Characteristics of Rare Inherited Retinal Dystrophies in Adaptive Optics—A Study on 53 Eyes

Abstract

Inherited retinal dystrophies (IRDs) are genetic disorders that lead to the bilateral degeneration of the retina, causing irreversible vision loss. These conditions often manifest during the first and second decades of life, and their primary symptoms can be non-specific. Diagnostic processes encompass assessments of best-corrected visual acuity, fundoscopy, optical coherence tomography, fundus autofluorescence, fluorescein angiography, electrophysiological tests, and genetic testing. This study focuses on the application of adaptive optics (AO), a non-invasive retinal examination, for the assessment of patients with IRDs. AO facilitates the high-quality, detailed observation of retinal photoreceptor structures (cones and rods) and enables the quantitative analysis of parameters such as cone density (DM), cone spacing (SM), cone regularity (REG), and Voronoi analysis (N%6). AO examinations were conducted on eyes diagnosed with Stargardt disease (STGD, N=36), cone dystrophy (CD, N=9), and cone-rod dystrophy (CRD, N=8), and on healthy eyes (N=14). There were significant differences in the DM, SM, REG, and N%6 parameters between the healthy and IRD-affected eyes (p<0.001 for DM, SM, and REG; p=0.008 for N%6). The mean DM in the CD, CRD, and STGD groups was 8900.39/mm2, 9296.32/mm2, and 16,209.66/mm2, respectively, with a significant inter-group difference (p=0.006). The mean SM in the CD, CRD, and STGD groups was 12.37 μm, 14.82 μm, and 9.65 μm, respectively, with a significant difference observed between groups (p=0.002). However, no significant difference was found in REG and N%6 among the CD, CRD, and STGD groups. Significant differences were found in SM and DM between CD and STGD (p=0.014 for SM; p=0.003 for DM) and between CRD and STGD (p=0.027 for SM; p=0.003 for DM). Our findings suggest that AO holds significant potential as an impactful diagnostic tool for IRDs.

Progression of Rare Inherited Retinal Dystrophies May Be Monitored by Adaptive Optics Imaging

“…Our goal was to discern whether differences existed in the adaptive optics cone parameters in eyes diagnosed with CD, CRD, and STGD. In both the initial exam of the study described in this article and in our other study [ 20 ], we found differences in DM, SM, and REG among the different diagnosis groups. However, these differences were not confirmed in the follow-up of our current study.…”

“…In a previous study, we identified low cone density as a risk factor for incomplete data acquisition due to the poor quality of the obtained images, rendering quantitative analysis of photoreceptor parameters impossible [ 20 ]. These results align with those presented in the current article, as they are based on a similar cohort of patients.…”

“…The cone and rod spacing is increased in IRDs compared to healthy retinas [ 18 ]. Additionally, poor image quality, likely resulting from inadequate fixation in eyes with low visual acuity, is a problem that, in some cases, makes image acquisition impossible [ 19 , 20 ]. In STGD, as well as in other IRDs, the “dark spaces” depicting areas of disrupted cone structure and abnormal cone reflectance have been described [ 21 , 22 ].…”

Modeling inherited retinal diseases using human induced pluripotent stem cell derived photoreceptor cells and retinal pigment epithelial cells

“…The ability to evaluate the retina at a cellular level highlights new anatomical readouts that can be used to evaluate the ability of 2D and 3D cultures to mimic the retina. These parameters include cellular density, spacing, and regularity ( 124 , 125 ). These insights can further guide the development of organoid or retina-on-a-chip technologies for more accurate biological representation.…”