Assessment of Choriocapillaris Flow Prior to Nascent Geographic Atrophy Development Using Optical Coherence Tomography Angiography.

Purpose: To assess the relationship between choriocapillaris (CC) loss and the development of nascent geographic atrophy (nGA) using optical coherence tomography angiography (OCTA) imaging. Methods: In total, 105 from 62 participants with bilateral large drusen, without late age-related macular degeneration (AMD) or nGA at baseline, were included in this prospective, longitudinal, observational study. Participants underwent swept-source OCTA imaging at 6-month intervals. CC flow deficit percentage (FD%) and drusen volume measurements were determined for the visit prior to nGA development or the second-to-last visit if nGA did not develop. Global and local analyses, the latter based on analyses within superpixels (120 × 120-µm regions), were performed to examine the association between CC FD% and future nGA development. Results: A total of 15 (14%) eyes from 12 (19%) participants developed nGA. There was no significant difference in global CC FD% at the visit prior to nGA development between eyes that developed nGA and those that did not (P = 0.399). In contrast, CC FD% was significantly higher in superpixels that subsequently developed nGA compared to those that did not (P < 0.001), and a model utilizing CC FD% was significantly better at predicting foci of future nGA development at the superpixel level than a model using drusen volume alone (P ≤ 0.040). Conclusions: This study showed that significant impairments in CC blood flow could be detected locally prior to the development of nGA. These findings add to our understanding of the pathophysiologic changes that occur with atrophy development in AMD.

MULTISCALE CORRELATION OF MICROVASCULAR CHANGES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH RETINAL SENSITIVITY IN DIABETIC RETINOPATHY.

PURPOSE: To assess global, zonal, and local correlations between vessel density changes measured by optical coherence tomography angiography and retinal sensitivity measured by microperimetry across diabetic retinopathy severity. METHODS: Diabetic patients and nondiabetic controls underwent optical coherence tomography angiography imaging and microperimetry testing. Pearson's correlation was used to assess associations between average sensitivity and skeletonized vessel density (SVD) or foveal avascular zone area centrally. Linear mixed effects modeling was used to assess relationships between local SVD measurements and their spatially corresponding retinal sensitivity measurements. RESULTS: Thirty-nine eyes from 39 participants were imaged. In all slabs, there was a statistically significant positive correlation between retinal sensitivities and SVDs on both global and zonal scales. No statistically significant correlation was found between central retinal sensitivities and the foveal avascular zone areas. Assessment of 1,136 spatially paired retinal sensitivity and SVD measurements revealed a statistically significant local relationship; this seemed to be driven by eyes with proliferative diabetic retinopathy that had reduced retinal sensitivities. CONCLUSION: This study supports positive correlations between SVD and retinal sensitivity at global and zonal spatial scales in diabetic eyes. However, our analysis did not find evidence of statistically significant correlations between retinal sensitivity and SVD on a local scale until advanced diabetic retinopathy.

Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis.

Transcription and metabolism both influence cell function, but dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. We discovered, using a chemical suppressor screen, that inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for transcriptional intermediary factor 1 gamma (tif1γ). This rescue depends on the functional link of DHODH to mitochondrial respiration. The transcription elongation factor TIF1γ directly controls coenzyme Q (CoQ) synthesis gene expression. Upon tif1γ loss, CoQ levels are reduced, and a high succinate/α-ketoglutarate ratio leads to increased histone methylation. A CoQ analog rescues mon's bloodless phenotype. These results demonstrate that mitochondrial metabolism is a key output of a lineage transcription factor that drives cell fate decisions in the early blood lineage.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN SMALL CHOROIDAL MELANOMAS AND CHOROIDAL NEVI.

PURPOSE: To evaluate the use of swept-source optical coherence tomography angiography to detect distinct vascular features in small choroidal melanomas and choroidal nevi. METHODS: Patients with a choroidal nevus or a treatment-naïve choroidal melanoma were imaged with color fundus photography, ultrasound, and swept-source optical coherence tomography angiography (12 × 12 mm). High-risk features including overlying fluid, orange pigment, shaggy photoreceptors, acoustic hollowness, depth >2 mm, and basal diameter >5 mm were assessed. Optical coherence tomography angiography vascular markers included: choroidal vessel visualization, choroidal vessel depth, and choriocapillaris flow signal, assessed qualitatively by comparison with surrounding, unaffected choriocapillaris. RESULTS: Twenty-nine lesions were included in this study, seven flat choroidal nevi, 17 elevated choroidal nevi, and 5 choroidal melanomas. Distinct vascular patterns were noted between flat nevi, elevated nevi, and small choroidal melanomas. Choroidal melanomas displayed two types of vasculature: "nevus-like" vasculature with straight parallel vessels and complex vasculature with vascular loops and crosslinking. Visualized choroidal vessels were significantly deeper in melanomas (110 µm) than elevated (84 µm) or flat nevi (70 µm). In a size-matched subanalysis of 5 elevated choroidal nevi and 5 choroidal melanomas, choroidal melanomas had increased mean choroidal vessel depth (P = 0.015), deepest choroidal vessel visualized (P = 0.034), and presence of a deep choroidal vessel >155 µm (P = 0.048). CONCLUSION: Swept-source optical coherence tomography angiography may detect distinct vascular features in choroidal nevi and small choroidal melanomas.

A practical guide to optical coherence tomography angiography interpretation.

BACKGROUND: Optical coherence tomography angiography (OCTA) can image the retinal vasculature in vivo, without the need for contrast dye. This technology has been commercially available since 2014, however, much of its use has been limited to the research setting. Over time, more clinical practices have adopted OCTA imaging. While countless publications detail OCTA's use for the study of retinal microvasculature, few studies outline OCTA's clinical utility. BODY: This review provides an overview of OCTA imaging and details tips for successful interpretation. The review begins with a summary of OCTA technology and artifacts that arise from image acquisition. New methods and best practices to prevent image artifacts are discussed. OCTA has the unique ability among retinovascular imaging modalities to individually visualize each retinal plexus. Slabs offered in standard OCTA devices are reviewed, and clinical uses for each slab are outlined. Lastly, the use of OCTA for the clinical interpretation of retinal pathology, such as diabetic retinopathy and age-related macular degeneration, is discussed. CONCLUSION: OCTA is evolving from a scientific tool to a clinical imaging device. This review provides a toolkit for successful image interpretation in a clinical setting.

Repeatability and reproducibility of vessel density measurements on optical coherence tomography angiography in diabetic retinopathy.

PURPOSE: Understanding the precision of measurements on and across optical coherence tomography angiography (OCTA) devices is critical for tracking meaningful change in disease. The purpose of this study is to investigate the repeatability and reproducibility of vessel area density and vessel skeleton density measurements from various commercial OCTA devices in diabetic eyes. METHODS: Patients were imaged three consecutive times each on three different OCTA devices. En face OCTA images of the superficial capillary plexus, deep capillary plexus, and full retinal layer were exported for analysis. Vessel area density and vessel skeleton density were calculated. The coefficient of repeatability (CoR) was calculated to assess the repeatability of these measurements, and linear mixed models were utilized to assess the reproducibility of these measurements. RESULTS: Forty-four eyes from 27 diabetic patients were imaged. Normalized CoR values ranged between 3.44 and 6.65% when calculated for vessel area density and between 1.35 and 23.39% when calculated for vessel skeleton density. When stratified by disease severity, the swept-source OCTA device consistently produced the smallest CoR values for vessel area density in the full retinal layer. Vessel area density measurements were repeatable across the two spectral-domain devices in the full retinal layer when all severities were combined, as well as in diabetic patients without retinopathy, mild nonproliferative diabetic retinopathy (NPDR), and moderate NPDR. CONCLUSION: Vessel area density measured in the full retinal layer may be a more precise measure than vessel skeleton density to follow diabetic retinopathy patients both on the same device and across devices.