Chiu Hsun-I, Cheng Hui-Chen, Wu Chih-Chiau, Chen Shih-Jen, Hwang De-Kuang, Huang Yi-Ming, Chou Yu-Bai, Lin Po-Kang, Lin Tai-Chi, Chen Ko-Hua, Lin Pei-Yu, Chang Yu-Fan, Wang An-Guor
Department of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Ophthalmology, Taipei Veterans General Hospital, No. 201 Shipai Road, Sec. 2, Taipei, 112, Taiwan.
Ophthalmol Ther. 2025 May 7. doi: 10.1007/s40123-025-01151-w.
To evaluate the progression rate and identify potential genetic risk factors for poor visual outcome in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy.
Ocular variables, including best-corrected visual acuity (BCVA), hypoautofluorescent area in fundus autofluorescence (FAF) and others were analyzed in patients with a diagnosis of CQ/HCQ retinopathy based on comprehensive ocular and demographic examinations. Whole exome sequencing (WES) was used to investigate the candidate genes associated with inherited retinal diseases. Multivariate analysis was used to analyze the correlation between pathogenic genetic mutation and visual outcome, with poor vision defined as BCVA < 6/12.
Forty-one patients with an average age of 61.1 ± 13.6 years, daily dose of 8.2 ± 3.6 mg/kg, and treatment period of 12.4 ± 5.6 years were recruited with a mean follow-up of 3.3 ± 2.8 years. Longitudinal observation revealed that eyes continued to have visual acuity decline with a mean progression rate of 0.065 ± 0.164 (ΔLogMAR/year) and structural change with a mean progression rate of 2.16 ± 4.32 (Δhypoautofluorescent area-to-disc-area ratio per year) despite drug cessation. Pathogenic genetic mutations were found in nine of 29 patients (31%) and were associated with poor visual acuity (odds ratio, OR = 17.402, p = 0.024). Elevated HCQ dose and renal disease were related to increased hypoautofluorescent area in FAF (OR = 17.659, p < 0.001, and OR = 7.285, p = 0.007, respectively).
The study highlights the importance of identifying genetic mutations and monitoring hypoautofluorescent areas in FAF for predicting and managing visual outcomes in patients with CQ/HCQ retinopathy.
评估氯喹/羟氯喹（CQ/HCQ）视网膜病变的进展率，并确定导致视力预后不良的潜在遗传风险因素。
基于全面的眼部和人口统计学检查，对诊断为CQ/HCQ视网膜病变的患者的眼部变量进行分析，包括最佳矫正视力（BCVA）、眼底自发荧光（FAF）中的低自发荧光区域等。采用全外显子组测序（WES）研究与遗传性视网膜疾病相关的候选基因。采用多变量分析来分析致病基因突变与视力预后之间的相关性，视力差定义为BCVA < 6/12。
招募了41例患者，平均年龄61.1±13.6岁，每日剂量8.2±3.6mg/kg，治疗期12.4±5.6年，平均随访3.3±2.8年。纵向观察显示，尽管停药，但眼睛的视力仍持续下降，平均进展率为0.065±0.164（ΔLogMAR/年），结构变化的平均进展率为2.16±4.32（每年低自发荧光区域与视盘面积之比的变化）。29例患者中有9例（31%）发现致病基因突变，且与视力差相关（比值比，OR = 17.402，p = 0.024）。较高的HCQ剂量和肾病与FAF中低自发荧光区域增加有关（分别为OR = 17.659，p < 0.001和OR = 7.285，p = 0.007）。
该研究强调了识别基因突变和监测FAF中的低自发荧光区域对于预测和管理CQ/HCQ视网膜病变患者视力预后的重要性。
