Functional benefits of subretinal gene augmentation therapy with Voretigene Neparvovec for inherited retinal disease associated with biallelic mutations in RPE65

Abstract

Purpose : Subretinal gene therapy with Voretigene Neparvovec (VN) for inherited retinal disease with biallelic mutations in RPE65 (RPE65-IRD) was approved for clinical use in Europe in 2018. We investigated outcome parameters that best reflect patient-relevant benefit and age dependence.

Methods : Retrospective single center study of consecutive case series of 19 patients/30 eyes (7-40y), treated with VN between 2/20 and 3/22 for RPE65-IRD. Data for pediatric (<20y) and adult patients (≥22y) were analysed separately. Functional tests included best-corrected visual acuity (BCVA), Low luminance VA (LLVA), Goldmann Visual Fields (GVF), 2 color-threshold perimetry (2CTP), and dark-adapted fullfield stimulus test (FST). Structural assessments included wide-angle multimodal imaging. Irregular patient visits required to allocate individual time points to longer times i.e. month 1 (M1, <42 days past treatment (dpt.), M3 (42 - <131 dpt.), M6 (132 - <221 dpt) etc.

Results : We treated 10 pediatric and 20 adult eyes. Table 1 lists the results for BCVA, LLVA, GVF, and FST from baseline to M12. LLVA shows the greatest difference with significant improvements in the pediatric group (Fig. 1). Improvement of FST to blue was significant in both groups but not statistically different between groups. FST to blue showed best the shift from cone to rod mediated vision in both groups, but higher at younger age. 2CTP confirmed the results with spatial resolution.

Conclusions : LLVA is a useful read-out parameter in VN therapy, easily applicable in clinical use, and of high practical use. The data correspond with patients’ reports of better recognizing objects such as a mobile phone screen in dim light after treatment.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Table 1. Correlation of baseline vs. M12 absolute data. In case no data was recorded at M12 data from M9 or M18 were taken. Statistical analyses used GraphPad Prism V. 9.5.0 for Windows. Statistical tests were two-sided, and results considered significant for p < 0.05. all eyes were treated statistically independent. Correlation of changes between pediatric and adult patients was calculated with the Mann-Whitney-U test.

 

Fig. 1 Longitudinal change of (a) median BCVA and (b) LLVA (ETDRS charts) in 5 pediatric (10 eyes) and 14 adult patients (20 eyes) following subretinal gene therapy with VN. Indicated are median values and 5% and 95% confidence intervals.