Short term morphological rescue of the fovea after gene ther
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. The first gene therapy voretigene neparvovec (Luxturna™) for patients with LCA and EOSRD cause by bi-allelic mutations in the RPE65 gene has been approved. An example of short-term change in the foveal morphology after functionally successful gene therapy with voretigene neparvovec in a 15-year old patient.

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

--During follow-up over a period of 3 months after the treatment, an improvement of the central foveal morphology 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 sensitivity.

--In daily life, the patient reported her visional experience after the treatment as ‘brighter’.

Conclusively, rapid changes in the correlates of photoreceptor morphology after successful gene therapy in patients with LCA/EORD can be quantifiable on individual level.