Abstract
Purpose :
Secondary cone degeneration in RHO-associated retinitis pigmentosa (RHO-RP) is due to dependence on rod-mediated cone survival. In this study, we use adaptive optics (AO) retinal imaging to quantitatively investigate for progressive changes in cone photoreceptor size and regularity in RHO-RP.
Methods :
Multimodal imaging, including non-confocal split detection from a custom-built AO instrument, was acquired in 7 patients with molecularly confirmed RHO-RP. Cone photoreceptors were identified and segmented at regions of interests (ROIs) selected across retinal eccentricities between 1.0 to 5.5 mm by expert graders assisted by deep learning software (PMID33507868) and compared to normative data measured from 24 healthy subjects at matched eccentricities. Longitudinal AO imaging was performed in 3 patients (3 visits; time between visits 1.8±1.1 years, mean±SD), for which two longitudinally registered ROIs were selected for each visit (located at 1 mm and at an eccentric location near the transition zone/hypoautofluorescent border).
Results :
Cone photoreceptor diameter was enlarged across all measured eccentricities in the RHO-RP cohort by an average of 22.1±5.6% (n=19,408 cones from 7 patients, p<0.01). In general, cone diameter was more variable in RHO-RP compared to healthy individuals, resulting in an increased ratio of maximum to minimum cone diameter within each ROI (3.3±0.8 vs. 2.1±0.3; n=182 ROIs, p<0.01). Longitudinal AO imaging revealed overall stability in cone diameter enlargement over three visits (n=1,008 cones from 3 patients, p=0.52). Despite the relatively constant and stable enlargement in cone diameter, there was a decrease in the percentage of cones with six sided Voronoi neighbors when comparing eccentric locations to the 1mm location (48.2±9.4% vs 59.6±6.8%, p<0.01). This disruption to hexagonal packing was stable across 3 visits (p=0.51). Our results are suggestive of increased disorganization of the expected hexagonal topography of the cone mosaic near the boundary of preserved cones.
Conclusions :
Monitoring cone photoreceptor size and regularity may lead to new insights about the impact of rod degeneration on the cone mosaic. Correlation of these structural changes to visual function may yield diagnostic, prognostic, and treatment applications, particularly with the advent of RHO-RP gene therapy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.