Characteristics and prognosis of visual field of G11778A mutation Leber hereditary optic neuropathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Xia Yanting ¹ ,  Liao Liang ¹ , Zhang Taotao ² , Zhou Jian ¹ , Wei Qiping ¹

1. Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China;
2. Beijing University of Chinese Medicine, Beijing 100029, China;

Corresponding author：

Liao Liang, Email: 58273677@qq.com

Keywords：

Visual fields; Optic atrophy, hereditary, Leber; Genes; G11778A mutation

DOI：

10.3760/cma.j.cn511434-20200427-00180

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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 by χ² 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.

Citation： Xia Yanting, Liao Liang, Zhang Taotao, Zhou Jian, Wei Qiping. Characteristics and prognosis of visual field of G11778A mutation Leber hereditary optic neuropathy. Chinese Journal of Ocular Fundus Diseases, 2021, 37(3): 180-188. doi: 10.3760/cma.j.cn511434-20200427-00180 Copy

1.	张丽珊, 黄鹰, 李方园, 等. 中国人Leber遗传性视神经病家系线粒体DNA突变的研究[J]. 中华医学杂志, 1994, 74(6): 349-351.Zhang LS, Huang Y, Li FY, et al. Mitochondrial DNA mutation in Leber's hereditaryoptic neuropathy in China[J]. Natl Med J China, 1994, 74(6): 349-351.
2.	郭莉, 贾小云, 肖学珊, 等. 原因不明的视神经炎线粒体DNA突变检测[J]. 中华眼底病杂志, 2000, 16(2): 78-79.Guo L, Jia XY, Xiao XS, et al. Screening for mt-DNA mutations in optic neuritis of unknown reason[J]. Chin J Ocul Fundus Dis, 2000, 16(2): 78-79.
3.	韦企平, 孙艳红, 宫晓红, 等. 中国人Leber遗传性视神经病变线粒体DNA突变的主要类型和临床特征[J]. 中华眼底病杂志, 2004, 20(2): 78-80.Wei QP, Sun YH, Gong XH, et al. The main types and clinical features of mitochondrial DNA mutations in Chinese Leber hereditary optic neuropathy[J]. Chin J Ocul Fundus Dis, 2004, 20(2): 78-80.
4.	祝肇荣, 卢俊. LVC程序视野检查在青光眼合并白内障患者的应用[J]. 上海第二医科大学学报, 2003, 23(5): 455-457. DOI: 10.3969/j.issn.1674-8115.2003.05.022.Zhu ZR, Lu J. Application of LVC procedure visual field examination in patients with glaucoma and cataract[J]. Journal of Shanghai Second Medical University, 2003, 23(5): 455-457. DOI: 10.3969/j.issn.1674-8115.2003.05.022.
5.	Nowomiejska K, Kiszka A, Koman-Wierdak E, et al. Analysis of visual field defects obtained with semiautomated kinetic perimetry in patients with Leber hereditary optic neuropathy[J/OL]. J Ophthalmol, 2018, 2018: 5985702[2018-03-21]. https://doi.org/10.1155/2018/5985702. DOI: 10.1155/2018/5985702.
6.	Newman NJ, Biousse V, Newman SA, et al. Progression of visual field defects in leber hereditary optic neuropathy: experience of the LHON treatment trial[J]. Am J Ophthalmol, 2005, 141(6): 1061-1067. DOI: 10.1016/j.ajo.2005.12.045.
7.	韦企平, 路明, 张丽霞, 等. Leber遗传性视神经病变24例临床分析[J]. 北京中医药大学学报, 2001, 24(2): 62-64. DOI: 10.3321/j.issn: 1006-2157.2001.02.024.Wei QP, Lu M, Zhang LX, et al. Clinical analysis of 24 cases of Leber hereditary optic neuropathy[J]. Journal of Beijing University of Traditional Chinese Medicine, 2001, 24(2): 62-64. DOI: 10.3321/j.issn: 1006-2157.2001.02.024.
8.	程先华, 杨沫, 魏世辉, 等. Leber遗传性视神经病变的临床特点[J]. 眼科, 2017, 26(5): 343-346. DOI: 10.13281/j.cnki.issn.1004-4469.2017.05.012.Cheng XH, Yang M, Wei SH, et al. Clinical characteristics of Leber's hereditary optic neuropathy[J]. Ophthalmology, 2017, 26(5): 343-346. DOI: 10.13281/j.cnki.issn.1004-4469.2017.05.012.
9.	Yum HR, Chae H, Shin SY, et al. Pathogenic mitochondrial DNA mutations and associated clinical featurs in Korean patients with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(12): 8095-8101. DOI: 10.1167/iovs.14-15311.
10.	Ran R, Yang S, He H, et al. A retrospective analysis of characteristics of visual field damage in patients with Leber’s hereditary optic neuropathy[J/OL]. Springerplus, 2016, 5(1): 843[2016-01-23]. http://europepmc.org/article/MED/27386292. DOI: 10.1186/s40064-016-2540-7.
11.	王瑛, 樊宁, 刘旭阳, 等. G11778A位点突变的9例Leber遗传性视神经病变患者的临床特征[J]. 国际眼科杂志, 2016, 16(10): 1952-1955. DOI: 10.3980/j.issn.1672-5123.2016.10.44.Wang Y, Fan N, Liu XY, et al. Clinical characteristics of 9 Leber hereditary optic neuropathy patients with G11778A mutation[J]. Int Eye Sci, 2016, 16(10): 1952-1955. DOI: 10.3980/j.issn.1672-5123.2016.10.44.
12.	Sadun AA, Salomao SR, Berezovsky A, et al. Subclinical carriers and conversions in Leber hereditary optic neuropathy: a prospective psychophysical study[J]. Trans Am Ophthalmol Soc, 2006, 104: 51-61.
13.	Hwang TJ, Karanjia R, Moraes-Filho MN, et al. Natural history of conversion of Leber's hereditary optic neuropathy: a prospective case series[J]. Ophthalmology, 2017, 124(6): 843-850. DOI: 10.1016/j.ophtha.2017.01.002.
14.	韦企平, 孙艳红. Leber遗传性视神经病变的临床和基础研究现状[J]. 中国中医眼科杂志, 2010, 20(2): 63-66.Wei QP, Sun YH. Current status of clinical and basic research on Leber's hereditary optic neuropathy[J]. Chinese Journal of Chinese Ophthalmology, 2010, 20(2): 63-66.
15.	Oostra RJ, Bolhuis PA, Wijburg FA, et al. Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome[J]. J Med Genet, 1994, 31(4): 280-286. DOI: 10.1136/jmg.31.4.280.
16.	Moon Y, Kim US, Han J, et al. Clinical and optic disc characteristics of patients showing visual recovery in Leber hereditary optic neuropathy[J]. J Neuroophthalmol, 2020, 40(1): 15-21. DOI: 10.1097/WNO.0000000000000830.
17.	Liu HL, Yuan JJ, Tian Z, et al. What are the characteristics and progression of visual field defects in patients with Leber hereditary optic neuropathy: a prospective single-centre study in China[J/OL]. BMJ open, 2019, 9(3): e025307[2019-03-15]. http://europepmc.org/article/MED/30878986. DOI: 10.1136/bmjopen-2018-025307.

1. 张丽珊, 黄鹰, 李方园, 等. 中国人Leber遗传性视神经病家系线粒体DNA突变的研究[J]. 中华医学杂志, 1994, 74(6): 349-351.Zhang LS, Huang Y, Li FY, et al. Mitochondrial DNA mutation in Leber's hereditaryoptic neuropathy in China[J]. Natl Med J China, 1994, 74(6): 349-351.
2. 郭莉, 贾小云, 肖学珊, 等. 原因不明的视神经炎线粒体DNA突变检测[J]. 中华眼底病杂志, 2000, 16(2): 78-79.Guo L, Jia XY, Xiao XS, et al. Screening for mt-DNA mutations in optic neuritis of unknown reason[J]. Chin J Ocul Fundus Dis, 2000, 16(2): 78-79.
3. 韦企平, 孙艳红, 宫晓红, 等. 中国人Leber遗传性视神经病变线粒体DNA突变的主要类型和临床特征[J]. 中华眼底病杂志, 2004, 20(2): 78-80.Wei QP, Sun YH, Gong XH, et al. The main types and clinical features of mitochondrial DNA mutations in Chinese Leber hereditary optic neuropathy[J]. Chin J Ocul Fundus Dis, 2004, 20(2): 78-80.
4. 祝肇荣, 卢俊. LVC程序视野检查在青光眼合并白内障患者的应用[J]. 上海第二医科大学学报, 2003, 23(5): 455-457. DOI: 10.3969/j.issn.1674-8115.2003.05.022.Zhu ZR, Lu J. Application of LVC procedure visual field examination in patients with glaucoma and cataract[J]. Journal of Shanghai Second Medical University, 2003, 23(5): 455-457. DOI: 10.3969/j.issn.1674-8115.2003.05.022.
5. Nowomiejska K, Kiszka A, Koman-Wierdak E, et al. Analysis of visual field defects obtained with semiautomated kinetic perimetry in patients with Leber hereditary optic neuropathy[J/OL]. J Ophthalmol, 2018, 2018: 5985702[2018-03-21]. https://doi.org/10.1155/2018/5985702. DOI: 10.1155/2018/5985702.
6. Newman NJ, Biousse V, Newman SA, et al. Progression of visual field defects in leber hereditary optic neuropathy: experience of the LHON treatment trial[J]. Am J Ophthalmol, 2005, 141(6): 1061-1067. DOI: 10.1016/j.ajo.2005.12.045.
7. 韦企平, 路明, 张丽霞, 等. Leber遗传性视神经病变24例临床分析[J]. 北京中医药大学学报, 2001, 24(2): 62-64. DOI: 10.3321/j.issn: 1006-2157.2001.02.024.Wei QP, Lu M, Zhang LX, et al. Clinical analysis of 24 cases of Leber hereditary optic neuropathy[J]. Journal of Beijing University of Traditional Chinese Medicine, 2001, 24(2): 62-64. DOI: 10.3321/j.issn: 1006-2157.2001.02.024.
8. 程先华, 杨沫, 魏世辉, 等. Leber遗传性视神经病变的临床特点[J]. 眼科, 2017, 26(5): 343-346. DOI: 10.13281/j.cnki.issn.1004-4469.2017.05.012.Cheng XH, Yang M, Wei SH, et al. Clinical characteristics of Leber's hereditary optic neuropathy[J]. Ophthalmology, 2017, 26(5): 343-346. DOI: 10.13281/j.cnki.issn.1004-4469.2017.05.012.
9. Yum HR, Chae H, Shin SY, et al. Pathogenic mitochondrial DNA mutations and associated clinical featurs in Korean patients with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(12): 8095-8101. DOI: 10.1167/iovs.14-15311.
10. Ran R, Yang S, He H, et al. A retrospective analysis of characteristics of visual field damage in patients with Leber’s hereditary optic neuropathy[J/OL]. Springerplus, 2016, 5(1): 843[2016-01-23]. http://europepmc.org/article/MED/27386292. DOI: 10.1186/s40064-016-2540-7.
11. 王瑛, 樊宁, 刘旭阳, 等. G11778A位点突变的9例Leber遗传性视神经病变患者的临床特征[J]. 国际眼科杂志, 2016, 16(10): 1952-1955. DOI: 10.3980/j.issn.1672-5123.2016.10.44.Wang Y, Fan N, Liu XY, et al. Clinical characteristics of 9 Leber hereditary optic neuropathy patients with G11778A mutation[J]. Int Eye Sci, 2016, 16(10): 1952-1955. DOI: 10.3980/j.issn.1672-5123.2016.10.44.
12. Sadun AA, Salomao SR, Berezovsky A, et al. Subclinical carriers and conversions in Leber hereditary optic neuropathy: a prospective psychophysical study[J]. Trans Am Ophthalmol Soc, 2006, 104: 51-61.
13. Hwang TJ, Karanjia R, Moraes-Filho MN, et al. Natural history of conversion of Leber's hereditary optic neuropathy: a prospective case series[J]. Ophthalmology, 2017, 124(6): 843-850. DOI: 10.1016/j.ophtha.2017.01.002.
14. 韦企平, 孙艳红. Leber遗传性视神经病变的临床和基础研究现状[J]. 中国中医眼科杂志, 2010, 20(2): 63-66.Wei QP, Sun YH. Current status of clinical and basic research on Leber's hereditary optic neuropathy[J]. Chinese Journal of Chinese Ophthalmology, 2010, 20(2): 63-66.
15. Oostra RJ, Bolhuis PA, Wijburg FA, et al. Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome[J]. J Med Genet, 1994, 31(4): 280-286. DOI: 10.1136/jmg.31.4.280.
16. Moon Y, Kim US, Han J, et al. Clinical and optic disc characteristics of patients showing visual recovery in Leber hereditary optic neuropathy[J]. J Neuroophthalmol, 2020, 40(1): 15-21. DOI: 10.1097/WNO.0000000000000830.
17. Liu HL, Yuan JJ, Tian Z, et al. What are the characteristics and progression of visual field defects in patients with Leber hereditary optic neuropathy: a prospective single-centre study in China[J/OL]. BMJ open, 2019, 9(3): e025307[2019-03-15]. http://europepmc.org/article/MED/30878986. DOI: 10.1136/bmjopen-2018-025307.

Chinese Journal of Ocular Fundus Diseases

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

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