Objective To observe the molecular genetic characteristics of seven Chinese families with Leberprime;s hereditary optic neuropathy (LHON). Methods Ophthalmologic examinations were performed on seven probands, maternal members from seven Chinese families and 134 healthy controls. There were two LHON patients in seven Chinese families except probands. The entire mitochondrial genome was amplified using 24 pairs of oligonucleotide primers with overlapping fragments.The mutational site was analyzed through comparison of the Results and Cambridge reference sequence. The penetrance of mutation site was calculated and the haplotype was analyzed. Results Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated with ND4 G11778A, ND1 G3460A and ND6 T14484C mutations. The ND1 T3394C mutation in probands and other matrilineal relatives was present in four out of 134 Chinese healthy controls. Strikingly, these families exhibited very low penetrance of visual impairment. The penetrance was 12.50%, 22.22%, 16.76%, 6.25%, 9.09%, 11.11% and 28.57%. The Results of phylogenetic tree analysis of submitochondrial haplotype showed that these mtDNA polymorphism sites belong to the Asian haplogroups M9, M9, M, D4, M, M9 and M9. Conclusions T3394C mutation exists in seven Chinese LHON pedigrees, and the penetrance was ranged from 6.25% to 28.57%. The patients have different clinical manifestations.
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.
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.
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.
Objective To investigate the characteristics and risk factors of optic nerve atrophy in eyes with complicated retinal detachment after silicone oil tamponade during the procedure of vitreoretinal operation. Methods The clinical data of 97 patients with complicated retinal detachment who had optic nerve atrophy after silicone oil tamponade during the procedure of vitreoretinal operation were an alyzed retrospectively. Logistic regression analysis by SPSS statistical software was used to analyze the factors like age, disease history, primary diseases, preoperative ocular condition, complications in and after the operation, the time taking out the silicone oil, and emulsification of the silicone oil, and Ple;0.05 was considered to be the symbol of significant difference. Results All of the affected eyes had optic discs with clear border, including paler optic disc in 65 eyes, pale one in 21 eyes, and paler optic disc with enlargement of the cup/disc (ge; 0.6) in 11 eyes. The result of logistic regression analysis showed that the intraocular pressure (P=0.022) and the visual acuity (P=0.001) during the silicone oil removal were in the equation. Conclusion The risk factor of optic nerve atrophy is the chronic increase of intraocular pressure after silicone oil tamponade. (Chin J Ocul Fundus Dis, 2006, 22: 305-307)
Optic atrophy,hereditary／diagnosis; Polymerase chain reaction; DNA,mitochondrial; Point mutation; Sequence analysis
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.
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.
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.