Visual Outcomes and Optical Coherence Tomography Biomarkers of Vision Improvement in Patients With Leber Hereditary Optic Neuropathy Treated With Idebenone
CONCLUSION: We identified OCT biomarkers associated with long-term (ie, 2-year) visual outcomes in patients with LHON treated with idebenone therapy in the first year after disease onset. Thinning of the GC-IPL in the superior and temporal parafoveal regions was associated with worse long-term visual outcomes in these patients.
Solutions to a Radical Problem: Overview of Current and Future Treatment Strategies in Leber’s Hereditary Opic Neuropathy
Leber’s Hereditary Optic Neuropathy (LHON) is the most common primary mitochondrial DNA disorder. It is characterized by bilateral severe central subacute vision loss due to specific loss of Retinal Ganglion Cells and their axons. Historically, treatment options have been quite limited, but ongoing clinical trials show promise, with significant advances being made in the testing of free radical scavengers and gene therapy. In this review, we summarize management strategies and rational of…
Phenotypic Variation of Autosomal Recessive Leber Hereditary Optic Neuropathy (arLHON) in One Family
Leber hereditary optic neuropathy (LHON) is a rare disease with a prevalence of 1 in 25,000 births. LHON usually presents in young males, with painless loss of visual acuity in one or both eyes. Recently an autosomal recessive form of the disease (arLHON or LHONAR) has been described, which is caused by a biallelic mutation in the DNAJC30 gene (usually a missense mutation c.152A>G). The phenotypic and clinical characteristics of patients with arLHON are similar to those of mtLHON, but some…
Proteomic Profiling Reveals Increased Glycolysis, Decreased Oxidoreductase Activity and Fatty Acid Degradation in Skin Derived Fibroblasts from LHON Patients Bearing m.G11778A
LHON is a common blinding inherited optic neuropathy caused by mutations in mitochondrial genes. In this study, by using skin fibroblasts derived from LHON patients with the most common m.G11778A mutation and healthy objects, we performed proteomic analysis to document changes in molecular proteins, signaling pathways and cellular activities. Furthermore, the results were confirmed by functional studies. A total of 860 differential expression proteins were identified, containing 624 upregulated…
Randomized trial of bilateral gene therapy injection for m.11778G > A MT-ND4 Leber optic neuropathy
Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G > A mutation in the MT-ND4 gene being the most common disease-causing mitochondrial DNA (mtDNA) variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G > A mutation, using a recombinant…
The Relative Preservation of the Central Retinal Layers in Leber Hereditary Optic Neuropathy
(1) Background: The purpose of this study was to evaluate the thickness of retinal layers in Leber hereditary optic neuropathy (LHON) in the atrophic stage compared with presumably inherited bilateral optic neuropathy of unknown cause with the aim of seeing if any LHON-specific patterns exist. (2) Methods: 14 patients (24 eyes) with genetically confirmed LHON (LHON group) were compared with 13 patients (23 eyes) with negative genetic testing results (mtDNA + WES) and without identified etiology…
Case report: Long-term follow-up of two patients with LHON caused by DNAJC30:c.152G>A pathogenic variant-case series
CONCLUSIONS: Presented are two autosomal recessive LHON (arLHON, OMIM:619382) cases with the same DNAJC30:c.152G>A pathogenic variant and different degrees of spontaneous visual recovery despite progressive RNFL thinning during a long-term follow-up. This mutation should be screened in every atypical LHON patient.
Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy
CONCLUSIONS: Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.
Optic nerve lesion length is a biomarker of visual disability in the pre-chronic phase of Leber’s hereditary optic neuropathy
CONCLUSION: ON length with T2-STIR hyperintensities was positively associated with both BCVA and MD, and it was suspected to be a biomarker of visual disability in the pre-chronic phase of LHON.
Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation
CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection.