Faculty Bibliography

PURPOSE/OBJECTIVE:To compare clinical, optical coherence tomography (OCT), and fundus autofluorescence (FAF) characteristics of peripapillary versus (vs.) macular variants of combined hamartoma of the retina and retinal pigment epithelium (combined hamartoma). DESIGN/METHODS:Retrospective observational, comparative case series METHODS:SETTING: Multicentre collaborative study STUDY POPULATION: 50 eyes with a clinical diagnosis of combined hamartoma OBSERVATIONAL ANALYSIS: A comparative analysis of color fundus photographs (CFPs), OCT and FAF was performed for peripapillary and macular variants of combined hamartoma. MAIN OUTCOME MEASURES/METHODS:Pigmentation and OCT features of macular and peripapillary combined hamartoma RESULTS: The review of imaging from 50 eyes of 49 patients diagnosed with combined hamartoma identified 18 (36%) peripapillary lesions, 27 (54%) macular lesions and 5 (10%) peripheral lesions. A comparative analysis of peripapillary vs. macular combined hamartoma identified differences in the following features: lesion pigmentation on CFPs corresponding to hypoautofluorescent FAF (88% vs. 0%, p<0.001) and OCT features of full thickness involvement (88% vs. 3%, p<0.001), preretinal fibrosis (27% vs. 81%, p<0.001), maxi peaks (5% vs. 88%, p<0.001), intraretinal cystoid spaces (72% vs. 40%, p<0.038), outer plexiform layer involvement (5% vs. 96%, p<0.001), ellipsoid zone disruption (83% vs. 3%, p<0.001), RPE disruption (77% vs. 3%, p<0.001) and choroidal neovascularization (16% vs. 0%, p=0.028). CONCLUSIONS:This comparative analysis identified a higher frequency of pigmentation with hypoautofluorescence, full thickness retinal involvement, intraretinal cystoid spaces, ellipsoid zone disruption, RPE disruption and choroidal neovascularization in peripapillary combined hamartoma. These findings suggest that lesions occurring near or at the optic nerve are associated with a more severe degree of pigmentary changes and retinal disruption than those located in the macula.

PURPOSE: To describe a patient with a presumed retinal pigment epithelium (RPE) tumor originating from unilateral RPE dysgenesis. METHODS: Case report. RESULTS: A 30-year-old woman with an unremarkable medical and ocular history was referred for an evaluation of progressive central metamorphopsia in her left eye. Visual acuity was 20/20 in her right eye and 20/25 in her left eye. Funduscopic examination of the left eye revealed an elevated mass within an area of unilateral RPE dysgenesis showing hyperpigmentation and hypopigmentation with scalloped margins. Fundus autofluorescence of the lesion showed a marginal pattern of hyperautofluorescence and hypoautofluorescence that was the inverse of the fluorescein angiography pattern. A well-circumscribed subretinal mass appeared to originate from the unilateral RPE dysgenesis lesion with surrounding subretinal fluid extending beneath the fovea. Ultrasonography showed medium-to-high reflectivity of the mass with no evidence of choroidal involvement. Optical coherence tomography showed a subretinal hyporeflective mass consistent with a tumor of RPE origin. The tumor appeared to invade the overlying retina where fluorescein angiography showed hyperfluorescent leakage and OCT angiography showed retinal vascular deformation. Indocyanine green angiography showed no evidence of choroidal neovascularization. Findings in the right fundus were normal. Over a 5-month follow-up, intravitreal anti-vascular endothelial growth factor therapy induced a resolution of subretinal exudation and modest reduction in tumor thickness. CONCLUSION: To the authors' knowledge, this is the first report of a presumed RPE tumor described as originating from unilateral RPE dysgenesis. Multimodal imaging was crucial for establishing the diagnosis and showing that the patient's visual symptoms were a product of the exudation produced by the tumor's invasion of the retina.

PURPOSE/OBJECTIVE:In an eye with geographic atrophy (GA) secondary to age-related macular degeneration, we correlated ex vivo histologic features with findings recorded in vivo using optical coherence tomography (OCT), near-infrared reflectance imaging, and fundus autofluorescence. METHODS:In the left eye of an 86-year-old white woman, in vivo near-infrared reflectance and eye-tracked OCT B-scans at each of 6 clinic visits and a baseline fundus autofluorescence image were correlated with ex vivo - high-resolution histologic images of the preserved donor eye. RESULTS:Clinical imaging showed a small parafoveal multilobular area of GA, subfoveal soft drusen, refractile drusen, hyperreflective lines near the Bruch membrane, subretinal drusenoid deposit (reticular pseudodrusen), and absence of hyperautofluorescent foci at the GA margin. By histology, soft drusen end-stages included avascular fibrosis with highly reflective cholesterol crystals. These accounted for hyperreflective lines near the Bruch membrane in OCT and plaques in near-infrared reflectance imaging. Subretinal drusenoid deposit was thick, continuous, extracellular, extensive outside the fovea, and associated with distinctive retinal pigment epithelium dysmorphia and photoreceptor degeneration. A hyporeflective wedge corresponded to ordered Henle fibers without cellular infiltration. The external limiting membrane descent, which delimits GA, was best visualized in high-quality OCT B-scans. Retinal pigment epithelium and photoreceptor changes at the external limiting membrane descent were consistent with our recent histologic survey of donor eyes. CONCLUSION/CONCLUSIONS:This case informs on the extent, topography, and lifecycle of extracellular deposits. High-quality OCT scans are required to reveal all tissue features relevant to age-related macular degeneration progression to GA, especially the external limiting membrane descent. Histologically validated signatures of structural OCT B-scans can serve as references for other imaging modalities.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PURPOSE/OBJECTIVE:To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). DESIGN/METHODS:Retrospective, longitudinal study SUBJECTS: One-hundred and thirty-three subjects (217 eyes) with chronic CSC. METHODS:A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF) and optical coherence tomography (OCT). MAIN OUTCOME MEASURES/METHODS:Best corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1, 5 and 10-year follow-up visits, and causes of vision loss at final visit. RESULTS:Data from 6,228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 males (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least one eye and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1 or 5-year follow-up visits (both p≥0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (p=0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization, outer retinal disruption on OCT and FAF changes were associated with poorer vision at final visit (all p≤0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (p=0.001). CONCLUSION/CONCLUSIONS:Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.

The authors report a case of nonconforming focal choroidal excavation (FCE) identified in an eye following blunt, nonperforating trauma to the globe. Multimodal imaging was undertaken including color fundus photographs, enhanced depth imaging optical coherence tomography, fluorescein angiography, and fundus autofluorescence. This shows that FCE may result from blunt ocular trauma. The authors hypothesize that loss of structural support provided by an intact Bruch's membrane may be a key factor in precipitating the specific morphological changes associated with FCE occurring in a range of clinical settings. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:187-190.].

PURPOSE/OBJECTIVE:To correlate multimodal retinal imaging with high-resolution epoxy resin histologic analysis aligned to in vivo tomograms in a patient with exudative aneurysmal type 1 (AT1) neovascularization and hemorrhage secondary to age-related macular degeneration (AMD). DESIGN/METHODS:Case study and clinicopathologic correlation. PARTICIPANT/METHODS:An 84-year-old man of European descent with AT1 neovascularization secondary to AMD with a 6-year follow-up with combined antiangiogenic and photodynamic therapy. METHODS:Multimodal imaging from each clinic visit, including fluorescein angiography, indocyanine green angiography, and OCT, was correlated with ex vivo OCT and high-resolution histologic images of the donor eye, aligned to the en face images showing hemorrhage and exudation. MAIN OUTCOME MEASURES/METHODS:Location of the branching vascular network and the aneurysmal vascular dilations in angiography, correlated with histologic findings. RESULTS:Clinically, a hemorrhagic detachment of the retinal pigment epithelium (RPE) in the macular area was associated with an AT1 neovascularization extending near the optic nerve head, where the choroid, which was thin overall, was extremely thin. Resolution of the hemorrhage accompanied by progressive macular atrophy and internal changes in the reflectivity of the RPE detachment were observed. Histologic analysis suggested a physical continuity from a hyalinized choroidal artery to a capillary bed (branching vascular network) in the sub-RPE-basal lamina (BL) space without visualization of aneurysmal dilations. CONCLUSIONS:Clinicopathologic correlation of AT1 neovascularization from an intact treated eye with dye-based angiographic and OCT scans supports the proposed nomenclature of AT1 neovascularization over polypoidal choroidal vasculopathy. We described continuity of the sub-RPE-BL branching vascular network with choroidal arteries and histologic correlates of common OCT signatures of neovascular AMD. The thinness of choroid in this patient of European descent contrasts with that reported for Asian populations, in which AT1 neovascularization is associated commonly with pachychoroid disease characteristics. This case reinforces the different manifestations of AT1 neovascularization across and within diverse ethnicities and diseases.

Pachychoroid is a relatively novel concept describing a phenotype characterized by attenuation of the choriocapillaris overlying dilated choroidal veins, and associated with progressive retinal pigment epithelium dysfunction and neovascularization. The emphasis in defining pachychoroid-related disorders has shifted away from simply an abnormally thick choroid (pachychoroid) toward a detailed morphological definition of a pathologic state (pachychoroid disease) with functional implications, which will be discussed in this review. Several clinical manifestations have been described to reside within the pachychoroid disease spectrum, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome. These conditions all exhibit the characteristic choroidal alterations and are believed to represent different manifestations of a common pathogenic process. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical and imaging features, management considerations, as well as current understanding of pathogenesis of these disorders within the context of the recent findings related to pachychoroid disease.