Observation of Peripapillary Choroidal Vascularity in Natural Disease Course and After Gene Therapy for Leber's Hereditary Optic Neuropathy

Purpose: To compare peripapillary choroidal vascularity among Leber's Hereditary Optic Neuropathy (LHON) patients at different stages of natural course and healthy controls using optical coherence tomography (OCT), and to evaluate peripapillary choroidal vascularity changes in LHON patients before and after gene therapy.Methods: 57 LHON patients and 15 healthy controls were enrolled in this prospective clinical study. LHON patients were divided into three duration groups based on stage of disease progression. Both patients and healthy controls underwent OCT scans focused on the optic disc at baseline with Heidelberg Spectralis, and patients underwent OCT at 1, 3, and 6 months after gene therapy. OCT images were converted and binarized using ImageJ software. Choroidal thickness (CT), total choroidal area (TCA), and choroidal vascularity index (CVI) in each quadrant of OCT images were measured to evaluate peripapillary choroidal vascularity.Results: At baseline, the average CT was not significantly different between LHON patients at different stages and between healthy controls (P = 0.468). Although average TCA and average CVI were slightly higher in LHON patients at different stages than in healthy controls, the difference was not statistically significant (P = 0.282 and 0.812, respectively). After gene therapy, The average TCA at 1 month after gene therapy was significantly higher than that before gene therapy (P = 0.003), while no significant differences were found in the average CT or average CVI in LHON patients before and 1,3 and 6 months after gene therapy using pairwise comparisons (all P > 0.05).Conclusions: No significant difference was found in choroidal vascularity of LHON patients at different stages and healthy controls. Choroidal vascularity seems to stay stable after gene therapy.

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Progress in Gene Therapy to Prevent Retinal Ganglion Cell Loss in Glaucoma and Leber’s Hereditary Optic Neuropathy

Neural Plasticity ◽

10.1155/2018/7108948 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Sara E. Ratican ◽

Andrew Osborne ◽

Keith R. Martin

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Optic Nerve ◽

Genome Editing ◽

Optic Neuropathy ◽

Single Gene ◽

Leber’S Hereditary Optic Neuropathy ◽

Leber's Hereditary Optic Neuropathy ◽

Potential Use ◽

Hereditary Optic Neuropathy

The eye is at the forefront of the application of gene therapy techniques to medicine. In the United States, a gene therapy treatment for Leber’s congenital amaurosis, a rare inherited retinal disease, recently became the first gene therapy to be approved by the FDA for the treatment of disease caused by mutations in a specific gene. Phase III clinical trials of gene therapy for other single-gene defect diseases of the retina and optic nerve are also currently underway. However, for optic nerve diseases not caused by single-gene defects, gene therapy strategies are likely to focus on slowing or preventing neuronal death through the expression of neuroprotective agents. In addition to these strategies, there has also been recent interest in the potential use of precise genome editing techniques to treat ocular disease. This review focuses on recent developments in gene therapy techniques for the treatment of glaucoma and Leber’s hereditary optic neuropathy (LHON). We discuss recent successes in clinical trials for the treatment of LHON using gene supplementation therapy, promising neuroprotective strategies that have been employed in animal models of glaucoma and the potential use of genome editing techniques in treating optic nerve disease.

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