Retest-Reliability of Cone and Rod Function Assessments in Pseudoxanthoma elasticum: PROPXE Study Report 3

Purpose: To determine the test-retest reliability of visual function parameters in patients with genetically confirmed Pseudoxanthoma elasticum (PXE), as a necessary step toward evaluating their suitability as outcome measures in future therapeutic trials. Methods: In this prospective natural history study (PROPXE, ClinicalTrials.gov ID: NCT05662085), patients with PXE underwent comprehensive visual function evaluation in one study eye at baseline and at a month 2 retest visit. Functional testing included light- and dark-adapted steady state microperimetry and dark-adaptometry at 8{degrees}, 15{degrees} 30{degrees}, and 46{degrees} eccentricity. Test-retest reliability was evaluated using Bland-Altman statistics. Results: Twenty-six patients (14 female, 12 male; median [IQR] age 55 years [43; 59]) with genetically confirmed PXE were included in the study. Overall, the steady-state microperimetry limits of agreement (LoA) were {+/-}2 dB for mean sensitivity and {+/-}6.8 dB for pointwise sensitivity in both scotopic (cyan and red) and mesopic conditions. The LoAs of rod intercept time as a measure of dark adaptometry were {+/-} 12 min at the inner measurement points (8{degrees} and 15{degrees}) and {+/-} 18 min at the outer measurement points (30{degrees} and 46{degrees}). Conclusions: Scotopic and mesopic microperimetry LoAs are similar to earlier published test-retest analyses in other retinal diseases. Dark-adaptometry curve parameters were markedly more variable compared to previous data in healthy volunteers. This is likely attributable to the severe dark adaptation abnormalities in PXE, leading to long test durations. Translational Relevance: The evaluation of functional biomarkers is critical for designing future clinical trials aimed at slowing PXE progression.