Faculty Bibliography

PURPOSE/OBJECTIVE:To report a case of branch retinal artery occlusion associated with paracentral acute middle maculopathy on spectral-domain optical coherence tomography presumably related to heavy cannabis consumption. METHODS:Retrospective case report. Spectral-domain optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography were performed. RESULTS:A 21-year-old healthy man described the acute onset of superior visual field loss in his right eye. He admitted smoking approximately 15 g daily of cannabis for several weeks during COVID-19 confinement. Ophthalmoscopic examination of the right eye showed inferotemporal retinal whitening. Spectral-domain optical coherence tomography illustrated evidence of the ischemic cascade with diffuse hyperreflectivity of the inner and middle retinal layers within the central region of the retinal infarct and paracentral acute middle maculopathy at the border of the infarct. Optical coherence tomography angiography demonstrated predominant flow signal loss at the level of the deep retinal capillary plexus. Fluorescein angiography and complete systemic workup were unremarkable. CONCLUSION/CONCLUSIONS:Branch retinal artery occlusion and paracentral acute middle maculopathy may be related to heavy cannabis use as the result of transient arterial vasospasm.

PURPOSE/OBJECTIVE:Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks and associated systemic diseases. METHODS:126 Subjects with AMD were classified as SDD (with or without soft drusen), or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke. RESULTS:There were 62 SDD subjects and 64 non-SDD subjects, 51 total had CVD or stroke.SDD correlated significantly with: lower mean serum HDL (61±18 vs. 69±22 mg/dl, p= 0.038, t test); CVD and stroke (34/51 SDD, p= 0.001, chi square); ARMS2 risk allele (p= 0.019, chi square), but not with CFH risk allele (p = 0.66). Non-SDD (drusen only) correlated/trended with: APOE2 (p= 0.032) and CETP (p= 0.072) risk alleles (chi square). Multivariate independent risks for SDD were: CVD and stroke (p= 0.008), and ARMS2 homozygous risk (p= 0.038). CONCLUSION/CONCLUSIONS:SDD and non-SDD subjects have distinct systemic associations, serum and genetic risks. SDD are associated with CVD and stroke, ARMS2 risk, and lower HDL; non-SDD with higher HDL, CFH risk and two lipid risk genes. These and other distinct associations suggest these lesions are markers for distinct diseases.

Purpose:To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods:Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results:Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capillary plexus (DCP) inflow derived from small-diameter vessels succeeding ICP arterioles. The most prevalent outflow pathways coursed through superficial draining venules (74%). DCP draining venules ordinarily merged with ICP draining venules and drained independently of superficial venules in 21% of cases. The morphology of DCP draining venules in structural HighRes OCT is distinct from other vessels crossing the inner nuclear layer and can be used to identify superficial veins. Conclusions:Vascular connectivity analysis supports a hybrid circuitry of blood flow within the human parafoveal macula. Translational Relevance:Characterization of parafoveal macular blood flow connectivity in vivo using a precise segmentation of HighRes OCT is consistent with ground-truth microscopy studies and shows a hybrid circuitry.

Importance/UNASSIGNED:By validating optical coherence tomography angiography (OCTA) in the analysis of type 3 macular neovascularization secondary to age-related macular degeneration, the overall value of clinical OCTA for disease observation, diagnosis, and staging is increased. Objective/UNASSIGNED:To assess the association of in vivo OCTA of type 3 macular neovascularization secondary to age-related macular degeneration with corresponding ex vivo histology. Design, Setting, and Participants/UNASSIGNED:This study included clinical imaging, laboratory microscopy, and eye-tracked clinicopathologic correlation of a single case from a community-based practice evaluated at a university-based research laboratory from 2014 to 2019. Exposures/UNASSIGNED:Infrared reflectance and eye-tracked spectral-domain OCTA clinical imaging was correlated with ex vivo high-resolution histologic images of the preserved donor eye. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding with clinical OCTA signatures. Projection artifact removal based on 2-dimensional vessel-shape estimation and a Gaussian blur filter demonstrated a robust preservation of neovascular flow signal. Main Outcomes and Measures/UNASSIGNED:Histology findings associated with clinical OCTA signatures. Three-dimensional view of neovascularization via video. Results/UNASSIGNED:A White woman in her 90s with type 3 neovascularization secondary to age-related macular degeneration was treated with 37 intravitreal injections of ranibizumab and aflibercept in the right eye. The index lesion displayed a drusenoid pigment epithelium detachment, characteristic of type 3 neovascularization. OCTA decorrelation signal in the index lesion corresponded in histology to a collagen-ensheathed vascular complex contacting basal laminar deposit that outlasted the retinal pigment epithelium. The subretinal pigment epithelium-basal laminar space contained calcified material and glial processes. No connection between the choriocapillaris and this space was observed. Video showed a columnar tangle of flow signal in the outer nuclear layer, with inflow and outflow vessels connecting to the superficial artery and vein. Conclusions and Relevance/UNASSIGNED:While this study presents only 1 case in which a vascular connection between subretinal pigment epithelium-basal laminar space and choriocapillaris was undetected, these results support the potential value of OCTA for diagnosis. OCTA decorrelation signal of type 3 neovascularization corresponded with intraretinal neovessels on histology. Projection artifact removal based on 2-dimensional vessel-shape estimation and Gaussian blur filter demonstrated their potential value for further use in OCTA decorrelation signal processing.

PURPOSE/OBJECTIVE:To describe the recovery timeline of spots and dots in multiple evanescent white dot syndrome. METHODS:Sequential multimodal retinal imaging including fundus autofluorescence and cross-sectional and en face optical coherence tomography was performed to track the development and resolution of spots and dots in a case of multiple evanescent white dot syndrome. RESULTS:En face optical coherence tomography showed that the spots are the result of ellipsoid zone loss and are hyperautofluorescent due to unmasking of the underlying retinal pigment epithelium autofluorescence. Conversely, the dots are hyperreflective with cross-sectional and en face optical coherence tomography and hyperautofluorescent, which we propose may be due to accumulation of degenerated photoreceptor material including fluorophores with autofluorescent capability such as precursors of A2E. The earlier resolution of the hyperautofluorescent spots allowed for later detection of the hyperautofluorescent dots. CONCLUSION/CONCLUSIONS:This case report illustrates the different recovery timelines of spots and dots in multiple evanescent white dot syndrome. Although both lesion types are hyperautofluorescent, the mechanism of autofluorescence is distinctive and may be explained by their contrasting pathoanatomy.

INTRODUCTION/UNASSIGNED:White dot syndromes are a heterogeneous group of diseases that affect different layers in the retina and choroid. Multimodal imaging is fundamental in the diagnosis, but also can be crucial in unveiling the pathogenesis of these entities. MATERIAL AND METHODS/UNASSIGNED:Literature review. RESULTS/UNASSIGNED:Optical coherence tomography (OCT) provides depth-resolved, histological grade images of the vitreous, retina, and choroid. This technology is very useful to localize the primary nature and level of pathology of the various white dot syndromes. En face OCT can provide additional information regarding the interrelationship of lesion types. Vascular involvement at the level of the retina, choriocapillaris or choroid can be assessed by en face OCT angiography (OCT-A) and is not limited by masking, leakage or staining as can occur with conventional angiography (fluorescein or indocyanine green angiography) which requires dye injection. CONCLUSION/UNASSIGNED:OCT and OCTA are fundamental in the diagnosis and follow-up of white dots syndromes.

PURPOSE/OBJECTIVE:To determine the prevalence and characteristics of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) in eyes with patchy atrophy due to pathologic myopia (PM). METHOD/METHODS:Five hundred eyes of 253 patients with patchy atrophy were examined between 2014 and 2020 at the Advanced Clinical Center for Myopia. The main outcome measures included the prevalence and characteristics of active MFC/PIC lesions diagnosed by optical coherence tomography (OCT). RESULTS:Fifty-five of the 500 eyes (11%) diagnosed with patchy atrophy had OCT features of active MFC/PIC lesions such as focal elevations of the RPE filled with medium hyperreflectivity material, curvilinear scars (Schlaegel lines), and/or areas of outer retinal atrophy. At the time when the MFC/PIC was diagnosed, the mean age was 57.3±12.0 years, and the mean axial length was 29.2±1.8 mm. Macular neovascularization (MNV) was found in 45 of eyes (81.8%) with MFC/PIC vs 151 eyes without such findings (33.9%; P <0.001). In 25 of the 55 eyes (45.5%), active MFC/PIC lesions were found before the development of the patchy atrophy. The Bruch's membrane defects were co-located with these lesions. CONCLUSIONS:Active MFC/PIC lesions were identified in a minority of eyes with PM, and a subset of these lesions were observed to progress to findings indistinguishable from myopic patchy atrophy. Evidence of MFC/PIC in eyes with PM appeared to be a risk factor for the development of MNV.

PURPOSE/OBJECTIVE:To investigate a possible microvascular component of poppers maculopathy (PMP) using optical coherence tomography angiography (OCTA). METHODS:Twelve patients suffering from poppers maculopathy were included. Health records, optical coherence tomography (OCT), and OCTA data was gathered and compared to a healthy control group (HC). PMP lesion type was determined by manifestation in OCT. OCTA-based evaluation of retinal vascular plexus and choriocapillaris (CC) was executed. Vessel density (VD) and vessel length density (VLD) in superficial and deep capillary plexus (SCP, DCP), as well as flow deficits (FD), within the foveal avascular zone (FAZ) in CC were assessed. RESULTS:Median age of PMP patients was 40 (min 24; max 64) years, all male. Eleven patients presented with ellipsoid zone-type lesions; one patient showed a vitelliform-type lesion. No qualitative microvascular changes between PMP patients and HC were identified. Quantitative values for VD and VLD of SCP and DCP did not differ in between the two groups. The analysis of FDs in CC showed no deviation from PMP patients to HC. CONCLUSIONS:No vascular anomalies in qualitative and quantitative analysis in OCTA were detected in PMP patients. The constitution of the CC within FAZ of PMP patients does not differ from HC when assessed as FD.