ABSTRACT
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. Methods:A 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. Results:The 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). Conclusions:The 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.
ABSTRACT
Objective:To investigate the association between the rehabilitation of visual function and retinal nerve fiber layer (RNFL) thickness in Leber hereditary optic neuropathy (LHON) patients receiving gene therapy for the disease.Methods:A multi-center, non-randomized, single-arm clinical trial was conducted.A total of 159 LHON patients were enrolled in Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Taihe Hospital and Ezhou Central Hospital from December 2017 to December 2018.All of the patients were administered with a single unilateral intravitreal injection (0.05 μl) of recombinant adeno-associated virus 2 carrying reduced nicotinamide adenine dinucleotide dehydrogenase subunit 4 (rAAV2-ND4) and were followed up before and 1, 3, 6 and 12 months after treatment.The best corrected visual acuity (BCVA) converted to logarithm of the minimum angle of resolution (LogMAR) unit was assessed with a standard logarithmic visual acuity chart.Perimetry indicators including visual field index (VFI) and mean deviation (MD) were measured with Humphrey Field Analyzer.RNFL thickness in the superior, inferior, temporal, nasal optic disc and the average RNFL thickness were detected with Spectralis ? HRA+ OCT.The 12-month postoperative BCVA, visual field, and RNFL thickness were taken as the primary outcomes.According to the improvement of BCVA, VFI and MD at 12 months after therapy, there were 81 vision improved eyes with injection, 62 vision unimproved eyes with injection, 65 vision improved eyes without injection, and 78 vision unimproved eyes without injection, 48 VFI improved eyes with injection, 71 VFI unimproved eyes with injection, 47 VFI improved eyes without injection, and 72 VFI unimproved eyes without injection, 52 MD improved eyes with injection, 67 MD unimproved eyes with injection, 47 MD improved eyes without injection, and 72 MD unimproved eyes without injection.The correlations between BCVA, VFI, MD and RNFL thickness were evaluated by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Wuhan Tongji Hospital (No.TJ-IRB20180316), Taihe Hospital (No.2017-01), Ezhou Central Hospital (No.2017-K-05) and People's Hospital of Wuhan University (No.WDRY2020-K202).Written informed consent was obtained from each patient or custodian prior to entering the study cohort. Results:Among the patients receiving rAAV-ND4 gene therapy, the 12-month postoperative BCVA (LogMAR) in the injected eyes and uninjected eyes was 1.37±0.55 and 1.29±0.59, which were significantly better than 1.70±0.41 and 1.53±0.51 before treatment (baseline), respectively ( t=4.920, 3.550; both at P<0.001).The 12-month postoperative VFI of the patients were significantly improved and the 12-month postoperative MD of the patients were significantly lowered in comparison with those at baseline in the injected eyes (both at P<0.001).Similar improvements of VFI and MD were observed in the uninjected eyes (both at P<0.01).RNFL of the patients was thinner after the therapy.In the vision improved eyes with injection, the BCVA was negatively correlated with superior, inferior, temporal, nasal and average RNFL thickness ( r=-0.362, -0.292, -0.307, -0.308; all at P<0.05).In the VFI improved eyes with injection, VFI was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.439, 0.356, 0.294, 0.401; all at P<0.05).In the MD improved eyes with injection, MD was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.495, 0.424, 0.377, 0.474; all at P<0.05). Conclusions:The recovery of visual function is associated with RNFL thickness after the intravitreal injection of rAAV2-ND4 in LHON eyes.Recovery of visual acuity is better in the eyes with thicker RNFL.
ABSTRACT
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.
ABSTRACT
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).Methods:A 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.Results:Compared 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). Conclusion:The PhNR amplitudes of FERG in LHON patients and carriers decrease significantly compared to controls.
