Chinese expert consensus on the standardized application of multi-luminance mobility test in clinical trials for inherited retinal dystrophy_Chinese Journal of Ocular Fundus Diseases

Authors：

 Fundus Disease Group of Ophthalmology Society of Chinese Medical Association ,  Fundus Disease Committee of Ophthalmologist Branch of Chinese Medical Doctor Association

Corresponding?author：

Fundus Disease Group of Ophthalmology Society of Chinese Medical Association, Email: xdsun@sjtu.edu.cn

Keywords：

Inherited retinal dystrophy; Multi-luminance mobility test; Endpoint evaluation; Clinical trial; Expert consensus

DOI：

10.3760/cma.j.cn511434-20241231-00513

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

With the advancement of research on rare ocular diseases such as inherited retinal dystrophy (IRD) has advanced in recent years, especially breakthroughs in therapeutic approaches represented by cell and gene therapy, potential intervention strategies have emerged for these conditions. Establishing standardized endpoints and evaluation methods for visual function in patients with IRD has become crucial for assessing disease progression, safety, and therapeutic efficacy of innovative treatments. Best corrected visual acuity (BCVA) is widely recognized as one of the primary endpoints for assessing visual function. However, for IRD patients with severe rod photoreceptor dysfunction, who often present with profound low vision or even legal blindness, the applicability of BCVA as a traditional visual function indicator is limited. The multi-luminance mobility test (MLMT) has emerged as a functional visual assessment tool that evaluates the ability to navigate obstacle courses under varying illumination levels. By establishing graded evaluation standards, MLMT objectively quantifies the impact of lighting conditions on patients’ nobility and spatial orientation, providing a novel quantitative tool for assessing visual function in IRD clinical trials. Currently, there is a lack of unified and standardized guidelines for the use of MLMT in China, posing challenges to its implementation in practical clinical research. To address this, Ocular Fundus Disease Society of Chinese Medical Association and Chinese Medical Doctor Association convened a multidisciplinary team comprising clinical experts in genetic retinal diseases, statisticians, and optical specialists to investigate the current applications and technical characteristics of MLMT, ultimately formulating consensus recommendations for its use as a clinical trial endpoint for IRD gene therapies. This consensus aims to provide a set of MLMT operating norms applicable to China's national conditions, guide clinical practice and research in ophthalmology and related disciplines, and promote the standardization process of IRD clinical trials in China, so as to better serve the IRD patient population and promote the development of related fields.

Citation： Fundus Disease Group of Ophthalmology Society of Chinese Medical Association, Fundus Disease Committee of Ophthalmologist Branch of Chinese Medical Doctor Association. Chinese expert consensus on the standardized application of multi-luminance mobility test in clinical trials for inherited retinal dystrophy. Chinese Journal of Ocular Fundus Diseases, 2025, 41(3): 169-177. doi: 10.3760/cma.j.cn511434-20241231-00513 Copy

1.	Schneider N, Sundaresan Y, Gopalakrishnan P, et al. Inherited retinal diseases: linking genes, disease-causing variants, and relevant therapeutic modalities[J/OL]. Prog Retin Eye Res, 2021, 89: 101029[2021-11-25]. https://pubmed.ncbi.nlm.nih.gov/34839010/. DOI: 10.1016/j.preteyeres.2021.101029.
2.	Georgiou M, Robson AG, Fujinami K, et al. Phenotyping and genotyping inherited retinal diseases: molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes[J/OL]. Prog Retin Eye Res, 2024, 100: 101244[2024-01-24]. https://pubmed.ncbi.nlm.nih.gov/38278208/. DOI: 10.1016/j.preteyeres.2024.101244.
3.	den Hollander AI, Roepman R, Koenekoop RK, et al. Leber congenital amaurosis: genes, proteins and disease mechanisms[J]. Prog Retin Eye Res, 2008, 27(4): 391-419. DOI: 10.1016/j.preteyeres.2008.05.003.
4.	中國眼遺傳病診療小組, 中國眼科遺傳聯盟. Leber先天黑矇診療的中國專家共識(2023)[J]. 中華實驗眼科雜志, 2023, 41(9): 833-842. DOI: 10.3760/cma.j.cn115989-20230523-00188.Chinese Hereditary Ocular Disease Diagnosis and Treatment Group, Chinese Hereditary Ocular Disease Alliance. Chinese expert consensus on diagnosis and treatment of Leber congenital amaurosis (2023)[J]. Chin J Exp Ophthalmol, 2023, 41(9): 833-842. DOI: 10.3760/cma.j.cn115989-20230523-00188.
5.	張曉慧, 李楊. 視錐細胞營養不良及錐-桿營養不良相關基因研究進展[J]. 國際眼科縱覽, 2006, 30(6): 368-372. DOI: 10.3760/cma.j.issn.1673-5803.2006.06.003.Zhang XH, Li Y. Genetics of cone dystrophy and cone-rod dystrophy[J]. Int Rev Ophthalmol, 2006, 30(6): 368-372. DOI: 10.3760/cma.j.issn.1673-5803.2006.06.003.
6.	Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial[J]. Lancet, 2017, 390(10097): 849-860. DOI: 10.1016/S0140-6736(17)31868-8.
7.	Pierce EA, Aleman TS, Jayasundera KT, et al. Gene editing for CEP290-associated retinal degeneration[J]. N Engl J Med, 2024, 390(21): 1972-1984. DOI: 10.1056/NEJMoa2309915.
8.	Yang P, Pardon LP, Ho AC, et al. Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study[J]. Lancet, 2024, 404(10456): 962-970. DOI: 10.1016/S0140-6736(24)01447-8.
9.	Bennett J, Wellman J, Marshall KA, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial[J]. Lancet, 2016, 388(10045): 661-672. DOI: 10.1016/S0140-6736(16)30371-3.
10.	Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial[J]. Lancet, 2009, 374(9701): 1597-1605. DOI: 10.1016/S0140-6736(09)61836-5.
11.	中華醫學會眼科學分會眼底病學組, 中國醫師協會眼科醫師分會眼底病專業委員會. 中國遺傳性視網膜疾病臨床試驗視覺功能評估及終點指標推薦專家共識[J]. 中華眼底病雜志, 2022, 38(8): 626-635. DOI: 10.3760/cma.j.cn511434-20220808-00443.Fundus Disease Group, Ophthalmology Branch of Chinese Medical Association, and Fundus Disease Professional Committee of Ophthalmology branch of Chinese Medical Doctor Association. Expert consensus and recommendations on the evaluation of visual function and outcome measurements in clinical trials for inherited retinal diseases in China[J]. Chin J Ocul Fundus Dis, 2022, 38(8): 626-635. DOI: 10.3760/cma.j.cn511434-20220808-00443.
12.	中華人民共和國司法部司法鑒定管理局. SF/Z JD0103004-2016視覺功能障礙法醫學鑒定規范[S]. 2016.Administration of Judicial Expertise, Ministry of Justice, PRC. SF/Z JD0103004-2016 Standard for forensic medical identification of visual dysfunction[S]. 2016.
13.	Food and Drug Administration. Human gene therapy for retinal disorders[EB/OL]. (2020-01-01)[2024-12-17]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/human-gene-therapy-retinal-disorders.
14.	Chung DC, Bertelsen M, Lorenz B, et al. The natural history of inherited retinal dystrophy due to biallelic mutations in the RPE65 gene[J]. Am J Ophthalmol, 2019, 199: 58-70. DOI: 10.1016/j.ajo.2018.09.024.
15.	Chung DC, McCague S, Yu ZF, et al. Novel mobility test to assess functional vision in patients with inherited retinal dystrophies[J]. Clin Exp Ophthalmol, 2018, 46(3): 247-259. DOI: 10.1111/ceo.13022.
16.	Jung R, Kempf M, Holocher S, et al. Multi-luminance mobility testing after gene therapy in the context of retinal functional diagnostics[J]. Graefe's Arch Clin Exp Ophthalmol, 2024, 262(2): 601-607. DOI: 10.1007/s00417-023-06237-4.
17.	Kumaran N, Ali RR, Tyler NA, et al. Validation of a vision-guided mobility assessment for RPE65-associated retinal dystrophy[J]. Transl Vis Sci Technol, 2020, 9(10): 5. DOI: 10.1167/tvst.9.10.5.
18.	陳耀龍, 楊克虎, 王小欽, 等. 中國制訂/修訂臨床診療指南的指導原則(2022版)[J]. 中華醫學雜志, 2022, 102(10): 697-703. DOI: 10.3760/cma.j.cn112137-20211228-02911.Chen YL, Yang KH, Wang XQ, et al. China's guiding principles for formulating/revising clinical guidelines (2022 edition)[J]. Natl Med J China, 2022, 102(10): 697-703. DOI: 10.3760/cma.j.cn112137-20211228-02911.
19.	Aleman TS, Miller AJ, Maguire KH, et al. A virtual reality orientation and mobility test for inherited retinal degenerations: testing a proof-of-concept after gene therapy[J]. Clin Ophthalmol, 2021, 15: 939-952. DOI: 10.2147/OPTH.S292527.
20.	國家市場監督管理總局. 市場監管總局關于調整實施強制管理的計量器具目錄的公告(2020年第42號)[EB/OL]. (2020-10-26)[2024-12-17]. https://www.samr.gov.cn/zw/zfxxgk/fdzdgknr/jjjzs/art/2023/art_d095685b12544ed3aa6dbc3aaf7c136e.html.State Administration for Market Regulation. Announcement of the State Administration for Market Regulation on adjusting the catalogue of measuring instruments subject to compulsory management (No. 42 of 2020)[EB/OL]. (2020-10-26)[2024-12-17]. https://www.samr.gov.cn/zw/zfxxgk/fdzdgknr/jjjzs/art/2023/art_d095685b12544ed3aa6dbc3aaf7c136e.html.
21.	國家食品藥品監督管理總局. 醫療器械使用質量監督管理辦法[EB/OL]. (2015-10-21)[2024-12-17]. https://www.gov.cn/gongbao/content/2016/content_5033899.htm.State Food and Drug Administration. Measures for the supervision and Administration of the use quality of medical devices[EB/OL]. (2015-10-21)[2024-12-17]. https://www.gov.cn/gongbao/content/2016/content_5033899.htm.
22.	Humayun MS, Dorn JD, da Cruz L, et al. Interim results from the international trial of Second Sight's visual prosthesis[J]. Ophthalmology, 2012, 119(4): 779-788. DOI: 10.1016/j.ophtha.2011.09.028.
23.	國家藥品監督管理局, 中華人民共和國國家衛生健康委員會. 藥物臨床試驗質量管理規范[EB/OL]. (2020-04-23)[2024-12-17]. https://www.gov.cn/gongbao/content/2020/content_5525106.htm.State Drug Administration, National Health Commission of the People's Republic of China. Good quality management for drug clinical trials[EB/OL]. (2020-04-23)[2024-12-17]. https://www.gov.cn/gongbao/content/2020/content_5525106.htm.

1. Schneider N, Sundaresan Y, Gopalakrishnan P, et al. Inherited retinal diseases: linking genes, disease-causing variants, and relevant therapeutic modalities[J/OL]. Prog Retin Eye Res, 2021, 89: 101029[2021-11-25]. https://pubmed.ncbi.nlm.nih.gov/34839010/. DOI: 10.1016/j.preteyeres.2021.101029.
2. Georgiou M, Robson AG, Fujinami K, et al. Phenotyping and genotyping inherited retinal diseases: molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes[J/OL]. Prog Retin Eye Res, 2024, 100: 101244[2024-01-24]. https://pubmed.ncbi.nlm.nih.gov/38278208/. DOI: 10.1016/j.preteyeres.2024.101244.
3. den Hollander AI, Roepman R, Koenekoop RK, et al. Leber congenital amaurosis: genes, proteins and disease mechanisms[J]. Prog Retin Eye Res, 2008, 27(4): 391-419. DOI: 10.1016/j.preteyeres.2008.05.003.
4. 中國眼遺傳病診療小組, 中國眼科遺傳聯盟. Leber先天黑矇診療的中國專家共識(2023)[J]. 中華實驗眼科雜志, 2023, 41(9): 833-842. DOI: 10.3760/cma.j.cn115989-20230523-00188.Chinese Hereditary Ocular Disease Diagnosis and Treatment Group, Chinese Hereditary Ocular Disease Alliance. Chinese expert consensus on diagnosis and treatment of Leber congenital amaurosis (2023)[J]. Chin J Exp Ophthalmol, 2023, 41(9): 833-842. DOI: 10.3760/cma.j.cn115989-20230523-00188.
5. 張曉慧, 李楊. 視錐細胞營養不良及錐-桿營養不良相關基因研究進展[J]. 國際眼科縱覽, 2006, 30(6): 368-372. DOI: 10.3760/cma.j.issn.1673-5803.2006.06.003.Zhang XH, Li Y. Genetics of cone dystrophy and cone-rod dystrophy[J]. Int Rev Ophthalmol, 2006, 30(6): 368-372. DOI: 10.3760/cma.j.issn.1673-5803.2006.06.003.
6. Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial[J]. Lancet, 2017, 390(10097): 849-860. DOI: 10.1016/S0140-6736(17)31868-8.
7. Pierce EA, Aleman TS, Jayasundera KT, et al. Gene editing for CEP290-associated retinal degeneration[J]. N Engl J Med, 2024, 390(21): 1972-1984. DOI: 10.1056/NEJMoa2309915.
8. Yang P, Pardon LP, Ho AC, et al. Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study[J]. Lancet, 2024, 404(10456): 962-970. DOI: 10.1016/S0140-6736(24)01447-8.
9. Bennett J, Wellman J, Marshall KA, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial[J]. Lancet, 2016, 388(10045): 661-672. DOI: 10.1016/S0140-6736(16)30371-3.
10. Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial[J]. Lancet, 2009, 374(9701): 1597-1605. DOI: 10.1016/S0140-6736(09)61836-5.
11. 中華醫學會眼科學分會眼底病學組, 中國醫師協會眼科醫師分會眼底病專業委員會. 中國遺傳性視網膜疾病臨床試驗視覺功能評估及終點指標推薦專家共識[J]. 中華眼底病雜志, 2022, 38(8): 626-635. DOI: 10.3760/cma.j.cn511434-20220808-00443.Fundus Disease Group, Ophthalmology Branch of Chinese Medical Association, and Fundus Disease Professional Committee of Ophthalmology branch of Chinese Medical Doctor Association. Expert consensus and recommendations on the evaluation of visual function and outcome measurements in clinical trials for inherited retinal diseases in China[J]. Chin J Ocul Fundus Dis, 2022, 38(8): 626-635. DOI: 10.3760/cma.j.cn511434-20220808-00443.
12. 中華人民共和國司法部司法鑒定管理局. SF/Z JD0103004-2016視覺功能障礙法醫學鑒定規范[S]. 2016.Administration of Judicial Expertise, Ministry of Justice, PRC. SF/Z JD0103004-2016 Standard for forensic medical identification of visual dysfunction[S]. 2016.
13. Food and Drug Administration. Human gene therapy for retinal disorders[EB/OL]. (2020-01-01)[2024-12-17]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/human-gene-therapy-retinal-disorders.
14. Chung DC, Bertelsen M, Lorenz B, et al. The natural history of inherited retinal dystrophy due to biallelic mutations in the RPE65 gene[J]. Am J Ophthalmol, 2019, 199: 58-70. DOI: 10.1016/j.ajo.2018.09.024.
15. Chung DC, McCague S, Yu ZF, et al. Novel mobility test to assess functional vision in patients with inherited retinal dystrophies[J]. Clin Exp Ophthalmol, 2018, 46(3): 247-259. DOI: 10.1111/ceo.13022.
16. Jung R, Kempf M, Holocher S, et al. Multi-luminance mobility testing after gene therapy in the context of retinal functional diagnostics[J]. Graefe's Arch Clin Exp Ophthalmol, 2024, 262(2): 601-607. DOI: 10.1007/s00417-023-06237-4.
17. Kumaran N, Ali RR, Tyler NA, et al. Validation of a vision-guided mobility assessment for RPE65-associated retinal dystrophy[J]. Transl Vis Sci Technol, 2020, 9(10): 5. DOI: 10.1167/tvst.9.10.5.
18. 陳耀龍, 楊克虎, 王小欽, 等. 中國制訂/修訂臨床診療指南的指導原則(2022版)[J]. 中華醫學雜志, 2022, 102(10): 697-703. DOI: 10.3760/cma.j.cn112137-20211228-02911.Chen YL, Yang KH, Wang XQ, et al. China's guiding principles for formulating/revising clinical guidelines (2022 edition)[J]. Natl Med J China, 2022, 102(10): 697-703. DOI: 10.3760/cma.j.cn112137-20211228-02911.
19. Aleman TS, Miller AJ, Maguire KH, et al. A virtual reality orientation and mobility test for inherited retinal degenerations: testing a proof-of-concept after gene therapy[J]. Clin Ophthalmol, 2021, 15: 939-952. DOI: 10.2147/OPTH.S292527.
20. 國家市場監督管理總局. 市場監管總局關于調整實施強制管理的計量器具目錄的公告(2020年第42號)[EB/OL]. (2020-10-26)[2024-12-17]. https://www.samr.gov.cn/zw/zfxxgk/fdzdgknr/jjjzs/art/2023/art_d095685b12544ed3aa6dbc3aaf7c136e.html.State Administration for Market Regulation. Announcement of the State Administration for Market Regulation on adjusting the catalogue of measuring instruments subject to compulsory management (No. 42 of 2020)[EB/OL]. (2020-10-26)[2024-12-17]. https://www.samr.gov.cn/zw/zfxxgk/fdzdgknr/jjjzs/art/2023/art_d095685b12544ed3aa6dbc3aaf7c136e.html.
21. 國家食品藥品監督管理總局. 醫療器械使用質量監督管理辦法[EB/OL]. (2015-10-21)[2024-12-17]. https://www.gov.cn/gongbao/content/2016/content_5033899.htm.State Food and Drug Administration. Measures for the supervision and Administration of the use quality of medical devices[EB/OL]. (2015-10-21)[2024-12-17]. https://www.gov.cn/gongbao/content/2016/content_5033899.htm.
22. Humayun MS, Dorn JD, da Cruz L, et al. Interim results from the international trial of Second Sight's visual prosthesis[J]. Ophthalmology, 2012, 119(4): 779-788. DOI: 10.1016/j.ophtha.2011.09.028.
23. 國家藥品監督管理局, 中華人民共和國國家衛生健康委員會. 藥物臨床試驗質量管理規范[EB/OL]. (2020-04-23)[2024-12-17]. https://www.gov.cn/gongbao/content/2020/content_5525106.htm.State Drug Administration, National Health Commission of the People's Republic of China. Good quality management for drug clinical trials[EB/OL]. (2020-04-23)[2024-12-17]. https://www.gov.cn/gongbao/content/2020/content_5525106.htm.

Next Article
Clinical phenotype and genotype analysis of retinitis pigmentosa sine pigmento caused by BBS gene mutations

Chinese Journal of Ocular Fundus Diseases

Chinese expert consensus on the standardized application of multi-luminance mobility test in clinical trials for inherited retinal dystrophy

Abstract Full text Figures/Tables Video References Cited by

Next Article

Format

Content