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Purpose Macular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with antiangiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histologic analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD. Design Case study and clinicopathologic correlation. Participant A White woman in whom age-related macular degeneration (AMD) findings of inactive subretinal fibrosis (right eye) were followed for 9 years using FAF and OCT, with no detectable subretinal fluid or other recurrent exudation and no intravitreal injections before her death at age 90 years. Methods The right eye was preserved 6.25 hours after death, postfixed in osmium tannic acid paraphenylenediamine, and prepared for submicrometer epoxy resin sections (n = 115), with 19 matched to clinical OCT B-scans. Main Outcome Measures Light microscopic morphology of a hyperautofluorescent (hyperFAF) area due to prior exudation (“floodplain” hyperFAF), hypoautofluorescent (hypoFAF) spots of MA, and areas of unremarkable FAF. Results Floodplain hyperFAF was visible throughout the 9 years of follow-up, with several hypoFAF atrophic spots expanding within it over time. The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic yet continuous RPE in histology. The hypoFAF spots inside the floodplain corresponded to complete RPE and outer retinal atrophy (cRORA) on OCT and loss of both photoreceptors and RPE in histology. In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer. Conclusions This direct clinicopathologic correlation for FAF imaging is the first for nAMD. Fundus autofluorescence is a projection image that involves optical signal modulation by photoreceptors as well as emission signal sources in RPE. Hyperautofluorescence due to an exudative floodplain signifies loss of photoreceptors over continuous RPE. Hypoautofluorescence in MA signifies loss of both cell layers. For maximal value, fundus autofluorescence imaging should be interpreted with the multilayer perspective provided by OCT. Prevention of exudation in nAMD may preserve photoreceptors.

A panel of imaging experts was assembled to review neovascular age-related macular degeneration optical coherence tomography angiography descriptors published to date, and test agreement on use of these terms, which was found to be low. Optical coherence tomography angiography (OCTA) has been used to identify and characterize macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). 1 , 2 , 3 , 4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment. 1 , 2 , 3 , 4 , 5 , 6 The proliferation of studies however has resulted in an OCTA terminology that has been variable and inconsistent. To address inconsistency of nomenclature and allow harmonization, a multidisciplinary panel of retinal imaging experts with a history of relevant research contributions to the field was assembled with the purpose of reviewing published terminology and to recommend a reduced list of key terms pertinent to OCTA. The group was called UNICORN, because of its ultimate goal of generating a UNIfied COmmentary of the committee of inteRnational experts on the nomenclature for Neovascular AMD in OCTA. In this report we describe the first steps, which included a review of OCTA descriptors of neovascular AMD (nAMD) published to date, and an exercise that tested agreement of these terms among retinal imaging experts. Prior to the first UNICORN meeting, a non-systematic review of the literature was performed, using the search terms “optical coherence tomography angiography” or “OCT angiography” or “OCT-A”, AND “neovascular macular degeneration” or “neovascular age-related macular degeneration” or “neovascular AMD” or “nAMD” or “wet age-related macular degeneration” or “wet AMD” or “wet ARMD”. A dictionary of OCTA descriptors relating to the features of MNV in AMD was generated and circulated to the panel.

Introduction: This retrospective analysis assessed geographic atrophy (GA) progression in fellow eyes from the Proxima B trial intermediate age-related macular degeneration (iAMD) subcohort using high-resolution multimodal imaging anchored on optical coherence tomography (OCT). Methods: Thirty-two patients from the Proxima B iAMD subcohort were assessed; all had GA with no macular neovascularization (MNV) in the contralateral eye. Imaging data, including color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence (FAF), and spectral-domain OCT, were obtained. Features preceding progression/conversion to advanced AMD (drusen, reticular pseudodrusen [RPD], MNV, incomplete/complete retinal pigment epithelium and outer retinal atrophy [iRORA/cRORA]) were assessed. Results: Of 30 fellow eyes with available follow-up images, 12 converted to GA (FAF), 2 converted to MNV, and 16 were nonconverters during the review period (median: 17.8 months). iRORA/cRORA features (present in all converters at baseline) were identified on OCT in eyes that progressed to GA. Median time interval from iRORA to cRORA and from cRORA to GA was 7 months each. GA development/progression was either drusen- or RPD-associated (n = 6 each). Eyes with baseline RPD showed faster GA progression versus eyes with drusen (1.49 vs. 0.38 mm2/year). Conclusions: RPD presence was associated with rapid GA lesion enlargement and may provide an early indication of faster GA progression.

Purpose To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). Design Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials. Participants Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n = 32). Methods Changes in visual function and imaging/anatomic parameters were evaluated over time using a mixed model for repeated measurement accounting for key baseline characteristics. Main Outcome Measures Prespecified end points included change in GA area from baseline, best-corrected visual acuity (BCVA) score assessed by Early Treatment Diabetic Retinopathy Study (ETDRS), and visual acuity under low-luminance (LLVA). Results At 24 months, adjusted mean (standard error) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). Progression of GA was greater in patients with baseline nonsubfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (standard error) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months were −13.88 (1.40) and −7.64 (1.20) in Proxima A, −9.49 (1.29) and −7.57 (1.26) in Proxima B fellow eye CNV cohort, and −11.48 (3.39) and −8.37 (3.02) in Proxima B fellow eye intermediate AMD cohort, respectively. Conclusions The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.

BACKGROUND: To analyse cellular and spatiotemporal factors of neurodegeneration and gliosis in a patient with submacular haemorrhage (SMH) secondary to type 1 macular neovascularization in neovascular age-related macular degeneration (nAMD). METHODS: This is a case study and clinicopathologic correlation of an 84-year-old white man with nAMD treated with antiangiogenic drugs and photodynamic therapy during a 6-year follow-up. Eyes were recovered for histology 8.23 h after death. In vivo multimodal imaging including optical coherence tomography (OCT) and en face modalities was compared with ex vivo OCT and high-resolution histologic images, using a custom image registration procedure. SMH components were defined (intraretinal, subretinal, sub-retinal pigment epithelium (RPE), and dehemoglobinized blood). Neurodegenerative changes in each of these areas were described. One anonymous donor eye with haemorrhagic nAMD was also reviewed as a comparator. RESULTS: By in vivo OCT, progressive resolution of the haemorrhage and gradual transformation of sub-RPE fluid to fibrous hyperreflective tissue, progressive macular atrophy, and variation in external limiting membrane (ELM) visibility were observed. Histology showed intense photoreceptor loss with preservation and self-adhesion of macular Müller glia resulting in ELM condensation. The comparator eye exhibited shed cone inner segments among subretinal erythrocytes. CONCLUSION: This is the most detailed clinicopathologic correlation of nAMD with SMH resolution to date, and the first in the OCT era. Our results reveal profound macular neurodegeneration and gliosis, signified by condensed ELM, soon after haemorrhage begins. Intensified OCT reflectivity of the ELM, an important retinal barrier, has potential as a biomarker for severe photoreceptor loss and gliosis.

PURPOSE To report a case of acute zonal occult outer retinopathy in which adaptive optics (AO) facilitated visualization of abnormal photoreceptors previously thought to be in an area of normal retina on conventional optical coherence tomography (OCT). METHODS Case report. RESULTS A 51-year-old woman presents with 11-month history of photopsias and scotoma in the temporal visual field of her left eye. Ocular imaging including fluorescein angiography, fundus autofluorescence and OCT suggested the diagnosis of acute zonal occult outer retinopathy in the left eye. Adaptive optics optical coherence tomography (AO-OCT) revealed photoreceptor abnormalities not previously identified in conventional OCT, in areas apparently normal on multimodal imaging. On enface and cross-sectional AO-OCT, round and evenly spaced hyperreflectivity corresponding to normal cone mosaic (Pattern 1) was adjacent to unevenly and disrupted cone hyperreflectivity (Pattern 2) and areas with hyporeflectivity or no cone reflectivity (Pattern 3). Cross-sectional AO-OCT of Patterns 2 and 3 also revealed attenuation of ellipsoid zone with loss of interdigitation zone. CONCLUSION Adaptive optics OCT documented cone photoreceptors in finer details than conventional OCT and revealed early changes in a patient with acute zonal occult outer retinopathy, in an area of the retina thought to be normal on conventional multimodal imaging. These findings may provide important insight into pathogenesis and progression of the disease.

To correlate in vivo imaging to histology in an eye with macular atrophy owing to age-related macular degeneration (AMD; complete retinal pigment epithelium [RPE] and outer retinal atrophy [cRORA]) to evaluate the utility of new optical coherence tomography (OCT) suggested by previous histology.Case study with clinicopathologic correlation.In vivo eye-tracked cross-sectional OCT scans at 13 and 8 months before death were compared to postmortem histopathology. On OCT, the atrophy border was identified as either the descent of the external limiting membrane (ELM) toward the Bruch membrane (BrM) (representing gliosis) or the presence of choroidal hypertransmission (representing lack of shadowing by RPE). Thicknesses of RPE, basal laminar deposit (BLamD), and BrM were measured at 500 and 100 μm on the nonatrophic and atrophic sides of these borders, on in vivo eye-tracked OCT and histology matched to the same location.In all OCT scans, the ELM descent was visible. The RPE-BLamD band significantly thickened toward it (P.005), over time (P = .015 and P = .043, at 500 and 100 μm, respectively). On OCT, the ELM descent delineated a smaller atrophic area than did hypertransmission. RPE-BLamD thicknesses manually measured on OCT overestimated histologic thicknesses. BrM visibility varied with RPE status.Visible on OCT, the ELM descent is a histopathologic atrophy border supporting new terminology of cRORA, whereas hypertransmission reveals RPE degeneration. RPE-BLamD thickening across the macula, toward the atrophy and over time is confirmed. The presence of gliosis and thick RPE-BLamD suggests that macular atrophy is a late stage in disease progression, encouraging anatomic endpoints at earlier AMD stages than atrophy enlargement.

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea. Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggests that specific characteristics may be important in predicting disease progression and outcomes. This review synthesizes current understanding of GA progression in AMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics. In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement are discussed. Overall, GA progression rates reported in the literature for total study populations range from 0.53 to 2.6 mm2/year (median, ∼1.78 mm2/year), assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging. Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multifocality, FAF patterns, and fellow eye status. Because best-corrected visual acuity does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including microperimetry, low-luminance visual acuity, reading speed assessments, and patient-reported outcomes. Understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.

Purpose To analyse morphologic features of the choroid in Non-pathological myopic eyes using spectral-domain (SD) optical coherence tomography (OCT). Methods Retrospective analysis of enhanced depth SD-OCT images of Non-pathological myopic eyes in comparison with age-matched healthy controls was performed. Choroidal thickness (CT) and large choroidal vessel thickness (LCVT) were measured at the fovea, 750 µm nasally from fovea (N750) and 750 µm temporally (T750) from fovea. Medium choroidal vessel thickness (MCVT) was calculated by subtracting LCVT from CT. Choriocapillaris was encompassed by MCVT, given its reduced thickness. Linear regression analysis evaluated the relationship between age and axial with CT, LCVT and MCVT. Results The study group comprised 42 eyes of 31 patients (mean age 46.13 ± 15.63; 15 females). Control group included 57 eyes of 34 patients (mean age of 42.3 ± 15.29; 24 females). Mean axial length in myopic eyes and control group was 26.57 ± 1.27 and 23.59 ± 0.99 mm respectively. Myopic eyes showed significant thinning of MCVT and CT at all locations (p 0.05). With each decade, thinning of up to 37 µm in CT was noted along with thinning of LCVT (up to 22.6 µm) and MCVT (up to 25 µm). Each mm increase in axial length caused 38.2 µm thinning of choroid along with LCVT (30 µm). Conclusion Significant thinning of MCVT was noted in non-pathological myopic eyes in comparison to healthy subjects. It appears that MCVT has stronger relationship with age and axial length.

Supplemental Digital Content is Available in the Text. Direct clinicopathologic correlation of an eye with geographic atrophy secondary to age-related macular degeneration provides histologic correlates of features commonly seen by optical coherence tomography, such as end-stages of drusen, subretinal drusenoid deposit, plaques near the Bruch membrane, and hyporeflective wedge., Purpose: 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 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: 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.

A paracentesis prior to an intravitreal injection is a very safe procedure and can prevent IOP-spikes after injections. As these spikes pose the risk of inducing glaucomatous changes particularly in patients with frequent injections and/or with a risk profile, a regular paracentesis prior to an injection may be considered and discussed with the patient.

To describe qualitative and quantitative optical coherence tomography (OCT) angiography (OCTA) parameters for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and their applicability as potential clinical trial endpoints.A review of current literature related to the topic of OCTA and AMD.There are a number of promising OCTA parameters that can be used to diagnose the presence of CNV and to monitor the activity and progression of the lesion, pre- and post-treatment morphological characteristics, CNV dimensions, and automated quantitative parameters such as vessel density.The OCTA parameters described in this review have promise for the future development of clinical trial endpoints, but require further validation before they can be widely used.

Nonexudative choroidal neovascularization (CNV) is a new phenomenon that has only recently been described in the literature with the advent of optical coherence tomography angiography (OCTA) imaging. The authors present a 1-year longitudinal follow-up of a nonexudative CNV lesion secondary to age-related macular degeneration. This report describes the appearance of the lesion on two commercially available spectral-domain OCTA devices and one prototype swept-source OCTA device. Management of these cases is still debatable. Watchful waiting with regular follow-up using serial OCTA to monitor disease progression has been valuable in this case., National Institutes of Health (U.S.) (Grant R01-EY011309), United States. Air Force Office of Scientific Research (Grant FA9550-15-1-0473), United States. Air Force Office of Scientific Research (Grant FA9550-12-1-0499)

The body of knowledge of in vivo investigation of the choroid has been markedly enhanced by recent technological advances in optical coherence tomography (OCT). New insights elucidating the morphological features of the choriocapillaris and choroidal vasculature, in both physiological and pathological conditions, indicate that the choroid plays a pivotal role in many posterior segment diseases. In this article, a review of the histological characteristics of the choroid, which must be considered for the proper interpretation of in vivo imaging, is followed by a comprehensive discussion of fundamental principles of the current state-of-the-art in OCT, including cross-sectional OCT, en face OCT, and OCT angiography using both spectral domain OCT and swept source OCT technologies. A detailed review of the tomographic features of the choroid in the normal eye is followed by relevant findings in prevalent chorioretinal diseases, focusing on major causes of vision loss such as typical early and advanced age-related macular degeneration, polypoidal choroidal vasculopathy, central serous chorioretinopathy, pachychoroid spectrum disorders, diabetic choroidopathy, and myopia.

Purpose We explored via multimodal imaging and histology an eye with mixed-types 1 and 2 macular neovascularization (MNV) and complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in age-related macular degeneration. Methods An 82-year-old white man was followed 7 years by optical coherence tomography and treated with intravitreal anti-vascular endothelial growth factor for 3 years. At the last clinic visit, visual acuity was stable at 20/50. Two months later the patient died, and eyes were preserved at 8.33 hours after death. Submicrometer epoxy resin sections of osmicated tissue were stained with toluidine blue and evaluated by oil immersion microscopy. Results A shallow irregular RPE elevation on optical coherence tomography correlated with type 1 MNV with fibrocellular scar and neocapillaries (close to RPE), at a density similar to underlying native choriocapillaris (0.37 vs. 0.42). Type 2 MNV covered the native RPE and was enveloped at the margins by RPE, without neocapillaries. Native RPE cells transdifferentiated from age-normal to melanotic and entered type 1 MNV and choroid. Some photoreceptors persisted over MNV. The cRORA initiated at a collapsed druse, expanded during follow-up, and exhibited low choriocapillaris density (0.05). Conclusions An eye with maintained vision on 3 years of anti-vascular endothelial growth factor therapy had type 1 MNV sustaining RPE. Type 2 MNV enveloped by RPE was visible in optical coherence tomography and histology. Persistence of photoreceptors and RPE over MNV contrasted with drusen-associated cRORA. Translational relevance Vision during long-term anti-vascular endothelial growth factor treatment persists by MNV partially preserving outer retinal cells and by RPE enveloping type 2 MNV.

Supplemental Digital Content is Available in the Text. High-resolution histology at the border of geographic atrophy (or complete retinal pigment epithelium and outer retinal atrophy) secondary to age-related macular degeneration reveals marked gliosis and near-total photoreceptor depletion, abundant extracellular deposits, and long-standing abnormalities of Bruch membrane and choriocapillaris, indicating severe and potentially irreversible tissue damage at this stage of the disease., Purpose: To systematically characterize histologic features of multiple chorioretinal layers in eyes with geographic atrophy, or complete retinal pigment epithelium (RPE) and outer retinal atrophy, secondary to age-related macular degeneration, including Henle fiber layer and outer nuclear layer; and to compare these changes to those in the underlying RPE-Bruch membrane—choriocapillaris complex and associated extracellular deposits. Methods: Geographic atrophy was delimited by the external limiting membrane (ELM) descent towards Bruch membrane. In 13 eyes, histologic phenotypes and/or thicknesses of Henle fiber layer, outer nuclear layer, underlying supporting tissues, and extracellular deposits at four defined locations on the non-atrophic and atrophic sides of the ELM descent were assessed and compared across other tissue layers, with generalized estimating equations and logit models. Results: On the non-atrophic side of the ELM descent, distinct Henle fiber layer and outer nuclear layer became dyslaminated, cone photoreceptor inner segment myoids shortened, photoreceptor nuclei and mitochondria translocated inward, and RPE was dysmorphic. On the atrophic side of the ELM descent, all measures of photoreceptor health declined to zero. Henle fiber layer/outer nuclear layer thickness halved, and only Müller cells remained, in the absence of photoreceptors. Sub-RPE deposits remained, Bruch membrane thinned, and choriocapillaris density decreased. Conclusion: The ELM descent sharply delimits an area of marked gliosis and near-total photoreceptor depletion clinically defined as Geographic atrophy (or outer retinal atrophy), indicating severe and potentially irreversible tissue damage. Degeneration of supporting tissues across this boundary is gradual, consistent with steady age-related change and suggesting that RPE and Müller cells subsequently respond to a threshold of stress. Novel clinical trial endpoints should be sought at age-related macular degeneration stages before intense gliosis and thick deposits impede therapeutic intervention.

Purpose To describe the retinal microvasculature of the eyes with nonarteritic retinal artery occlusion (RAO) based on optical coherence tomography angiography. Methods Cross-sectional, prospective, observational study performed from September 2014 through February 2015. En face projection of optical coherence tomography angiography images centered at the macula and optic disk of the eyes presenting with RAO were acquired using the RTVue XR Avanti with AngioVue software. Qualitative analysis of the morphology of the superficial and deep retinal capillary plexuses, and radial peripapillary capillaries was performed. Retinal vasculature images using optical coherence tomography angiography were correlated with fluorescein angiography images. Results Seven patients (seven eyes) were enrolled in the study, including three eyes with central RAO and four eyes with branch RAO. Distinct differences in the distribution of zones of decreased vascular perfusion between the superficial and deep retinal capillary plexus corresponding to areas of delayed dye perfusion on fluorescein angiography were demonstrated in 6 of 7 (86.5%) eyes. Conclusion This small series suggests that optical coherence tomography angiography imaging can accurately discern retinal capillary plexuses at different levels in the eyes with RAO and may be sensitive for more precisely characterizing the extent of macular ischemia and monitoring vascular flow changes during the course of the disease.

The choroidal vasculature is the primary source of both oxygen and blood-borne nutrients to the outer retina, including the retinal pigment epithelium (RPE), photoreceptors, and otherwise avascular...

The purpose of this review is to summarize the current knowledge on choriocapillaris loss in advanced age macular degeneration (AMD). Several histopathological studies in animal models and human eyes had showed that the choriocapillaris density decreases with age. However, the role of choriocapillaris loss is still unclear in AMD and its advanced forms, either choroidal neovascularization (CNV) or geographic atrophy (GA). Some authors have hypothesized that choriocapillaris loss might precede overt retinal pigment epithelium atrophy. Others have hypothesized that deposition of complement complexes on and around the choriocapillaris could be related to the tissue loss observed in early AMD. The development of imaging modalities, such as optical coherence tomography angiography (OCTA), have led to a better understanding of underlying physiopathological mechanisms in AMD. OCTA showed atrophy of choriocapillaris underneath and beyond the region of photoreceptors and RPE loss, in agreement with previous histopathologic studies. The evolution of OCTA technology suggests that CNV seems to originate from regions of severe choriocapillaris alteration. Significant progress has been made in the understanding of development and progression of GA and CNV. In vivo investigation of the choriocapillaris using OCTA may lead to new insights related to underlying disease mechanisms in AMD.

Purpose To correlate histologic results with previously recorded multimodal imaging results from a patient with type 3 neovascularization secondary to age-related macular degeneration (AMD). Design Case study, clinical imaging, laboratory imaging, and eye-tracked clinicopathologic correlation. Participant An 86-year-old white woman with type 3 neovascularization secondary to AMD treated with 6 intravitreal injections of bevacizumab. Methods Multimodal retinal imaging at each clinic visit was correlated with ex vivo and high-resolution histologic images of the preserved donor eye. Clinical imaging included serial near-infrared reflectance and eye-tracked spectral-domain OCT. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding to clinical OCT signatures. Main Outcome Measures Histologic correlates for clinical OCT signatures were sought, including reflectivity of the vascular complex, intraretinal hyperreflective foci and intraretinal cellularity, analysis of the topography of pathologic features, and evaluation of the sub–retinal pigment epithelium (RPE) plus basal lamina (BL) space. Results Clinical imaging showed a deep neovascular lesion in close relationship with a mixed serous and drusenoid pigment epithelium detachment (PED), characteristic of type 3 neovascularization. Antiangiogenic therapy achieved a complete resolution of exudation. The PED progressively flattened with each treatment, leaving a persistent triangular hyperreflectivity in the outer retina. This persistent deep lesion histologically correlated with a vascular complex implanted into sub-RPE basal laminar deposit. No connection between the choriocapillaris and the sub-RPE plus BL space was observed. Both RPE-derived and lipid-filled cells were correlated with clinical intraretinal hyperreflective foci. The sub-RPE plus BL space contained macrophages, lymphocytes, Muller cell processes, and subducted RPE. Conclusions Clinicopathologic correlation of type 3 neovascularization showed vascular elements of retinal origin accompanied by collagenous material and Muller cell processes implanting into thick sub-RPE basal laminar deposit, which may simulate the appearance of chorioretinal anastomosis. Surrounding RPE-derived and lipid-filled cells thought to be microglia correlated with clinical intraretinal hyperreflective foci.

Recent technological advances in ophthalmic imaging, especially those in optical coherence tomography (OCT), revealed morphological changes of the choroid related to a wide number of pathological chorioretinal conditions, indicating a pivotal role in underlying disease mechanisms, in natural history of diseases, and also in response to therapeutic interventions.

To describe the appearance of a scleral-derived feeder vessel in a highly myopic eye with secondary choroidal neovascularization (CNV) as visualized on both en face high-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype, and a commercially available spectral-domain (SD) OCTA, with the corresponding en face and cross-sectional structural OCT images. In this case report, a 60-year-old white male presented with high myopia and secondary CNV in the right eye, previously treated with anti-vascular endothelial growth factor, and was imaged on both SD-OCT and SS-OCT. The neovascular complex could be visualized on both devices. Structural en face SS-OCT images demonstrated a large choroidal-scleral feeder vessel that was not visualized with SD-OCT. The authors concluded that structural en face SS-OCT better visualizes scleral feeder vessel compared to SD-OCT due to the longer wavelength (∼1,050 nm) with increased choroidal penetration and decreased sensitivity roll-off in the SS-OCT system. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:960–964.]

Fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been the gold standard for the evaluation of retinal and choroidal vasculature in the last three decades and have revolutionized the diagnosis of retinal and choroidal vascular diseases. The advantage of these imaging modalities lies in their ability to document retinal and choroidal vasculature through the dynamic assessment of contrast transit over time in the intravascular and extravascular spaces. However, disadvantages include the absence of depth resolution, blurring of details by contrast leakage, and the inability to selectively evaluate different levels of the retinal and choroidal microvasculature. In addition, these angiographic methods require intravenous dye, which may cause adverse reactions such as nausea, vomiting, and rarely, anaphylaxis. Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique that, in contrast to dye-based angiography, is faster and depth-resolved, allowing in some cases for more precise evaluation of the vascular plexuses of the retina and choroid. The method has been demonstrated in the assessment of various vascular diseases such as venous occlusions, diabetic retinopathy, macular neovascularization, and others. Limitations of this imaging modality include a small registered field of view and the inability to visualize leakage and dye transit over time. It is also subject to a variety of artifacts, including those generated by blinking and eye movement during image acquisition. However, more than an alternative for FA and ICGA, OCTA is bringing new insights to our understanding of retinal and choroidal vascular structure and is changing fundamental paradigms in the clinical management of pathologic conditions. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:848–861.]

PURPOSE To describe a patient with birdshot retinochoroidopathy (BRC) with bilateral choroidal neovascularization (CNV) who was treated with intravitreal injection of bevacizumab and antiinflammatory medications. METHOD Interventional case report. PATIENT A 35-year-old woman with bilateral CNV associated with BRC. RESULTS The patient was treated with intravitreal injection of triamcinolone, photodynamic therapy, and intravitreal injection of bevacizumab in one eye, while the fellow eye was treated with intravitreal injection of triamcinolone. Immunosuppressive therapy was performed in the course of the treatment. Not only did the neovascularization respond, but the birdshot lesions vanished as well. DISCUSSION BRC can have secondary CNV that, as in the current case, responds favorably to treatment. We serendipitously observed regression of the choroidal inflammatory lesions with intravitreal injection of triamcinolone.

Background: Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), has been given via intravitreal injection as an off-label therapy for both neovascular age-related macular degeneration and for macular edema secondary to retinal vascular disease. The authors describe three patients with macular edema secondary to retinal venous occlusion whose edema initially responded to intravitreal bevacizumab but subsequently recurred in excess of that observed before treatment. Methods: This is a retrospective case series of three patients with macular edema secondary to retinal vein occlusion treated with intravitreal bevacizumab. Results: In all three patients, the rebound retinal edema observed was more pronounced than that present before treatment. Conclusion: These cases suggest a potential limitation of using relatively short-acting VEGF antagonists in retinal vascular disease of a chronic nature. Frequent repeated injections may be required to prevent a rebound effect with no clearly defined endpoint. Until the long-term safety of multiple injections of these agents is established, the authors recommend caution in using this treatment strategy.

Purpose To characterize qualitative and quantitative features of the choroid in normal eyes using enface swept-source optical coherence tomography (SS-OCT). Methods Fifty-two eyes of 26 consecutive normal subjects were prospectively recruited to obtain multiple three-dimensional 12x12mm volumetric scans using a long-wavelength high-speed SS-OCT prototype. A motion-correction algorithm merged multiple SS-OCT volumes to improve signal. Retinal pigment epithelium (RPE) was segmented as the reference and enface images were extracted at varying depths every 4.13μm intervals. Systematic analysis of the choroid at different depths was performed to qualitatively assess the morphology of the choroid and quantify the absolute thicknesses as well as the relative thicknesses of the choroidal vascular layers including the choroidal microvasculature (choriocapillaris, terminal arterioles and venules; CC) and choroidal vessels (CV) with respect to the subfoveal total choroidal thickness (TC). Subjects were divided into two age groups: younger (, National Institutes of Health (U.S.) (R01-EY011289-27), National Institutes of Health (U.S.) (R44EY022864-01), National Institutes of Health (U.S.) (R01-CA075289-16), United States. Air Force Office of Scientific Research (FA9550-10-1-0551), United States. Air Force Office of Scientific Research (FA9550-10-1-0063)

To report the frequency of choroidal neovascularization (CNV) in Caucasian patients with chronic central serous chorioretinopathy (CSC). Retrospective consecutive series of 272 eyes (136 patients) who were diagnosed as having chronic CSC based on clinical and multimodal fundus imaging findings and documented disease activity for at least 6 months. The CNVs were mainly determined by indocyanine-green angiography. Patients were evaluated and followed for a maximum of 6 years, with an average follow-up of 14 ± 12 months. Distinct CNV was identified in 41 eyes (34 patients). Based on fluorescein angiography, 37 eyes showed occult with no classic CNV, 3 eyes showed predominantly classic and 1 eye had a disciform CNV. Furthermore, indocyanine-green angiography revealed polypoidal choroidal vasculopathy lesions, in 27 of the 37 eyes, classified as occult CNV on fluorescein angiography. In total, 17.6% of our patients with chronic CSC were found to have CNV that upon indocyanine-green angiography were recognized as being polypoidal choroidal vasculopathy. In our series of Caucasian patients, we found a significant correlation between chronic CSC and CNV, in which the majority of patients with CNV were found to have polypoidal choroidal vasculopathy. Our findings suggest that indocyanine-green angiography is an indispensable tool in the investigation of chronic CSC

Background Best disease is an autosomal dominant retinal dystrophy with a variable phenotypic expression. Clinically, it is characterized by a vitelliform lesion in the macula because of the deposition of yellow material in a dome-shaped configuration, believed to be lipofuscin that accumulates within and beneath the retinal pigment epithelium. Best disease is occasionally complicated by the development of choroidal neovascularization (CNV), which typically occurs in the macula. We report a case of peripapillary CNV in Best disease. Methods Interventional case report. Results A 12-year-old boy who was previously diagnosed with Best disease was treated with reduced fluence photodynamic therapy for subfoveal CNV in the right eye. After 2 months, he presented with peripapillary CNV in the left eye, which was treated with repeated sessions of reduced fluence photodynamic therapy. Conclusion Ophthalmologists must be aware that peripapillary CNV may occasionally complicate Best disease and can be successfully treated with photodynamic therapy.

Purpose To describe the characteristics as well as the sensitivity and specificity of detection of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) using spectral-domain optical coherence tomography. Design Observational, retrospective study. Participants Seventy-two eyes of 61 subjects (48 eyes of 43 subjects with CNV, 24 eyes of 18 subjects without CNV). Methods Patients imaged using the prototype AngioVue OCTA system (Optovue, Inc, Fremont, CA) between August 2014 and October 2014 at New England Eye Center were assessed. Patients in whom CNV was identified on OCTA were evaluated to define characteristics of CNV on OCTA: size using greatest linear dimension (small, 2 mm), appearance (well-circumscribed, poorly circumscribed), and presence of subretinal and intraretinal fluid. Concurrently, an overlapping second cohort of patients who underwent same-day OCTA and fluorescein angiography (FA) for suspected CNV was evaluated to estimate sensitivity and specificity of OCTA in detecting CNV using FA as ground truth. Main Outcome Measures Choroidal neovascularization appearance, CNV size, and presence of subretinal and intraretinal fluid. Results In 48 eyes, CNV was visualized on OCTA. Thirty-one eyes had CNV associated with neovascular age-related macular degeneration. Size of CNV was small in 23% (7/31), medium in 42% (13/31), and large in 35% (11/31). Poorly circumscribed vessels, subretinal fluid, and intraretinal fluid each were seen in 71% (22/31). Seven eyes had CNV associated with central serous chorioretinopathy. Size of CNV was small in 71% (5/7) and large in 29% (2/7). Seventy-one percent (5/7) had well-circumscribed vessels, 86% (6/7) had subretinal fluid, and 14% (1/7) had intraretinal fluid. Thirty eyes with OCTA and same-day FA were evaluated to determine sensitivity and specificity of CNV detection on OCTA. Sensitivity was 50% (4/8) and specificity was 91% (20/22). Conclusions Using OCTA allows the clinician to visualize CNV noninvasively and may provide a method for identifying and guiding treatment of CNV. The specificity of CNV detection on OCTA compared with FA seems to be high. Future studies with larger sample sizes are needed to elaborate better on the sensitivity and specificity of CNV detection and to illustrate clinical usefulness.

Objective To define morphologic features of polypoidal choroidal vasculopathy (PCV) using en face images from swept-source optical coherence tomography (SS OCT). Design Prospective cross-sectional study. Methods The study included 10 eyes from 6 patients with PCV and 10 eyes from 5 age-matched normal subjects. All subjects were prospectively scanned with a prototype SS OCT system. A motion correction algorithm was applied to correct and merge scans into a single volumetric dataset. En face images were generated at intervals of 4.13 μm (1 pixel) relative to the Bruch membrane. Results Age ± standard deviation for the normal group was 62.4 (±12.1) years and for the PCV group was 68.3 (±5.2) years. En face SS OCT imaging of PCV eyes demonstrated the relationship between larger pigment epithelial detachments (PEDs) and small adjoining PEDs that correlated with the polypoidal lesions seen on indocyanine green angiography in all PCV eyes. En face SS OCT demonstrated choroidal vascular abnormalities in 7 out of 7 eyes with PCV, and in 2 out of 3 enrolled fellow eyes in patients with unilateral PCV. Out of 7 PCV eyes, focal choroidal vascular dilation was noted in 3 eyes and diffuse choroidal vascular dilation was noted in 1 eye. In addition, a branching vascular network was noted above the Bruch membrane in 1 eye, below the Bruch membrane within the choriocapillaris in 1 eye, and in the larger choroidal vascular layer in 1 eye. Conclusions En face SS OCT provides an in vivo tool to visualize the pathologic features and the choroidal vasculature in PCV., National Institutes of Health (U.S.) (R01-EY011289-28), National Institutes of Health (U.S.) (R01-EY013178-12), National Institutes of Health (U.S.) (R01-CA075289-16), United States. Air Force Office of Scientific Research (FA9550-10-1-0551), United States. Air Force Office of Scientific Research (FA9550-12-1-0499)

Objective To characterize en face features of the retinal pigment epithelium (RPE) and choroid in eyes with chronic central serous chorioretinopathy (CSCR) using a high-speed, enhanced-depth swept-source optical coherence tomography (SS-OCT) prototype. Design Consecutive patients with chronic CSCR were prospectively examined with SS-OCT. Participants Fifteen eyes of 13 patients. Methods Three-dimensional 6×6 mm macular cube raster scans were obtained with SS-OCT operating at 1050 nm wavelength and 100 000 A-lines/sec with 6 μm axial resolution. Segmentation of the RPE generated a reference surface; en face SS-OCT images of the RPE and choroid were extracted at varying depths every 3.5 μm (1 pixel). Abnormal features were characterized by systematic analysis of multimodal fundus imaging, including color photographs, fundus autofluorescence, fluorescein angiography, and indocyanine-green angiography (ICGA). Main Outcome Measures En face SS-OCT morphology of the RPE and individual choroidal layers. Results En face SS-OCT imaging at the RPE level revealed absence of signal corresponding to RPE detachment or RPE loss in 15 of 15 (100%) eyes. En face SS-OCT imaging at the choriocapillaris level showed focally enlarged vessels in 8 of 15 eyes (53%). At the level of Sattler's layer, en face SS-OCT documented focal choroidal dilation in 8 of 15 eyes (53%) and diffuse choroidal dilation in 7 of 15 eyes (47%). At the level of Haller's layer, these same features were observed in 3 of 15 eyes (20%) and 12 of 15 eyes (80%), respectively. In all affected eyes, these choroidal vascular abnormalities were seen just below areas of RPE abnormalities. In 2 eyes with secondary choroidal neovascularization (CNV), distinct en face SS-OCT features corresponded to the neovascular lesions. Conclusions High-speed, enhanced-depth SS-OCT at 1050 nm wavelength enables the visualization of pathologic features of the RPE and choroid in eyes with chronic CSCR not usually appreciated with standard spectral domain (SD) OCT. En face SS-OCT imaging seems to be a useful tool in the identification of CNV without the use of angiography. This in vivo documentation of the RPE and choroidal vasculature at variable depths may help elucidate the pathophysiology of disease and can contribute to the diagnosis and management of chronic CSCR., National Institutes of Health (U.S.) (R01-EY011289-27), National Institutes of Health (U.S.) (R01-EY013178-12), National Institutes of Health (U.S.) (R01-EY018184-05), National Institutes of Health (U.S.) (R44EY022864-01), National Institutes of Health (U.S.) (GR01-CA075289-16), National Institutes of Health (U.S.) (R01-NS057476-05), National Institutes of Health (U.S.) (R44-EY022864-01), United States. Air Force Office of Scientific Research (FA9550-10-1-0551), United States. Air Force Office of Scientific Research (FA9550-10-1-0063), Research to Prevent Blindness, Inc. (United States), Massachusetts Lions Club, German Science Foundation (DFG-GSC80-SAOT)

Purpose To compare analyses of choroidal thickness and volume in healthy eyes measured concurrently with prototype long-wavelength swept-source optical coherence tomography (OCT) and commercially available spectral-domain optical coherence tomography (OCT) with and without enhanced depth imaging (EDI). Design Prospective cross sectional study. Methods The study included 19 healthy subjects (19 eyes), who were prospectively recruited to undergo 2 consecutive imaging sessions on the same randomly selected eye using spectral domain OCT and a prototype long-wavelength swept-source OCT. On spectral domain OCT, 2 line scans, 1 with and 1 without EDI, and 1 volumetric scan were obtained. On swept-source OCT, 1 line scan and 1 volumetric scan were obtained. Scan patterns on swept-source OCT were created to simulate those available on Cirrus HD-OCT to keep the time of image acquisition constant. Swept-source OCT volumetric scans were motion corrected using a novel registration algorithm. Choroidal thickness and volume were analyzed. Results The choroidoscleral interface was clearly visualized in 19/19 (100%) of eyes imaged by swept-source OCT, compared to 14/19 (73.6%) and 13/19 (68.4%) eyes imaged by spectral domain OCT, with and without EDI, respectively. There was no significant difference in choroidal thickness measurements on the line scans obtained on either system ( P = 0.10). Choroidal volume could not be assessed on volumetric scans from spectral domain OCT. Mean choroidal volume from swept-source OCT volumetric scans was 11.77 ± 3.13 mm 3 (6.43 mm 3 -17.15 mm 3 ). Conclusion This is the first study that compares simultaneously a prototype long-wavelength swept-source OCT to a commercially available spectral domain OCT for a detailed analysis of choroid in healthy eyes. Swept-source OCT shows potential for better choroidal analysis. Studies using swept-source OCT in diseased eyes will further define this new technology's utility in chorioretinal diseases.

Objective To analyze the frequency of major age-related macular degeneration (AMD)-associated alleles in patients with multifocal choroiditis (MFC). Methods A cohort of 48 patients with MFC was compared with previously characterized cohorts of patients with advanced AMD (368 samples) and matched unaffected controls (368 samples). Allele and genotype frequencies of single nucleotide polymorphisms for the following AMD-associated alleles were evaluated: risk alleles in complement factor H ( CFH ) gene (Y402H and IVS14) and LOC387715/HTRA1 gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3) and complement factor B loci (H9L and R32Q). Results Frequencies of all major AMD-associated alleles in the CFH locus indicate a strong, statistically significant association of CFH gene single nucleotide polymorphisms and MFC. However, the same analysis for the single nucleotide polymorphisms in complement factor B and 10q26 loci matched the results in the control group. Conclusions Like AMD, the MFC phenotype is strongly associated with the major alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling evidence of a strong association between CFH polymorphisms and MFC, which contributes to the understanding of MFC pathogenesis and suggests new potential therapeutic targets.

The authors observed an unusual closed loop-like vessel formation in the macula and describe its regression caused by the heterogenous treatment effects of intravitreal ranibizumab injections in an eye with exudative age-related macular degeneration associated with multiple retinochoroidal anastomoses.

Purpose To evaluate the change in visual acuity and retinal appearance in patients after early initiation of intravitreal bevacizumab treatment for central retinal vein occlusion (CRVO). Design Retrospective, interventional case series. Methods Patients with CRVO of fewer than three months' duration receiving intravitreal bevacizumab as primary treatment were evaluated. Patients received an intravitreal 1.25 mg (0.05 ml) bevacizumab injection. Changes in visual acuity, central macular thickness, venous tortuosity and diameter, and optic disk edema were noted. Results Six eyes of five consecutive patients with CRVO treated with intravitreal bevacizumab injection were reviewed retrospectively. The patients did not have other ocular conditions that could have compromised visual acuity. The mean baseline visual acuity was 20/428 (logarithm of the minimum angle of resolution [logMAR] units, 1.33). The mean follow-up period was 12 months (range, seven to 15 months), and the number of bevacizumab injections ranged from four to 10. The patients showed a statistically significant decrease in optic nerve head swelling, venous tortuosity, and venous diameter, with the largest proportion of change occurring within one month of the first bevacizumab injection. The mean visual acuity at last follow-up was 20/53 (logMAR units, 0.42; P = .035, as compared with baseline). In no patient did collateral vessels at the optic nerve head develop. Conclusions The patients experienced a dramatic improvement in the visual acuity and clinical fundus appearance, without collateral vessel formation. These findings are difficult to explain with current theories of the pathophysiologic features of CRVO. These findings also suggest early initiation of anti–vascular endothelial growth factor (VEGF) treatment should be studied in a larger trial for CRVO.

Purpose To analyze total thickness, morphology and individual vascular layers of the choroid in eyes with Stargardt disease using spectral-domain optical coherence tomography (SD OCT). Design Cross-sectional retrospective review. Methods Twenty-eight patients with Stargardt disease (53 eyes) with a mean age of 46 (15–79) years and 30 healthy subjects (30 eyes) with a mean age of 49 (22–79) years who underwent 1-line raster scanning with SD OCT were identified. Diagnosis of Stargardt disease was based on ophthalmic history and complete ophthalmic evaluation. The healthy subjects had best-corrected visual acuity of 20/20 or better with no chorioretinal pathology. Two independent raters assessed the total thickness, morphology, and the individual vascular layers of the choroid. Results The choroid was irregularly shaped in 26 of 41 eyes (64%) with Stargardt disease when compared to 0 of 30 healthy eyes (0%). Mean subfoveal total choroidal thickness and mean subfoveal large choroidal vessel layer thickness were significantly reduced in eyes with Stargardt disease when compared to healthy eyes (272.8 ± 32.8 μm vs 225.4 ± 69.9 μm; P = .03 and 219.5 ± 30.6 vs169.2 ± 70.1; P = .04, respectively). The maximal choroidal thickness was subfoveal in 9 of 41 eyes (22%), focal choroidal thinning was observed in 21 of 41 eyes (51%), and attenuation of large choroidal vessel layer was observed in 8 of 41 eyes (20%) with Stargardt disease. There was no association of the best-corrected visual acuity with any choroidal morphologic feature, except that it was better by a mean of 0.61 ± 0.21 in eyes that had preservation of large choroidal vessel layer (33 of 41, 80%) when compared to those that had attenuation of large choroidal vessel layer ( P = .007). Conclusion This study shows alterations in the total thickness, morphology, and the individual vascular layers of the choroid in eyes with Stargardt disease on SD OCT. These findings may potentially contribute to the clinical staging and monitoring of Stargardt disease.

Importance Choroidal neovascularization (CNV) is a major cause of vision loss in chronic central serous chorioretinopathy (CSCR). Detecting CNV using fluorescein angiography (FA) may be challenging owing to the coexistence of features related to the primary diagnosis of CSCR. Optical coherence tomography angiography (OCTA) allows noninvasive visualization of retinal and choroidal vasculature via motion contrast and may contribute to the unequivocal diagnosis of CNV in this population. Objective To evaluate the sensitivity of spectral-domain OCTA in detecting CNV associated with chronic CSCR. Design, Setting, and Participants Observational cross-sectional study including 23 patients (27 eyes) who presented at the New England Eye Center between August 1, 2014, and November 30, 2014, with suspected CNV complicating chronic CSCR and underwent standard assessment for CNV diagnosis, including FA imaging. Participants were prospectively recruited to receive imaging tests using prototype OCTA software on a commercially available spectral-domain OCT. Orthogonal registration and the merging of 2 consecutive image sets were used to obtain 3 × 3-mm and 6 × 6-mm OCT angiograms centered at the macula. Two independent readers masked to other imaging findings performed a qualitative analysis on OCTA depictions of vascular flow representing CNV and the morphologic appearance of CNV. Main Outcomes and Measures Choroidal neovascularization location as well as retinal pigment epithelial detachment internal reflectivity and the presence of subretinal and intraretinal fluid. Sensitivity and specificity of OCTA in detecting CNV were estimated using FA as the standard examination reference. Results Choroidal neovascularization was diagnosed in 8 of 27 eyes (30%) based on FA imaging analysis. Optical coherence tomography angiography and corresponding OCT B-scans detected 100% (8 of 8) of these CNV lesions and correctly excluded 100% (19 of 19) of eyes with CSCR without CNV. Sensitivity was 100% (95% CI, 0.62-1) and specificity was 100% (95% CI, 0.82-1). Morphologic appearance, location, and position of the CNV relative to the retinal pigment epithelium and Bruch membrane were described using OCTA that combined flow and structural information. Conclusions and Relevance This study suggests that OCT alone (OCTA and coregistered OCT B-scans) features sensitivity and specificity comparable with FA for the detection of CNV in eyes with chronic CSCR.

IMPORTANCE: The complement factor H R1210C rare variant confers the strongest genetic risk for age-related macular degeneration and earlier age at onset; however, its associated phenotype has not been well characterized. OBJECTIVE: To describe specific fundus features of a white population with the R1210C rare variant. DESIGN, SETTING, AND PARTICIPANTS: Fundus features specific for diagnosis and disease staging were retrospectively characterized by systematic review of all available fundus images for each patient, including color photography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography, at a tertiary ophthalmologic referral center. For this retrospective observational study conducted from 2012 to 2014, enrolled patients with the variant and their family members without the variant were identified from the Age-Related Macular Degeneration Study for a family-based study arm. For patients with the variant but without a family member enrolled in the study, age-matched comparison individuals without the variant were selected randomly from the database. MAIN OUTCOMES AND MEASURES: The presence of drusen in the macula (macular drusen score) and estimated number (total macular drusen score) were assessed. The presence of drusen in the extramacular regions (extramacular drusen score), pigmentary abnormalities, and disease staging were also evaluated. Binary logistic regression models were used to evaluate the association between rare variant status and ocular phenotypes. RESULTS: Images from a total of 143 patients (283 eyes), including 62 patients with the rare variant, were analyzed. Drusen score covariates were associated with the R1210C rare variant. A larger proportion of patients carrying the variant had the highest level of macular and total macular drusen scores compared with those without the variant (57.9% vs 16.7% and 52.9% vs 14.2%, respectively; P for trend < .001 for both scores). Patients carrying the rare variant had a much greater likelihood of having advanced disease (odds ratio, 7.0; 95% CI, 3.1-16.2; P < .001). A higher prevalence of geographic atrophy was observed among patients carrying the variant (odds ratio, 13.7; 95% CI, 5.0-37.7; P < .001). CONCLUSIONS AND RELEVANCE: The typical phenotype of the complement factor H R1210C rare variant is associated with extensive drusen accumulation in the macula and throughout the fundus, as well as with a high risk for having advanced disease. Better characterization of genetic profiles in age-related macular degeneration may be important for screening and future therapeutic strategies for this vision-threatening condition.