Longitudinal Assessment of Cone Structure, Choriocapillaris, and Retinal Sensitivity in Choroideremia

To investigate longitudinal changes in cone structure, choriocapillaris, and retinal sensitivity in choroideremia.

We assessed cone spacing z scores using adaptive optics scanning light ophthalmoscopy, analyzed choriocapillaris flow deficits (CCFDs) on swept-source optical coherence tomography angiography, and measured retinal sensitivity via microperimetry. Linear mixed-effects models estimated annual change rates in these parameters.

We analyzed 225 regions of interest from 14 eyes of 7 participants with choroideremia, including 6 participants (12 eyes) with follow-up imaging over a median of 3.3 years. The cone spacing z score increased by 0.57 ± 0.18 per year (P = 0.02), independent of distance to the fundus autofluorescence (FAF) border (P = 0.92). CCFD increased by 3.43 ± 0.52% per year at 1° inside (P < 0.001) and 2.03 ± 0.73% per year at 1° outside the FAF border (P = 0.01), but did not change significantly in other regions. Retinal sensitivity changed by -1.50 ± 0.34 dB/year at 1° inside (P < 0.001) and -1.94 ± 0.52 dB/year at 1° outside (P = 0.001) the FAF border, but did not change significantly in other areas. Greater retinal sensitivity loss correlated with closer proximity to the FAF border, greater baseline sensitivity, greater cone spacing z score, and larger CCFDs (P < 0.001 for each).

Cone spacing z score increased uniformly within the residual macular area, and CCFD and retinal sensitivity changed more rapidly within 1° of the FAF border. Regions in this zone are projected to lose 7 dB of sensitivity in approximately 3.5 years, shedding light into future clinical trial design.