Using adaptive optics scanning laser ophthalmoscopy (AOSLO), we measured retinal blood velocity and flow in healthy control eyes and eyes of diabetic patients with or without retinopathy. This cross-sectional study included 39 eyes of 30 patients with diabetes (DM) with mild non-proliferative diabetic retinopathy (NPDR) or without retinopathy (DM no DR) and 21 eyes of 17 healthy age-matched controls. Participants were imaged with a commercial optical coherence tomography angiography (OCTA) device (RTVue-XR Avanti) and AOSLO device (Apaeros Retinal Imaging System, Boston Micromachines). We analyzed AOSLO-based retinal blood velocity and flow, and OCTA-based vessel density of the superficial (SCP), deep retinal capillary plexus (DCP), and full retina. Retinal blood velocity was significantly higher in eyes with DM no DR and lower in NPDR across all vessel diameters compared to controls. Retinal blood flow was significantly higher in DM no DR and lower in NPDR in vessel diameters up to 60 μm compared to controls. When comparing flow outliers (low-flow DM no DR eyes and high-flow NPDR eyes), we found they had a significantly different retinal vessel density compared to the remaining eyes in the respective groups. Retinal blood velocity and flow is increased in eyes with DM no DR, while these parameters are decreased in eyes with mild NPDR compared to healthy age-matched controls. The similarity of OCTA vessel density among outliers in the two diabetic groups suggests an initial increase followed by progressive decline in blood flow and OCTA vessel density with progression to clinical retinopathy, which warrants further investigation.

PURPOSE. To examine inner retinal hyperreflective features on adaptive optics scanning laser ophthalmoscopy (AOSLO) in individuals with early cognitive impairment. METHODS. In this prospective, cross-sectional study, we enrolled 12 participants with either amnestic mild cognitive impairment (aMCI, n ¼ 10) or early dementia due to Alzheimer's disease (eAD, n ¼ 2) and 12 age-, sex-, and race-matched cognitively normal controls. All participants completed AOSLO imaging of the inner retina. AOSLO montages of the peripapillary area were graded for hyperreflective features including granular membranes, mottled membranes, and nummular features. Regions of interest on AOSLO were compared qualitatively to corresponding optical coherence tomography (OCT) cross sections. OCT was also used to analyze peripapillary retinal nerve fiber layer (RNFL) thickness. RESULTS. Cognitively impaired individuals had a significantly higher number of granular membranes with a larger overall area compared to controls. The proportion of cognitively impaired individuals with two or more granular membranes was 41.7% compared to none in the control group. Granular membrane area was also inversely correlated with cognitive performance on the Montreal Cognitive Assessment. There was no difference between the two groups in terms of other membrane types or RNFL thickness. CONCLUSIONS. Individuals with early cognitive impairment related to Alzheimer's show hyperreflective granular membranes on high-resolution imaging, which we hypothesize to be manifestations of inner retinal gliosis. The presence of these subtle hyperreflective membranes may obscure underlying RNFL thinning in these eyes on OCT imaging. The distinctive phenotype of granular membranes surrounding the optic nerve on AOSLO may represent a new potential biomarker of early Alzheimer's.

In this cross-sectional observational study, we investigated the relationship between photoreceptor layer disruption and telangiectasia in patients diagnosed with early stage macular telangiectasia type 2 (MacTel). A total of 31 eyes (17 patients) with MacTel were imaged with adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography angiography (OCTA). Confocal AOSLO was used to visualize dark regions of nonwaveguiding outer segments, which we refer to as “photoreceptor lesions”. En-face OCTA images of the deep capillary plexus (DCP) were used in conjunction with confocal AOSLO to evaluate the topographic relationship between areas of capillary telangiectasias and photoreceptor lesions. Among seven eyes with early stage MacTel (stage 0–2 based on OCT), we identified ten photoreceptor lesions, all of which were located within parafoveal quadrants containing DCP telangiectasia on OCTA. Seven of the lesions corresponded to the intact ellipsoid zone on spectral-domain OCT (SD-OCT), and three of these also corresponded to the intact interdigitation zone. This work demonstrates a topographic relationship between AOSLO photoreceptor lesions and DCP telangiectasias, and it also suggests that these lesions with normal SD-OCT appearance may represent areas of photoreceptors at risk for dysfunction. Thus, confocal AOSLO may have a meaningful role in detecting early photoreceptor abnormalities in eyes with MacTel.

Purpose To evaluate retinal hemodynamic responses to anti-vascular endothelial growth factor (VEGF) injection in eyes with diabetic macular edema using optical coherence tomography angiography (OCTA). We performed a comparison of two different thresholding methods to identify the most accurate for studying the vessel density (VD) in diabetic macular edema eyes. Methods The study prospectively included 26 eyes of 22 subjects (aged 60.2 ± 13.7 years) who underwent OCTA scan before and after anti-VEGF injection (mean interval between OCTA = 31.1 ± 17.3 days). We analyzed adjusted flow index, VD, and Skeletonized vessel length density in the parafoveal area (3-mm annulus with a 1-mm inner circle), along with full-thickness fovea avascular zone area and central foveal thickness (CFT). Using averaged scans VD as the ground truth, we compared two different algorithms for VD at the different plexuses. Longitudinal changes were assessed using a generalized linear model correcting for central foveal thickness and Q-score. Results We found significantly decreased adjusted flow index in the DCP layer ( P = 0.010) at the follow-up. Furthermore, foveal avascular zone ( P < 0.001) and central foveal thickness ( P = 0.003) showed significant decrease on follow-up compared with baseline. Comparing the thresholding algorithms showed that vessel length density–based thresholding was more accurate for quantifying the DCP VD. Conclusions The adjusted flow index decreased significantly in the DCP layer on follow-up OCTA scan, suggesting vascular flow disruption and decreased deep retinal perfusion after anti-VEGF injection. Our results also highlight the fact that the choice of thresholding method is particularly critical for DCP quantification in eyes with diabetic macular edema. Translational Relevance Findings confirmed impaired deep retinal capillary flow after anti-VEGF injection.