Correlation between fundus autofluorescence pattern and retinal sensitivity measured by microperimetry in patients with choroideremia

Abstract

Purpose : Choroideremia is an X-linked inherited retinal degeneration, characterised by loss of the retinal pigment epithelium (RPE) followed by photoreceptor cell death. Fundus autofluorescence (FAF) imaging reveals three distinct RPE patterns in the early stages: smooth, mottled and atrophic appearances (Figure 1). It is not known how structural RPE patterns on FAF relate to retinal function as measured by microperimetry (MP).

Methods : A retrospective review of patients with choroideremia, who had smooth and mottled regions on FAF imaging in both eyes, was performed. These were selected from patients recruited for clinical trial NCT02407678. The smooth and mottled regions on FAF images at baseline were delineated and superimposed on to the MP plots (MAIA, 10-2 grid with 68 points) ensuring alignment of retinal vessels. Eight age and gender-matched controls were used to determine expected normal sensitivity values for each point on the MP plots. These were then used to calculate mean sensitivities for the zones corresponding to smooth and mottled regions in the participants. Mean changes from expected normal values in smooth and mottled regions were compared with a paired t-test.

Results : 30 patients fulfilled the inclusion criteria for the clinical trial (mean age 32.2±8.8 years). Of these, eight had distinct smooth and mottled regions in both eyes (mean age 32.3±9.8 years). The mean MP sensitivities for the smooth and mottled regions were 26.5±3.2 dB and 21.0±4.1 dB, respectively. The mean change from expected values was significantly higher in the mottled compared to the smooth regions (4.6 dB loss versus 1.7 dB loss; 95% confidence interval 1.2 to 4.5; p=0.002). In areas of RPE loss, there was no detectable sensitivity.

Conclusions : This study identifies a correlation between retinal function on MP and structure on FAF imaging in patients with choroideremia. The smooth region is more likely to contain intact ellipsoid zone and preserved photoreceptor anatomy (Stevanovic et al, 2020). There are therefore three RPE patterns seen on FAF imaging in choroideremia: i) an early stage with smooth reflectance which correlates to normal retinal anatomy and similar to normal function; ii) an intermediate ‘mottled’ stage associated with measurably impaired photoreceptor function; and iii) the late stage in which RPE loss is complete and function as assessed with MP is absent.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.