Mesopic microperimetry in Stargardt disease: Application and reliability

PURPOSE: Mesopic microperimetry (mMP) is a promising functional endpoint in clinical trials for Stargardt disease type 1 (STGD1). This study evaluated the test-retest variability of mMP and influencing factors, which is essential for ensuring reliability in future STGD1 trials. METHODS: One hundred and fifteen eyes from 68 patients enrolled in the prospective, tertiary, multicentre STArgardt Remofuscin Treatment Trial (STARTT) underwent mMP testing using the macular integrity assessment (MAIA) microperimeter (CenterVue, Padova, Italy) at both the screening (first) and baseline (second) visits of the trial. Test-retest variability was assessed using Bland-Altman analyses and coefficients of repeatability (CoR). Retinal sensitivity metrics included mean sensitivity (MS) and pointwise sensitivity (PWS). Other factors including fixation stability, exam duration and learning effect were analysed. RESULTS: MS demonstrated the lowest variability (CoR: 3.53 dB, 95% CI: 3.07-3.99), while PWS exhibited the highest (CoR: 12.69 dB, 95% CI: 12.47-12.91). Variability decreased in sensitivity ranges from -1 to 3 dB and 16 to 32 dB and from central to peripheral regions. Test duration (Spearman's ρ = 0.609, p < 0.001) and fixation losses (Spearman's ρ = 0.284, p = 0.003) were significantly associated with increased variability. Other fixation stability metrics showed no correlation. No learning effect was observed. CONCLUSIONS: Given its high variability, PWS should be used cautiously. MS offers lower variability but may mask localised functional changes. A parafoveal ring strategy may improve reliability but requires validation. Limiting test duration to ≤450 seconds and comprehensive operator training are recommended to minimise potential bias.