrusen appearance caused by subretinal drusenoid deposits. METHODS: Eyes from the original study identifying subretinal deposits of material as the cause of pseudodrusen appearance were evaluated in a retrospective study of outer retinal morphology. The distance between the inner plexiform layer and the retinal pigment epithelium, termed the photoreceptor length, was measured from optical coherence tomography approximately 2 mm superior to the fovea at baseline and at follow-up visits. The choroidal thickness was measured directly under this retinal area. RESULTS: Of the 21 eyes available for follow-up, 9 (42.9%) eventually developed choroidal neovascularization over a mean 2.9-year follow-up period. Regression of subretinal drusenoid deposits was seen in 9 eyes (42.9%) as well. Those with regression of subretinal drusenoid deposits had a decrease in the photoreceptor length with the final photoreceptor length being 74.4% of the initial length (P < 0.001). In eyes with regression, the underlying choroid was 81.4% of its initial value (P = 0.01) at the final follow-up. Eyes with regression also showed loss of the ellipsoid band. Eyes without regression had no change in photoreceptor length, choroidal thickness, or outer retinal architecture. CONCLUSION: Eyes with regression of subretinal drusenoid deposits develop outer retinal atrophy and loss of the underlying choroidal thickness. This finding seems common in eyes having pseudodrusen and represents a late form of age-related macular degeneration that is not in current classification systems. Further study is needed to determine both the true prevalence and the effects on visual function.

Seventy percent of the blood flow to the eye goes to the choroid, a structure that is vitally important to the function of the retina. The in vivo structure of the choroid in health and disease is incompletely visualized with traditional imaging modalities, including indocyanine green angiography, ultrasonography, and spectral domain optical coherence tomography (OCT). Use of new OCT modalities, including enhanced depth imaging OCT, image averaging, and swept-source OCT, have led to increased visualization of the choroidal anatomy. The correlation of these new anatomical findings with other imaging modalities results increases understanding of many eye diseases and recognises of new ones. The status of the choroid appears to be a crucial determinant in the pathogenesis of diseases such as age-related choroidal atrophy, myopic chorioretinal atrophy, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. Extension of these imaging techniques has provided insights into abnormalities of the sclera and optic nerve. Future developments will include blood flow information, 3D rendering of various ocular structures, and the ability to evaluate changes in 3D structural information over time (4D imaging).

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.

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.