Assessing relationship between vascular integrity and macular sensitivity in patients with Usher Syndrome

Abstract

Purpose : Successful gene augmentation therapy requires both photoreceptors/RPE recovery and intact inner retinal structures (neural and vascular) to complete visual processing. Understanding what residual vascular function is present in the degenerating retina is important for determining therapeutic potential

Methods : Usher Syndrome patients (USH2A and MYO7A), and age-matched healthy controls underwent macular (6x6mm) OCT angiography (OCTA, AngioVue), structural OCT (Spectralis) and microperimerty (MAIA). En face OCT angiograms of inner retina (IR), superficial capillary plexus (SCP), and deep capillary plexus (DCP) were generated. FIJI and MATLAB software were used for OCTA processing and quantification. Vessel density was calculated as the percentage area occupied by flow signal. The width of the preserved ellipsoid zone (EZ) and external limiting membrane (ELM) in patients was measured. All results were presented in mean ± standard deviation (SD). Generalized estimating equations (GEE) were used to compare between groups

Results : Twelve eyes from 7 MYO7A subjects (36.8±10.9 years) and 30 eyes from 17 USH2A patients (34.7±12.3 years) and 26 eyes from 14 controls (30.4±7.1 years) were included. Mean age was statistically equivalent between groups (p=0.14, ANOVA). Decreased retinal perfusion was observed globally in Usher patients (p < 0.001), but more pronounced peripherally. No genotype dependent difference in vessel density was observed (IR-p=0.74; SCP-p=0.73; DCP-p=0.95). Usher patients showed reduced outer retinal thickness, and marked decrease in average threshold compared to normative database on microperimetry (14.75±8.38 dB). Qualitatively, areas of degenerated retina were spatially corresponding to regions with hypoperfusion and decreased sensitivity. The width of the preserved EZ (IR-ρ=0.59) and ELM (IR-ρ=0.51) and average threshold (IR-ρ=0.66) were significantly correlated with vessel density of retinal plexuses (Spearman’s rho)

Conclusions : OCTA shows a correlation between areas of relatively intact, functioning retina and vascular perfusion in Usher Syndrome patients. This correlation is better for the deep than superficial capillary plexus. Whether the loss in the deep plexus is real or an artifact of reduced flow requires further investigation

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.