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

Shuo Yang, Hong Yang, Si-Qi Ma, Shuai-Shuai Wang, Heng He, Min-Jian Zhao, Bin Li, Shuo Yang, Hong Yang, Si-Qi Ma, Shuai-Shuai Wang, Heng He, Min-Jian Zhao, Bin Li

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.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Best corrected visual acuity. (A) Eyes with changes of

Figure 2

The correlation between changes in…

Figure 2

The correlation between changes in the objective examination parameters and the change in…

Figure 2
The correlation between changes in the objective examination parameters and the change in the BCVA during the 12 months prior to initiation of gene therapy. (A) The changes in the MD and VFI were significantly correlated with changes in the BCVA. (B) The changes in the P100 of the VEP were significantly correlated with the changes in the BCVA. BCVA = best corrected visual acuity, MD = mean defect, VEP = visual evoked potential, VFI = visual field index.
Figure 2
Figure 2
The correlation between changes in the objective examination parameters and the change in the BCVA during the 12 months prior to initiation of gene therapy. (A) The changes in the MD and VFI were significantly correlated with changes in the BCVA. (B) The changes in the P100 of the VEP were significantly correlated with the changes in the BCVA. BCVA = best corrected visual acuity, MD = mean defect, VEP = visual evoked potential, VFI = visual field index.

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