Purpose: To compare perfused capillary density (PCD) in diabetic patients and healthy controls using optical coherence tomography angiography (OCTA). Methods: Forty controls, 36 diabetics without clinical retinopathy (NoDR), 38 with nonproliferative retinopathy (NPDR), and 38 with proliferative retinopathy (PDR) were imaged using SD-OCT. A 3×3 mm full-thickness parafoveal OCTA scan was obtained from each participant. Following manual delineation of the foveal avascular zone (FAZ), FAZ area, perimeter, and acircularity index were determined. Seven consecutive equidistant 200-µm-wide annular segments were drawn at increasing eccentricities from the FAZ margin. Annular PCD (%) was defined as perfused capillary area divided by the corresponding annulus area after subtraction of noncapillary blood vessel areas. Nonparametric Kruskal-Wallis testing with Bonferroni correction was performed in pairwise comparisons of group PCD values. Results: The NoDR group demonstrated consistently higher PCD compared to the control group in all seven annuli, reaching statistical significance (36.6±3.30% vs 33.6±3.98%, P=0.034) at the innermost annulus (FAZ margin to 200-µm out). The NPDR and PDR groups demonstrated progressively decreasing PCD. Differences in FAZ metrics between the NoDR and control groups did not reach statistical significance. Conclusions: Relative to healthy controls, increased PCD values in the NoDR group likely represent an autoregulatory response to increased metabolic demand, while the decrease in PCD

Enlargement of the foveal avascular zone (FAZ) due to progressive capillary nonperfusion is associated with visual deterioration in patients with diabetic retinopathy. The FAZ area has long been considered an important clinical marker of advancing retinopathy. However, a large body of literature shows that the FAZ area varies considerably in healthy eyes, resulting in substantial overlap between controls and diabetics, thus reducing its discriminatory value. In this study, within-subject FAZ area enlargement was obtained by the comparison of the structural FAZ area to the functional FAZ area using simultaneouslyacquired, corresponding en face OCT reflectance and OCT angiography images. Our study suggests that en face OCT reflectance images provide useful anatomic baselines of structural FAZ morphology prior to the onset of disease. Measurements of within-subject FAZ area enlargement appear to be a more sensitive method for identifying the onset of diabetic retinopathy as compared to using OCT angiographic measurements of FAZ alone.

Background/aimsTo assess foveal avascular zone (FAZ) morphology and parafoveal capillary perfusion in patients with various stages of sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A).MethodsThis is a multi-institutional retrospective study of patients with various stages of SCR compared with healthy controls. Parafoveal OCT-A images obtained using a commercial spectral domain-OCT system were reviewed. Foveal-centred 3×3 mm full vascular slab OCT-As were used for image processing and data analysis. FAZ area, perimeter, and acircularity index were determined on the OCT-A image after manual delineation of the FAZ border. Quadrant-based parafoveal capillary density and per cent area deviating from normal distribution were also measured.ResultsFifty-two patients with SCR (33 non-proliferative and 19 proliferative) and 20 age and race-matched healthy controls were included. One randomly selected eye per study participant was analysed. FAZ perimeter and acircularity index were significantly greater in SCR eyes when compared with the controls. While parafoveal capillary density was significantly lower, per cent area deviated from normal distribution was significantly higher in SCR eyes than that of the control. However, no statistically significant difference between the two SCR stages was observed. In quadrant-based analysis, the temporal quadrant showed greater parafoveal capillary dropout due to SCR, with the most profound effect in patients with proliferative SCR.ConclusionsAbnormal FAZ morphology and altered parafoveal capillary perfusion were found in patients with SCR. Our customised OCT-A image analysis method uniquely highlights significant quantitative alterations in perfusion density mapping in a qualitative display, with minimal obscuration of OCT-A image detail.

Purpose We evaluate the impact of age and signal strength index (SSI) on foveal avascular zone (FAZ) metrics and parafoveal capillary density measured using optical coherence tomography angiography (OCT-A), and propose a deviation mapping approach that accounts for age-group, SSI, eccentricity, and variation in FAZ size. Methods Parafoveal OCT-A with full vascular layer was obtained for 261 controls and four patients with retinal abnormalities. Parafoveal capillary densities were measured within eight consecutive 200-μm wide annuli from the FAZ border. In controls, the impacts of age and SSI on FAZ metrics and parafoveal capillary density were evaluated. Deviation maps highlighting regions with density at the lower and upper tails of the age-group and eccentricity matched distribution were generated. Results Linear regressions showed significant correlations between age, SSI, and mean parafoveal capillary density. There was a significant difference in FAZ metrics and parafoveal capillary densities with different age groups after controlling for SSI using univariate analysis. However, the effect of age on parafoveal capillary density disappeared after controlling for SSI using multivariate linear regression analysis. Our deviation mapping approach was able to identify regions with abnormal density in four patients. Conclusions Our findings suggest that the relationship between parafoveal capillary density and age is confounded by SSI. Parafoveal capillary density is SSI- and eccentricity-dependent. An age-group and eccentricity matched normative database was used as the basis for a parafoveal capillary density deviation mapping technique, providing an intuitive way to assess the status of parafoveal capillary density in individual eyes. Translational Relevance Understanding the impact of age and SSI on parafoveal capillary density is critical for providing accurate interpretation of OCT-A. We demonstrate an age-group and eccentricity matched deviation mapping technique for an intuitive assessment of retinal regions with abnormal density.

Objectives To examine interocular asymmetry of foveal avascular zone (FAZ) and parafoveal capillary density metrics in sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A). Methods This cross-sectional, retrospective study evaluated SCR patients and unaffected controls who underwent 3x3mm macular OCT-A imaging using a spectral domain-OCT system. FAZ (area, perimeter, and acircularity index) and parafoveal capillary density metrics were computed for both eyes of each participant. In unaffected controls, interocular difference in FAZ and parafoveal capillary density metrics were evaluated using Bland-Altman plots. SCR patients with interocular difference outside the upper 97.5% and lower 2.5% limits of agreement from controls were defined as having interocular asymmetry. Area under receiver operating characteristic curve (AROC) was also performed to determine the ability of the absolute interocular difference to differentiate between subjects with SCR-including nonproliferative SCR (NP-SCR) and proliferative SCR (P-SCR)-and unaffected controls. Results Thirty-one patients with SCR (21 NP-SCR and 10 P-SCR) and 14 race-matched and agematched controls were included for analysis. Interocular asymmetry was seen for all FAZ and parafoveal capillary density metrics in NP-SCR and P-SCR subjects. SCR subjects showed greater disease severity in the left-eye for FAZ and parafoveal capillary density metrics.

Anti-VEGF treatment of diabetic macular edema (DME) complicating diabetic retinopathy (DR) has greatly improved structural and visual outcomes for patients with diabetes mellitus. However, up to 50% of patients are either nonresponsive or refractory to anti-VEGF treatment (no improvement in BCVA or central macular thickness (CMT)). It is believed that factors such as mitochondrial structural and functional damage, due to oxidative stress, are partially responsible for this lack of improvement. Flavoprotein fluorescence (FPF) has been shown to be a sensitive marker of mitochondrial function and has been found to correlate with the degree of diabetic retinopathy. FPF may also provide additional information regarding therapeutic response of patients receiving anti-VEGF treatment for DME. Eight patients with DR and DME with clinically significant DME (CSDME) who underwent anti-VEGF (bevacizumab) treatment were imaged before injection and at follow-up visit using FPF in addition to standard color fundus photography and OCT CMT. A strong correlation r = 0.98 (p = 0.000015) between the FPF decrease and the BCVA improvement was observed; BCVA improved as FPF values decreased. Notably, in the same patients, the correlation between OCT CMT decrease and BCVA improvement (r = 0.688) was not found to be significant (p = 0.13). These findings suggest that FPF can detect improvement in metabolic function preceding structural improvement and even with small changes in edema. Additionally, FPF may be supplementary to current diagnostic methods for earlier detection of therapeutic response to anti-VEGF treatment in patients with DME.

Purpose Hemodynamic changes surrounding the optic nerve head are known to occur in thyroid-related orbitopathy (TRO). This pilot study explores the capillary and non-capillary peripapillary perfusion changes of the retina in TRO eyes without dysthyroid optic neuropathy (DON) using optical coherence tomography angiography (OCT-A). Methods Non-capillary and capillary peripapillary perfusion densities were calculated using single 4.5 × 4.5mm en face “RPC layer” OCT-A scans of 8 TRO patients without DON (8 eyes, mean age 40.6 years, range 23–69 years). Results were compared to a previously published dataset of 133 healthy controls (133 eyes, mean 41.5 years, range 11–83 years). The strength of association was measured between OCT-A perfusion densities and clinical measures of TRO. Results Non-capillary peripapillary perfusion density in TRO eyes was found to be significantly decreased compared to healthy controls (TRO group 15.4 ± 2.9% vs controls 21.5 ± 3.1%; p < 0.0001). Capillary peripapillary perfusion densities showed no significant difference (TRO group 42.5 ± 1.8% vs controls 42.5 ± 1.5%; p = 1.0). Clinical measures of disease did not correlate well with OCT-A perfusion densities (p>0.05). Conclusion These findings may represent decreased blood flow and subclinical ischemia to the optic nerve. We discuss possible pathogenic mechanisms of thyroid-related vasculopathy, including vessel wall thickening due to immunologically-induced media enlargement.

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