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In order to explore the spectrum of mitochondrial DNA (mtDNA) mutations in Korean patients with Leber's hereditary optic neuropathy (LHON), we investigated the spectrum of mtDNA mutations in 145 Korean probands confirmed with the diagnosis of LHON. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and mtDNA mutations were identified by direct sequencing. Analysis of mtDNA mutations revealed seven primary LHON mutations including the nucleotide positions (nps) 11778A (101 probands, 69.2%), 14484C (31 probands, 21.2%), 3460A (5 probands, 3.4%), and G3635A, G3733A, C4171A, and G13051A mutations in one proband each. In addition, two provisional mtDNA mutations at nps T3472C, and G13259A were each found in one proband, respectively. Another provisional mtDNA mutation at np T3394C was found in two probands. In conclusion, the spectrum of mtDNA mutations in Korean patients with LHON may differ from other ethnicities, which is characterized by high prevalence of 11778A and 14484C mutations, and a low prevalence of the 3460A mutation., (© 2024. The Author(s).)

Purpose: We sought to identify the phenotypic and genotypic characteristics of Korean children with genetically confirmed Leber's hereditary optic neuropathy (LHON)., Methods: The medical records of 64 genetically confirmed LHON patients were reviewed. Seventeen patients aged 13 years or younger with optic atrophy with positive mitochondrial DNA (mtDNA) mutations were considered to demonstrate childhood-onset LHON. The non-childhood-onset group included 47 patients with genetically confirmed LHON who experienced disease onset later than 13 years of age. The type of mtDNA mutation, visual acuity (VA), color vision, fundus photography, retinal nerve fiber layer (RNFL) thickness, and visual field were investigated., Results: Sequence analysis of the mitochondrial genome revealed five different kinds of LHON-associated mtDNA mutations among our childhood-onset patients, including m.11778G>A (58.8%), m.3496G>T (11.8%), m.3497C>T (5.9%), m.11696G>A (5.9%), and m.14502T>C (5.9%). The mean final best-corrected VA in the childhood-onset group was better than that in the non-childhood-onset group with the value of logMAR 0.29 (0.09-0.75) vs. 0.55 (0.27-1.29) (expressed as median (interquartile range); p = 0.05). Spontaneous visual recovery was observed in 35.3% of the childhood-onset group but in only 12.8% of the non-childhood-onset group (p = 0.04). Eight patients (47.1%) showed interocular asymmetry of the disease, with two presenting true unilateral involvement of the optic nerve and the other six patients demonstrating unilateral subclinical manifestations with bilateral optic atrophy., Conclusion: Involvement of secondary mitochondrial mutations was confirmed in patients with childhood-onset LHON. Characteristic clinical features of childhood-onset LHON included a higher proportion of subacute or insidious onset of symptoms, better VA, higher spontaneous recovery, and asymmetrical ocular involvement.

Background: We aimed to evaluate the current practice patterns of neuro-ophthalmologists in diagnosis and management of three optic neuropathies using a national survey in South Korea and to further compare the practices of neuro-ophthalmologists divided into junior and senior groups based on their clinical practice experience., Methods: An anonymous, 15-question survey on the diagnosis and treatment of traumatic optic neuropathy (TON), nonarteritic anterior ischemic optic neuropathy (NAION), and Leber's hereditary optic neuropathy (LHON) was sent to all neuro-ophthalmologists registered with the Korean Neuro-ophthalmology Society. The questions addressed physician's practice duration as neuro-ophthalmologist, choices of MRI scans and laboratory tests for the diagnosis in suspected optic neuropathy, clinical experiences with steroids (e.g., side effects), and choices of treatment modalities and reason in in each optic neuropathy. All participants were classified into senior (≥ 10 years) and junior (< 10 years) groups., Results: A total of 63 responders (response rate 78.8%) answered the questionnaire. All responders performed the basic blood tests and brain imaging for evaluating optic neuropathy. Observation was the most preferred option for TON (47.6%) and NAION (63.5%). Steroid use was the second most preferred, and the most selected indication of steroid was "when the patient wants" (58.7%) for TON and "severe visual loss or last eye" (66%) for NAION. The most preferred treatment for LHON was "prescribing idebenone" (69.7%) with a dose of 900 mg/day (63.8%). Forty-nine respondents (77.8%) experienced side effects of steroids. There was no significant difference between the senior and junior groups in all questionnaire answers (all p > 0.05)., Conclusion: Optic neuropathies are being managed similarly by the two groups in South Korea, and many of them still use steroids. We provided reliable reasons for our results compared with other countries.

Purpose: To identify the spectrum of pathogenic mitochondrial DNA (mtDNA) mutations and clinical features in Korean patients with genetically confirmed Leber's hereditary optic neuropathy (LHON)., Methods: The medical records of 34 unrelated, genetically confirmed LHON patients were reviewed. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and primary or secondary mtDNA mutations were identified by direct sequencing. We analyzed the visual acuity (VA), color vision, RNFL thickness, and visual field (VF) at the final visit from 20 patients who were followed-up for more than 6 months after the onset of LHON., Results: Among 34 patients, 21 (61.8%) had the homoplasmic primary mutation, 11 (32.4%) had the homoplasmic secondary mutation, and 2 (5.9%) had the heteroplasmic primary mutation along with the homoplasmic secondary mutation. Analysis of mtDNA sequences revealed six different types of LHON-associated mutations: two primary LHON-associated primary mutations, m.11778G>A (20 patients, 58.8%) and m.14484T>C (3 patients, 8.8%), and four secondary LHON-associated mutations, which were m.3394T>C (3 patients, 8.8%), m.3497C>T (4 patients, 11.8%), m.11696G>A (4 patients, 11.8%), and m.14502T>C (2 patients, 5.9%). Secondary mutation-carrying patients demonstrated a decreased in RNFL thickness, similar to those in primary mutation-carrying LHON patients. These patients had a higher female ratio (P = 0.019), better VA (P = 0.043) and color vision (P = 0.005), as well as better VF., Conclusions: In addition to common primary LHON-associated mutations, our study identified secondary mtDNA mutations, which should be considered when evaluating patients with optic atrophy., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)