Retinal Dystrophy Associated With RLBP1 Retinitis Pigmentosa: A Five-Year Prospective Natural History Study

Abstract

Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation.

Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments.

Results: Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period.

Conclusions: This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.

Figure 1.

(A) Weighted visual acuity (BCVA) of all patients with RLBP1 RD throughout the duration of this study as a function of age. Each shape in respective color represents each patient. (B) Weighted contrast sensitivity of all patients with RLBP1 RD throughout the duration of this study as a function of age. Each shape in respective color represents each patient. (C) Weighted HVF MD of all patients with RLBP1 RD throughout the duration of this study as a function of age. Each shape in respective color represents each patient.

Figure 2.

(A) Mean DA sensitivity during six hours in patients with RLBP1 RD in comparison with healthy volunteers. (B) DA kinetic curves (mean ± SEM) at short (blue 450 nm) and long (red 632 nm) wavelengths in patients with RLBP1 RD. BAS, baseline.

Figure 3.

Difference between short (blue 450 nm) and long (red 632 nm) wavelength DA sensitivity: A difference of ≥2.0 log-units in DA sensitivity recovery scores between short and long wavelengths after one hour in the dark explains the role of rods in recovering sensitivity at one-hour after bleaching. BAS, baseline.

Figure 4.

DA prebleach sensitivity of all patients with RLBP1 RD throughout the duration of this study as a function of age. Each shape in respective color represents each patient.

Figure 5.

(A) Endpoints sensitive to disease progression at two years. (B) Endpoints sensitive to disease progression at 5 years. **For these measures higher value indicates worse result; therefore the SNR sign was reversed to compare across all measures. SNR, signal-to-noise ratio.

Figure 6.

Bland-Altman plot for the test-retest repeatability across endpoints. EZ, ellipsoid zone; IR, inner retinal layer; ONL, outer nuclear layer; PR, photoreceptor.