Category: LHON

Modifier variants in metabolic pathways are associated with an increased penetrance of Leber’s Hereditary Optic Neuropathy

Leber’s hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease characterised by bilateral painless vision loss. Despite being the most prevalent mitochondrial disorder, the precise pathophysiological mechanisms underlying the penetrance of LHON remain poorly understood. Nuclear modifier genes have been long suspected to affect phenotype-severity, however, specific cellular pathways implicated in the disease penetrance have been only suggested recently. In recent years,…

Recurrent Optic Neuritis as a Misleading Presentation of Leber Hereditary Optic Neuropathy: The Need for High Clinical Suspicion in Young Men

A 29-year-old Chinese gentleman presented with acute-onset right eye (RE) central scotoma and blurring of vision. Upon presentation, RE visual acuity (VA) was 6/30. The RE optic disc (OD) was mildly swollen, but other findings were unremarkable. A computed tomography (CT) imaging study showed no evidence of a space-occupying lesion. The erythrocyte sedimentation rate (ESR) and other laboratory blood results were normal. The patient was empirically treated with a course of steroids for optic…

Leber hereditary optic neuropathy: utilities and carer burden from British and Irish participants

CONCLUSIONS: Findings suggest the HUI-3 may be more sensitive to the HRQL impact of vision loss compared to the EQ-5D and TTO method. The data indicate the potential value of an effective treatment for LHON. Qualitative findings describe the impact of LHON on carers. However, the burden described in the qualitative data was incongruent with quantitative measures, particularly the EQ-5D-5L. This demonstrates the value of conducting mixed-methods research and the importance of selecting measures…

Isolated and Syndromic Genetic Optic Neuropathies: A Review of Genetic and Phenotypic Heterogeneity

Nonsyndromic and syndromic hereditary optic neuropathies (HONs) encompass a variety of genetic illnesses that cause progressive optic nerve damage, resulting in considerable vision impairment. These disorders result from pathogenic variants in mitochondrial or nuclear DNA, impacting essential cellular processes like oxidative phosphorylation, mitochondrial dynamics, and neuroprotection. Advances in next-generation sequencing (NGS) have significantly improved the identification of genetic…

Inhibition of cGMP-Signalling Rescues Retinal Ganglion Cells From Axotomy-Induced Degeneration

The axons of retinal ganglion cells (RGCs) form the optic nerve, which relays visual information to the brain. RGC degeneration is the root cause of a variety of blinding diseases linked to optic nerve damage, including glaucoma, the second leading cause of blindness worldwide. The underlying cellular mechanisms of RGC degeneration are largely unclear; yet, they have been connected to excessive production of the signalling molecule nitric oxide (NO) by nitric oxide synthase (NOS). NO activates…

Leber Hereditary Optic Neuropathy With Magnetic Resonance Imaging Findings Suggestive of Optic Perineuritis and Optic Neuritis: A Diagnostic Challenge

Leber hereditary optic neuropathy (LHON) is a rare mitochondrial disorder characterized by subacute, painless, and bilateral vision loss, typically affecting young men. LHON is caused by mitochondrial DNA mutations, most commonly m.11778G>A, m.14484T>C, and m.3460G>A. LHON has incomplete penetrance, with a higher prevalence in men, and its diagnosis is often delayed because of clinical overlap with other optic nerve disorders, such as optic neuritis. Herein, we report the case of a 37-year-old…

Alterations in ganglion cell and nerve fiber layer in Leber hereditary optic neuropathy across clinical stages

CONCLUSION: In our analysis, we observed an unusual pattern in the genetic mutations, with G3460A being the second most frequent, rather than T14484C, which may be attributed to the limited sample size. 14 patients experienced acute or subacute vision loss, while eight were assessed for chronic disease. Those with chronic LHON demonstrated significantly thinner GCL and RNFL. These results underscore the importance of accelerating both diagnosis and treatment to facilitate prompt intervention for…