Adaptive Optics Reveals Photoreceptor Abnormalities in Diabetic Macular Ischemia

Abstract

Diabetic macular ischemia (DMI) is a phenotype of diabetic retinopathy (DR) associated with chronic hypoxia of retinal tissue. The goal of this prospective observational study was to report evidence of photoreceptor abnormalities using adaptive optics scanning laser ophthalmoscopy (AOSLO) in eyes with DR in the setting of deep capillary plexus (DCP) non-perfusion. Eleven eyes from 11 patients (6 women, age 31–68), diagnosed with DR without macular edema, underwent optical coherence tomography angiography (OCTA) and AOSLO imaging. One patient without OCTA imaging underwent fluorescein angiography to characterize the enlargement of the foveal avascular zone. The parameters studied included photoreceptor heterogeneity packing index (HPi) on AOSLO, as well as DCP non-perfusion and vessel density on OCTA. Using AOSLO, OCTA and spectral domain (SD)-OCT, we observed that photoreceptor abnormalities on AOSLO and SD-OCT were found in eyes with non-perfusion of the DCP on OCTA. All eight eyes with DCP non-flow on OCTA showed photoreceptor abnormalities on AOSLO. Six of the eight eyes also had outer retinal abnormalities on SD-OCT. Three eyes with DR and robust capillary perfusion of the DCP had normal photoreceptors on SD-OCT and AOSLO. Compared to eyes with DR without DCP non-flow, the eight eyes with DCP non-flow had significantly lower HPi (P = 0.013) and parafoveal DCP vessel density (P = 0.016). We found a significant correlation between cone HPi and parafoveal DCP vessel density (r = 0.681, P = 0.030). Using a novel approach with AOSLO and OCTA, this study shows an association between capillary non-perfusion of the DCP and abnormalities in the photoreceptor layer in eyes with DR. This observation is important in confirming the significant contribution of the DCP to oxygen requirements of photoreceptors in DMI, while highlighting the ability of AOSLO to detect subtle photoreceptor changes not always visible on SD-OCT.

Alterations to the Foveal Cone Mosaic of Diabetic Patients

“…14,51,59 In these studies, as in ours, nonperfusion in the retinal vasculature was associated with the observed photoreceptor mosaic abnormalities, but they were not present in all regions with nonperfusion further supporting the likelihood of an additional factor influencing photoreceptor changes in diabetics. This additional factor may be colocalized nonperfusion in the choriocapillaris 58 or localized areas of breakdown of the outer blood retinal barrier 60,61 compromising the outer retinal layers.…”

Retinal Capillary Plexus Pattern and Density from Fovea to Periphery Measured in Healthy Eyes with Swept-Source Optical Coherence Tomography Angiography

“…Linsenmeier and Zhang, using oxygen-sensitive microelectrodes and oximetry, have found that under both dark and light conditions, the choroidal and retinal circulation could supply, in different proportions, the metabolic demand of photoreceptors 29 . Nesper et al, in a cohort of patients with diabetic retinopathy, have observed using adaptive optics and OCTA photoreceptor changes in areas of capillary dropout in the DCP, suggesting that the integrity of the DCP is needed for photoreceptor metabolism 30 . Assuming that retinal capillaries are present in areas where there is a cellular demand, the small decrease in photoreceptor and INL density towards the periphery could explain the relative stability of the DCP density in this area 26 .…”

The impact of ganglion cell layer cysts in diabetic macular oedema treated with anti‐vascular endothelial growth factor

“…Despite continuous treatment, the extent of ELM disruption increased, implying that DME must be aggressively treated to prevent continuous degeneration of the outer retina due to chronic, persistent DME and ischaemia (Nesper et al. ).…”