Leber hereditary optic neuropathy is an optic neuropathy associated with mitochondrial DNA. The disease affects young men mainly, which is considered to be due to denaturation of the retinal nerve ganglion cell and axonal loss of optic nerve, leading to optic atrophy. Nowadays, there are some development in studying Leber hereditary optic neuropathy by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). It is great help to know the disease, forecast the progression of disease, and take action on intervention. In addition, there is a lack of in-depth study on OCT and OCTA characteristics among different mutation sites of LHON, different genders of the same site, different families of the same site or even different branches of the same family. It is expected to be improved in the future work.
Objective To find the new mutations of Leber's hereditary optic neuropathy (LHON). Methods Two LHON families were enrolled in this study. The probands and all maternal members in this two families were underwent ophthalmologic examinations. The ages of probands were seven and 14 years old respectively. A total of 358 healthy adults were enrolled in this study as control group. The genomic DNA from whole blood of participants were extracted. The entire mitochondrial genome of probands were PCR amplified and sequenced in 24 overlapping fragments using primers as designed. At the same time, the mtDNA of maternal relatives and 358 controls were also detected. Fourteen primate species were selected from GenBank to analyzed the phylogenetics of mitochondrial sequence. Results There was no ND4 G11778A, ND1 G3460A, ND6 T14484C mutational site in all maternal members. Molecular analysis of mtDNA in this two families identified the homoplasmic tRNAGluA14683G mutation and distinct set of variants belonging to the Asian haplogroup F1a1 and G2. The site was at theTpsi;C stem oftRNAGlu and extremely conserved among 14 primate species. It was anticipated that the A14683G increased the highly conserved C-G basepairing. Furthermore, the A14683G was absence in control group. Conclusion The tRNAGluA14683G mutation is likely a new mutation associated with LHON.
ObjectiveTo analyze the characteristics and prognosis of visual field of Leber hereditary optic neuropathy (LHON) with G11778A mutation.MethodsA retrospective clinical study. Twenty-two (44 eyes) of LHON patients diagnosed with G11778A site mutation by mt-DNA examination from May 2008 to February 2018 in Ophthalmology Department of Dongfang Hospital of Beijing University of Chinese Medicine, were enrolled in this study. All patients underwent best corrected visual acuity (BCVA), visual field and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The thickness of the retinal nerve fiber layer (RNFL) in the 200μm×200μm annular region 1.73 mm outside the optic disc was measured by OCT. At least 7 visual field examinations were performed within one month before and after 2, 4, 8, 12, 18, 24 and 30 months of the course of disease by using Octopus 101 perimetry. Among 44 eyes, 27 eyes were detected with G2 procedure (G2 group) and 17 eyes were detected with LVC procedure (LVC group). The mean field defect (MD) and mean optical sensitivity (MS) were used as the main outcome indexes. According to the onset age, the patients were further divided into the ≤14 years old group and＞14 years old group. There was a significant difference in initial logMAR BCVA between the G2 group and LVC group (t=4.994, P=0.000), but there was no significant difference in gender (χ2=1.896, P=0.169) and age (t=0.337, P=0.708) between the two groups. Independent sample t test was used for comparison between groups, paired t test was used for comparison within groups, and one-way analysis of variance was used for comparison between groups. The statistical data were compared by χ2 test.ResultsIn the G2 group, the MD value of the subgroup of children (≤14 years old) decreased gradually during the follow-up period, and the MD value since 18 months after onset was significantly lower than the value of 2 months after onset (t=3.813, 4.590, 5.033; P=0.002, 0.001, 0.000). No obvious visual field index changes were seen in other subgroups (P＞0.05). The central scotoma was the most common type of visual field defect in the early stage, and the diffuse defect was the most common type of visual field defect in the late stage. There was a significant difference in the types of visual field distribution between the early and late stage in G2 group (χ2=17.414, P=0.015). There was no significant difference in the type of visual field distribution between the early and late stage in LVC group (χ2=4.541, P=0.474). The MD value in the G2 group remained stable within 8 months after onset, but significantly improved after 18 months after onset (t=2.100, 3.217, 3.566; P=0.046, 0.003, 0.001). The MS in the LVC group did not significantly improve during follow-up (P＞0.05). The average visual acuity of the G2 group was significantly improved from 12 months (t=3.039, 3.678, 4.264, 5.078; P=0.008, 0.002, 0.001, 0.000). The visual acuity of the eyes in the G2 group was better than that of the LVC group during all follow-up periods (P≤0.05). The RNFL thickness of all patients continued to decrease after onset, but the RNFL thickness was significantly higher at 4, 8, 18, 24, 30 months in the G2 group than those in the LVC group (t=2.471, 2.269, 2.474, 2.509, 2.782; P=0.018, 0.028, 0.017, 0.016, 0.008).ConclusionsThe main types of visual field defect of LHON with G11778A mutation are the central scotoma in the early stage, while the diffuse defect and central scotoma are both very common in the later stage. The visual field of LHON patients examined by G2 procedure is significantly improved during the follow-up, as well as the visual acuity improved significantly, and the visual field improvement in younger cases (≤14 years old) is better than that of older cases (＞14 years old), but the visual field of the LVC procedure cases did not improve during follow-up.
Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease. It is clinically recognizable by painless, bilateral loss of vision, and the prognosis of vision is generally poor. In recent years, the information provided by optical coherence tomography (OCT) and OCT angiography (OCTA) has greatly improved people's understanding of LHON, and new progress has been made in the intervention and treatment of LHON. A detailed understanding of the structural changes of retina and choroid under OCT and OCTA of the natural course and after treatment of LHON, may provide reference for revealing the pathogenesis, prediction of onset time, differential diagnosis, follow-up of treatment effect and prognosis of LHON.
Optic atrophy,hereditary／diagnosis; Polymerase chain reaction; DNA,mitochondrial; Point mutation; Sequence analysis
Objective To observe the clinical classification and manifestation of diabetic optic neuropathy (DON) in patients with non-proliferative diabetic retinopathy (NPDR).Methods Two hundreds and twenty four patients (440 eyes) with NPDR diagnosed by fundus fluorescein angiography (FFA) were included in this study. All patients were examined including visual acuity, intraocular pressure, slit-lamp microscopy, color fundus photography and visual field.The morphology of optic disc and peripapillary retinal nerve fiber layer (RNFL) thickness were observed and measured by optical coherence tomography (OCT). The levels of HbA1C and lipid were detected. According to the examination results, the patients were divided into DON group and control group. DON groups were further subdivided into diabetic papillopathy (DP), anterior ischemic optic neuropathy (AION) and optic atrophy subgroups. The incidence of DP, AION and optic atrophy were observed. And the differences of RNFL thickness and systemic related indexes among groups were statistically analyzed. Results Among the 440 eyes, DON was found in 19 eyes (4.3%), without DON was found in 421 eyes (95.7%). There were two eyes (10.5%) with DP, 12 eyes (63.2%) with AION and five eyes (26.3%) with optic atrophy in the DON group. Both of the DP eyes were without obvious DR. There was no statistical significance between the incidence of AION in without obvious DR, mild, in moderate and severe NPDR stage (chi;2= 0.019,P＞0.05). Compared with control group, the horizontal disc diameter, vertical disc diameter and C/D ratio were smaller in eyes with AION (t=-2.425,-3.432,-3.871;P＜0.05); the duration of diabetes was significantly prolonged (t=2.320,P＜0.05).Conclusions There are three kinds of DON in patients with NPDR, which include DP, AION and optic atrophy. Optic disk and C/D ratio are small, and the duration of diabetes course is long in AION patients.
Leber's hereditary optic neuropathy (LHON) is a rare hereditary optic nerve disease. At present, the understanding of its etiology and pathogenesis is relatively clear. With the emergence of new drugs such as idebenone and the possibility of gene therapy for LHON, it has brought hope for patients to recover. However, because genetic testing technology has not been widely developed in China, clinical misdiagnosis of LHON as optic neuritis still occurs from time to time. How to make timely identification and correct diagnosis of LHON still poses certain challenges for Chinese ophthalmologists. In addition, in terms of treatment, the choice of treatment methods and treatment costs in the pre-onset (gene mutation carriers) and different periods after the onset of LHON are also huge challenges for patients and their families.
Mutations in optic atrophy (OPA) genes can lead to a similar phenotype, namely optic atrophy, which can manifest as isolated optic atrophy or be accompanied by other systemic symptoms, mostly related to the nervous system. Currently, a total of 13 OPA genes have been discovered, covering a variety of inheritance patterns, including chromosomal dominant inheritance, autosomal recessive inheritance, and X-linked inheritance. Through genetic testing and analysis of patients, it is possible to accurately determine whether they carry mutation genes related to optic atrophy, and predict the progression of the disease and potential complications accordingly. This not only provides valuable genetic counseling and fertility planning guidance for patients and their families, but also helps better understand the disease, discover new therapeutic targets, and lay the foundation for developing more precise and effective drugs or gene therapies in the future.
Objectives To observe the clinical characteristics of Leber congenital amaurosis (LCA) and analyze the features to differentiate LCA from other similar disorders.Methods Prospective study of 15 LCA patients which include 10 males and 5 females, aged from 2 to 31 years with the mean age 13.6 years. Medical history, family history, perinatal conditions, as well as complete ocular evaluations were well documented. Among the subjects, 12 patients underwent optometry check, 10 patients underwent ERG and 8 patients had OCT testing. Results All of the patients had nystagmus and sluggish pupillary reflex. The visual acuity distributed from light perception to 0.1. Fivepatients (33.3%) were presented with photophobia, while 7 patients (46.7%) had nyctalopia. Among 12 cases underwent refraction examination, 6 patients (50%) had spherical equivalent of ge;+5D；1 patient（8.3%）had spherical equivalent of ge;+5D; 2 patients (16.7%) had bilateral mild to moderate hyperopia；1 patient (8.3%) had one emmertropic eye and one mild myopic eye; 2 patients (16.7%) had moderate to high myopia. Eight patients (53.3%) had enophthalmus,4 patients (26.7%) had oculodigital sign. All of the 10 patients underwent ERG showed extinguished waveform. Under OCT assesement, 7 patients had decreased fovea thickness; 1 patient had increased fovea thickness, complicated by epiretinal membrane; mild abnormality of microstructure of the retina with diminished and disrupted IS/OS hyperreflectivity were found in 2 cases；while more pronounced disarrangement of the retinal layers were found in 6 cases，inner layers were better reserved in all patients.Conclusions Severe visual impairment or blindness, nystagmus, pupillary reflex, extinguished ERG and hyperopia are main clinical characteristics of LCA.
ObjectiveTo observe the changes of vision and visual evoked potentials (VEP) in patients with Leber hereditary optic neuropathy (LHON) before and after gene therapy.MethodsA retrospective cohort study. From December 2017 to October 2018, 35 cases of 70 eyes of m11778G.A/MT-ND4 mutant LHON patients who were diagnosed in the Tongji Hospital of Huazhong University of Science and Technology and received gene therapy were included in the study. There were 30 males (87.71%) and 5 females (12.29%), with the mean age of 23.31±6.72 years. The gene therapy method was intravitreal injection of rAAV2-ND4 (recombinant adeno-associated virus carrying NADH-ubiquinone oxidoreductase subunit 4 gene) into one eye. The eye with poor visual acuity was chosen as the injection eye. If both eyes had the same visual acuity, the right eye was designated as the injection eye. Seventy eyes were divided into the injected eye group and the non-injected eye group, in which were both 35 eyes. The best corrected visual acuity (BCVA) and pattern VEP (PVEP) examinations were performed in the injected eye group and the non-injected eye group before treatment (baseline), 1, 3, and 6 months after injection. Compare the changes of BCVA and PVEP between the injected eye group and the non-injected eye group at baseline, 1 month, 3 months, and 6 months after injection. Independent sample t test, paired sample t test or two independent sample nonparametric test were performed to compare the two groups.ResultsCompared with baseline, 1, 3, and 6 months after treatment, the BCVA of the injected eye group (t=3.530, 4.962, 5.281; P=0.001, 0.000, 0.000) and the non-injected eye group (t=3.288, 2.620, 2.252; P= 0.002, 0.013, 0.031) increased, and the difference was statistically significant; there was no statistically significant difference between VEP IT (tinjected eye group=−0.158, 1.046, −1.134; Pinjected eye group = 0.875, 0.303, 0.190; tnon-injected eye group=0.773, −0.607, −0.944; Pnon-injected eye group= 0.445, 0.548, 0.352) and VEP A (Zinjected eye group=−0.504, −0.934, −1.065; Pinjected eye group= 0.614, 0.351, 0.287; Znon-injected eye group=−0.521, −0.115, −0.491; Pnon-injected eye group = 0.602, 0.909, 0.623).ConclusionAfter gene therapy, the visual acuity of the injected and non-injected eyes of LHON patients improved; PVEP did not change significantly, and remained stable compared with baseline.