Short term morphological rescue of the fovea after gene therapy with voretigene neparvovec

Abstract

Purpose : Leber congenital amaurosis type 2 (LCA2) and early-onset severe retinal dystrophy (EOSRD) are linked to visual impairment with nyctalopia and visual acuity reduction in early childhood. In 2017, the first gene therapy voretigene neparvovec (Luxturna^TM) for patients with LCA and EOSRD cause by bi-allelic mutations in the RPE65 gene has been approved. Here we report on an example of short-term change in the foveal morphology after functionally successful gene therapy with voretigene neparvovec in a 15-year old patient.

Methods : The clinical examinations included best corrected visual acuity (BCVA), spectral domain optical coherence tomography (OCT) and adaptive optics retinal imaging.

Results : During follow-up over a period of three months after the treatment an improvement of the photoreceptor structure could be observed in OCT, with a clear demarcation of the external limiting membrane and changes in the photoreceptor mosaic on adaptive optics retinal imaging. These morphological rescue parameters correlated in part with the improvement in foveal mediated vision after the treatment and adaptive optics imaging. Although the visual acuity improved only slightly at month 3, objective central cone evaluation with chromatic pupil campimetry showed an increase in the central function. In daily life, the patient reported her visional experience after the treatment as ‘brighter’.

Conclusions : Rapid changes in the photoreceptor morphology after successful gene therapy in patients with LCA/EORD can be quantifiable on individual level.

This is a 2021 ARVO Annual Meeting abstract.