Current screening practice in patients under long-term hydroxychloroquine medication in Taiwan: A nationwide population-based cohort study

Hydroxychloroquine (HCQ), an analog of chloroquine, is widely used in various rheumatologic and dermatologic disorders. However, it may cause severe retinopathy with long-term use. The guidelines proposed by the American Academy of Ophthalmology suggested a baseline fundus examination and an annual screening after 5 years by using automated visual fields (VF) plus spectral-domain optical coherence tomography (SD-OCT). Both multifocal electroretinogram (mfERG) and fundus autofluorescence (FAF) can also be used to improve the accuracy of diagnosis. The purpose of this study was to examine if the current HCQ screening practice in Taiwan was sufficient according to the guidelines to prevent severe macular complications. This study could remind every doctor to explain visual side effects thoroughly to every patient using HCQ, and refer patients for the ophthalmologic survey to eliminate potential visual impairment caused by this medicine. This nationwide population-based cohort study included all patients who started taking HCQ (n = 5826) from January 1, 1997, to December 31, 2007, in the Longitudinal Health Insurance Database 2000. The ICD codes used for HCQ retinopathy were 362.10, 362.55, 362.89, and 362.9. Patients previously diagnosed these retinal disorders were excluded. Demographic data including sex, age, diagnostic tools used, and the date of the initial diagnosis of the subsequent HCQ-related retinal disorder were collected. Patients were divided into 2 groups. The patients taking HCQ <5 years were defined as group 1, and >5 years as group 2. The risk of developing retinal diseases between these 2 groups was compared with a 2-sample t-test for continuous variables, and Fisher's exact test for discrete variables. Multiple logistic regressions were used for odds ratio calculation. The baseline examination ratio of the automated VF, SD-OCT scans, and multifocal electroretinograms (mfERGs) in the first 3 months were only 0.2% in both groups. The screening ratio of the 3 examination tools after 5 years were 1.1% in group 1 and 1.2% in group 2. 2.5% and 3.9% of patients developed a retinal disorder after HCQ use in group 1 and 2, respectively. The risk of developing retinal disorder was significantly higher in group 2 (relative risk = 1.53, P = .006). The odds ratio (OR) was also significantly higher in group 2 (1.67 with 95% cumulative incidence 1.20–2.30) The examination ratio according to the guidelines was very low in Taiwan. Thus, it is very important for doctors who prescribe HCQ to schedule both baseline and annual ophthalmology screening tests and inform patients of possible severe ocular complications, even in the patient taking HCQ <5 years. It is also important for ophthalmologists to review medical history carefully to find out the causes of retinotoxicity. Medications should be stopped, if possible when toxicity is recognized or strongly suspected.