Faculty Bibliography

PURPOSE: To describe a series of patients exhibiting annular retinal pigment epithelial (RPE) lesions in the context of chronic central serous chorioretinopathy. Design; Retrospective comparative case series. METHODS: Consecutive patients with chronic central serous chorioretinopathy were identified from the clinical practices of 3 retina specialists. A subset of patients exhibiting annular RPE lesions on fundus autofluorescence was included for chart review and examination of multimodal imaging (study group). Patients with alternative etiologies for neurosensory detachment or pigment epitheliopathy were excluded. A second consecutive cohort of patients, with acute central serous chorioretinopathy, was also examined for the presence of annular lesions (comparative group). RESULTS: Sixty-seven patients with chronic central serous chorioretinopathy were identified. Fourteen eyes of 12 patients exhibited annular lesions (study eyes). Mean visual acuity of study eyes was 20/27 (logMAR 0.13, SD 0.11). Annular lesions were composed of hyperautofluorescent stellate lesions arranged in an open or closed ring with intervening foci of punctate hypoautofluorescence. Optical coherence tomography showed RPE hyperplasia at the perimeters of annular lesions with loss of ellipsoid reflectivity and preserved RPE at the lesion center. Annular lesions were confined to the posterior poles and appeared to have developed at the margins of chronic neurosensory detachment. Forty-three eyes of 30 patients with acute central serous chorioretinopathy comprised the comparative group and none of these eyes exhibited annular lesions. CONCLUSIONS: Annular lesions occur in up to a fifth of patients with chronic central serous chorioretinopathy but carry a relatively good visual prognosis. Curvilinear RPE figures and demarcation lines are seen in various retinal conditions but the characteristics of annular lesions described here suggest that they are specific to chronic central serous chorioretinopathy.

Purpose: To assess outer retinal tubulation (ORT) morphology from spectral-domain optical coherence tomography (SD-OCT) volumes and donor eye histology, analyze ORT reflectivity, and estimate the number of cones surviving in ORT. Methods: In SD-OCT volumes from nine patients with advanced AMD, ORT was analyzed en face and in B-scans. The hyperreflective ORT border in cross-section was delineated and surface area calculated. Reflectivity was compared between ORT types (Closed, Open, Forming, and Branching). A flatmount retina from a donor with neovascular AMD was labeled to visualize the external limiting membrane that delimits ORT and allow measurements of cross-sectional cone area, center-to-center cone spacing, and cone density. The number of cones surviving in ORT was estimated. Results: By en face SD-OCT, ORT varies in complexity and shape. Outer retinal tubulation networks almost always contain Closed cross-sections. Spectral-domain OCT volumes containing almost exclusively Closed ORTs showed no significant direction-dependent differences in hyperreflective ORT border intensity. The surface areas of partial ORT assessed by SD-OCT volumes ranged from 0.16 to 1.76 mm2. From the flatmount retina, the average cross-sectional area of cone inner segments was 49.1 +/- 7.9 mum2. The average cone spacing was 7.5 +/- 0.6 mum. Outer retinal tubulation cone density was 20,351 cones/mm2. The estimated number of cones in ORT in a macula ranged from 26,399 to 186,833 cones, which is 6% to 44% of the cones present in a healthy macula. Conclusions: These first estimates for cone density and number of cones surviving in ORT suggest that ORT formation considerably distorts the photoreceptor mosaic. Results provide additional insight into the reflectivity characteristics and number of ORT cones observable in living patients by SD-OCT, as cones persist and disease progresses.

PURPOSE: To describe the natural course, visual outcomes and anatomic changes and provide histological correlates in eyes with intraretinal hyperreflective foci associated with acquired vitelliform lesions. DESIGN: Retrospective cohort study and imaging-histology correlation in a single donor eye. METHODS: Participants: Patients with intraretinal hyperreflective foci and acquired vitelliform lesions from two tertiary referral centers were evaluated from January 2002-January 2014. MAIN OUTCOME MEASURES: The chronology of clinical and imaging features of retinal anatomic changes and the pattern of intraretinal hyperreflective foci migration were documented using spectral-domain optical coherence tomography (OCT). One donor eye with intraretinal hyperreflective foci was identified in a pathology archive by ex vivo OCT and was studied with high-resolution light and electron microscopic examination. RESULTS: Intraretinal hyperreflective foci were associated with acquired vitelliform lesions in 25 of 254 eyes (9.8%) with a strong female preponderance (86% of patients). Focal disruptions to the ellipsoid zone and external limiting membrane overlying the acquired vitelliform lesions were observed prior to the occurrence of intraretinal hyperreflective foci in 75% of cases. Histological evaluation showed that intraretinal hyperreflective foci represent cells of retinal pigment epithelium origin that are similar to those found in the vitelliform lesions themselves and contain lipofuscin granules, melanolipofuscin granules and melanosomes. The occurrence of intraretinal hyperreflective foci was not a significant determinant of final visual acuity (p=0.34), but development of outer retinal atrophy was significant (p=0.003). CONCLUSIONS: Intraretinal hyperreflective foci associated with acquired vitelliform lesions is of retinal pigment epithelium origin, and the natural course and functional changes are described.

PURPOSE: To correlate clinical manifestations with choroidal morphology in pachychoroid disorders, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, and polypoidal choroidal vasculopathy, using en face swept-source optical coherence tomography (OCT). METHODS: Patients with pachychoroid spectrum diagnoses were identified nonconsecutively through a review of charts and multimodal imaging. Each eye was categorized as uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, or polypoidal choroidal vasculopathy. All patients included in this series then underwent bilateral swept-source OCT. RESULTS: Sixty-six eyes of 33 patients were included. Numbers assigned to diagnostic categories were 8 uncomplicated pachychoroid, 13 pachychoroid pigment epitheliopathy, 27 central serous chorioretinopathy, 15 pachychoroid neovasculopathy, and 3 polypoidal choroidal vasculopathy. One eye was classified as normal. Swept-source OCT choroidal thickness maps confirmed increased thickness under the areas of pachychoroid pigment epitheliopathy, central serous chorioretinopathy, type 1 NV (pachychoroid neovasculopathy), or polyps (polypoidal choroidal vasculopathy). En face swept-source OCT showed dilated outer choroidal vessels in all eyes. In several eyes with a chronic disease, focal choriocapillaris atrophy with inward displacement of deep choroidal vessels was noted. CONCLUSION: Although clinical manifestations of pachychoroid spectrum disorders vary considerably, these entities share morphologic findings in the choroid, including increased thickness and dilated outer choroidal vessels. En face swept-source OCT localizes these changes to disease foci and shows additional findings that may unify our understanding of disease pathogenesis.

PURPOSE: To report the association of pure type 2 neovascularization (NV) in age-related macular degeneration occurring almost exclusively in patients with reticular pseudodrusen. METHODS: An observational retrospective cohort study of all eyes receiving antivascular endothelial growth factor therapy for newly diagnosed neovascular age-related macular degeneration by a single practitioner over a 6-year period. Only patients with treatment-naive, pure type 2 NV who also had either pre-neovascular imaging of the study eye or imaging of a nonneovascular fellow eye available to determine baseline characteristics including drusen type and choroidal thickness were incuded. RESULTS: Of 694 patients treated for neovascular age-related macular degeneration, only 8 met the inclusion criteria with pure type 2 NV. Of these, 7 (88%) had exclusively reticular pseudodrusen (5 in the nonneovascular fellow eye, 2 in the study eye before developing NV). Six (75%) patients in the affected neovascular eye and 6 (75%) in the fellow nonneovascular eye had choroidal thickness <120 mum. Mean follow-up was 46 months (range, 3.0-63.3). Best-corrected vision improved from 20/89 (range, 20/30-20/796) at baseline to 20/60 (range, 20/20-20/399) at last follow-up. CONCLUSION: Pure type 2 NV is rare in age-related macular degeneration, occurring almost exclusively in patients with reticular pseudodrusen and thin choroids.

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.