ObjectiveTo observe the effects of penetrance, different time of onset and mutation sites on retinal nerve fiber layer (RNFL) and macular thickness in patients with Leber's hereditary optic neuropathy (LHON).MethodsThis was a cross-sectional observational study. A total of 88 patients with LHON and 1492 relatives of the maternal relatives (gene carriers) who received treatment in People’s Liberation Army General Hospital from 2015 to 2017 were included in the study. Among the 1492 family members, there were 694 males and 798 females. Peripheral venous blood was extracted from all subjects for mitochondrial DNA testing, and penetrance was calculated. A total of 117 patients underwent BCVA and SD-OCT examinations, including 82 patients and 35 gene carriers. The BCVA examination was performed using the Snellen visual acuity chart, which was converted into logMAR visual acuity. The thickness of RNFL, ganglion cell complex (GCC) and inner limiting membrane (ILM)-RPE were measured with OCT instrument. The mean follow-up was 50.02±86.27 months. The disease course was divided into 6 stages including ≤3 months, 4-6 months, 7-12 months and >12 months. The thickness of RNFL, GCC and ILM-RPE in patients with different time of onset and mutation sites were comparatively analyzed by covariance analysis. Categorical variables were expressed as a percentage, and the χ2 test was used for comparison among multiple groups.ResultsAmong the 1492 family members, 285 were diagnosed with LHON and highly suspected clinical manifestations (19.10%), including 190 males (21.98%) and 95 females (11.90%). The total penetrance rates of 11778, 14484 and rare mutation sites were 19.84% (228/1149), 20.50% (33/161), and 13.19% (24/182) respectively; male penetrance rates were 28.87% (153/530), 27.28% (20/72), and 18.48% (17/92) and female penetrance rates were 12.12% (75/619),14.61% (13/89) and 7.78% (7/90). There was no significant difference in total (χ2=4.732), male (χ2=4.263) and female (χ2=4.263) penetrance between different mutation sites (P=0.094, 0.110, 0.349). Compared with non-pathogenic carriers, the thickness of the RNFL, GCC and ILM-RPE were all different in the four stages ( ≤3months, 4-6 months, 7-12 months and >12 months). The thickness of RNFL, GCC and ILM-RPE decreased with the time of onset (P=0.000). There were significant differences in the thickness of each of the GCC and ILM-RPE layers in the macular area of LHON patients with different mutation sites (P＜0.05). Among them, the site 11778 and 3460 had the most severe damage in all quadrants of macular GCC and ILM-RPE layer, followed by 14484 site, and the rare site had the least damage in all quadrants.ConclusionsThe penetrance of LHON patients is 19.10%. With the extension of the onset time (within 1 year), the RNFL layer of the optic disc and all quadrants of the macular GCC and ILM-RPE layer gradually thinned. Compared with 11778 and rare site, 14484 site, and the rare site had the lighter damage on the thickness of RNFL, GCC and ILM-RPE.
ObjectiveTo analyze the clinical features and prognosis of adult optic neuritis patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-ON) or aquaporin 4 antibody (AQP4-ON).MethodsA retrospective study. From December 2015 to February 2018, in the Beijing Chaoyang Hospital of Capital Medical University and Chinese PLA General Hospital, 162 eyes of 132 patients with positive serum MOG antibody and AQP4 were included in the study. There were 42 MOG-ON patients (49 eyes, 31.8%), 90 AQP4-ON patients (113 eyes, 68.2%). The clinical features of optic neuritis (annual recurrence frequency, incidence of optic disc edema), brain and optic nerve enhanced MRI, serum autoimmune antibodies and cerebrospinal fluid test results were compared between MOG-ON and AQP4-ON patients. All patients were treated with intravenous methylprednisolone sodium succinate in the acute phase and then switched to oral prednisone acetate tablets. The average follow-up time was 15 months. The glucocorticoid dependence, visual prognosis, spinal cord symptoms, and myelitis at the last follow-up were comparatively analyzed between MOG-ON and AQP4-ON patients. The comparison of the count data was performed by χ2 test, and the measurement data were compared by t test.ResultsCompared with AQP4-ON patients, MOG-ON patients had higher annual recurrence frequency (t=3.760, P=0.005), higher incidence of optic disc edema (χ2=14.777, P＜0.001), higher incidence of hormone dependence (χ2=25.496, P＜0.001), and better visual prognosis (χ2=28.759, P＜0.001). MOG-ON patients were more likely to involve the optic nerve, AQP4-ON patients were more likely to involve the optic chiasm and the optic tract. There was a significant difference in the location of lesions between MOG-ON and AQP4-ON patients (χ2= 5.447, P= 0.015). The proportion of AQP4-ON patients with autoimmune antibodies was significantly higher than that of MOG-ON patients (χ2 = 20.453, P＜0.001). The results of cerebrospinal fluid test showed that the white blood cell count of patients with MOG-ON and AQP4-ON were within the normal range, but the IgG level of AQP4-ON patients was significantly higher than that of MOG-ON patients (t=8.669, P＜0.001). At the last follow-up, there were 7 and 29 patients of myelitis in MOG-ON and AQP4-ON patients respectively (χ2=3.494, P=0.046).ConclusionsThe clinical characteristics of MOG-ON were different from AQP4-ON. The incidence of optic disc edema and recurrence rate were higher, but the proportion of autoimmune antibodies was lower. MOG-ON was more likely to show hormone dependence, but the visual prognosis was better. AQP4-ON was easily involved in optic chiasm and optic tract, and the incidence of myelitis was higher.
ObjectiveTo investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity. MethodsA cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. ResultsThe CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm2, (57.78±12.35) root/mm2, (3.27±1.34) mm/mm2, and (13.74±3.05) mm/mm2, (70.95±13.14) root/mm2, and (4.22±1.03) mm/mm2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant (t=4.089, 3.795, 2.773; P＜0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm2, (3.80±1.19) mm/mm2, (47.97±8.86) fibers/mm2, and (9.25±2.19) mm/mm2, (2.72±1.19) mm/mm2, (39.43±13.86) fibers/mm2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant (t=－4.002, －2.706, －2.306; P＜0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm2, respectively. The difference in corneal DC density between the two subgroups was statistically significant (P＜0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON (r=－0.422, －0.456; P＜0.05). ConclusionsThere are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.