PurposeTo describe an automated algorithm to quantify the foveal avascular zone (FAZ), using optical coherence tomography angiography (OCTA), and to compare its performance for diagnosis of diabetic retinopathy (DR) and association with best-corrected visual acuity (BCVA) to that of extrafoveal avascular area (EAA).MethodsWe obtained 3 × 3-mm macular OCTA scans in diabetic patients with various levels of DR and healthy controls. An algorithm based on a generalized gradient vector flow (GGVF) snake model detected the FAZ, and metrics assessing FAZ size and irregularity were calculated. We compared the automated FAZ segmentation to manual delineation and tested the within-visit repeatability of FAZ metrics. The correlations of two conventional FAZ metrics, two novel FAZ metrics, and EAA with DR severity and BCVA, as determined by Early Treatment Diabetic Retinopathy Study (ETDRS) charts, were assessed.ResultsSixty-six eyes from 66 diabetic patients and 19 control eyes from 19 healthy participants were included. The agreement between manual and automated FAZ delineation had a Jaccard index > 0.82, and the repeatability of automated FAZ detection was excellent in eyes at all levels of DR severity. FAZ metrics that incorporated both FAZ size and shape irregularity had the strongest correlation with clinical DR grade and BCVA. Of all the tested OCTA metrics, EAA had the greatest sensitivity in differentiating diabetic eyes without clinical evidence of retinopathy, mild to moderate nonproliferative DR (NPDR), and severe NPDR to proliferative DR from healthy controls.ConclusionsThe GGVF snake algorithm tested in this study can accurately and reliably detect the FAZ, using OCTA data at all DR severity grades, and may be used to obtain clinically useful information from OCTA data regarding macular ischemia in patients with diabetes. While FAZ metrics can provide clinically useful information regarding macular ischemia, and possibly visual acuity potential, EAA measurements may be a better biomarker for DR.

IMPORTANCE Diabetic retinopathy (DR) is a leading cause of vision loss that is managed primarily through qualitative clinical examination of the retina. Optical coherence tomography angiography (OCTA) may offer an objective and quantitative method of evaluating DR. OBJECTIVE To quantify capillary nonperfusion in 3 vascular plexuses in the macula of eyes patients with diabetes of various retinopathy severity using projection-resolved OCTA (PR-OCTA). DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study at a tertiary academic center comprising 1 eye each from healthy control individuals and patients with diabetes at different severity stages of retinopathy. Data were acquired and analyzed between January 2015 and December 2017. MAIN OUTCOMES AND MEASURES Foveal avascular zone area, extrafoveal avascular area (EAA), and the sensitivity of detecting levels of retinopathy. RESULTS The study included 39 control individuals (20 women [51%]; mean [SD] age, 43.41 [19.37] years); 16 patients with diabetes without retinopathy (8 women [50%]; mean [SD] age, 56.50 [12.43] years); 23 patients with mild to moderate nonproliferative DR (18 women [78%] ; mean [SD] age, 62.48 [10.55] years); and 32 patients with severe nonproliferative DR or proliferative DR (12 women [38%]; mean age, 53.41 [14.05] years). Mean (SD) foveal avascular zone area was 0.203 (0.103) mm 2 for control individuals, 0.192 (0.084) mm 2 for patients with diabetes without retinopathy, 0.243 [0.079] mm 2 for mild to moderate nonproliferative DR, and 0.359 (0.275) mm 2 for severe nonproliferative DR or proliferative DR. Mean (SD) EAA in whole inner retinal slab in these groups, respectively, were 0.020 (0.031) mm 2 , 0.034 (0.047) mm 2 , 0.038 (0.040) mm 2 , and 0.237 (0.235) mm 2. The mean (SD) sum of EAA from 3 segmented plexuses in each of the respective groups were 0.103 (0.169) mm 2 , 0.213 (0.242) mm 2 , 0.451 (0.243) mm 2 , and 1.325 (1.140) mm 2. With specificity fixed at 95%, using EAA in inner retinal slab, the sensitivity of detecting patients with diabetes from healthy control individuals was 28% (95% CI, 18%-40%), 31% for patients with DR (95% CI, 19%-45%), and 47% for patients with severe DR (95% CI, 29%-65%) from whole inner retinal EAA. With the sum of EAA from 3 individual plexuses, the sensitivities were 69% (95% CI, 57%-80%), 82% (95% CI, 70%-91%), and 97% (95% CI, 85%-100%), respectively. Avascular areas were not associated with signal strength index. The commercial vessel density from the 2-plexus scheme distinguished the groups with lower sensitivity and were dependent on SSI. CONCLUSIONS AND RELEVANCE Automatically quantified avascular areas from a 3-layer segmentation scheme using PR-OCTA distinguished levels of retinopathy with a greater sensitivity than avascular areas from unsegmented inner retinal slab or measurements from a commercially available vessel density in 2-layer scheme. Additional studies are needed to investigate the applicability of nonperfusion parameters in clinical settings.

Aniridia is most commonly caused by haploinsufficiency of the PAX6 gene, characterised by variable iris and foveal hypoplasia, nystagmus, cataracts, glaucoma and aniridia related keratopathy (ARK). Genotype-phenotype correlations have previously been described, however detailed longitudinal studies of aniridia are less commonly reported. We identified eighty-six patients from sixty-two unrelated families with molecularly confirmed heterozygous PAX6 variants from a United Kingdom (UK)-based single-centre ocular genetics service. They were categorised into mutation groups and retrospective review of baseline to most recent clinical characteristics (ocular and systemic) were recorded. One hundred and seventy-two eyes were evaluated, with a mean follow up period of 16.3 ± 12.7 years. Nystagmus was recorded in 87.2%, and foveal hypoplasia in 75%. Cataracts were diagnosed in 70.3%, glaucoma in 20.6% and ARK in 68.6% of eyes. Prevalence, age of diagnosis and surgical intervention varied amongst mutation groups. Overall, the missense mutation sub-group had the mildest phenotype, and surgically naïve eyes maintained better visual acuity. Systemic evaluation identified type 2 diabetes in 12.8%, which is twice the UK prevalence. This is the largest longitudinal study of aniridia in the United Kingdom, providing insights into prognostic indicators for patients and guiding clinical management of both ocular and systemic features.

Purpose Use projection-resolved OCT angiography to investigate the autoregulatory response in the 3 parafoveal retinal plexuses under hyperoxia. Design Prospective cohort study. Participants Nine eyes from 9 healthy participants. Methods One eye from each participant was scanned using a commercial spectral-domain OCT system. Two repeated macular scans (3 × 3 mm2) were acquired at baseline and during oxygen breathing. The split-spectrum amplitude-decorrelation algorithm was used to detect blood flow. The projection-resolved algorithm was used to suppress projection artifacts and resolve blood flow in 3 distinct parafoveal plexuses. The Wilcoxon signed-rank test was used to compare baseline and hyperoxic parameters. The coefficient of variation, intraclass correlation coefficient, and pooled standard deviation were used to assess the reliability of OCT angiography measurements. Main Outcome Measures Flow index and vessel density were calculated from the en face angiograms of each of the 3 plexuses, as well as from the all-plexus inner retinal slab. Results Hyperoxia induced significant reduction in the flow index (−11%) and vessel density (−7.8%) of only the deep capillary plexus (P < 0.001) and in the flow index of the all-plexus slab (P = 0.015). The flow index also decreased in the intermediate capillary plexus and the superficial vascular complex, but these changes were small and not statistically significant. The projection-resolved OCT angiography showed good within-session baseline repeatability (coefficient of variation, 0.8%–5.2%; intraclass correlation coefficient, 0.93–0.98) in all parameters. Relatively large between-day response reproducibility was observed (pooled standard deviation, 1.7%–9.4%). Conclusions Projection-resolved OCT angiography was able to show that the retinal autoregulatory response to hyperoxia affects only the deep capillary plexus, but not the intermediate capillary plexus or superficial vascular complex.

This is a comprehensive review of the principles and applications of adaptive optics (AO) in ophthalmology. It has been combined with flood illumination ophthalmoscopy, scanning laser ophthalmoscopy, as well as optical coherence tomography to image photoreceptors, retinal pigment epithelium (RPE), retinal ganglion cells, lamina cribrosa and the retinal vasculature. In this review, we highlight the clinical studies that have utilised AO to understand disease mechanisms. However, there are some limitations to using AO in a clinical setting including the cost of running an AO imaging service, the time needed to scan patients, the lack of normative databases and the very small size of area imaged. However, it is undoubtedly an exceptional research tool that enables visualisation of the retina at a cellular level.