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Objective: To characterize the multimodal retinal findings of myopic macular pits, a feature of myopic degeneration., Methods: A case series of patients with myopic macular pits were studied with multimodal imaging including color fundus photography, fundus autofluorescence (FAF), near infrared reflectance (NIR), spectral domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICG)., Results: Nine eyes of 6 patients with myopic macular pit were examined. Four patients presented with multiple pits and 3 with bilateral involvement. All pits were localized in a region of severe macular chorioretinal atrophy associated with myopic posterior staphyloma. In 3 eyes, the entrance of the posterior ciliary artery through the sclera was noted at the base of the pit. Schisis overlying the pit or adjacent to the pit was identified in 3 patients., Conclusion: Myopic macular pits are an additional rare sign of myopic degeneration, developing in regions of posterior staphyloma complicated by severe chorioretinal atrophy and thin sclera., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Safe, affordable, and convenient transportation may help older adults (age 65 and older) stay independent, access healthcare services, and maintain their quality of life. While older adults in the United States primarily rely on private automobiles, those who reduce or cease driving may require alternative forms of transportation. Ride share services show promise as an alternative mode of transportation for older adults, particularly for those who no longer drive., Methods: We employed a qualitative research design to explore barriers and facilitators of older adults' use of ride share services and compare findings to younger adults (age 18 to 64). We conducted 96 telephone interviews (68 older adults and 28 younger adults), and 10 in-person focus groups (56 older adults and 17 younger adults), including individuals who used a ride share service and those who never used a ride share service. We conducted qualitative data analysis to identify key themes and developed a conceptual framework to organize and describe findings., Results: The qualitative analysis revealed the most important facilitator of older adults' use of ride share services was the desire to remain independent, particularly among those with health conditions and special needs that prevented them from using other transportation. Other facilitators included driver assistance (door-to-door service), a polite and courteous driver, a clean vehicle, and prompt and dependable service. Barriers among older adults included safety concerns, affordability, technology, and a lack of ride share services in the community. Among younger adults, technology was a facilitator of use., Conclusion: Ride share services are a promising transportation option. Findings highlight a need to tailor these services to older adults' needs. Ride share services that are safe, reliable, and offer driver assistance and telephone scheduling have the potential to support older adults' health, mobility, and independence., Competing Interests: Declarations of interest Bayne, Siegfried, and Beck declare no conflicts of interest. Freund has received financial support from Regeneron Pharmaceuticals and from ITN Affiliates.

Purpose: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course., Design: Multicenter retrospective observational case series., Participants: Sixty-three patients with SIC in 1 eye., Methods: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography., Main Outcome Measures: Standardized grading of imaging features., Results: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 μm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution., Conclusions: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration., Design: Retrospective case series., Participants: Fifteen eyes from 12 patients identified from 10 United States centers., Methods: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings., Main Outcome Measures: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies., Results: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033)., Conclusions: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Type 1 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) may sustain hypoxic and micronutrient-insufficient outer retinal cells compensatorily. We explored this hypothesis via histologic analysis of an eye with a shallow irregular retinal pigment epithelial elevation (SIRE) on OCT and good vision., Design: Case study and clinicopathologic correlation., Participant: A white woman with untreated nonexudative neovascular AMD and 20/30 visual acuity (left eye) and neovascular AMD (right eye), with 9 years' multimodal imaging before dying at 90 years of age., Methods: The left eye was preserved 6.25 hours after death and prepared for submicrometer epoxy resin sections and transmission electron microscopy aligned to clinical OCT B-scans. Inside and outside the MNV area, layer thicknesses, phenotypes, and vascular density of native choriocapillaris and neovessels were measured. Lengths of choriocapillaries and intervening gaps in the index eye and in early AMD eyes and healthy eyes with similar age (n = 19 each) from the Project MACULA (Maculopathy Unveiled by Laminar Analysis) online histopathologic resource (http://projectmacula.cis.uab.edu/) were measured with custom software (Caps and Gaps)., Main Outcome Measures: Descriptive features, vascular density, histologic and OCT layer thicknesses, and distribution of choriocapillaries and intervening gaps., Results: The SIRE correlated to a type 1 MNV that expanded slowly without evidence of exudation and with numerous choroidal vessels traversing Bruch's membrane defects, some visible on OCT. Tissue layers in and adjacent to the MNV area showed continuous RPE and characteristic AMD deposits. Capillary-like neovessels with fenestrations and caveolae resembling native choriocapillaris lined the retinal pigment epithelium (RPE) with a vascular density comparable with surrounding non-MNV areas. Relative to early AMD and healthy aged eyes, the index eye showed similar capillary lengths but larger gaps between vessels, indicating dropout. Outer nuclear layer thickness was preserved and showed less photoreceptor degeneration over areas of relative choriocapillaris health, including the type 1 MNV., Conclusions: Eyes with nonexudative type 1 MNV in AMD may progress to exudation, yet this stable MNV complex supported outer retinal structure for 9 years. Distinguishing features were numerous connecting vessels, high density of neovessels, continuous RPE, and slow growth. Maintaining beneficial type 1 MNV may be a therapeutic strategy., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data., Design: Consensus meeting., Participants: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists., Methods: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components., Main Outcome Measures: A consensus classification of neovascular AMD., Results: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated., Conclusions: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression., Design: Consensus meeting., Participants: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists., Methods: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA., Main Outcome Measures: Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates., Results: OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA., Conclusions: An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventions. Longitudinal data are required to quantify the implied risk of vision loss associated with these terms. The CAM classification provides initial definitions to enable these future endeavors, acknowledging that the classification will be refined as new data are generated., (Copyright © 2019 American Academy of Ophthalmology. All rights reserved.)

Purpose: To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC)., Design: Retrospective, longitudinal study., Participants: A total of 133 participants (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 OCT., Main Outcome Measures: 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 6228 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 male patients (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least 1 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 (CNV), outer retinal disruption on OCT, and FAF changes were associated with poorer vision at the 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)., 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., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases., Design: Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis., Participants: Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4)., Methods: Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging., Main Outcome Measures: Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging., Results: Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns., Conclusions: Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging., (Copyright © 2018. Published by Elsevier Inc.)

Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration (AMD) subtype and is seen particularly in Asians. Previous studies have suggested disparity in response to intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred treatment for PCV has remained unclear. Recent research has provided novel insights into the pathogenesis of PCV, and imaging studies based on OCT suggest that PCV belongs to a spectrum of conditions characterized by pachychoroid, in which disturbance in the choroidal circulation seems to be central to its pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV. Importantly, 2 large, multicenter randomized clinical trials evaluating the safety and efficacy of anti-VEGF monotherapy and combination with photodynamic therapy (PDT) recently reported initial first-year outcomes, providing level I evidence to guide clinicians in choosing the most appropriate therapy for PCV. In this review, we summarize the latest updates in the epidemiologic features, pathogenesis, and advances in imaging and treatment trials, with a focus on the most recent key clinical trials. Finally, we propose current management guidelines and recommendations to help clinicians manage patients with PCV. Remaining gaps in current understanding of PCV, such as significance of polyp closure, high recurrence rate, and heterogeneity within PCV, are highlighted where further research is needed., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD)., Design: Consensus meeting., Participants: Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers., Methods: As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy., Main Outcome Measures: A consensus classification system for atrophy and OCT-based criteria to identify atrophy., Results: OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear., Conclusions: A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions., (Copyright © 2017 American Academy of Ophthalmology. All rights reserved.)

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 mm 2 /year (median, ∼1.78 mm 2 /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., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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, Müller cell processes, and subducted RPE., Conclusions: Clinicopathologic correlation of type 3 neovascularization showed vascular elements of retinal origin accompanied by collagenous material and Müller 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., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen., Design: Retrospective, observational cohort study and experimental laboratory study., Participants: Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1)., Methods: We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy., Main Outcome Measures: Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes., Results: The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P < 0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P < 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen., Conclusions: Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To document outer retinal tubulation (ORT) formation in advanced retinal disorders., Design: Retrospective, observational study., Participants: Consecutive cases with retinal diseases showing outer retinal disruption and atrophy of the retinal pigment epithelium (RPE) associated with ORT on spectral-domain (SD) optical coherence tomography (OCT) at the final available visit., Methods: Cross-sectional SD OCT scans showing ORT at the last available visit were compared with eye-tracked baseline scans. Only patients showing the formation of ORT over time with absence of ORT at baseline were analyzed., Main Outcome Measures: Steps in ORT formation based on shapes of the external limiting membrane (ELM) descent (flat, curved, reflected, and scrolled) at the border of outer retinal and RPE atrophy, ORT characteristics (open, closed), and time between steps through a long-term follow-up., Results: From 170 eyes of 86 patients with ORT, 38 eyes of 30 patients (11 men, 19 women) with a mean age of 78.87 years (range, 56-96 years) met inclusion criteria. Of these 38 eyes, 23 (60%) had geographic atrophy secondary to age-related macular degeneration (AMD) and 2 eyes (5%) had geographic atrophy secondary to pattern dystrophy. Twelve eyes (32%) had neovascular AMD and 1 eye (3%) had neovascularization secondary to pseudoxanthoma elasticum, all showing similar ORT formative steps. Seventy-three different retinal areas (1434 cross-sectional images) were analyzed over a mean follow-up of 69.5 months (range, 21-93 months). At 73 borders, grading of eye-tracked follow-up SD OCT line scans showed a flat ELM descent at least once at 34 borders (47%), a curved ELM at 47 borders (64%), a reflected ELM at 37 borders (51%), and a scrolled ELM at 24 borders (33%). Of 81 ORTs, 73 (90%) were closed and 8 (10%) were open. The mean time for ORT formation was 14.9 months (range, 1.4-71.3 months)., Conclusions: We propose progressive steps in the development of ORT and analyze the time of progression between these steps. Analyzing the borders of atrophy to determine the origin of ORT provides new insights into the pathophysiology of advanced retinal disease highlighting a role for Müller cells and may inform future therapeutic strategies., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Drusenoid pigment epithelium detachment (DPED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histologic correlates for spectral-domain (SD) optical coherence tomography (OCT) signatures in DPED and determined the frequency and origin of these OCT signatures in a clinical cohort of DPED eyes., Design: Laboratory imaging and histologic comparison, and retrospective, observational cohort study., Participants: Four donor eyes with histopathologic diagnosis of AMD (2 with nonneovascular DPED and 2 with neovascular pigment epithelium detachment [PED]) and 49 eyes of 33 clinic patients with nonneovascular DPED more than 2 mm in diameter., Methods: Donor eyes underwent multimodal ex vivo imaging, including SD OCT, then processing for high-resolution histologic analysis. All clinic patients underwent SD OCT, near-infrared reflectance, and color photography., Main Outcome Measures: Histologic correlates for SD OCT signatures in DPED, estimate of coverage by different retinal pigment epithelium (RPE) phenotypes in the DPED surface; frequency and origin of histologically verified SD OCT signatures in a clinical cohort of DPED eyes, and comparisons of histologic features between neovascular PED and DPED resulting from AMD., Results: Intraretinal and subretinal hyperreflective foci as seen on SD OCT correlated to RPE cells on histologic examination. Hypertransmission of light below the RPE-basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material resulting from acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared with PEDs associated with neovascular AMD, DPEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits., Conclusions: Multiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be followed and quantified reliably using eye-tracked serial SD OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic end points and response to therapy in AMD clinical trials., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To summarize the results of 2 consensus meetings (Classification of Atrophy Meeting [CAM]) on conventional and advanced imaging modalities used to detect and quantify atrophy due to late-stage non-neovascular and neovascular age-related macular degeneration (AMD) and to provide recommendations on the use of these modalities in natural history studies and interventional clinical trials., Design: Systematic debate on the relevance of distinct imaging modalities held in 2 consensus meetings., Participants: A panel of retina specialists., Methods: During the CAM, a consortium of international experts evaluated the advantages and disadvantages of various imaging modalities on the basis of the collective analysis of a large series of clinical cases. A systematic discussion on the role of each modality in future studies in non-neovascular and neovascular AMD was held., Main Outcome Measures: Advantages and disadvantages of current retinal imaging technologies and recommendations for their use in advanced AMD trials., Results: Imaging protocols to detect, quantify, and monitor progression of atrophy should include color fundus photography (CFP), confocal fundus autofluorescence (FAF), confocal near-infrared reflectance (NIR), and high-resolution optical coherence tomography volume scans. These images should be acquired at regular intervals throughout the study. In studies of non-neovascular AMD (without evident signs of active or regressed neovascularization [NV] at baseline), CFP may be sufficient at baseline and end-of-study visit. Fluorescein angiography (FA) may become necessary to evaluate for NV at any visit during the study. Indocyanine-green angiography (ICG-A) may be considered at baseline under certain conditions. For studies in patients with neovascular AMD, increased need for visualization of the vasculature must be taken into account. Accordingly, these studies should include FA (recommended at baseline and selected follow-up visits) and ICG-A under certain conditions., Conclusions: A multimodal imaging approach is recommended in clinical studies for the optimal detection and measurement of atrophy and its associated features. Specific validation studies will be necessary to determine the best combination of imaging modalities, and these recommendations will need to be updated as new imaging technologies become available in the future., (Copyright © 2017 American Academy of Ophthalmology. All rights reserved.)

Purpose: To determine if the area of the foveal avascular zone (FAZ) is correlated with visual acuity (VA) in diabetic retinopathy (DR) and retinal vein occlusion (RVO)., Design: Cross-sectional study., Participants: Ninety-five eyes of 66 subjects with DR (65 eyes), branch retinal vein occlusion (19 eyes), and central retinal vein occlusion (11 eyes)., Methods: Structural optical coherence tomography (OCT; Spectralis, Heidelberg Engineering) and OCT angiography (OCTA; Avanti, Optovue RTVue XR) data from a single visit were analyzed. FAZ area, point thickness of central fovea, central 1-mm subfield thickness, the occurrence of intraretinal cysts, ellipsoid zone disruption, and disorganization of retinal inner layers (DRIL) length were measured. VA was also recorded. Correlations between FAZ area and VA were explored using regression models. Main outcome measure was VA., Results: Mean age was 62.9±13.2 years. There was no difference in demographic and OCT-derived anatomic measurements between branch retinal vein occlusion and central retinal vein occlusion groups (all P ≥ 0.058); therefore, data from the 2 groups were pooled together to a single RVO group for further statistical comparisons. Univariate and multiple regression analysis showed that the area of the FAZ was significantly correlated with VA in DR and RVO (all P ≤ 0.003). The relationship between FAZ area and VA varied with age (P = 0.026) such that for a constant FAZ area, an increase in patient age was associated with poorer vision (rise in logarithm of the minimum angle of resolution visual acuity). Disruption of the ellipsoid zone was significantly correlated with VA in univariate and multiple regression analysis (both P < 0.001). Occurrence of intraretinal cysts, DRIL length, and lens status were significantly correlated with VA in the univariate regression analysis (P ≤ 0.018) but not the multiple regression analysis (P ≥ 0.210). Remaining variables evaluated in this study were not predictive of VA (all P ≥ 0.225)., Conclusions: The area of the FAZ is significantly correlated with VA in DR and RVO and this relationship is modulated by patient age. Further study about FAZ area and VA correlations during the natural course of retinal vascular diseases and following treatment is warranted., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)