Exploring rare mitochondrial DNA in Leber hereditary optic neuropathy
CONCLUSIONS: Our study probes into the clinical and genetic diversity of LHON with rare mtDNA mutations, revealing varied clinical presentations, such as more frequent unilateral involvement and enhanced optic nerve T2 MRI signals. Visual recovery was significantly better in the younger cohort. These results suggest the need for broader genetic testing in atypical LHON cases and offer insights into better prognostic strategies for new therapies.
Visual Recovery in Leber’s Hereditary Optic Neuropathy Plus: A Case Report and Literature Insight
CONCLUSION: This case underscores the importance of considering LHON plus in young patients with bilateral optic neuropathy and systemic features, particularly when the MT:14484C>T mutation is present, as early mitochondrial support can lead to favorable outcomes.
Efficacy and safety of intravitreal rAAV2-ND4 therapy for Leber’s hereditary optic neuropathy
CONCLUSION: This Phase 1/2 trial demonstrated no serious safety concerns among the 12 participants. And dose of 4.5 × 10⁹ vg, 0.05 mL was to be used in future Phase 3 study.
Establishment of human Leber’s hereditary optic neuropathy model using iPSC-derived retinal organoids
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease caused by mitochondrial DNA mutations, leading to central vision loss and retinal ganglion cell (RGC) degeneration. Progress in understanding LHON and developing treatments has been limited by the lack of human-like models. In this study, we aimed to establish a human retinal model of LHON using retinal organoids (ROs) from LHON patient-derived induced pluripotent stem cells (LHON-iPSCs). We first confirmed LHON-iPSCs were…
First Case in Lithuania of an Autosomal Recessive Mutation in the DNAJC30 Gene as a Cause of Leber’s Hereditary Optic Neuropathy
CONCLUSION: This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians.
Age-Associated Differences in Optic Disc Findings of Leber’s Hereditary Optic Neuropathy
We aimed to investigate the relationship between age and acute-phase optic disc findings in Leber’s Hereditary Optic Neuropathy (LHON). We examined 27 LHON patients (27 eyes) with the m.11778 G>A mutation within two months of onset, with acute-phase optic disc findings. We analyzed the relationship between age and three key optic disc features: peripapillary telangiectasia, disc hyperemia, and retinal nerve fiber layer (RNFL) swelling. The median age of onset was 37 years (range: 10-68), with 22…
A Case of Late-Onset Leber’s Hereditary Optic Neuropathy in Association with Heteroplasmic m.11778G>A/ND4 Mutation
A 68-year-old man described a progressive, painless, and bilateral reduction of visual acuity, with greater difficulties in central vision, over a period of 3 years. His past medical history was unremarkable, and he admitted a long exposure to tobacco smoking and moderate daily alcohol intake. The first ophthalmological evaluation confirmed a bilateral reduction of visual acuity, without other major findings. Visual fields showed a central scotoma in the right eye and a temporal…
Whole mitochondrial genome sequencing in individuals with Leber hereditary optic neuropathy negative for the common pathogenic mitochondrial DNA variants
CONCLUSION: Our study of a well-characterized Indian LHON cohort uncovered rare mtDNA variants that should be considered when assessing undiagnosed optic neuropathy cases. Additionally, it underscores the effectiveness of NGS in identifying heteroplasmic mtDNA variants. This indicates that whole mitochondrial genome sequencing via NGS is a more efficient and preferred approach for routine molecular genetic testing.
Rasch analysis of the NEI-VFQ-25: vision-related quality of life in Leber hereditary optic neuropathy after lenadogene nolparvovec gene therapy
CONCLUSIONS: The scoring structure of the original NEI-VFQ-25 has limitations that undermine its psychometric validity as a measure of VRQoL. Using the Rasch-revised NEI-VFQ-25, we determined that improvement in VRQoL after treatment with lenadogene nolparvovec was driven predominantly by an improvement in socioemotional functioning.
Outcomes of idebenone therapy for Leber hereditary optic neuropathy in a cohort of patients from Wales
CONCLUSION: The present cohort demonstrates evidence of CRR in a high proportion of patients reaching 27 months of treatment. Further follow-up and a larger cohort of patients will provide further insight into the real-world efficacy of idebenone in LHON.