Electroretinogram changes in patients and carriers with Leber hereditary optic neuropathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Miao Qingmei , Cheng Yufang , Yuan Jiajia , Zheng Hongmei ,  Chen Changzheng

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, China;

Corresponding?author：

Chen Changzheng, Email: whuchenchzh@163.com

Keywords：

Leber hereditary optic neuropathy; Electroretinogram; Photopic negative response; Retinal nerve fiber layer

DOI：

10.3760/cma.j.cn511434-20220110-00020

Video：

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Objective To observe the characteristics of pattern electroretinogram (PERG) and the photopic negative response (PhNR) of flash electroretinogram (FERG) in patients and carriers with Leber hereditary optic neuropathy (LHON). Methods A cross sectional, observational study. Thirty-two patients (64 eyes) diagnosed with LHON (LHON group) and 15 normal members with the same mutation in patient's family (carrier group) were included in this study from February 2021 to November 2021 in the Department of Ophthalmology of Renmin Hospital of Wuhan University. All patients in LHON group were males (100.0%, 32/32) and the average age was 23.34±7.41 years. In the carrier group of 15 cases (30 eyes), there were 2 males (13.3%, 2/15) and 13 females (86.7%, 12/15). The average age was 43.44±7.65 years. Twenty-four healthy subjects (48 eyes) in the same period were selected as the control group. Among them, there were 8 males (33.3%, 8/24) and 16 females (66.7%, 16/24). The average age was 23.42±2.54 years. All subjects were examined with the GT-2008V-VI visual electrophysiology instrument of Chongqing Gotec Medical Equipment Limited Company for PERG and FERG. P50 and N95 amplitudes of PERG and PhNR, a wave and b wave amplitudes of FERG were recorded. The peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the nasal, superior, temporal, inferior and average quadrants were measured by spectral domain optical coherence tomography (SD-OCT). The amplitudes of a wave, b wave, PhNR, P50 wave, N95 wave and pRNFL thickness between the three groups were compared by one-way ANOVA. Pearson correlation analysis was used to analyze the correlation between different parameters. Results Compared with the control group, the amplitudes of PhNR in LHON group and carrier group decreased significantly (F=11.973, P＜0.001). The results of correlation analysis showed that the amplitude of PhNR in LHON group was significantly correlated with the thickness of nasal and temporal pRNFL (r=0.249, 0.272; P=0.048, 0.030). There was no significant difference in P50 wave amplitude between patients , carriers and controls (F=1.342, P=0.265). There was no significant difference in N95 wave amplitude between patients and controls (P=0.960). Conclusion The PhNR amplitudes of FERG in LHON patients and carriers decrease significantly compared to controls.

Citation： Miao Qingmei, Cheng Yufang, Yuan Jiajia, Zheng Hongmei, Chen Changzheng. Electroretinogram changes in patients and carriers with Leber hereditary optic neuropathy. Chinese Journal of Ocular Fundus Diseases, 2022, 38(12): 988-993. doi: 10.3760/cma.j.cn511434-20220110-00020 Copy

1.	Amore G, Romagnoli M, Carbonelli M, et al. Therapeutic options in hereditary optic neuropathies[J]. Drugs, 2021, 81(1): 57-86. DOI: 10.1007/s40265-020-01428-3.
2.	Meyerson C, Van Stavern G, McClelland C. Leber hereditary optic neuropathy: current perspectives[J]. Clin Ophthalmol, 2015, 9: 1165-1176. DOI: 10.2147/OPTH.S62021.
3.	韋企平, 孫艷紅, 宮曉紅, 等. 中國人Leber遺傳性視神經病變線粒體DNA突變的主要類型和臨床特征[J]. 中華眼底病雜志, 2004, 20(2): 78-80. DOI: 10.3760/j.issn:1005-1015.2004.02.004.Wei QP, Sun YH, Gong XH, et al. The major types and clinical manifestations of mitochondrial DNA mutations in Chinese patients with Leber′s hereditary optic neuropathy[J]. Chin J Ocul Fundus Dis, 2004, 20(2): 78-80. DOI: 10.3760/j.issn:1005-1015.2004.02.004.
4.	Majander A, Robson AG, Joao C, et al. The pattern of retinal ganglion cell dysfunction in Leber hereditary optic neuropathy[J]. Mitochondrion, 2017, 36: 138-149. DOI: 10.1016/j.mito.2017.07.006.
5.	Botelho GIS, Salom?o SR, Tengan CH, et al. Impaired ganglion cell function objectively assessed by the photopic negative response in affected and asymptomatic members from brazilian families with Leber's hereditary optic neuropathy[J/OL]. Front Neurol, 2020, 11: 628014[2021-01-18]. https://pubmed.ncbi.nlm.nih.gov/33584522/. DOI: 10.3389/fneur.2020.628014.
6.	Cvenkel B, Sustar M, Perovsek D. Ganglion cell loss in early glaucoma, as assessed by photopic negative response, pattern electroretinogram, and spectral-domain optical coherence tomography[J]. Doc Ophthalmol, 2017, 135(1): 17-28. DOI: 10.1007/s10633-017-9595-9.
7.	Moss HE, Park JC, McAnany JJ. The photopic negative response in idiopathic intracranial hypertension[J]. Invest Ophthalmol Vis Sci, 2015, 56(6): 3709-3714. DOI: 10.1167/iovs.15-16586.
8.	Park JC, Moss HE, McAnany JJ. Electroretinography in idiopathic intracranial hypertension: comparison of the pattern ERG and the photopic negative response[J]. Doc Ophthalmol, 2018, 136(1): 45-55. DOI: 10.1007/s10633-017-9620-z.
9.	Gotoh Y, Machida S, Tazawa Y. Selective loss of the photopic negative response in patients with optic nerve atrophy[J]. Arch Ophthalmol, 2004, 122(3): 341-346. DOI: 10.1001/archopht.122.3.341.
10.	Karanjia R, Berezovsky A, Sacai PY, et al. The photopic negative response: an objective measure of retinal ganglion cell function in patients with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2017, 58(6): 300-306. DOI: 10.1167/iovs.17-21773.
11.	Guy J, Feuer WJ, Porciatti V, et al. Retinal ganglion cell dysfunction in asymptomatic G11778A: Leber hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 841-848. DOI: 10.1167/iovs.13-13365.
12.	Ziccardi L, Sadun F, De Negri AM, et al. Retinal function and neural conduction along the visual pathways in affected and unaffected carriers with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2013, 54(10): 6893-6901. DOI: 10.1167/iovs.13-12894.
13.	Lam BL, Feuer WJ, Abukhalil F, et al. Leber hereditary optic neuropathy gene therapy clinical trial recruitment: year 1[J]. Arch Ophthalmol, 2010, 128(9): 1129-1135. DOI: 10.1001/archophthalmol.2010.201.
14.	Bach M, Brigell MG, Hawlina M, et al. ISCEV standard for clinical pattern electroretinography (PERG): 2012 update[J]. Doc Ophthalmol, 2013, 126(1): 1-7. DOI: 10.1007/s10633-012-9353-y.
15.	Robson AG, Frishman LJ, Grigg J, et al. ISCEV standard for full-field clinical electroretinography (2022 update)[J]. Doc Ophthalmol, 2022, 144(3): 165-177. DOI: 10.1007/s10633-022-09872-0.
16.	Frishman L, Sustar M, Kremers J, et al. ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram[J]. Doc Ophthalmol, 2018, 136(3): 207-211. DOI: 10.1007/s10633-018-9638-x.
17.	Odom J V, Bach M, Brigell M, et al. ISCEV standard for clinical visual evoked potentials: (2016 update)[J]. Doc Ophthalmol, 2016, 133(1): 1-9. DOI: 10.1007/s10633-016-9553-y.
18.	Marmoy OR, Viswanathan S. Clinical electrophysiology of the optic nerve and retinal ganglion cells[J]. Eye (Lond), 2021, 35(9): 2386-2405. DOI: 10.1038/s41433-021-01614-x.
19.	Tamada K, Machida S, Yokoyama D, et al. Photopic negative response of full-field and focal macular electroretinograms in patients with optic nerve atrophy[J]. Jpn J Ophthalmol, 2009, 53(6): 608-614. DOI: 10.1007/s10384-009-0731-2.
20.	Al-Nosairy KO, Thieme H, Hoffmann MB. Diagnostic performance of multifocal photopic negative response, pattern electroretinogram and optical coherence tomography in glaucoma[J/OL]. Exp Eye Res, 2020, 200: 108242[2020-09-11]. https://pubmed.ncbi.nlm.nih.gov/32926894/. DOI: 10.1016/j.exer.2020.108242.
21.	Preiser D, Lagreze WA, Bach M, et al. Photopic negative response versus pattern electroretinogram in early glaucoma[J]. Invest Ophthalmol Vis Sci, 2013, 54(2): 1182-1191. DOI: 10.1167/iovs.12-11201.
22.	黃麗娜, 申曉麗, 樊寧. 正常人視網膜電圖明視負波反應的研究[J]. 中國實用眼科雜志, 2012, 30(3): 292-295. DOI: 10.3760/cma.j.issn.1006-4443.2012.03.017.Huang LN, Shen XL, Fan N. The investigation of electroretinogram photopic negative response in normal subjects[J]. Chin J Pract Ophthalmol, 2012, 30(3): 292-295. DOI: 10.3760/cma.j.issn.1006-4443.2012.03.017.
23.	Sadun AA, Win PH, Ross-Cisneros FN, et al. Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve[J]. Trans Am Ophthalmol Soc, 2000, 98: 223-232.
24.	Hirooka K, Yokoyama K, Tokumo K, et al. Comparison of the humphrey field analyzer and photopic negative response of focal macular electroretinograms in the evaluation of the relationship between macula structure and function[J/OL]. Front Med (Lausanne), 2021, 8: 649971[2021-02-26]. https://pubmed.ncbi.nlm.nih.gov/33718414/. DOI: 10.3389/fmed.2021.649971.
25.	Wang M, Guo H, Li S, et al. Electrophysiological and structural changes in Chinese patients with LHON[J/OL]. J Ophthalmol, 2020, 2020: 4734276[2020-03-30]. https://pubmed.ncbi.nlm.nih.gov/32318281/. DOI: 10.1155/2020/4734276.
26.	Kurtenbach A, Leo-Kottler B, Zrenner E. Inner retinal contributions to the multifocal electroretinogram: patients with Leber's hereditary optic neuropathy (LHON). Multifocal ERG in patients with LHON[J]. Doc Ophthalmol, 2004, 108(3): 231-240. DOI: 10.1007/s10633-004-8676-8.
27.	Lam BL, Feuer WJ, Schiffman JC, et al. Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy: preparation for gene therapy clinical trial[J]. JAMA Ophthalmol, 2014, 132(4): 428-436. DOI: 10.1001/jamaophthalmol.2013.7971.
28.	Jarc-Vidmar M, Tajnik M, Brecelj J, et al. Clinical and electrophysiology findings in Slovene patients with Leber hereditary optic neuropathy[J]. Doc Ophthalmol, 2015, 130(3): 179-187. DOI: 10.1007/s10633-015-9489-7.
29.	Manfready RA, Hedges TR, Mendoza-Santiesteban CE. Structural and functional degeneration of retinal nerves in sibling carriers of a Leber's hereditary optic neuropathy mutation[J/OL]. Can J Ophthalmol, 2018, 53(1): e1-e4[2017-08-04]. https://pubmed.ncbi.nlm.nih.gov/29426449/. DOI: 10.1016/j.jcjo.2017.05.010.
30.	Parisi V, Ziccardi L, Sadun F, et al. Functional changes of retinal ganglion cells and visual pathways in patients with chronic Leber's hereditary optic neuropathy during one year of follow-up[J]. Ophthalmology, 2019, 126(7): 1033-1044. DOI: 10.1016/j.ophtha.2019.02.018.
31.	Riordan-Eva P, Sanders MD, Govan GG, et al. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation[J]. Brain, 1995, 118(Pt 2): 319-337. DOI: 10.1093/brain/118.2.319.
32.	Holder GE. Significance of abnormal pattern electroretinography in anterior visual pathway dysfunction[J]. Br J Ophthalmol, 1987, 71(3): 166-171. DOI: 10.1136/bjo.71.3.166.

1. Amore G, Romagnoli M, Carbonelli M, et al. Therapeutic options in hereditary optic neuropathies[J]. Drugs, 2021, 81(1): 57-86. DOI: 10.1007/s40265-020-01428-3.
2. Meyerson C, Van Stavern G, McClelland C. Leber hereditary optic neuropathy: current perspectives[J]. Clin Ophthalmol, 2015, 9: 1165-1176. DOI: 10.2147/OPTH.S62021.
3. 韋企平, 孫艷紅, 宮曉紅, 等. 中國人Leber遺傳性視神經病變線粒體DNA突變的主要類型和臨床特征[J]. 中華眼底病雜志, 2004, 20(2): 78-80. DOI: 10.3760/j.issn:1005-1015.2004.02.004.Wei QP, Sun YH, Gong XH, et al. The major types and clinical manifestations of mitochondrial DNA mutations in Chinese patients with Leber′s hereditary optic neuropathy[J]. Chin J Ocul Fundus Dis, 2004, 20(2): 78-80. DOI: 10.3760/j.issn:1005-1015.2004.02.004.
4. Majander A, Robson AG, Joao C, et al. The pattern of retinal ganglion cell dysfunction in Leber hereditary optic neuropathy[J]. Mitochondrion, 2017, 36: 138-149. DOI: 10.1016/j.mito.2017.07.006.
5. Botelho GIS, Salom?o SR, Tengan CH, et al. Impaired ganglion cell function objectively assessed by the photopic negative response in affected and asymptomatic members from brazilian families with Leber's hereditary optic neuropathy[J/OL]. Front Neurol, 2020, 11: 628014[2021-01-18]. https://pubmed.ncbi.nlm.nih.gov/33584522/. DOI: 10.3389/fneur.2020.628014.
6. Cvenkel B, Sustar M, Perovsek D. Ganglion cell loss in early glaucoma, as assessed by photopic negative response, pattern electroretinogram, and spectral-domain optical coherence tomography[J]. Doc Ophthalmol, 2017, 135(1): 17-28. DOI: 10.1007/s10633-017-9595-9.
7. Moss HE, Park JC, McAnany JJ. The photopic negative response in idiopathic intracranial hypertension[J]. Invest Ophthalmol Vis Sci, 2015, 56(6): 3709-3714. DOI: 10.1167/iovs.15-16586.
8. Park JC, Moss HE, McAnany JJ. Electroretinography in idiopathic intracranial hypertension: comparison of the pattern ERG and the photopic negative response[J]. Doc Ophthalmol, 2018, 136(1): 45-55. DOI: 10.1007/s10633-017-9620-z.
9. Gotoh Y, Machida S, Tazawa Y. Selective loss of the photopic negative response in patients with optic nerve atrophy[J]. Arch Ophthalmol, 2004, 122(3): 341-346. DOI: 10.1001/archopht.122.3.341.
10. Karanjia R, Berezovsky A, Sacai PY, et al. The photopic negative response: an objective measure of retinal ganglion cell function in patients with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2017, 58(6): 300-306. DOI: 10.1167/iovs.17-21773.
11. Guy J, Feuer WJ, Porciatti V, et al. Retinal ganglion cell dysfunction in asymptomatic G11778A: Leber hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 841-848. DOI: 10.1167/iovs.13-13365.
12. Ziccardi L, Sadun F, De Negri AM, et al. Retinal function and neural conduction along the visual pathways in affected and unaffected carriers with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci, 2013, 54(10): 6893-6901. DOI: 10.1167/iovs.13-12894.
13. Lam BL, Feuer WJ, Abukhalil F, et al. Leber hereditary optic neuropathy gene therapy clinical trial recruitment: year 1[J]. Arch Ophthalmol, 2010, 128(9): 1129-1135. DOI: 10.1001/archophthalmol.2010.201.
14. Bach M, Brigell MG, Hawlina M, et al. ISCEV standard for clinical pattern electroretinography (PERG): 2012 update[J]. Doc Ophthalmol, 2013, 126(1): 1-7. DOI: 10.1007/s10633-012-9353-y.
15. Robson AG, Frishman LJ, Grigg J, et al. ISCEV standard for full-field clinical electroretinography (2022 update)[J]. Doc Ophthalmol, 2022, 144(3): 165-177. DOI: 10.1007/s10633-022-09872-0.
16. Frishman L, Sustar M, Kremers J, et al. ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram[J]. Doc Ophthalmol, 2018, 136(3): 207-211. DOI: 10.1007/s10633-018-9638-x.
17. Odom J V, Bach M, Brigell M, et al. ISCEV standard for clinical visual evoked potentials: (2016 update)[J]. Doc Ophthalmol, 2016, 133(1): 1-9. DOI: 10.1007/s10633-016-9553-y.
18. Marmoy OR, Viswanathan S. Clinical electrophysiology of the optic nerve and retinal ganglion cells[J]. Eye (Lond), 2021, 35(9): 2386-2405. DOI: 10.1038/s41433-021-01614-x.
19. Tamada K, Machida S, Yokoyama D, et al. Photopic negative response of full-field and focal macular electroretinograms in patients with optic nerve atrophy[J]. Jpn J Ophthalmol, 2009, 53(6): 608-614. DOI: 10.1007/s10384-009-0731-2.
20. Al-Nosairy KO, Thieme H, Hoffmann MB. Diagnostic performance of multifocal photopic negative response, pattern electroretinogram and optical coherence tomography in glaucoma[J/OL]. Exp Eye Res, 2020, 200: 108242[2020-09-11]. https://pubmed.ncbi.nlm.nih.gov/32926894/. DOI: 10.1016/j.exer.2020.108242.
21. Preiser D, Lagreze WA, Bach M, et al. Photopic negative response versus pattern electroretinogram in early glaucoma[J]. Invest Ophthalmol Vis Sci, 2013, 54(2): 1182-1191. DOI: 10.1167/iovs.12-11201.
22. 黃麗娜, 申曉麗, 樊寧. 正常人視網膜電圖明視負波反應的研究[J]. 中國實用眼科雜志, 2012, 30(3): 292-295. DOI: 10.3760/cma.j.issn.1006-4443.2012.03.017.Huang LN, Shen XL, Fan N. The investigation of electroretinogram photopic negative response in normal subjects[J]. Chin J Pract Ophthalmol, 2012, 30(3): 292-295. DOI: 10.3760/cma.j.issn.1006-4443.2012.03.017.
23. Sadun AA, Win PH, Ross-Cisneros FN, et al. Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve[J]. Trans Am Ophthalmol Soc, 2000, 98: 223-232.
24. Hirooka K, Yokoyama K, Tokumo K, et al. Comparison of the humphrey field analyzer and photopic negative response of focal macular electroretinograms in the evaluation of the relationship between macula structure and function[J/OL]. Front Med (Lausanne), 2021, 8: 649971[2021-02-26]. https://pubmed.ncbi.nlm.nih.gov/33718414/. DOI: 10.3389/fmed.2021.649971.
25. Wang M, Guo H, Li S, et al. Electrophysiological and structural changes in Chinese patients with LHON[J/OL]. J Ophthalmol, 2020, 2020: 4734276[2020-03-30]. https://pubmed.ncbi.nlm.nih.gov/32318281/. DOI: 10.1155/2020/4734276.
26. Kurtenbach A, Leo-Kottler B, Zrenner E. Inner retinal contributions to the multifocal electroretinogram: patients with Leber's hereditary optic neuropathy (LHON). Multifocal ERG in patients with LHON[J]. Doc Ophthalmol, 2004, 108(3): 231-240. DOI: 10.1007/s10633-004-8676-8.
27. Lam BL, Feuer WJ, Schiffman JC, et al. Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy: preparation for gene therapy clinical trial[J]. JAMA Ophthalmol, 2014, 132(4): 428-436. DOI: 10.1001/jamaophthalmol.2013.7971.
28. Jarc-Vidmar M, Tajnik M, Brecelj J, et al. Clinical and electrophysiology findings in Slovene patients with Leber hereditary optic neuropathy[J]. Doc Ophthalmol, 2015, 130(3): 179-187. DOI: 10.1007/s10633-015-9489-7.
29. Manfready RA, Hedges TR, Mendoza-Santiesteban CE. Structural and functional degeneration of retinal nerves in sibling carriers of a Leber's hereditary optic neuropathy mutation[J/OL]. Can J Ophthalmol, 2018, 53(1): e1-e4[2017-08-04]. https://pubmed.ncbi.nlm.nih.gov/29426449/. DOI: 10.1016/j.jcjo.2017.05.010.
30. Parisi V, Ziccardi L, Sadun F, et al. Functional changes of retinal ganglion cells and visual pathways in patients with chronic Leber's hereditary optic neuropathy during one year of follow-up[J]. Ophthalmology, 2019, 126(7): 1033-1044. DOI: 10.1016/j.ophtha.2019.02.018.
31. Riordan-Eva P, Sanders MD, Govan GG, et al. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation[J]. Brain, 1995, 118(Pt 2): 319-337. DOI: 10.1093/brain/118.2.319.
32. Holder GE. Significance of abnormal pattern electroretinography in anterior visual pathway dysfunction[J]. Br J Ophthalmol, 1987, 71(3): 166-171. DOI: 10.1136/bjo.71.3.166.

Chinese Journal of Ocular Fundus Diseases

Electroretinogram changes in patients and carriers with Leber hereditary optic neuropathy

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