G11778A位点突变Leber遗传性视神经病变的视野特点和变化趋势

目的观察并分析G11778A位点突变Leber遗传性视神经病变(LHON)患眼视野特点和变化趋势。方法回顾性临床研究。2008年5月至2018年2月在北京中医药大学东方医院眼科经线粒体DNA检测确诊的G11778A位点突变LHON患者22例44只眼纳入研究。患眼均行最佳矫正视力(BCVA)、视野、光相干断层扫描(OCT)检查。BCVA检查采用国际标准视力表进行,统计时换算为最小分辨角对数(logMAR)视力。采用OCT仪测量以视盘为中心1.73 mm外200μm×200μm环形区域的视网膜神经纤维层(RNFL)厚度。采用Octopus 101型视野计于患者病程2、4、8、12、18、24、30个月时间点前后1个月内分别完成至少7次以上视野检查。因初诊时患者BCVA和配合度的不同,其中27只眼采用G2程序进行视野检查(G2程序组),以视野平均缺损(MD)为主要结局指标;17只眼采用LVC程序进行视野检查(LVC程序组),以视野平均光敏感度(MS)为主要结局指标。两组患者性别构成比(χ²=1.896)、年龄(t=0.337)比较,差异无统计学意义(P=0.169、0.708);logMAR BCVA比较,差异有统计学意义(t=4.994,P=0.000)。根据患者发病年龄是否>14岁,再将两组患者分为年龄≤14岁组、>14岁组。组间比较采用独立样本t检验,组内比较采用配对t检验,多组间比较采用单因素方差分析;计数资料比较采用χ²检验。结果G2程序≤14岁组患眼随病程延长视野MD值逐渐降低;与病程2个月比较,病程18个月后视野MD值明显降低,差异有统计学意义(t=3.813、4.590、5.033,P=0.002、0.001、0.000)。G2程序>14岁组患眼不同病程视野MD值比较,差异无统计学意义(P>0.05)。LVC程序≤14岁组、>14岁组患眼不同病程视野MD、MS值比较,差异均无统计学意义(P>0.05)。患眼早期视野缺损主要表现为中心暗点,晚期则为弥漫性视野缺损。早期、晚期视野缺损类型眼数比较,G2程序组差异有统计学意义(χ²=17.414,P=0.015);LVC程序组差异无统计学意义(χ²=4.541,P=0.474)。G2程序组患眼病程8个月内视野MD值基本维持稳定;与病程2个月视野MD值比较,病程18个月后视野明显改善,MD值下降,差异有统计学意义(t=2.100、3.217、3.566,P=0.046、0.003、0.001)。LVC程序组患眼随访期间视野MS无明显改善(P>0.05)。G2程序组患眼,与病程2个月BCVA比较,病程12个月后BCVA明显提高,差异有统计学意义(t=3.039、3.678、4.264、5.078,P=0.008、0.002、0.001、0.000)。G2程序组患眼不同病程BCVA均优于LVC程序组,差异有统计学意义(P≤0.05)。G2程序组(t=8.400、9.330、10.989、11.967、12.211、12.803)、LVC程序组(t=10.668、13.036、13.833、18.922、20.387、20.851)患眼随病程延长RNFL厚度持续降低,差异有统计学意义(P值均为0.000)。G2程序组患眼病程4、8、18、24、30个月RNFL厚度均高于LVC程序组,差异有统计学意义(t=2.471、2.269、2.474、2.509、2.782,P=0.018、0.028、0.017、0.016、0.008)。结论G11778A位点突变LHON患眼视野缺损早期主要表现为中心暗点,晚期主要表现为弥漫性缺损和中心暗点。G2程序组患眼随访期间视野明显改善,BCVA显著提高;G2程序组中年龄≤14岁者视野改善优于年龄>14岁者。LVC程序组患眼随访期间视野MS无明显改善。

Characteristics and prognosis of visual field of G11778A mutation Leber hereditary optic neuropathy

Objective To analyze the characteristics and prognosis of visual field of Leber hereditary optic neuropathy(LHON)with G11778A mutation.Methods A 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 byχ² test.Results In 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).Conclusions The 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.