Abstract
Purpose :
To characterize photoreceptor (PR)-retinal pigment epithelium (RPE)-choriocapillaris (CC) cellular changes in patients with late-onset retinal degeneration (L-ORD).
Methods :
Four participants with L-ORD (CTRP5 mutation; P1, P2: pre-clinical; P3, P4: advanced) and two healthy control (HC) volunteers were imaged with the FDA 3.4 MHz Fourier-domain mode-locked-adaptive optics (AO) system. AO-OCT and AO-OCT angiography modes were applied to resolve the cellular details in the PR-RPE-CC complex from the fovea to 12° temporal retina. Morphological parameters were quantified in terms of cone PR density and outer segment length (OSL), RPE density and area, and normalized CC density. The PR analysis was performed with an automated volumetric cone segmentation method based on a deep-learning approach, while RPE and CC quantification was done manually.
Results :
The two pre-clinical stage participants demonstrate differences in OSL, but no other measured parameter, when compared to HCs. The cone density monotonically decreases from ~44,300 cells/mm2 at 1° to 7,100 cells/mm2 at 12°. The RPE density decreases at a slower rate from ~7,100 cells/mm2 at the fovea to 5,500 cells/mm2 at 12°, resulting in an RPE area increase from 143 um2 to 182 um2 at the corresponding locations. The normalized CC density exhibits very little difference across the macula with an average density of 58%. Conversely, the OSL is shorter than HCs at all locations with an overall reduction of 48.8% and 25% in P1 and P2, respectively. In an advanced stage, further structural disruptions are evident: the OSL is further shortened and the PR density is reduced; RPE cell density decreases by an average of 60% resulting in a 268% increase in cell area; many reticular pseudo-drusen appear across the macula; and there is a loss of CC vasculature that accompanies the cellular changes. Overall, a widespread collapse in the PR-RPE-CC complex was observed in P3 and P4.
Conclusions :
The 3.4 MHz AO-OCT allows characterization of cellular-level structural changes in L-ORD. The results in preclinical LORD suggests that although CTRP5 is expressed in the RPE, the early insults include subtle structural changes to the photoreceptors. Further investigation will yield insights into the pre-clinical disease stage, which may stimulate development of targeted therapies and provide imaging outcomes to monitor in interventional trials.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.