Evaluation of Leber's hereditary optic neuropathy patients prior to a gene therapy clinical trial

Abstract

Gene therapy may be a promising approach for the treatment of Leber hereditary optic neuropathy. The aim of this study was to evaluate patients with this condition who were recruited into an upcoming gene therapy clinical trial and to assess any changes in the detection parameters to provide support for the clinical trial. Sixteen patients with Leber hereditary optic neuropathy were evaluated using visual function tests 12 months before the initiation of gene therapy. Then, the results of visual acuity (VA), visual field (VF), RNFL (retinal nerve fiber layer) thickness, and Pattern-reversal Visual evoked potential (PR-VEP) were compared and analyzed. A total of 32 eyes of 16 patients were evaluated. Based on the best-corrected visual acuity (BCVA), 24 eyes were relatively stable compared with the baseline evaluation, and 8 eyes had significant changes, including 5 eyes that showed improvement and 3 eyes that showed impairment. In all eyes, the changes in the best-corrected visual acuity were significantly correlated with the changes in the visual field index (VFI), mean defect (MD), and P100 of the visual evoked potential. In the eyes with relatively stable BCVA and those with an obvious improvement in the BCVA, only the visual mean defect showed a significant change; the other indicators were not significantly different. Aside from the patients showing a tendency of spontaneous improvement, the others were in accordance with the requirement. The effects of Leber hereditary optical neuropathy (LHON) gene therapy should be evaluated primarily based on visual acuity. Additionally, visual field, neural fiber thickness, and electrophysiology should be considered in the evaluation.

Prognostic factors for visual acuity in patients with Leber's hereditary optic neuropathy after rAAV2‐ND4 gene therapy

“…Before the advent of gene therapy, there was no treatment for LHON that exhibited confirmed efficacy. Spontaneous visual recovery was observed in 4% to 25% of the patients with mutations at site 11 778 . Young age at onset, slow disease progression, mild degree of vision loss and thicker retinal nerve fibre layer were considered predictors of good visual acuity recovery.…”

“…Spontaneous visual recovery was observed in 4% to 25% of the patients with mutations at site 11 778. 2,9,[14][15][16][17] Young age at onset, 18 slow disease progression, 19 mild degree of vision loss 3 and thicker retinal nerve fibre layer 20 were considered predictors of good visual acuity recovery. Analysis of the factors influencing spontaneous visual acuity recovery showed that baseline characteristics may also affect the visual acuity prognosis of LHON patients with mutations at site 11 778 who were treated with gene therapy.…”

“…The results of an early‐stage clinical trial (http://clinicaltrials.gov Register No. : NCT01267422) showed significant efficacy, with more than 66% of patients achieving significant improvement in visual function . Thus far, gene therapy is effective in some patients and ineffective in others.…”

“…: NCT01267422) showed significant efficacy, with more than 66% of patients achieving significant improvement in visual function. [8][9][10] Thus far, gene therapy is effective in some patients and ineffective in others. Therefore, it is important to identify the factors affecting visual acuity prognosis in LHON patients with mutation at site 11 778, after receiving gene therapy.…”

Visual Field Variability after Gene Therapy for Leber’s Hereditary Optic Neuropathy

“…Our research, however, has ruled out the possibility of spontaneous vision recovery. First, 1 year before clinical treatment, patients with spontaneous VA were excluded, and the improvement of VA in 9 patients treated from 3 months after treatment started to increase with a similar trend [7, 9]. Second, Lam et al [20] also conducted an in-depth study of the effect of increased spontaneous vision on gene therapy.…”