Abstract
Purpose :
Development of chorioretinal atrophy after voretigene neparvovec is a recently described adverse effect affecting a subgroup of patients. There are indications that it is connected to a good initial functional rod rescue. We investigated whether the initial improvement in the local rod sensitivity is correlated to the retinotopically corresponding development of chorioretinal atrophy.
Methods :
Data from ten eyes of six subjects who developed chorioretinal atrophy after voretigene neparvovec were analyzed. Fundus autofluorescence (Spectralis, Heidelberg Engineering) and local rod sensitivity in central 30 degrees measured by dark adapted chromatic perimetry (DACP, Medmont) were analyzed. Local rod sensitivity gain at 1 month after treatment was extracted from areas that developed post-treatment atrophy at month 6 and compared to local rod sensitivity gain extracted from areas that were not affected (paired t-test).
Results :
One subject had no measurable improvement in the DACP, five subjects had a clear rod rescue (range of max. improvement 9 dB to 45 dB, mean 26 ± 15 dB).
Atrophic areas at 6 months, not present at baseline, were on average 25 ± 13% of the entire 30 degrees area (min. 9%, max. 51%).
The mean average improvement of the rods sensitivity in 30 degrees at month 1 was 9 ± 9.1 dB. The mean improvement in the atrophic areas was 7 ± 8.5 dB and in the areas without atrophy 10 ± 9.4 dB. The difference between the areas with and without atrophy was statistically significant (p=0.04).
Conclusions :
The results suggest that the retinal areas developing chorioretinal atrophy after voretigene neparvovec are not those ones with the highest functional benefit. In eyes with this adverse effect, the affected areas of lower functional rods rescue have a higher tendency to develop atrophy in the first months after treatment. We hypothesize that retinal locations of an intermediate degeneration stage and lower functionality suffer from metabolic stress induced by the therapy and have higher risk for cellular death. Cells with a high functional benefit in areas of better-preserved tissue benefit functionally and seem to be more resistant to atrophy. The treatment induced increase of the local metabolism presents a stress test that can either stabilize cells with good rescue or accelerate atrophy in more progressed areas.
Long term observation is needed to explore the growth of the atrophic changes.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.