Faculty Bibliography

PURPOSE/OBJECTIVE:To evaluate the clinical characteristics, multimodal imaging features, and long-term treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) and bacillary layer detachment (BALAD) treated with intravitreal anti-VEGF therapy. DESIGN/METHODS:Retrospective, longitudinal, case series. PARTICIPANTS/METHODS:Treatment-naive patients with nAMD (n = 30) showing BALAD on OCT and undergoing anti-VEGF therapy. METHODS:Clinical records and multimodal imaging results of up to 4 years after diagnosis were reviewed. MAIN OUTCOME MEASURES/METHODS:Best-corrected visual acuity (BCVA) values were compared over time. The cumulative risk of and risk factors for subretinal fibrosis were assessed using Cox regression analyses, and adjusted hazard ratio (aHR) was computed. RESULTS:Thirty eyes of 30 patients were included. Macular neovascularization (MNV) subtypes were distributed as follows: type 1, 63%; type 2, 27%; mixed type 1 and 2, 3%; type 3, 3%; aneurysmal type 1, 3%. The BCVA significantly improved after anti-VEGF loading phase (Snellen equivalent, from 20 of 118 to 20 of 71, P = 0.03), but it returned to the baseline levels at 4 years (Snellen equivalent, 20 of 103, P = 0.6). The cumulative risk of subretinal fibrosis was 77% at 4 years. The risk factors associated with subretinal fibrosis included hemorrhagic BALAD (aHR, 2.02; 95% confidence interval [CI] 1.54-3.22; P < 0.01) and the presence of subretinal hyperreflective material (aHR, 1.83; 95% CI 1.35-3.14; P < 0.01). CONCLUSIONS:BALAD was found in association with all types of MNV in patients with nAMD. Long-term observation revealed poor functional outcomes related to the high risk of subretinal fibrosis.

PURPOSE/OBJECTIVE:To evaluate hypotheses about the role of acquired vitelliform lesion (AVL) in age-related macular degeneration (AMD) pathophysiology. DESIGN/METHODS:Laboratory histology study; retrospective, observational case series METHODS: : Two donor eyes in a research archive with AVL and AMD were analyzed with light and electron microscopy for AVL content at locations matched to ex vivo B-scans. A retrospective, observational clinical cohort study of 42 eyes of 30 patients at two referral clinics) determined the frequency of optical coherence tomography (OCT) features stratified by AVL fate. RESULTS:Histologic and clinical cases showed subretinal drusenoid deposit (SDD) and drusen. Ultrastructural AVL components in two donor eyes included retinal pigment epithelium (RPE) organelles (3-22% of volume), outer segments (2-10%), lipid droplets (0.2-12%), and a flocculent material (57-59%). Of 48 AVL (mean follow-up 46 ± 39 months), 50% collapsed to complete RPE and outer retinal atrophy (cRORA), 38% were stable, 10% resorbed, and 2% developed neovascularization. The ETDRS grid central subfield contained 77% of AVL. Hyperreflective foci, ellipsoid zone disruption, and hyperreflective thickening of the RPE-basal lamina-Bruch's membrane band were common at maximum AVL expansion. Collapsing and non-collapsing AVL had different growth rates (rapid vs slow, respectively). CONCLUSIONS:AVL deposits contain unexpectedly low levels of RPE organelles and outer segments. Subfoveal predilection, reflectivity on OCT, hyperautofluorescence, yellow color, and growth-regression phases suggest dysregulation of lipid transfer pathways specific to cone photoreceptors and supporting cells in formation of AVL deposit, analogous to drusen and SDD. Prediction of AVL outcomes via growth rates should be confirmed in larger clinical studies.

PURPOSE:To analyze the nature of multiple evanescent white dot syndrome (MEWDS) and differentiate an idiopathic or primary form of MEWDS from a secondary form that is seen in association with other clinical conditions affecting the posterior segment of the eye. METHODS:Clinical and multimodal imaging findings including color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography of patients with secondary MEWDS are presented. RESULTS:Twenty consecutive patients with secondary MEWDS were evaluated. Fifteen patients were female. Most were young adults aged between 20 to 40 years with myopia (less than -6 diopters). Pathologic conditions associated with the secondary MEWDS reaction were high myopia (greater than -6 diopters) in two eyes, previous vitreoretinal surgery for rhegmatogenous retinal detachment in 2 eyes, and manifestations of multifocal choroiditis in 18 eyes. In all eyes, the MEWDS lesions followed a course of progression and resolution independent from the underlying condition. CONCLUSION:Secondary MEWDS seems to be an epiphenomenon ("EpiMEWDS") that may be seen in association with clinical manifestations disruptive to the choriocapillaris-Bruch membrane-retinal pigment epithelium complex.

Purpose/UNASSIGNED:To compare patterns of choroidal venous drainage in eyes with pachychoroid disease to those of healthy subjects using ultra-widefield indocyanine green angiography (UWF ICGA). Methods/UNASSIGNED:Patients with pachychoroid disease and healthy controls were recruited at two referral centers. UWF ICGA images were used to evaluate the proportion of the postequatorial fundus drained by major vortex vein systems in each quadrant and to study the incidence and topography of choroidal vascular hyperpermeability (CVH) and intervortex venous anastomoses. Widefield swept-source optical coherence tomography (SS-OCT) was used to evaluate choroidal thickness at the posterior pole in eyes with pachychoroid disease. Results/UNASSIGNED:Fifty-two pachychoroid eyes and 26 healthy eyes were evaluated. Eyes with pachychoroid disease showed a significant within-subject variance in the proportion of the postequatorial fundus drained by each vortex vein system (range, 4.1%-48.1%; P < 0.0001) that was not seen in controls (range, 17.3%-31.7%; P = 0.11). CVH was present in all pachychoroid disease eyes and three of 26 controls. Intervortex venous anastomoses were present in 46 of 52 pachychoroid disease eyes and nine of 26 control eyes. Vortex vein systems with large drainage areas showed greater density of CVH spots. SS-OCT demonstrated asymmetric choroidal drainage in the macula of 59% of pachychoroid eyes. CVH and intervortex venous anastomoses were more prominent in areas showing maximal choroidal thickness. Conclusions/UNASSIGNED:In eyes with pachychoroid disease, imbalanced choroidal venous drainage with congestion of specific vortex vein systems may contribute to a state of choroidal venous insufficiency characterized by regional choroidal thickening, CVH and remodeling of venous drainage routes.

PURPOSE/OBJECTIVE:To report new multimodal imaging features that enhance our understanding of the inflammatory and ischemic nature of acute idiopathic maculopathy (AIM) and to correlate structural and functional changes due to a reversible initial choroidal ischemia over a clinical course of 3.5 months. METHODS:A 31-year-old man presented with acute central vision loss in his right eye due to coxsackievirus-associated AIM. Serial multimodal retinal imaging including confocal true color fundus photography, blue-light fundus autofluorescence (BAF), near-infrared reflectance (NIR), spectral domain optical coherence tomography and swept-source optical coherence tomography (SD-OCT + SS-OCT), and en face SS-OCT angiography (SS-OCTA) were performed over a 3.5-month follow-up. Eidon true color confocal scanner camera (Centervue, Padova, Italy) was used for color and BAF imaging. Near-infrared reflectance and SD-OCT images were obtained with the Heidelberg Spectralis OCT (HRA2 + OCT; Heidelberg Engineering, Heidelberg, Germany). For SS-OCT and en face SS-OCT and SS-OCTA images, the PLEX Elite 9,000 (Carl Zeiss Meditec, Inc, Dublin, CA) was used. Central alterations in choriocapillaris flow were analyzed with SS-OCTA using the University of Washington choriocapillaris (CC) flow deficit quantification algorithm available through the ARI Network. Flow deficit area and density values were analyzed and compared between the first and last examinations. Corresponding en face OCT imaging was used to distinguish true flow defects from artifacts secondary to shadowing. RESULTS:In the acute stage of AIM, a bacillary layer detachment appearing as a yellow-grayish foveal elevation surrounded by a hypopigmented parafoveal ring was evident in a Bull's eye configuration, corresponding to a hyperreflective ring upon NIR and a hyperautofluorescent ring with BAF. SD + SS-OCT showed mostly intraretinal fluid consistent with a bacillary layer detachment in conjunction with a thickened inner choroid. At presentation, SS-OCTA demonstrated a marked reduction of choriocapillaris flow signal. At 1 week, early resolution of retinal fluid was followed by restoration of the ellipsoid zone at 5 weeks, while restoration of the interdigitation zone and reduction in retinal pigment epithelium/Bruch membrane complex thickening occurred more slowly. Swept-source OCT angiography showed a gradual, but incomplete, recovery of inner choroidal flow signal at 3.5-month follow-up. CONCLUSION/CONCLUSIONS:Acutely, AIM may present with a photoreceptor splitting foveal bacillary layer detachment associated with a marked reduction in inner choroidal flow signal on SS-OCTA. Thereafter, restoration of the outer retinal layers and gradual normalization of choroidal flow signal appear to support the often-benign nature of the disease.

PURPOSE/UNASSIGNED:To describe delayed detection of pericentral hydroxychloroquine (HCQ) toxicity. METHODS/UNASSIGNED:67-year-old Dominican woman with rheumatoid arthritis on HCQ presented for examination. RESULTS/UNASSIGNED:Spectral-domain optical coherence tomography (SD-OCT) demonstrated bilateral cystoid macular edema with parafoveal attenuation of the external limiting membrane (ELM) and the ellipsoid zone (EZ). ELM and EZ disruption was present in inferior macula. While subtle superior defects were present on 10-2 visual fields, superior pericentral defects were noted on 24-2 testing. Hyperautofluorescence along inferior arcades corresponded to SD-OCT and visual fields. Examination 2 years prior demonstrated nonspecific points of depression on 10-2 visual fields and normal central SD-OCT findings. EZ and ELM disruption was present in the perifoveal inferior macula. CONCLUSIONS/UNASSIGNED:Early pericentral distribution of HCQ toxicity is not limited to Asian patients. Detecting pericentral HCQ toxicity involves reviewing entire macular cube on OCT. When OCT changes are suspected on parafoveal OCT B-scans, visual field testing with 24-2 may be more sensitive than 10-2.

PURPOSE/OBJECTIVE:Melanotic cells with large spherical melanosomes, thought to originate from retinal pigment epithelium (RPE), are found in eyes with neovascular age-related macular degeneration (nvAMD). To generate hypotheses about RPE participation in fibrosis, we correlate histology to clinical imaging in an eye with prominent black pigment in fibrotic scar secondary to nvAMD. METHODS:Macular findings in a white woman with untreated inactive subretinal fibrosis due to nvAMD in her right eye were documented over 9 years with color fundus photography (CFP), fundus autofluorescence (FAF) imaging, and optical coherence tomography (OCT). After death (age 90 years), this index eye was prepared for light and electron microscopy to analyze 7 discrete zones of pigmentation in the fibrotic scar. In additional donor eyes with nvAMD, we determined the frequency of black pigment (n = 36 eyes) and immuno-labeled for retinoid, immunologic, and microglial markers (RPE65, CD68, Iba1, TMEM119; n = 3 eyes). RESULTS:During follow-up of the index eye, black pigment appeared and expanded within a hypoautofluorescent fibrotic scar. The blackest areas correlated to melanotic cells (containing large spherical melanosomes), some in multiple layers. Pale areas had sparse pigmented cells. Gray areas correlated to cells with RPE organelles entombed in the scar and multinucleate cells containing sparse large spherical melanosomes. In 94% of nvAMD donor eyes, hyperpigmentation was visible. Certain melanotic cells expressed some RPE65 and mostly CD68. Iba1 and TMEM119 immunoreactivity, found both in retina and scar, did not co-localize with melanotic cells. CONCLUSION/CONCLUSIONS:Hyperpigmentation in CFP results from both organelle content and optical superimposition effects. Black fundus pigment in nvAMD is common and corresponds to cells containing numerous large spherical melanosomes and superimposition of cells containing sparse large melanosomes, respectively. Melanotic cells are molecularly distinct from RPE, consistent with a process of transdifferentiation. The subcellular source of spherical melanosomes remains to be determined. Detailed histology of nvAMD eyes will inform future studies using technologies for spatially resolved molecular discovery to generate new therapies for fibrosis. The potential of black pigment as a biomarker for fibrosis can be investigated in clinical multimodal imaging datasets.

PURPOSE/OBJECTIVE:To describe the multimodal imaging findings of retinal lesions that clinically resemble retinal astrocytic hamartomas (RAHs), but also have unique characteristics that we believe represent a novel variant. METHODS:Observational study. Five eyes in five patients with solitary retinal lesion evaluated at the retina division of three institutions. We describe the multimodal imaging findings including fundus photography, fundus autofluorescence, fluorescein angiography, spectral-domain optical coherence tomography (OCT), swept-source OCT, swept-source OCT angiography and ultrasonography. RESULTS:The retinal lesions described shared similar appearance to RAHs but demonstrated unique features such as glistening granular appearance on fundus photographs with perivascular hyperreflectivity with OCT and OCT angiography. CONCLUSION/CONCLUSIONS:The lesions described herein appear to have unique characteristics that warrant a designation as a novel RAH variant. The name presumed retinal pericapillary astrocytic hamartoma is suggested.