Baseline Microperimetry and OCT in the RUSH2A Study: Structure−Function Association and Correlation With Disease Severity

Purpose:: To investigate baseline mesopic fundus-guided microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study. Design:: This was a prospective natural history study. The study setting was 16 clinical sites in Europe and North America. The study population comprised individuals with Usher syndrome type 2 (USH2) (n = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) (n = 47) associated with biallelic disease-causing sequence variants in USH2A. Methods:: General linear models were used to assess characteristics including disease duration, MP mean sensitivity, and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, including best corrected visual acuity (BCVA) and central subfield thickness (CST) within the central 1 mm, were assessed using Spearman correlation coefficients. The main outcome measures were the mean sensitivity on MP and the EZ area and CST on OCT. Results:: All participants (N = 127) underwent OCT, whereas MP was available at selected sites (n = 93). Participants with Usher syndrome type 2 (USH2, n = 80) and nonsyndromic autosomal recessive retinitis pigmentosa (ARRP, n = 47) had the following similar measurements: EZ area (median [interquartile range {IQR}): 1.4 [0.4, 3.1] mm² vs 2.3 [0.7, 5.7] mm²) and CST (median [IQR] = 247 [223, 280] µm vs 261 [246, 288], and mean sensitivity (median [IQR] = 3.5 (2.1, 8.4) dB vs 5.1 [2.9, 9.0] dB). Longer disease duration was associated with smaller EZ area (P < .001) and lower mean sensitivity (P = .01). Better BCVA, larger EZ area, and larger CST were correlated with greater mean sensitivity (r > 0.3 and P < .01). Better BCVA and larger CST were associated with larger EZ area (r > 0.6 and P < .001). Conclusions:: Longer disease duration correlated with more severe retinal structure and function abnormalities, and there were associations between MP and OCT metrics. Monitoring changes in retinal structure−function relationships during disease progression will provide important insights into disease mechanism in USH2A-related retinal degeneration.