Faculty Bibliography

PURPOSE/OBJECTIVE:To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN/METHODS:Consensus meeting. PARTICIPANTS/METHODS: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/METHODS: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.

PURPOSE/OBJECTIVE:To evaluate the subfoveal choroidal thickness (SFCT) and vascular architecture in the fellow eyes of patients with circumscribed choroidal hemangioma (CCH). METHODS:In this retrospective observational study, patients were selected from outpatient ophthalmology clinics at the Memorial Sloan Kettering Cancer Center and Vitreous Retina Macula Consultants of New York. Subfoveal choroidal thickness was measured using enhanced depth imaging spectral domain optical coherence tomography from the outer portion of Bruch membrane to the choroidal-scleral interface. Choroidal vascular architecture was qualitatively examined. The main outcome measure was SFCT in fellow eyes of patients with CCH, which was compared with an age- and gender-matched control group. RESULTS:Thirty-one fellow eyes (15 right eyes and 16 left eyes) of patients with CCH (23 males and 8 females) were examined. The fellow eye had a mean SFCT of 361.2 ± 99.9 μm compared with 252.0 ± 77.6 μm in the control group (P < 0.0001). Vascular architecture was disorganized in 13 (42%) fellow eyes and 1 (3%) control eye (P < 0.0001), with no apparent gradient of vessel sizes or discrete choroidal layers. The normal association between older age and a thinner choroid existed in control eyes but not in fellow eyes. Hemangioma thickness measured by ultrasound and the presence of subfoveal fluid in the CCH eye did not correlate with the fellow-eye SFCT. CONCLUSION/CONCLUSIONS:In patients with CCH, fellow eyes had thicker SFCT when compared with age- and gender-matched control eyes. Choroidal architecture was often irregular, without segmented vascular layers. These findings suggest that inherent choroidal changes may exist in patients with CCH.

PURPOSE/OBJECTIVE:To clarify the role of subretinal drusenoid deposits (SDD; pseudodrusen) in the progression of age-related macular degeneration through high-resolution histology. METHODS:In 33 eyes of 32 donors (early age-related macular degeneration, n = 15; geographic atrophy, n = 9; neovascular age-related macular degeneration, n = 7; unremarkable, n = 2), and 2 eyes of 2 donors with in vivo multimodal imaging including optical coherence tomography, examples of SDD contacting photoreceptors were assessed. RESULTS:Subretinal drusenoid deposits were granular extracellular deposits at the apical retinal pigment epithelium (RPE); the smallest were 4-µm wide. Outer segment (OS) fragments and RPE organelles appeared in some larger deposits. A continuum of photoreceptor degeneration included OS disruption, intrusion into inner segments, and disturbance of neurosensory retina. In a transition to outer retinal atrophy, SDD appeared to shrink, OS disappeared, inner segment shortened, and the outer nuclear layer thinned and became gliotic. Stage 1 SDD on optical coherence tomography correlated with displaced OS. Confluent and disintegrating Stage 2 to 3 SDD on optical coherence tomography and dot pseudodrusen by color fundus photography correlated with confluent deposits and ectopic RPE. CONCLUSION/CONCLUSIONS:Subretinal drusenoid deposits may start at the RPE as granular, extracellular deposits. Photoreceptor OS, RPE organelles, and cell bodies may appear in some advanced deposits. A progression to atrophy associated with deposit diminution was confirmed. Findings support a biogenesis hypothesis of outer retinal lipid cycling.

PURPOSE/OBJECTIVE:Preliminary to evaluate geometric indices (vessel sphericity and cylindricity) for volume-rendered optical coherence tomography angiography (OCTA) in healthy and diabetic eyes. METHODS:Twenty-six eyes of 13 healthy subjects and 12 eyes of patients with central ischemic, non-proliferative diabetic retinopathy were included. OCTA volume and surface area of the foveal vessels were measured and compared to determine OCTA sphericity and cylindricity indices and surface efficiency (SE). RESULTS:, p = 0.021). In relation to total foveolar tissue volume, the proportion of blood vessels was 22% in healthy individuals and only 20% in diabetics. The difference between the groups was more pronounced with respect to the total OCTA surface area, with a decrease of 13% in diabetics. A diabetic eye was most likely using geometric vessel indices analysis if the sphericity value was ≥ 0.190, with a cylindricity factor of ≥ 0.001. Reproducibility of the method was good. CONCLUSIONS:A method for OCTA surface area and volume measurements was developed. The application of the novel OCTA sphericity and cylindricity indices could be suitable as temporal biomarker to characterize stable disease or disease progression and may contribute to a better understanding in the evolution of diabetic retinopathy.

PURPOSE/OBJECTIVE:To describe the progression and regression of individual subretinal drusenoid deposits (SDDs) and surrounding photoreceptors and retina in patients with age-related macular degeneration (AMD) over a 3.5-year period using multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO). DESIGN/METHODS:Longitudinal observational study. PARTICIPANTS/METHODS:Four patients with intermediate AMD. METHODS:Six eyes of 4 patients with intermediate AMD each were imaged 4 times over 3.5 years. Five eyes of 3 patients showed only SDD and no drusen. Subretinal drusenoid deposit presence and progression were assessed by multimodal imaging and a 3-stage grading system based on spectral-domain (SD) OCT. Morphologic features and the fine structure of individual SDD lesions identified at baseline were examined by AOSLO at follow-up visits. Reflectivity of photoreceptors surrounding SDD were assessed with AOSLO and SD OCT. MAIN OUTCOME MEASURES/METHODS:Morphologic features, fine structure, and size of individual SDD lesions by AOSLO; photoreceptor integrity surrounding SDD via AOSLO and SD OCT; and retinal layer thicknesses via SD OCT. RESULTS:Individual SDDs followed independent lifecycle trajectories, exhibiting growth, shrinkage, fusion, and disappearance. Alterations in shape, morphologic features, and internal structure were not obviously the result of the presence of invading phagocytes. Of 822 lesions across all stages examined at baseline, 566 (69%) grew, 123 (15%) shrank, 47 (6%) remained of similar size, 86 (11%) disappeared, and 5 (0.6%) reappeared after regression. A return of characteristic photoreceptor reflectivity in AOSLO (punctate) and in SD OCT (prominent ellipsoid zone) was observed after regression of some SDD in 5 eyes of 4 patients. All eyes exhibited thinning of photoreceptor layers, despite intact retinal pigment epithelium (RPE), to approximately 70% of baseline thicknesses, as well as poorly visible or undetectable outer retinal bands. CONCLUSIONS:Adaptive optics scanning laser ophthalmoscopy and SD OCT imaging of individual SDDs over 3.5 years revealed independent trajectories of progression and regression, believed to reflect the activities of local outer retinal cells. Restoration of some photoreceptor reflectivity and intact RPE after SDD regression should be seen in the larger context of outer retinal atrophy, previously suggested as a new form of advanced AMD, and herein replicated.

PURPOSE/OBJECTIVE: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/METHODS:Consensus meeting. PARTICIPANTS/METHODS: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/METHODS: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.

PURPOSE/OBJECTIVE:Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV). METHODS:A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator. RESULTS:A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included. CONCLUSION/CONCLUSIONS:When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.

PURPOSE/OBJECTIVE:To characterize structural and angiographic findings in macular telangiectasia Type 2 (MacTel 2) and examine associations with visual acuity. METHODS:MacTel 2 patients with complete ophthalmologic examination, including fundus photography, autofluorescence, spectral-domain optical coherence tomography, and projection-resolved optical coherence tomography angiography, were retrospectively evaluated. RESULTS:There were 43 eyes of 22 patients with a mean age 63.9 (±10.3) years. Six patients had diabetes. Twenty-one eyes (48.8%) had retinal-choroidal anastomoses (RCAs) without any evidence of neovascularization extending laterally in a plane above or below the retinal pigment epithelium. None of the eyes had hemorrhage, lipid, or signs of subretinal exudation. When present, an average of 55 (±33.7) individual RCAs were clustered primarily in temporal juxtafoveal region of involved eyes. Right-angle veins were seen in all 21 eyes with RCAs, and hyperpigmentation was present in 18 (P < 0.001 for both). A conical collection of hyperreflective material spanning from Bruch membrane past external limiting membrane of ≥200-μm basal diameter was found in 21 eyes and labeled outer retinal hyperreflective lesion. Retinal-choroidal anastomoses occurred in clusters, often within the outer retinal hyperreflective lesion. This lesion colocalized with focal thinning of the outer nuclear layer and was surrounded by a larger defect in the ellipsoid zone. The presence of diabetes (P = 0.015), outer retinal hyperreflective lesion (P = 0.006), RCA (P = 0.005), and ellipsoid zone defect extent (P < 0.001) were associated with decreased visual acuity. CONCLUSION/CONCLUSIONS:Retinal-choroidal anastomoses occur in eyes with MacTel 2 without signs of exudation. Retinal-choroidal anastomoses occur in numerous clusters particularly in the temporal juxtafoveal macula. Diabetes, ellipsoid zone defect extent, RCAs, and the outer retinal hyperreflective lesion predict poorer vision in MacTel 2.

PURPOSE/OBJECTIVE:To describe two cases of retinal detachment with hydration folds and discuss the possible cause of these outer retinal abnormalities. METHODS:The medical and imaging records of two patients with retinal detachment and hydration folds were examined. PATIENTS/METHODS:A 43-year-old myopic woman who developed a retinal detachment secondary to a macular hole and a 35-year-old man referred with a rhegmatogenous retinal detachment masquerading as an exudative detachment were each found to have retinal hydration folds. RESULTS:On near-infrared reflectance imaging, the hydration folds appeared similar to eddy currents, and these corresponded to curvilinear outer retinal plications on optical coherence tomography. The photoreceptor outer segments appeared thickened and elongated, and there was apparent lateral expansion of the outer retinal layers. CONCLUSION/CONCLUSIONS:Hydration folds are found in rhegmatogenous retinal detachment and demonstrate reproducible imaging characteristics on near-infrared imaging and optical coherence tomography. The cause for such outer retinal plications is currently unknown. We suspect that they form as a result of hydration of the glycosaminoglycans in the interphotoreceptor matrix, which lies between the photoreceptors. Additional studies are warranted to explore this pathophysiology.

PURPOSE/OBJECTIVE:To study structural and angiographic optical coherence tomography (OCT) data of the macula from controls, diabetics, and those with glaucoma to evaluate neurovascular and structural relationships. METHODS:This is a retrospective study of 89 eyes from 49 patients in a community-based retinal referral practice with diabetes, glaucoma, and normal controls. The patients were evaluated with OCT to include retinal nerve fiber layer (RNFL) thickness measurement and ganglion cell layer (GCL) volume determination. The vascular density of the radial peripapillary capillary network and the vascular plexuses in the macula were evaluated with OCT angiography. The main outcome measures were the data obtained per disease state and the interrelationships the data displayed. RESULTS:The mean GCL volumes were significantly lower than the Control Group in both the Diabetic (P=.016) and Glaucoma groups (P<.001). The difference between the Diabetic and Glaucoma groups was not significant (P=.052). The mean global vascular density was greater in the Control group than the Diabetic group (P=.002,) and the Glaucoma group (P<.001). The mean RNFL thicknesses were lowest in the Glaucoma group. Both the Diabetic and Glaucoma groups had significantly lower radial peripapillary network and deep vascular plexus density values as compared with controls. CONCLUSIONS:While there are important differences in disease pathogenesis differ between diabetes and glaucoma, they share certain similarities in the structural and angiographic abnormalities eventually produced. This suggests that in addition to canonical pathways of disease, a component of both could represent neurodegenerative disease, offering the possibility for the development of new treatments.