Longitudinal natural history study of visual acuity in choroideremia_Chinese Journal of Ocular Fundus Diseases

Authors：

Han Xiaoxu ¹ , Zhang Dingding ² , Li Hui ¹ , Zou Xuan ¹ ,  Sui Ruifang ¹

1. Department of Ophthalmology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;
2. Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;

Corresponding author：

Sui Ruifang, Email: hrfsui@163.com

Keywords：

Choroideremia; Visual acuity; Longitudinal natural history; Binocular correlation

DOI：

10.3760/cma.j.cn511434-20231012-00416

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Objective To observe and analyze the rate of visual acuity progression and binocular symmetry in patients with choroideremia (CHM). Methods A single-center retrospective longitudinal cohort study. From April 2009 to August 2022, 38 eyes of 19 patients diagnosed with CHM through clinical and genetic testing at the Department of Ophthalmology, Peking Union Medical College Hospital, were included in this study. All patients underwent at least 2 follow-up visits with a minimum interval of 1 year between visits, and binocular best-corrected visual acuity (BCVA) results were recorded at each follow-up visit. Decimal visual acuity was converted into logarithm of the minimum angle of resolution (logMAR) for analysis. The patient group consisted of 19 males from 16 unrelated families. The age at initial visit was (39.52±13.24) years, with a (2.63±1.61) follow-up visits over a duration of (4.95±2.68) years. A total of 50 binocular BCVA data were included. Annual progression rate of visual acuity was calculated based on longitudinal and cross-sectional data. Spearman correlation coefficient and Bland-Altman method were used to evaluate the binocular symmetry. Results The rate of visual acuity progression was (0.095±0.148) logMAR units/year based on longitudinal data and (0.018±0.009) logMAR units/year based on cross-sectional data. The binocular symmetry for BCVA of the baseline values was strong; however, the binocular symmetry of progression rates for BCVA was moderate. Spearman correlation analysis showed that binocular symmetry in baseline BCVA was high (r=0.881, P＜0.001). The symmetry of binocular vision progression rates based on longitudinal data was moderately symmetric (r=0.528, P=0.020). Bland-Altman analysis showed that 94.7% of binocular baseline BCVA differences were within 95% confidence interval (CI) of 95% limit difference (LOA), indicating good symmetry of binocular baseline BCVA. The number of binocular BCVA progression rate differences within 95%CI of 95%LOA was 89.5%, suggesting moderate symmetry in binocular BCVA progression rate. The results of Spearman correlation coefficient and Bland-Altman analysis of binocular symmetry were basically consistent. Conclusions The rate of visual acuity progression of patients with CHM based on longitudinal and cross-sectional data is (0.095±0.148) and (0.018±0.009) logMAR units/year, respectively. Cross-sectional data from patients of different ages should not be used to infer the progression rate of the natural history. Binocular eyes with highly symmetrical baseline visual acuity may differ in the rate of visual acuity progression.

Citation： Han Xiaoxu, Zhang Dingding, Li Hui, Zou Xuan, Sui Ruifang. Longitudinal natural history study of visual acuity in choroideremia. Chinese Journal of Ocular Fundus Diseases, 2024, 40(5): 347-352. doi: 10.3760/cma.j.cn511434-20231012-00416 Copy

1.	Cremers FP, van de Pol DJ, van Kerkhoff LP, et al. Cloning of a gene that is rearranged in patients with choroideraemia[J]. Nature, 1990, 347(6294): 674-677. DOI: 10.1038/347674a0.
2.	van den Hurk JA, Schwartz M, van Bokhoven H, et al. Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene[J]. Human mutation, 1997, 9(2): 110-117. DOI: 10.1002/(SICI)1098-1004(1997)9:2<110::AID-HUMU2>3.0.CO;2-D.
3.	Patrício MI, Barnard AR, Xue K, et al. Choroideremia: molecular mechanisms and development of AAV gene therapy[J]. Expert Opin Biol Ther, 2018, 18(7): 807-820. DOI: 10.1080/14712598.2018.1484448.
4.	Heon E, Alabduljalil T, McGuigan Ⅲ DB, et al. Visual function and central retinal structure in choroideremia[J]. Invest Ophthalmol Vis Sci, 2016, 57(9): 377-387. DOI: 10.1167/iovs.15-18421.
5.	Shen LL, Ahluwalia A, Sun M, et al. Long-term natural history of visual acuity in eyes with choroideremia: a systematic review and meta-analysis of data from 1004 individual eyes[J]. Br J Ophthalmol, 2021, 105(2): 271-278. DOI: 10.1136/bjophthalmol-2020-316028.
6.	Seitz IP, Zhour A, Kohl S, et al. Multimodal assessment of choroideremia patients defines pre-treatment characteristics[J]. Graefe's Arch Clin Exp Ophthalmol, 2015, 253(12): 2143-2150. DOI: 10.1007/s00417-015-2976-4.
7.	Roberts MF, Fishman GA, Roberts DK, et al. Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia[J]. Br J Ophthalmol, 2002, 86(6): 658-662. DOI: 10.1136/bjo.86.6.658.
8.	van Schuppen SM, Talib M, Bergen AA, et al. Long-term follow-up of patients with choroideremia with scleral pits and tunnels as a novel observation[J]. Retina, 2018, 38(9): 1713-1724. DOI: 10.1097/iae.0000000000001844.
9.	Edwards TL, Jolly JK, Groppe M, et al. Visual acuity after retinal gene therapy for choroideremia[J]. N Engl J Med, 2016, 374(20): 1996-1998. DOI: 10.1056/NEJMc1509501.
10.	Lam BL, Davis JL, Gregori NZ, et al. Choroideremia gene therapy phase 2 clinical trial: 24-month results[J]. Am J Ophthalmol, 2019, 197: 65-73. DOI: 10.1016/j.ajo.2018.09.012.
11.	Bozkaya D, Zou H, Lu C, et al. Bilateral visual acuity decline in males with choroideremia: a pooled, cross-sectional meta-analysis[J]. BMC Ophthalmol, 2022, 22(1): 29. DOI: 10.1186/s12886-022-02250-z.
12.	Han X, Wu S, Li H, et al. Clinical characteristics and molecular genetic analysis of a cohort of patients with choroideremia[J]. Retina, 2020, 40(11): 2240-2253. DOI: 10.1097/iae.000000 0000002743.
13.	Song Y, Chen C, Xie Y, et al. Clinical and genetic findings in a Chinese cohort with choroideremia[J]. Eye (Lond), 2023, 37(3): 459-466. DOI: 10.1038/s41433-022-01950-6.
14.	Berson EL, Rosner B, Weigel-DiFranco C, et al. Disease progression in patients with dominant retinitis pigmentosa and rhodopsin mutations[J]. Invest Ophthalmol Vis Sci, 2002, 43(9): 3027-3036.
15.	Hariri AH, Ip MS, Girach A, et al. Macular spatial distribution of preserved autofluorescence in patients with choroideremia[J]. Br J Ophthalmol, 2019, 103(7): 933-937. DOI: 10.1136/bjophthalmol-2018-312620.

1. Cremers FP, van de Pol DJ, van Kerkhoff LP, et al. Cloning of a gene that is rearranged in patients with choroideraemia[J]. Nature, 1990, 347(6294): 674-677. DOI: 10.1038/347674a0.
2. van den Hurk JA, Schwartz M, van Bokhoven H, et al. Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene[J]. Human mutation, 1997, 9(2): 110-117. DOI: 10.1002/(SICI)1098-1004(1997)9:2<110::AID-HUMU2>3.0.CO;2-D.
3. Patrício MI, Barnard AR, Xue K, et al. Choroideremia: molecular mechanisms and development of AAV gene therapy[J]. Expert Opin Biol Ther, 2018, 18(7): 807-820. DOI: 10.1080/14712598.2018.1484448.
4. Heon E, Alabduljalil T, McGuigan Ⅲ DB, et al. Visual function and central retinal structure in choroideremia[J]. Invest Ophthalmol Vis Sci, 2016, 57(9): 377-387. DOI: 10.1167/iovs.15-18421.
5. Shen LL, Ahluwalia A, Sun M, et al. Long-term natural history of visual acuity in eyes with choroideremia: a systematic review and meta-analysis of data from 1004 individual eyes[J]. Br J Ophthalmol, 2021, 105(2): 271-278. DOI: 10.1136/bjophthalmol-2020-316028.
6. Seitz IP, Zhour A, Kohl S, et al. Multimodal assessment of choroideremia patients defines pre-treatment characteristics[J]. Graefe's Arch Clin Exp Ophthalmol, 2015, 253(12): 2143-2150. DOI: 10.1007/s00417-015-2976-4.
7. Roberts MF, Fishman GA, Roberts DK, et al. Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia[J]. Br J Ophthalmol, 2002, 86(6): 658-662. DOI: 10.1136/bjo.86.6.658.
8. van Schuppen SM, Talib M, Bergen AA, et al. Long-term follow-up of patients with choroideremia with scleral pits and tunnels as a novel observation[J]. Retina, 2018, 38(9): 1713-1724. DOI: 10.1097/iae.0000000000001844.
9. Edwards TL, Jolly JK, Groppe M, et al. Visual acuity after retinal gene therapy for choroideremia[J]. N Engl J Med, 2016, 374(20): 1996-1998. DOI: 10.1056/NEJMc1509501.
10. Lam BL, Davis JL, Gregori NZ, et al. Choroideremia gene therapy phase 2 clinical trial: 24-month results[J]. Am J Ophthalmol, 2019, 197: 65-73. DOI: 10.1016/j.ajo.2018.09.012.
11. Bozkaya D, Zou H, Lu C, et al. Bilateral visual acuity decline in males with choroideremia: a pooled, cross-sectional meta-analysis[J]. BMC Ophthalmol, 2022, 22(1): 29. DOI: 10.1186/s12886-022-02250-z.
12. Han X, Wu S, Li H, et al. Clinical characteristics and molecular genetic analysis of a cohort of patients with choroideremia[J]. Retina, 2020, 40(11): 2240-2253. DOI: 10.1097/iae.000000 0000002743.
13. Song Y, Chen C, Xie Y, et al. Clinical and genetic findings in a Chinese cohort with choroideremia[J]. Eye (Lond), 2023, 37(3): 459-466. DOI: 10.1038/s41433-022-01950-6.
14. Berson EL, Rosner B, Weigel-DiFranco C, et al. Disease progression in patients with dominant retinitis pigmentosa and rhodopsin mutations[J]. Invest Ophthalmol Vis Sci, 2002, 43(9): 3027-3036.
15. Hariri AH, Ip MS, Girach A, et al. Macular spatial distribution of preserved autofluorescence in patients with choroideremia[J]. Br J Ophthalmol, 2019, 103(7): 933-937. DOI: 10.1136/bjophthalmol-2018-312620.

Chinese Journal of Ocular Fundus Diseases

Longitudinal natural history study of visual acuity in choroideremia

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