Abstract
Purpose :
Gene therapy with voretigene neparvovec (Luxturna®) is the first causal treatment for RPE65-linked retinitis pigmentosa (RP). Despite good efficacy, growing chorioretinal atrophies affect many patients after treatment. Our data show a link between the development of atrophies and strong rod recovery, indicating a disturbance in retinal energy homeostasis due to sudden rod reactivation as a driving mechanism. Yet to date, there are no specific preventative measures for this type of degeneration.
The purpose of this study was to investigate potential neuroprotective effect of transcorneal electrical stimulation (TES) in patients with voretigene neparvovec-associated atrophies. TES has been shown to slow the progression of retinal degeneration and by stimulating the release of neurotrophic and anti-inflammatory factors. Through these mechanisms, TES may be able to support the survival of photoreceptors and thereby counteract atrophic processes after retinal gene therapy.
Methods :
Participants for this study were recruited among the RP patients who have been treated with voretigene neparvovec on both eyes. TES was performed using the Okustim® device (Okuvision) with a standard amplitude of 800 µA. Over a period of 3 months, TES was applied to one eye once per week for 30 min. Complete ophthalmological examinations, including psychophysiological, morphological, and metabolic tests (OCT, FAF, BCVA, oximetry, flavoprotein-imaging, etc.), were performed at several timepoints during and after the intervention period.
Results :
At present, preliminary results are available for 5 patients, 4 of whom had developed atrophies. Subjective benefits of TES reported by the patients include improved peripheral vision and contrast perception, and a recovery of phosphene perception during TES. Visual acuity improved in 1 patient. Multimodal retinal imaging shows stable findings over the observation period.
Conclusions :
TES is a potential neuroprotective treatment that might also play a supportive role in the context of retinal gene therapies. Our data indicate some degree of short-term improvement at the individual level. Still, more long-term research is needed to determine its effectiveness specifically as a countermeasure against Luxturna-associated retinal atrophies. Beyond that, we hope this study will raise awareness of the need for specialized neuroprotective measures following the gene therapy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.