Faculty Bibliography

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.

Background/UNASSIGNED:Aneurysmal type 1 neovascularization (AT1) is a term recently introduced to better describe the aneurysmal dilatation that may arise from neovascular lesions, more commonly known as polypoidal choroidal vasculopathy. The proposed term, AT1, includes an expanded clinical spectrum of aneurysmal (polypoidal) lesions observed in both different ethnicities and associated with varied clinical phenotypes. Case presentation/UNASSIGNED:A 61-year-old woman of European descent was referred for a new, asymptomatic retinal hemorrhage found on routine examination. Ophthalmoscopy revealed cuticular drusen in both eyes best appreciated on fundus autofluorescence, and a hemorrhagic retinal pigment epithelium detachment above the superior arcade in the right eye. In the fellow eye, a reddish appearing pigment epithelial detachment was noted nasal to the optic nerve. Indocyanine green angiography showed findings of AT1 in both eyes. Optical coherence tomography angiography showed intrinsic flow signal within the aneurysmal lesions. Conclusions/UNASSIGNED:Eyes with cuticular drusen may develop AT1 which, to our knowledge, has not been described. This is an important observation because the documented coexistence of AT1 in the setting of a variant of age-related macular degeneration lends supports to this new understanding of AT1 as a growth pattern of neovascular tissue proliferating between the RPE and Bruch membrane, rather than as a distinct disease entity.

Purpose/UNASSIGNED:To explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy. Methods/UNASSIGNED:There were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared reflectance, fluorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness. Results/UNASSIGNED:SDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 ± 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% confidence interval [CI] 1.1-8.5, P = 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular fields at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0-8.9, P = 0.0461 and 95% CI 1.3-32.4, P = 0.0218, respectively). MA development was not associated with a specific SDD phenotype. Conclusions/UNASSIGNED:MA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular field, conferred higher odds of subsequent MA development.

PURPOSE: To investigate the tractional alterations of the central bouquet (CB) in idiopathic epiretinal membranes (ERMs). DESIGN: Retrospective, consecutive, observational case series. METHODS: ERMs were classified according to a 4-stage grading system. The CB was defined as a circular area of approximately 100 mum composed of densely packed cones (and Muller cells) in the central fovea. Tractional abnormalities of the CB were identified with spectral-domain optical coherence tomography. Ex vivo histopathologic analysis was performed. RESULTS: In this study 263 eyes with ERMs were included. Mean follow-up was 21.2 +/- 16.7 months. At baseline, tractional abnormalities of the CB were diagnosed in 58 out of 263 eyes (22%) and divided into 3 categories: cotton ball sign (defined as a fuzzy hyperreflective area between the ellipsoid zone and the interdigitation zone in the central fovea), foveolar detachment, and acquired vitelliform lesion. The presence of ectopic inner foveal layers was negatively correlated with the presence of CB tractional abnormalities (P = .002). Visual acuity was highest in association with the cotton ball sign and lowest in the acquired vitelliform lesion group. Sequential morphologic progression was identified in 7 eyes. Ex vivo histopathologic analysis illustrated characteristic staining patterns supporting a potential mechanism of traction by Muller cells in the CB. CONCLUSIONS: The cotton ball sign, foveolar detachment, and acquired vitelliform lesion may comprise a continuum in the same clinical spectrum and may represent subsequent stages of CB abnormalities. Foveal Muller cells may play an integral role in the transmission of mechanical forces to the central foveal cones.