Longitudinal Change in Cone Structure and Retinal Sensitivity in Choroideremia

Abstract

Purpose : To investigate longitudinal changes in cone structure, choriocapillaris, and retinal sensitivity in choroideremia (CHM).

Methods : We imaged CHM patients with fundus autofluorescence (FAF), swept-source optical coherence tomography angiography (SS-OCTA), microperimetry, and adaptive optics scanning laser ophthalmoscopy (AOSLO). Regions of interest (ROIs) were marked (Fig. 1) and analyzed by a grader for each eye. Cone spacing Z-score, the number of standard deviations from the normal mean at a particular retinal eccentricity, was measured at each ROI. Choriocapillaris flow deficits (CCFD) were analysed on SS-OCTA scans using published methods. We performed linear mixed-effects model to estimate the change rate in cone spacing Z-score, CCFD, and retinal sensitivity.

Results : We included 225 ROIs in 14 eyes from 7 CHM patients. Six patients (12 eyes) underwent baseline and follow-up imaging, and 1 patient had only baseline imaging. Median follow-up was 3.3 years. Mean ± standard error cone spacing Z-score was 1.82 ± 0.14 at baseline, independent of distance from the FAF border (P = 0.80, Fig. 2A). The Z-score increased by 0.57 ± 0.18 annually (P = 0.02) and the rate was independent of distance from the FAF border (P = 0.92, Fig. 2B). CCFD increased by 3.4% annually within 1 degree of the FAF border (P = 0.047) but did not change significantly in other regions. Retinal sensitivity changed by -1.50 dB/year 1 degree within (P = 0.047) and by -1.94 dB/year 1 degree beyond (P = 0.016) the FAF border, but did not change significantly in other regions. Faster retinal sensitivity decline was associated with closer distance to the FAF border, higher baseline retinal sensitivity, higher baseline cone spacing Z-score, and higher baseline flow deficit in a multivariate model (P < 0.001 for each variable).

Conclusions : Cone spacing Z-score increased at a uniform rate within the retained macular area, while CCFD and retinal sensitivity changed more rapidly near the FAF border. Approximately 3.5 years are required to achieve a 7 dB sensitivity decline in regions within 1 degree of the FAF border.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Fig. 1. The residual FAF border (white) with overlay of microperimetry retinal sensitivity map and AOSLO confocal montage with ROIs (red).

 

Fig. 2. Baseline Cone spacing Z-score (A) and the annualized change rate of cone spacing Z-score (B) were independent of distance from the residual FAF border.