ObjectiveTo observe the clinical features of patients over 30 years old with Leber hereditary optic neuropathy (LHON). MethodsNine male LHON patients (18 eyes) were enrolled in this study. The patients aged from 34 to 56 years old, with an average age of (45.22±6.91) years. The course of the disease ranged from 7 days to 21 months, with a mean course of 5 months. Visual acuity, slit lamp microscope, chromoptometry, direct ophthalmoscope and fundus photography were measured for all patients, visual field examined for 6 patients (11 eyes). Mitochondrial DNA mutation was analyzed. The visual acuity was followed-up for 12 months. ResultsSeven of the 9 patients (77.78%) had family history. Five patients (55.56%) had both eyes involved simultaneously, and 4 patients (44.44%) had the eyes involved at different time. Three patients (33.33%) had sudden visual loss, and 6 patients (66.67%) had gradual visual loss. The visual acuity was light perception in 1 eye (5.55%), finger counting in 3 eyes (16.67%), 0.01-0.1 in 7 eyes (38.89%), 0.12-0.3 in 3 eyes (16.67%), equal or greater than 0.4 in 4 eyes (22.22%). Sixteen eyes (88.88%) had normal light reflex, 1 eye (5.55%) had no light reflex, and 1 eye (5.55%) had relative afferent papillary defect. Eight eyes (44.44%) had normal optic disk, 3 eyes (16.67%) had blurred optic disc border and disc telangiectasia, 7 eyes (38.89%) had pale disc and clear boundary. Among 11 eyes underwent visual field examination, 9 eyes (81.82%) had central or paracentral scotoma and 2 eyes (18.18%) had visual field narrowing. Among 9 patients, there were 7 patients (77.78%) with G11778A mutation, 1 patient (11.11%) with G11696A mutation, and 1 patient (11.11%) with T14484C mutation. In the last follow-up, the visual acuity was light perception in 1 eye (5.55%), finger counting in 4 eyes (22.22%), 0.01-0.1 in 6 eyes (33.33%), 0.12-0.3 in 3 eyes (16.67%), equal or greater than 0.4 in 4 eyes (22.22%).The visual acuity was improved in 9 eyes (50.00%), stable in 7 eyes(38.89%), and decreased in 2 eyes (11.11%). ConclusionLHON patients (older than 30 years) are more common in men, mostly with normal light reflex, central or paracentral scotoma and G11778A mutation.
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.