Objective To observe the characteristics of pattern electroretinogram (PERG) and the photopic negative response (PhNR) of flash electroretinogram (FERG) in patients and carriers with Leber hereditary optic neuropathy (LHON). MethodsA cross sectional, observational study. Thirty-two patients (64 eyes) diagnosed with LHON (LHON group) and 15 normal members with the same mutation in patient's family (carrier group) were included in this study from February 2021 to November 2021 in the Department of Ophthalmology of Renmin Hospital of Wuhan University. All patients in LHON group were males (100.0%, 32/32) and the average age was 23.34±7.41 years. In the carrier group of 15 cases (30 eyes), there were 2 males (13.3%, 2/15) and 13 females (86.7%, 12/15). The average age was 43.44±7.65 years. Twenty-four healthy subjects (48 eyes) in the same period were selected as the control group. Among them, there were 8 males (33.3%, 8/24) and 16 females (66.7%, 16/24). The average age was 23.42±2.54 years. All subjects were examined with the GT-2008V-VI visual electrophysiology instrument of Chongqing Gotec Medical Equipment Limited Company for PERG and FERG. P50 and N95 amplitudes of PERG and PhNR, a wave and b wave amplitudes of FERG were recorded. The peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the nasal, superior, temporal, inferior and average quadrants were measured by spectral domain optical coherence tomography (SD-OCT). The amplitudes of a wave, b wave, PhNR, P50 wave, N95 wave and pRNFL thickness between the three groups were compared by one-way ANOVA. Pearson correlation analysis was used to analyze the correlation between different parameters. ResultsCompared with the control group, the amplitudes of PhNR in LHON group and carrier group decreased significantly (F=11.973, P＜0.001). The results of correlation analysis showed that the amplitude of PhNR in LHON group was significantly correlated with the thickness of nasal and temporal pRNFL (r=0.249, 0.272; P=0.048, 0.030). There was no significant difference in P50 wave amplitude between patients , carriers and controls (F=1.342, P=0.265). There was no significant difference in N95 wave amplitude between patients and controls (P=0.960). ConclusionThe PhNR amplitudes of FERG in LHON patients and carriers decrease significantly compared to controls.
Leber hereditary optic neuropathy (LHON) is a matrilineal hereditary optic neuropathy in which mitochondrial DNA mutations lead to retinal ganglion cell degeneration. At present, the treatment for LHON is limited. Early symptomatic treatment and medical treatment may improve the vision of patients. In recent years, rapid progress has been made in gene therapy. Many clinical studies have confirmed its safety and efficacy. Monocular gene therapy is helpful to improve the visual function of LHON patients, and it can also improve the visual acuity of uninjected eyes. Patients do not have serious eye or systemic adverse events during the treatment period, showing good safety and tolerance. Studies with larger sample size and longer follow-up time are needed to further verify the efficacy and safety of gene therapy in the future. Gene therapy is expected to become a safe and effective treatment, bringing hope to LHON patients.
Leber’s hereditary optic neuropathy (LHON) is a paradigm maternal hereditary eye disease, mainly involving the retinal and macular fibers of the optic disc in the anterior ethmoid plate of the sclera. LHON has the characteristics of sex bias among males and incomplete penetrance. Primary mitochondrial DNA mutations m.11778G>A, m. 14484T>C, m.3460G>A are the molecular basis of LHON. However, other risk factors, such as secondary mitochondrial DNA mutations, mitochondrial haplotypes, nuclear modification genes, estrogen, vitamin B12 and environmental factors, work together to affect its phenotypic expression. The clinical diagnosis of LHON mainly limited to the detection of the primary mutation site of mitochondrial DNA. Therefore, comprehensive analysis of multiple risk factors of LHON will facilitate to construct multi-dimensional model of prevention, diagnosis and treatment system, which provide accurate and individualized medical services for patients. These may alleviate the incidence in LHON families. It also provides new ideas and different angles for the in-depth study of the pathogenesis of LHON.
Objective To analyze the thickness of peripapillary retinal nerve fiber layer (pRNFL) and photoreceptor (PR) sublayer in Leber hereditary optic neuropathy (LHON) and G11778A mutation carriers. MethodsA cross sectional study. From September 2020 to October 2021, 68 LHON patients (136 eyes) (patient group) and 40 G11778A mutation carriers (80 eyes) of LHON patients' families (carrier group) were included in the study. All patients were found to have G11778A mutation by Genetic testing. Forty healthy volunteers with 80 eyes matched to the age and gender of the patient group were recruited as a normal control group. All eyes were examined by optical coherence tomography (OCT). The pRNFL thickness was automatically measured by the built-in software of the OCT device. The total retinal thickness (MT) and the thickness of the outer bundle layer (OPL), outer nuclear layer (ONL), external limiting membrane to retinal pigment epithelium (ELM-RPE) in macular OCT images were measured by Image J software. Linear mixed model was used to analyze and compare the thickness of pRNFL, macular fovea and four layers above the nasal and temporal paracentral retina in patients, carriers and normal controls. The correlation between pRNFL and macular retinal sublayer thickness and the course of disease was also analyzed. ResultsThe thickness of the upper and lower pRNFL, temporal pRNFL and average pRNFL of the patients were smaller than those of the carriers and the normal control group (P＜0.01), and the nasal pRNFL thickness of the patients was smaller than that of the carriers (P＜0.01). Fovea: compared with the normal control group, the thickness of MT and ONT in the patient group was decreased, ONL thickness decreased in carrier group, with the significant different (P＜0.05). Parafovea: compared with normal control group, the thickness of MT and temporal ONL decreased and temporal OPL increased in the patients group, with the significant different (P＜0.05). In the carrier group, the thickness of MT and temporal, nasal ONL decreased, and the thickness of nasal OPL increased, with the significant different (P＜0.05). Compared with the carrier group, the MT thickness of the patient group was decreased, and the nasal ONL and nasal ELM-RPE thickness were increased, with the significant different (P＜0.05). Correlation analysis results showed that the thinning of pRNFL in the superior, nasal, temporal and average (r=－0.22, －0.21, －0.25, －0.22), and the thickening of ELM-RPE in foveo-temporal (r=0.19) were correlated with the course of disease (P＜0.05). ConclusionsThe pRNFL of LHON patients with G11778A mutation becomes thinner and is related to the course of the disease. There were significant differences in the thickness of MT and PR sublayers between patients and carriers compared to the normal control group.
ObjectiveTo observe Leber's hereditary optic neuropathy (LHON) microperimetry features, discuss its significance in diagnosis and treatment of LHON assessment. MethodsA retrospective clinical study. A total of 13 LHON patients (25 eyes) diagnosed in Department of Ophthalmology of the First Affiliated Hospital of Army Medical University from May 2015 to May 2020 (disease group) were included in the study, including 9 males (18 eyes) and 4 females (7 eyes), and beginning with the age of 15.0 (10.0, 57.0). Ten healthy volunteers (19 eyes) were selected as the normal group, including 7 males (13 eyes) and 3 females (6 eyes), aged 22.0 (6.0, 46.0) years at the first diagnosis. According to the course is divided into: asymptomatic group (carriers), subacute (＜6 months), the dynamic group (6-12 months), chronic group (＞12 months). There were 7, 6, 5 and 7 eyes, respectively. All eyes underwent best corrected visual acuity (BCVA) and microperimetry. BCVA test was performed using the international standard visual acuity chart, which was statistically converted to the logarithm of the minimum Angle of resolution (logMAR) visual acuity. MP-3 microperimetry was used to perform microperimetry, and the mean sensitivity (MS) values of five regions were recorded: center, superior, temporal, inferior, and nasal. Mann-Whitney U test was used for comparison between two groups, and Kruskal-Wallis H test was used for comparison between multiple groups. ResultsCompared with the normal group, MS in the center, superior, temporal, inferior and nasal of the diseased group decreased, and the differences were statistically significant (Z=－5.629, －4.906, －5.630, －5.631, －5.227; P＜0.05). There were significant differences in different regions of MS between different course groups (H=12.296, 11.583, 10.110, 12.994, 8.663; P＜0.05). There were significant differences in logMAR BCVA and central MS between asymptomatic group and subacute group (P=0.040, 0.007). There were significant differences in temporal, inferior and superior MS between subacute group and dynamic group (P=0.026, 0.017, 0.018). Dynamic and chronic group, MS above the difference was statistically significant (P=0.031). Idebenone treatment significantly improved visual field defects in 4 of 23 eyes. ConclusionsIn the early stage of LHON, the central visual field defect gradually progresses to the temporal, inferior and superior areas, and the temporal and inferior areas are more severe. Visual field defects reached a stable level at 6-12 months. MP-3 can assist in early diagnosis of LHON, and provide reliable basis for efficacy evaluation.