Voretigene Neparvovec Gene Therapy in Clinical Practice: A 12-Month, Single-Center, In-Depth Analysis of Beneficial...

To investigate the effects of voretigene neparvovec (VN) treatment in patients with RPE65-related retinal dystrophies, with particular focus on chorioretinal atrophy (CRA) and its impact on visual function.

Twenty-five patients treated with VN were evaluated over a 12-month follow-up and stratified according to the presence of postoperative CRA, classified into nummular, mixed and touchdown patterns.

Best-corrected visual acuity (BCVA) improved by a median of 11 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (P < 0.001). Semiautomated kinetic visual field (SKVF) showed a significant (P < 0.001) enlargement for both I4e and III4e stimulus sizes. Fullfield stimulus threshold (FST) results also improved significantly (P < 0.001), with median changes of -2.79 (-3.61 to -2.11) log cd·s/m2 for white, -3.02 (-4.05 to -2.24) log cd·s/m2 for blue, and -1.30 (-1.76 to -0.74) log cd·s/m2 for red stimuli. Fifteen patients developed CRA (60%), of whom nine exhibited progressive nummular/mixed CRA, which significantly expanded over time (P < 0.001), and six showed the localized, non-progressive touchdown pattern. Younger age and a clinical diagnosis of LCA were significantly associated with nummular/mixed CRA. No significant differences in BCVA or FST improvements were found between nummular/mixed and touchdown/no-CRA groups. Conversely, significant SKVF I4e enlargement occurred only in the touchdown/no-CRA subgroup (1624°2, 0-6278; P < 0.001), with a significant intergroup difference (P = 0.003).

Our findings confirmed the visual function improvements following VN and the relatively high prevalence of CRA, which seems to impact negatively only on SKVF enlargement.

These findings are useful to better understand risks and benefits of VN gene therapy.