Faculty Bibliography

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.

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.

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.

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.

Importance/UNASSIGNED:Congenital retinal macrovessel (CRM) is a rarely reported venous malformation of the retina that is associated with venous anomalies of the brain. Objective/UNASSIGNED:To study the multimodal imaging findings of a series of eyes with congenital retinal macrovessel and describe the systemic associations. Design, Setting, and Participants/UNASSIGNED:In this cross-sectional multicenter study, medical records were retrospectively reviewed from 7 different retina clinics worldwide over a 10-year period (2007-2017). Patients with CRM, defined as an abnormal, large, macular vessel with a vascular distribution above and below the horizontal raphe, were identified. Data were analyzed from December 2016 to August 2017. Main Outcomes and Measures/UNASSIGNED:Clinical information and multimodal retinal imaging findings were collected and studied. Pertinent systemic information, including brain magnetic resonance imaging findings, was also noted if available. Results/UNASSIGNED:Of the 49 included patients, 32 (65%) were female, and the mean (SD) age at onset was 44.0 (20.9) years. A total of 49 eyes from 49 patients were studied. Macrovessel was unilateral in all patients. Color fundus photography illustrated a large aberrant dilated and tortuous retinal vein in all patients. Early-phase frames of fluorescein angiography further confirmed the venous nature of the macrovessel in 40 of 40 eyes. Optical coherence tomography angiography, available in 17 eyes (35%), displayed microvascular capillary abnormalities around the CRM, which were more evident in the deep capillary plexus. Of the 49 patients with CRM, 39 (80%) did not illustrate any evidence of ophthalmic complications. Ten patients (20%) presented with retinal complications, typically an incidental association with CRM. Twelve patients (24%) were noted to have venous malformations of the brain with associated magnetic resonance imaging. Of these, location of the venous anomaly in the brain was ipsilateral to the CRM in 10 patients (83%) and contralateral in 2 patients (17%), mainly located in the frontal lobe in 9 patients (75%). Conclusions and Relevance/UNASSIGNED:Our study has identified an association between macrovessels in the retina and venous anomalies of the brain (24% compared with 0.2% to 6.0% in the normal population). Thus, we recommend new guidelines for the systemic workup of patients with CRM to include brain magnetic resonance imaging with contrast. These lesions may be more accurately referred to as retinal venous malformations, which may raise awareness regarding potential cerebral associations.

PURPOSE/OBJECTIVE:To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). DESIGN/METHODS:Consensus meeting. PARTICIPANTS/METHODS:Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. METHODS:As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. MAIN OUTCOME MEASURES/METHODS:A consensus classification system for atrophy and OCT-based criteria to identify atrophy. RESULTS:OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. CONCLUSIONS:A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

PURPOSE: To determine if directional or anatomical changes in tissue reflectivity of Henle fiber layer (HFL) may influence flow detection on optical coherence tomography angiography (OCT-A). METHODS: Cross-sectional analysis of consecutive cases undergoing OCT-A. Directional changes in visualization of HFL were either produced manually by moving the beam entrance within the pupil or observed occurring naturally because of tilting of the OCT line-scan within a myopic staphyloma. Areas of enhanced HFL visualization were identified on cross-sectional and en face structural OCT scans. Visualization of OCT-A flow within the superficial and the deep capillary plexuses were compared in areas with and without enhanced HFL reflectivity. RESULTS: Fifteen eyes from 9 patients were included, with a mean age of 49.6 +/- 17.9 years. On OCT-A, retinal areas with enhanced HFL reflectivity produced manually or by scan tilting within myopic staphylomas showed no changes in the superficial capillary plexus flow. However, deep capillary plexus flow was altered by variable projection of the superficial flow onto the deeper retinal layers. CONCLUSION: Directional changes in HFL reflectivity can alter the detection of deep capillary plexus flow imaged with OCT-A by influencing the projection of superficial flow onto the deeper retinal layers. We recommend that clinicians minimize scan tilting during scan acquisition and be aware of this phenomenon in eyes with posterior staphyloma.