Pathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine Retinopathy

Abstract Introduction To evaluate the progression rate and identify potential genetic risk factors for poor visual outcome in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy. Methods Ocular variables, including best-corrected visual acuity (BCVA), hypoautofluorescent area in fundus autofluoresce...

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Main Authors: Hsun-I. Chiu, Hui-Chen Cheng, Chih-Chiau Wu, Shih-Jen Chen, De-Kuang Hwang, Yi-Ming Huang, Yu-Bai Chou, Po-Kang Lin, Tai-Chi Lin, Ko-Hua Chen, Pei-Yu Lin, Yu-Fan Chang, An-Guor Wang
Format: Article
Language:English
Published: Adis, Springer Healthcare 2025-05-01
Series:Ophthalmology and Therapy
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Online Access:https://doi.org/10.1007/s40123-025-01151-w
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author Hsun-I. Chiu
Hui-Chen Cheng
Chih-Chiau Wu
Shih-Jen Chen
De-Kuang Hwang
Yi-Ming Huang
Yu-Bai Chou
Po-Kang Lin
Tai-Chi Lin
Ko-Hua Chen
Pei-Yu Lin
Yu-Fan Chang
An-Guor Wang
author_facet Hsun-I. Chiu
Hui-Chen Cheng
Chih-Chiau Wu
Shih-Jen Chen
De-Kuang Hwang
Yi-Ming Huang
Yu-Bai Chou
Po-Kang Lin
Tai-Chi Lin
Ko-Hua Chen
Pei-Yu Lin
Yu-Fan Chang
An-Guor Wang
author_sort Hsun-I. Chiu
collection DOAJ
description Abstract Introduction To evaluate the progression rate and identify potential genetic risk factors for poor visual outcome in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy. Methods 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. Results 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). Conclusions 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.
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spelling doaj-art-66ae4e755f964b97afd41a0e5fb914fc2025-08-20T02:06:28ZengAdis, Springer HealthcareOphthalmology and Therapy2193-82452193-65282025-05-011471465148010.1007/s40123-025-01151-wPathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine RetinopathyHsun-I. Chiu0Hui-Chen Cheng1Chih-Chiau Wu2Shih-Jen Chen3De-Kuang Hwang4Yi-Ming Huang5Yu-Bai Chou6Po-Kang Lin7Tai-Chi Lin8Ko-Hua Chen9Pei-Yu Lin10Yu-Fan Chang11An-Guor Wang12Department of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung UniversityAbstract Introduction To evaluate the progression rate and identify potential genetic risk factors for poor visual outcome in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy. Methods 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. Results 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). Conclusions 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.https://doi.org/10.1007/s40123-025-01151-wHydroxychloroquine retinopathyProgression rateRisk factorsGenetic mutation
spellingShingle Hsun-I. Chiu
Hui-Chen Cheng
Chih-Chiau Wu
Shih-Jen Chen
De-Kuang Hwang
Yi-Ming Huang
Yu-Bai Chou
Po-Kang Lin
Tai-Chi Lin
Ko-Hua Chen
Pei-Yu Lin
Yu-Fan Chang
An-Guor Wang
Pathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine Retinopathy
Ophthalmology and Therapy
Hydroxychloroquine retinopathy
Progression rate
Risk factors
Genetic mutation
title Pathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine Retinopathy
title_full Pathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine Retinopathy
title_fullStr Pathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine Retinopathy
title_full_unstemmed Pathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine Retinopathy
title_short Pathologic Genetic Mutations May Correlate with Poor Visual Outcome in Patients with Hydroxychloroquine Retinopathy
title_sort pathologic genetic mutations may correlate with poor visual outcome in patients with hydroxychloroquine retinopathy
topic Hydroxychloroquine retinopathy
Progression rate
Risk factors
Genetic mutation
url https://doi.org/10.1007/s40123-025-01151-w
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