Natural History of Microperimetry and Optical Coherence Tomography in USH2A-Retinopathy: A Structure-Function Association Study.

Objective: To describe the natural history of optical coherence tomography (OCT) and mesopic microperimetry (MP) parameters in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

Methods: Multi-center, international, prospective, longitudinal natural history study. Methods: STUDY POPULATION: 105 participants with biallelic disease-causing variants in USH2A with a clinical diagnosis of Usher Syndrome or autosomal recessive retinitis pigmentosa who underwent annual testing over 4 years. Methods: Ellipsoid zone (EZ) area and central sub-field thickness (CST) on OCT. Mean sensitivity (MS) and mean pointwise sensitivity at predefined functional transition points (MSFTP) on MP.

Results: 102 and 94 participants met criteria for OCT and MP analysis, respectively. The average EZ area was 3.9 ± 5.3 mm2 at baseline which decreased to 3.3 ± 4.1 mm2 at 4 years [rate of change (ROC) (-0.18 mm2/year)]. The average CST decreased from 249.7 ± 35.6 to 244.1 ± 39.3 microns over 4 years (-2.14 microns/year). The average MP MS declined from 6.0 ± 5.1 dB (baseline) to 4.5 ± 4.2 (4 years) (-0.39 dB/year). The MSFTP significantly decreased over time [17.9 dB (baseline) to 10.8 dB (4 years)]. Notably, at 4 years, there was a meaningful decrease (≥ 7dB) in MSFTP in 46% of study eyes.

Conclusions: This study establishes the natural history of key structural and functional parameters in USH2A-retinopathy. The MSFTP is a novel, robust parameter that showed clinically meaningful change over time and is a promising tool to monitor treatment efficacy in clinical trials.