Detection of Abnormalities in the RPE in Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency Chorioretinopathy Using Optical Coherence Tomography–Derived Optical Attenuation Coefficients

Purpose: To detect abnormalities in the RPE in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) chorioretinopathy, a novel method using optical attenuation coefficients (OACs) was used to enhance the contrast between regions with high and low attenuation. Methods: LCHADD patients were scanned over the central macula using two commercial optical coherence tomography (OCT) devices. Fundus autofluorescence (FAF) imaging was performed during the same visit to detect RPE abnormalities based on lipofuscin distribution. OAC was derived from OCT data. En face OAC of the retina (internal limiting membrane to Bruch's membrane [BM]), en face OCT of the RPE (16 µm above the BM to the BM), and corresponding FAF images were compared to evaluate the ability of the OAC to detect RPE abnormalities. Pairwise comparisons were performed across all LCHADD stages, along with correlations with traditional clinical metrics including LCHADD severity, best-corrected visual acuity, and plasma acylcarnitines. Results: Forty-three eyes from 22 LCHADD patients were evaluated and categorized into 6 stages. OAC images of the retina revealed RPE defects consistent with FAF, with clearer and more detailed visualization of RPE disruption. Compared with OCT images, OAC images facilitated visualization of pathological changes and provided a better visual comparison between the preserved and degenerated RPE at advanced stages. The mean retinal OAC decreased significantly (P < 0.001) with disease progression and differed significantly across disease stages (all P ≤ 0.002), showing strong correlations with traditional clinical metrics. Conclusions: OCT-based OAC is a promising tool for both the quantitative and qualitative assessment of RPE abnormalities in LCHADD chorioretinopathy.