Gene Therapy May Offer Option in Leber Hereditary Optic Neuropathy

Young Man Getting Eye Exam
A young man looking through a retinal camera at an optometry office during an eye exam.Click below for more of my OPTOMETRY images:
A novel gene therapy approach may manage MT-ND4 Leber hereditary optic neuropathy.

This article is part of Ophthalmology Advisor’s conference coverage from the 2021 meeting of the American Academy of Ophthalmology, held in New Orleans from November 12 to 15, 2021. The team at Ophthalmology Advisor will be reporting on a variety of the research presented by the ophthalmology experts at the AAO. Check back for more from the AAO 2021 Meeting.


A novel gene therapy, lenadogene nolparvovec, could be a promising treatment for MT-nd4 Leber hereditary optic neuropathy (LHON), according to research presented at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, held November 12-15. The data came from the phase 3 REFLECT trial ( Identifier: NCT03293524)

Participants included in this study were older than 15 years of age, possessed the m.11778G>A mutation, and reported experiencing vision loss for less than 1 year. These patients were given a single intravitreal injection of gene therapy in the affected eye and either given the same injection in the other eye or a placebo. 

The results were assessed 1.5 years after the administration of the gene therapy and differences in change from baseline logMAR best corrected visual acuity between the treated eye and the not-affected eye or the eye that received the placebo treatment were examined. Eye function and structure of the eyes were monitored throughout the entirety of the study. 

The researchers reported that patients treated with unilateral gene therapy in another investigation, the RESCUE and REVERSE trial ( Identifier: NCT03406104), experienced unexpected bilateral effects. Although the REFLECT trial is ongoing, the presenters said, “we expectantly await the results of this study that administered bilateral lenadogene nolparvovec in 50% of the participants.”

Visit Ophthalmology Advisor’s conference section for complete coverage of AAO 2021 meeting.



Newman NJ, Subramanian PS, Moster ML, et al. The phase 3 reflect trial: efficacy and safety of bilateral gene therapy for LHON. Paper presented at: The American Academy of Ophthalmology 2021 Annual Meeting; November 12-15, 2021; New Orleans. Abstract PA050.