Faculty Bibliography

PURPOSE/OBJECTIVE:To analyze the changes in visual acuity and subfoveal choroidal thickness in patients with non-neovascular age-related macular degeneration (AMD) and drusenoid pigment epithelium detachments (PED). DESIGN/METHODS:Consecutive observational case series. METHODS:Observational retrospective review of eyes diagnosed with drusenoid PED in a single clinical setting. Demographic and clinical data included age, gender, laterality, best corrected visual acuity (BCVA) and subfoveal choroidal thickness measured at baseline, before and after the collapse of the PED, and at the last available follow-up. The presence of geographic atrophy (GA) was also assessed. RESULTS:Thirty-seven eyes of 25 patients (18 females) were included in the analysis. Mean age at baseline was 71 ± 8.4 years. During a mean follow-up period of 4.9 ±1.9 years, PED collapse was observed in 25 eyes (68%). Mean BCVA, mean maximum PED height and mean subfoveal choroidal thickness significantly decreased from baseline to the last available follow-up (p<0.001) in patients showing PED collapse. Choroidal thinning was faster during the PED collapse (speed rate of 35.9 microns/year). From those, 23 eyes (92%) developed GA. A significant correlation between the area of GA and the decrease in choroidal thickness was found (p=0.010). CONCLUSIONS:Choroidal thickness significantly decreased in eyes showing drusenoid PED collapse, but not in eyes in which the PED persisted. A significant correlation with resultant GA area following PED collapse and the magnitude of choroidal thinning was found. Further studies are warranted to better understand the mechanisms involved in the occurrence of choroidal changes during the lifecycle of drusenoid PEDs.

PURPOSE/OBJECTIVE:Macular perivenous retinal whitening results from hypoperfusion-induced ischemia of the middle retina that can occur in central retinal vein occlusion (CRVO). We describe an unusual case of recurrent CRVO with macular perivenous retinal whitening and retino-ciliary venous sparing in the setting of 2 prothrombotic diseases, antiphospholipid syndrome and Type II cryoglobulinemia. METHODS:A 50-year-old man presented with intermittent loss of vision in his right eye related to a recurrent CRVO. Color photography, optical coherence tomography, and fluorescein angiography were performed and compared with those obtained during a previous CRVO that occurred 6 years earlier in the same eye. RESULTS:On presentation, visual acuity was hand motion in the right eye, 20/30 in the left eye. Funduscopic examination of the right eye showed vascular tortuosity, scattered retinal hemorrhages, and retinal whitening in the macula. Optical coherence tomography showed hyperreflectivity of the middle layers of the retina that correlated with the areas of retinal whitening. A discrete area of retinal sparing was noted in the superonasal macula that, on fluorescein angiography, corresponded to the distribution of a single retino-ciliary vein. A review of retinal imaging obtained during the patient's previous CRVO showed similar but more subtle findings of retino-ciliary sparing. Laboratory testing revealed antiphospholipid syndrome and Type II cryoglobulinemia. As the patient's CRVO progressed and subsequently stabilized after treatment in the following months, this area of venous sparing remained the only functional, nonischemic retinal tissue in his macula. Presumably, this vein possessed privileged and uncompromised blood flow by circumventing the occluded venous circulation. CONCLUSION/CONCLUSIONS:Macular perivenous retinal whitening should be considered in the differential diagnosis of retinal whitening and occurs in CRVO secondary to hypoperfusion-induced middle retinal ischemia. To our knowledge, this case represents the first description of retino-ciliary venous sparing of the retina in CRVO.

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PURPOSE: To compare the prevailing patterns of Haller vessel arrangements at the posterior pole between healthy eyes and those with central serous chorioretinopathy (CSC) using en face optical coherence tomography. METHODS: Eyes of normal subjects and patients with acute or chronic CSC underwent optical coherence tomography imaging (RTVue 100; Optovue Inc, Fremont, CA). En face sections at the level of the Haller layer were classified by two masked graders into five mutually exclusive morphologic categories (temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular). The relative prevalence of each Haller vessel arrangement pattern was determined for each phenotype. RESULTS: Numbers of eyes examined were as follows: 154 eyes of 77 normal subjects; 41 eyes of 31 patients with acute CSC; and 39 eyes of 33 patients with chronic CSC. The mean age of participants was 44.4 +/- 14.6 years for healthy subjects (M:F = 37:40), 48.5 +/- 8.2 years (M:F = 24:7) for acute CSC, and 65.3 +/- 13.1 years (M:F = 28:5) for chronic CSC. The relative prevalence of each Haller vessel arrangement pattern differed by phenotype. The temporal herringbone pattern was most prevalent in healthy eyes (49.2%), whereas a reticular pattern was most prevalent in eyes with acute and/or chronic CSC (combined, 48.8%). CONCLUSION: A significant difference was observed in the prevalence of respective Haller vessel arrangement patterns between eyes of normal subjects and those of patients with either acute or chronic CSC. Although further study is needed to determine the mechanistic factors underlying these differences, and the hemodynamic implications, our data suggest that en face optical coherence tomography may find a formal role in choroidal disease classification.

PURPOSE/OBJECTIVE:Mutations in the eyes shut homolog (EYS) gene are a frequent cause of autosomal recessive retinitis pigmentosa (arRP). This study used multi-modal retinal imaging to elucidate genotype-phenotype relationships in EYS-related RP (EYS-RP). DESIGN/METHODS:Cross-sectional study. METHOD/METHODS:Multimodal retinal imaging and electrophysiologic testing was assessed for 16 patients with genetic confirmation of EYS-RP. RESULTS:A total of 27 unique EYS variants were identified in 16 patients. Seven patients presented with an unusual crescent-shaped hyperautofluorescent (hyperAF) ring on fundus autofluorescence (FAF) imaging encompassing a large nasal-superior area of the posterior pole. Three patients had a typical circular or oval perifoveal hyperAF ring and six patients had no hyperAF ring. Spectral domain optical coherence tomography (SD-OCT) and en face OCT showed preserved ellipsoid zone and retinal thickness spatially corresponding to areas within the hyperAF rings. Eleven patients presented with a rod-cone dystrophy on full-field electroretinogram (ffERG), one patient presented with cone-rod dystrophy, and four patients did not undergo ERG testing. A significant spatial association was found between EYS variant position and autofluorescent phenotype, with variants occurring at a nucleotide position greater than GRch37 6:65300137 (c.5617C) being more associated with patients exhibiting autofluorescent rings at presentation. CONCLUSIONS:EYS-RP is a heterogeneous manifestation. Variants occurring in positions closer to the C-terminus of EYS are more common in patients presenting with autofluorescent rings on FAF imaging.

PURPOSE/OBJECTIVE:To describe a novel imaging technique, we call "dense B-scan optical coherence tomography angiography" (DB OCTA) in which thin dense raster scans are used to produce highly resolved structural B-scans with superimposed flow signal that provide precise correlation between retinal microstructure and blood flow. DESIGN/METHODS:Observational case series METHODS: Normal eyes and eyes with macular findings of interest were imaged with DB OCTA in which 150-400 OCT B-scans were acquired within a narrow area (from a single line to 1°) with a width of 10 to 30°. B-scans containing 5-7 consecutive frames were processed for OCTA signal and then combined and visualized post-acquisition by application of a Gaussian filter across neighboring scans. The result was a single, smoothed, high resolution image that contained both structural and flow information. Tracked follow-up DB OCTA was used to detect subtle changes in pathology over time. RESULTS:Two hundred and thirty-seven eyes from 205 subjects aged 18-100 years (mean 72.88 ± 14.74) with a diverse range of macular findings were imaged with DB OCTA. Highly resolved scans showing precise localization of flow signal were readily obtained, even in patients with poor visual acuity and/or poor fixation. We present clinical examples that demonstrate the utility of DB OCTA for visualizing the associations between retinal microstructure and blood flow. CONCLUSIONS:DB OCTA enables precise correlation between retinal microstructure and blood flow. The ability to obtain accurately aligned follow-up DB OCTA studies has the potential to refine the understanding and clinical management of a wide range of macular diseases.

PURPOSE/OBJECTIVE:To use the capillary-free zone along retinal arteries, a physiologic area of superficial avascularization, as an anatomic paradigm to investigate the reliability of optical coherence tomographic angiography (OCTA) for visualizing the deep retinal circulation. DESIGN/METHODS:Validity analysis and laboratory investigation. METHODS:Five normal human donor eyes (mean age 69.8 years) were perfusion-labelled with endothelial antibodies and the capillary networks of the perifovea were visualized using confocal scanning laser microscopy. Regions of the capillary-free zone along the retinal artery were imaged using OCTA in 16 normal subjects (age range 24-51 years). 3x3mm scans were acquired using the RTVue XR Avanti, PLEX Elite 9000, Heidelberg OCT2 and DRI-OCT Triton. Images of the superficial plexus, deep vascular plexus and a slab containing all vascular plexuses were generated using manufacturer recommended default settings. Comparisons between histology and OCTA were performed. RESULTS:Histologic analysis revealed that the capillary-free zone along the retinal artery was confined to the plane of the superficial capillary plexus and did not include the intermediate and deep capillary plexuses. Images derived from OCTA instruments demonstrated a prominent capillary-free zone along the retinal artery in slabs of the superficial plexus, deep plexus and all capillary plexuses. The number of deep retinal capillaries seen in the capillary-free zone was significantly greater on histology than OCTA (P < 0.001). CONCLUSION/CONCLUSIONS:Using the capillary-free zone as an anatomic paradigm we show that the deep vascular beds of the retina are not completely visualized using OCTA. This may be a limitation of current OCTA techniques.

Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration (AMD) subtype and is seen particularly in Asians. Previous studies have suggested disparity in response to intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred treatment for PCV has remained unclear. Recent research has provided novel insights into the pathogenesis of PCV, and imaging studies based on OCT suggest that PCV belongs to a spectrum of conditions characterized by pachychoroid, in which disturbance in the choroidal circulation seems to be central to its pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV. Importantly, 2 large, multicenter randomized clinical trials evaluating the safety and efficacy of anti-VEGF monotherapy and combination with photodynamic therapy (PDT) recently reported initial first-year outcomes, providing level I evidence to guide clinicians in choosing the most appropriate therapy for PCV. In this review, we summarize the latest updates in the epidemiologic features, pathogenesis, and advances in imaging and treatment trials, with a focus on the most recent key clinical trials. Finally, we propose current management guidelines and recommendations to help clinicians manage patients with PCV. Remaining gaps in current understanding of PCV, such as significance of polyp closure, high recurrence rate, and heterogeneity within PCV, are highlighted where further research is needed.

Conventionally rendered optical coherence tomography (OCT) images of the posterior segment contain shadows which influence the visualization of deep structures such as the choroid. The purpose of this study was to determine whether OCT shadow compensation (SC) alters the appearance of the choroid and the apparent choroidal vascularity index (CVI), an OCT-derived estimated ratio of luminal to total choroidal volume. All scans were shadow compensated using a previously published algorithm, binarized using a novel validated algorithm and extracted binarized choroid to estimate CVI. On 27 raw swept-source OCT volume-scans of healthy subjects, the effect of SC on CVI was established both qualitatively and quantitatively. In shadow compensated scans, the choroid was visualized with greater brightness than the neurosensory retina and the masking of deep tissues by retinal blood vessels was greatly reduced. Among study subjects, significant mean difference in CVI of -0.13 was observed between raw and shadow compensated scans. Conventionally acquired OCT underestimates both choroidal reflectivity and calculated CVI. Quantitative analysis based on subjective grading demonstrated that SC increased the contrast between stromal and luminal regions and are in agreement with true tissue regions. This study is warranted to determine the effects of SC on CVI in diseased eyes.