In Vivo Reprogramming Dysfunctional Retinal Ganglion Cells and Visual-phototransduction via Wireless Charging Nanogold for Leber’s Hereditary Optic Neuropathy
Gene therapy offers a promising treatment for Leber’s hereditary optic neuropathy (LHON), a disease of retinal ganglion cell (RGC) degeneration with severe vision loss caused by mitochondria-NADH dehydrogenase 4 (MT-ND4) mutations. However, optimizing mitochondria-targeted gene delivery to promote RGC regeneration and visual-photoreception recovery remains challenging in LHON. Here, mitochondria-targeted wireless charging gold nanoparticles (WCGs), doubling as a wireless charging-mediated…
Initial Macular Ganglion Cell Changes During Conversion of Leber Hereditary Optic Neuropathy
CONCLUSIONS: Nasal GCC thinning is a reliable early indicator of the conversion from normal vision to visual loss in LHON as demonstrated in 10 of 17 eyes. This pattern of GCC loss provides insights into the disease mechanism and highlights the utility of OCT analysis for early diagnosis. The nasal GCC loss suggests selective vulnerability of ganglion cells serving the foveal region in LHON. Early identification of nasal GCC changes may facilitate timely intervention as gene therapy and other…
Extraocular features of Leber hereditary optic neuropathy: A scoping review
CONCLUSION: Early detection of these systemic manifestations, especially in cardiac and neurological systems, could help with prompt intervention and improve patient outcomes. Further research into gene therapy and mitochondrial replacement techniques holds promising potential for developing more effective treatment strategies.
Technological advances in the diagnosis and management of inherited optic neuropathies
Preferential degeneration of retinal ganglion cells (RGCs) is a defining feature of the inherited optic neuropathies (IONs), a group of monogenic eye diseases predominately comprising Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). Their pathogenesis is characterised by mitochondrial dysfunction, which causes loss of RGCs leading to irreversible vision loss. Although currently incurable, there are several emerging therapeutic avenues encompassing gene…
‘Adrift From the World’: Exploring the Lived Experiences of Individuals Affected by an Inherited Optic Neuropathy in the United Kingdom – A Qualitative Study
CONCLUSIONS: Visual impairment due to an ION threatens the independence of affected individuals, leading to psychosocial losses and reduced emotional wellbeing. Despite the challenges they face, people living with an ION describe a “relatively” good VRQoL, often due to the positive impact of social support, enabling them to lead fulfilling lives.
Leber Hereditary Optic Neuropathy and Epilepsy in a Mexican Patient
This case describes a woman in her 30s who was diagnosed with Leber hereditary optic neuropathy (LHON), a genetic disorder causing vision loss associated with mitochondrial DNA mutations. Initially diagnosed in childhood, she also developed epilepsy in adolescence. Despite treatment with multiple anticonvulsants, her initial seizures were only partially controlled. Brain MRI and scalp EEG results indicated left temporal lobe epilepsy, and she ceased seizures after modification of her…
Acute Bilateral Vision Loss in a Young Male: A Case of Leber’s Hereditary Optic Neuropathy
Leber’s Hereditary Optic Neuropathy (LHON) is a rare mitochondrial genetic disorder that primarily affects young adult males, leading to acute or subacute painless central vision loss. The condition results from point mutations in mitochondrial DNA, most commonly affecting the ND1, ND4, or ND6 genes, which impair the function of complex I in the mitochondrial respiratory chain. This leads to selective degeneration of retinal ganglion cells and the optic nerve, causing severe and often…
Uncovering the Characteristics of Pupil Cycle Time (PCT) in Neuropathies and Retinopathies
Pupil cycle time (PCT) estimates the dynamics of a biofeedback loop established between pupil size and stimulus luminance, size or colour. The PCT is useful for probing the functional integrity of the retinopupillary circuits, and is therefore potentially applicable for assessing the effects of damage due to retinopathies or neuropathies. In previous studies, PCT was measured by manually counting the number of pupil oscillations during a fixed period to calculate the PCT. This method is scarce,…
Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy
CONCLUSIONS: Better baseline BCVA values and baseline thicker GCL and RNFL at OCT measurements are key predictive factors of the improved BCVA 1.5 years after treatment in patients with MT-ND4 LHON who received lenadogene nolparvovec at least 6 months after disease onset.
Leber’s Hereditary Optic Neuropathy
CONCLUSION: Although still uncommon, the presentation of LHON in middle-aged women is possible and should be considered as one of the differential diagnoses in a patient when painless vision loss occurs.