Faculty Bibliography

IMPORTANCE Optical coherence tomography (OCT) abnormalities of age-related macular degeneration (AMD) have not been fully characterized because of the complex morphology and a lack of correlative histologic studies. Expansion of our ability to interpret increasing attributes brings us closer to the goal of in vivo histologic analysis of the eye by OCT. OBJECTIVE To describe a new outer retinal finding of AMD using spectral-domain (SD) OCT and suggest histopathologic correlates. DESIGN, SETTING, AND PARTICIPANTS Twenty-five eyes of 16 patients with AMD with severe atrophy due to either choroidal neovascularization (CNV) or geographic atrophy (GA) and 53 donor eyes of 53 patients with late AMD were included. Imaging studies were conducted at a referral retinal practice and histopathology was done at a university research laboratory. EXPOSURES Findings in the outer retina were evaluated in SD-OCT images in eyes with atrophy of the retinal pigment epithelium (RPE) and compared with histopathologic findings in eyes with GA or CNV that also showed loss of the RPE. MAIN OUTCOMES AND MEASURES Spectral-domain OCT and histologic characteristics of the outer retina. RESULTS The mean (SD) age of the 16 patients was 82.7 (7.9) years. Twenty eyes had CNV and 5 eyes had GA. The mean best-corrected visual acuity was 0.800 logMAR (interquartile range, 0.350-1.000 logMAR), a Snellen equivalent of 20/126. A curvilinear hyperreflective density was identified above the Bruch membrane line within the atrophic area in the SD-OCT images. At the internal border, the material was contiguous with the outer portion of the RPE band. Below the material was a relatively hyporeflective space. The material was thrown into folds in cases with atrophy following CNV or was seen as a sheet with numerous bumps in eyes with GA. Review of histopathologic findings of eyes with advanced GA and CNV revealed a rippled layer of basal laminar deposits in an area of RPE atrophy that was located in the same level as the curvilinear line seen in the OCT images. CONCLUSIONS AND RELEVANCE We have described a new entity, termed outer retinal corrugations, which may correspond to histological findings of basal laminar deposits, extracellular deposits that persist in eyes with late AMD. Observation of this undulating band does not necessarily mean there is exudation or leakage; as a consequence, these patients do not need treatment based on this solitary finding.

PURPOSE:: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS:: Retrospective observational case series of patients with chronic fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding spectral domain optical coherence tomography scans of chronic PEDs were studied in detail over multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic features were identified, and then correlated with visual outcome. RESULTS:: Thirty-eight eyes of 34 patients with fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50 (range, 20/20-20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF injections (median, 23.0; range, 3-70) administered over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment epithelium. Additionally, 25 eyes demonstrated a hyporeflective cavity separating the choroidal neovascularization complex from the underlying choroid. CONCLUSION:: Chronic fibrovascular PEDs receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex of highly organized, layered, hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process is suppressed within the sub-retinal pigment epithelium space by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor population through preservation of the retinal pigment epithelium.

Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men. We studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC cases and 1400 matched controls. The expression of cadherin 5 (CDH5), the major cell-cell adhesion molecule in vascular endothelium, was down-regulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of 4 common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; p=0.00012; OR=1.5; 95%C.I. [1.2;1.8], and p=0.0014; OR=0.70; 95%C.I. [0.57;0.87], respectively. A common haplotype was present in 25.4% male CSC cases and in 35.8% controls (p=0.0002; OR=0.61, 95%CI [0.47-0.79]). We propose that genetically pre-determined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population

PURPOSE: To subclassify pseudodrusen based on their appearance in the multimodal imaging. DESIGN: Retrospective, observational series. METHODS: The color fundus photographs and infrared scanning laser ophthalmoscope (IR-SLO) images of patients with pseudodrusen were evaluated along with spectral domain optical coherence tomography (SD-OCT) by masked readers. Distinct types of pseudodrusen could be differentiated. RESULTS: There were 140 eyes of 93 patients with a mean age of 82.4 years. Multimodal imaging analysis showed 3 subtypes of pseudodrusen. One principal type was an orderly array of whitish discrete accumulations principally located in the perifovea, termed dot pseudodrusen. They appeared as hyporeflective spots, often with a target configuration, in IR-SLO images. The second type was interconnected bands of yellowish-white material forming a reticular pattern, called ribbon pseudodrusen, which were located in the perifovea. This subtype was faintly hyporeflective in IR-SLO imaging. Dot pseudodrusen were detected more commonly with IR-SLO imaging than color photography (P=. 014) and ribbon pseudodrusen were seen more frequently in color than in IR-SLO images (P<. 001). An uncommon third type of pseudodrusen, yellow-white globules primarily located peripheral to the perifoveal region, appeared hyperreflective in IR-SLO and were called peripheral pseudodrusen. All 3 types were seen as subretinal drusenoid deposits by SD-OCT. CONCLUSION: Pseudodrusen may be classified into at least 3 categories, each with optimal methods of detection and only one that formed a reticular pattern. These findings suggest pseudodrusen could contain differing constituents and therefore, may vary in conferred risk for progression to advanced age-related macular disease.

PURPOSE: To assess the visual and anatomic outcomes of central serous chorioretinopathy (CSC) after verteporfin photodynamic therapy (PDT). DESIGN: Retrospective case series. PARTICIPANTS: Patients with CSC who underwent PDT. METHODS: Members of the Macula Society were surveyed to retrospectively collect data on PDT treatment for CSC. Patient demographic information, PDT treatment parameters, fluorescein angiographic information, optical coherence tomography (OCT) metrics, pre- and post-treatment visual acuity (VA), and adverse outcomes were collected online using standardized forms. MAIN OUTCOME MEASURES: Visual acuities over time and presence or absence of subretinal fluid (SRF). RESULTS: Data were submitted on 265 eyes of 237 patients with CSC with a mean age of 52 (standard deviation [+/- 11]) years; 61 were women (26%). Mean baseline logarithm of the minimum angle of resolution (logMAR) VA was 0.39+/-0.36 (20/50). Baseline VAs were >/=20/32 in 115 eyes (43%), 20/40 to 20/80 in 97 eyes (37%), and /=3 lines in <1%, 29%, and 48% of eyes with baseline VA >/=20/32, 20/40 to 20/80, and 0.01). Complications were rare: Retinal pigment epithelial atrophy was seen in 4% of patients, and acute severe visual decrease was seen in 1.5% of patients. CONCLUSIONS: Photodynamic therapy was associated with improved VA and resolution of SRF. Adverse side effects were rare.

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.