Abstract
Purpose :
The best timing for therapeutic interventions in patients with Leber hereditary optic neuropathy (LHON) and asynchronous disease onset remains unclear.
We performed a retrospective, observational clinical study to assess the final functional and structural outcomes in each eye of LHON treated and untreated patients with asynchronous disease onset, in whom, each eye had different disease duration and therapy timing.
Methods :
100 eyes of 50 LHON patients (42 males and 8 females) with asynchronous disease onset carrying the m.11778G>A/MT-ND4 mitochondrial DNA point mutation, were examined in the chronic phase of the disease, at least 3 years after onset. The primary outcome measures were the final visual acuity (VA) and the final retinal nerve fiber layer thickness average (RNFL ave) measured by SS-OCT (DRI-OCT; Triton, Tokyo, Japan). 30 patients (60%) were treated with Idebenone at different dosage and times and 20 (40%) were untreated.
Results :
Globally, 19 patients (38%) presented a better functional result in the second affected eye, whereas 31 patients (62%) presented the same functional result in both eyes or better in the first affected eye. In the treated group, 8 (27%) patients had a better visual outcome in the second affected eye as opposed to 11 (55%) patients in the untreated group.
In the treated group the eyes final mean VA was 0.9±0.6 LogMar as compared to 1.2±0.4 in the untreated eyes group. The best visual outcome was achieved when the therapy was administered in the dynamic or chronic phases (after 6 months from onset) compared to the subacute phase (before 6 months) (respectively 0.6±0.7 Vs 1±0.5 LogMar).
The RNFL average thickness was 46±14 microns in the untreated eye group, 42±9 microns in the eyes treated in the subacute phase and 50±17 microns in the eyes treated in the dynamic/chronic phases.
Conclusions :
These preliminary results, yet lacking statistical power, suggest that the visual outcome of eyes in LHON patients with asynchronous onset is better in eyes treated in late disease stages, and seem to match the recent results from clinical trials with gene therapy. The reason for this counterintuitive observation with different types of therapy needs further investigation in larger cohorts of treated patients.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.