Faculty Bibliography

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).^1-4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment.^1-6 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.

PURPOSE/OBJECTIVE:To provide an image-based description of retinal features associated with risk for development of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD), as visualized with multimodal imaging anchored by structural optical coherence tomography. DESIGN/METHODS:Consensus meeting METHODS: As part of the Classification of Atrophy Meeting program, an international group of experts analyzed and discussed retinal multimodal imaging features in eyes with AMD associated with GA and/or risk of progression to GA. Attendees undertook pre-meeting grading exercises that were reviewed during the meeting sessions. Meeting presentations illustrated established and investigational multimodal imaging features and associated histology. These different features were then each discussed openly by the entire group to arrive at consensus definitions. These definitions were applied to 40 additional images that were graded independently by attendees, to further refine the consensus definitions and descriptions. RESULTS:Consensus was reached on images with descriptors for 12 features. These features included components of outer retinal atrophy (e.g., ellipsoid zone disruption), components of complete retinal pigment epithelium (RPE) and outer retinal atrophy (e.g., RPE perturbation with associated hypo- or hyper-transmission), features frequently seen in eyes with atrophy (e.g., refractile drusen) and features conferring risk for atrophy development (e.g., hyperreflective foci, drusen, and subretinal drusenoid deposits). CONCLUSIONS:An International consensus on terms and descriptions was reached on multimodal imaging features associated GA and with risk for GA progression in eyes with AMD. We believe this information will be useful to clinicians who manage patients with AMD, researchers who study AMD disease interventions and pathogenesis, and those who design clinical trials for therapies targeting earlier AMD stages than GA expansion.

PURPOSE/OBJECTIVE:To survey the pachychoroid spectrum literature to determine how the component diseases are defined. METHODS:English language articles mentioning pachychoroid, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, peripapillary pachychoroid syndrome, and pachyvessels from 1 January 2013 until 31 March 2020 were included. The disease definitions from the Methods sections were evaluated. Definitions were then grouped, if possible, by shared traits. Two definitions were considered similar if the traits mandated or excluded completely satisfy each. RESULTS:This study found there were 18 unique definitions for pachychoroid, 6 for pachychoroid pigment epitheliopathy, 12 for pachychoroid neovasculopathy, and 8 for pachyvessels. There were 39 papers that had no definition of the pachychoroid disease entity being studied. Even when the disease was defined, the criteria were often nebulous, such as "dilated vessels" or "thickened choroid". When parameters were listed, as when thresholds were established for choroidal thickness, they were set at levels below average values for choroidal thickness in the general population. CONCLUSIONS:The variation and ambiguity in disease definitions would make comparisons between publications difficult and hinder precise communication. In addition, the current definitions would classify a significant proportion of the general population as being in the pachychoroid spectrum of diseases.

PURPOSE/OBJECTIVE:To investigate the reflectivity of the structural optical coherence tomography images of the inner choroid as it relates to potential structural composition. METHODS:The reflectivity of slab images 29 - 49 µm and 45 - 65 µm below the RPE, obtained with the Zeiss Plex Elite 9000, were evaluated. The mean and standard deviation of a group of subjects with no ocular disorders were determined. Binarization of the images was done a threshold level established at the mean plus one standard deviation for each slab depth. The proportion of area binarized was evaluated with generalized estimating equations. Representative histologic images obtained from autopsy donors were stained with Masson's trichrome, a staining method helpful in evaluating collagen and ground substance of tissue. RESULTS:There were 67 eyes of 38 subjects with a mean age of 44.5 (range 22 - 82) years. Using generalized estimating equations, age was found to be a significant predictor for the proportion of binarized pixels in both the 29 - 49 µm (P=.034) and the 45 - 65 µm (P<.001) slabs. The histologic specimens illustrated the loss of ground substance with increasing compaction of collagen fibers in the choroidal stroma with advancing age. CONCLUSIONS:The reflectivity from the inner choroid is not uniform and changes with age. As suggested by the histologic specimens, we propose the OCT reflectance from the inner choroid is related, in part, to the packing density of collagen fibers present there.

PURPOSE/OBJECTIVE:To evaluate the vascular characteristics of the choriocapillaris in eyes with pachychoroid as compared with normal controls. METHODS:Eyes with pachychoroid disease were defined as those with a history of central serous chorioretinopathy or peripapillary pachychoroid syndrome. Pachychoroid without disease was defined as eyes with no history of disease with a subfoveal choroidal thickness ≥ the age-adjusted 95 percentile thickness. Frame averaged optical coherence tomography angiography images of the choriocapillaris obtained with a Zeiss Plex Elite were binarized, skeletonized, and evaluated for vascular branching parameters. RESULTS:There were 7 normal controls, 10 pachychoroid without disease, and 17 pachychoroid disease subjects. Mean choriocapillaris vessel segment length was 12.19 µm in eyes with pachychoroid disease as compared with 11.48 µm for normal controls and 11.62 µm for pachychoroid without disease (P=.003 and P=.006, respectively). The branches per mm were fewer in pachychoroid disease, 1215, as compared to normal controls, 1471, or pachychoroid without disease, 1384, (P<.001, and P = .002, respectively). The choriocapillaris vessel diameter was larger, but the fractal dimension was smaller in pachychoroid disease eyes as compared to normal or pachychoroid without disease eyes. There was no statistically significant difference between normal controls and pachychoroid without disease for any measured vascular parameter of the choriocapillaris. CONCLUSIONS:Choriocapillaris vascular parameters suggest that pachychoroid is not necessarily pathologic. It is possible choroidal thickening is an epiphenomenon and there are more significant vascular parameters that are related to disease. These concepts may help guide future prospective studies.

PURPOSE/OBJECTIVE:To evaluate the choroidal vascular patterns of patients with pachychoroid-related diseases in eyes images with wide-field indocyanine green (ICG) angiography. METHODS:Retrospective study of wide-field ICG angiographic images of patients with pachychoroid, peripapillary pachychoroid syndrome, central serous chorioretinopathy (CSC), and pachychoroid-associated neovascularization that were evaluated for anastomoses between vortex vein systems, which are ordinarily separated by a watershed zone. RESULTS:There were 21 subjects with a mean age of 57.4 years and 15 were male. Among the 42 eyes evaluated, CSC was found in 24 eyes (57.1%), peripapillary pachychoroid syndrome in 5 (11.9%), pachychoroid associated neovascularization in 7 (16.7%), and pachychoroid in 6 (14.3%). Every eye showed anastomosis between the superonasal, superotemporal, and inferotemporal vortex vein systems. The inferonasal vortex vein system was less likely to demonstrate anastomosis except for peripapillary pachychoroid syndrome, which showed anastomosis in all eyes. The anastomotic connections were prominent in the central macula in the central serous chorioretinopathy and pachychoroid-associated neovascularization cases, and around the nerve in the peripapillary pachychoroid syndrome cases. Although the large choroidal veins were particularly prominent in the neovascular cases, the number was fewer in the macular region than in other pachychoroid-related diseases in this series. Compared with a control group of 9 eyes, the inferotemporal-superotemporal-superonasal anastomotic connections were more common in the case group (P<.001), and inferonasal quadrant (p=.023 right, P=.01, left eye). CONCLUSIONS:Intervortex venous anastomosis is common in pachychoroid, CSC, peripapillary pachychoroid syndrome, and pachychoroid-associated neovascularization. This finding has important implications concerning pathogenesis and classification of disease.

PURPOSE/OBJECTIVE:To longitudinally characterize structural/angiographic findings of retinal-choroidal anastomosis (RCA) in macular telangiectasia type 2 (MacTel2). METHODS:Combined retrospective/prospective review of MacTel2 patients with >2 visits and >2 months follow-up, including examination, fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and projection-resolved OCT angiography. RESULTS:There were 24 eyes of 12 patients with mean age 61.1 (±7.3 [SD]) years and median follow-up 447 (range 81-1511) days. There were 5 eyes diagnosed with new RCA after not having any previously. RCA was diagnosed in 8 (33%) eyes initially and eventually 13 (54%). In the 8 eyes initially diagnosed with RCA, the number of RCAs and outer retinal hyperrflective lesions increased over the follow-up. The RCAs were found in clusters, generally temporal to the fovea. RCA was uniformly associated with complete retinal subsidence, defined as the loss of outer nuclear layer substance such that the middle retinal layers sank down toward retinal pigment epithelium (RPE), was also present in each case. Each RCA colocalized with a region of hyperreflectivity, previously termed outer retinal hyperreflective lesion (ORHL). There was a lack of fluorescein leakage, lipid, hemorrhage, or any structural correlates to fluid exudation, and no signs of subretinal/sub-RPE neovascularization. CONCLUSION/CONCLUSIONS:De novo RCA development appears to be associated with retinal subsidence, and after RCAs form, they increase in number and topographic distribution over time. Initially after formation, there was no sign of exudation. These data suggest descent of the deep capillary plexus occurs with RCA, devoid subretinal/sub-RPE neovascularization in MacTel2.

PURPOSE/OBJECTIVE:To evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes. METHODS:This retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes. RESULTS:Forty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy. CONCLUSION/CONCLUSIONS:Non-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.