Risk Factors for Retinopathy among long term Hydroxychloroquine users identified in JAMA study

In the cohort study of 4677 long-term hydroxychloroquine users with masked adjudication of retinopathy outcomes, female sex, increasing age, chronic kidney disease (CKD) stage 3 or greater, and tamoxifen use were each associated with a higher risk of hydroxychloroquine retinopathy.

“This study suggests considering these factors when making decisions about hydroxychloroquine dosing and screening for hydroxychloroquine retinopathy,” the researchers wrote.

Hydroxychloroquine retinopathy is a rare but serious complication characterized by damage to the retina, the light-sensitive tissue at the back of the eye. Long-term use of HCQ has been implicated in the development of retinopathy, which can lead to irreversible vision loss if left unchecked. Understanding the risk factors associated with this condition is paramount for early detection and intervention. Current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be linked with retinopathy risk.

Against the above background, April M. Jorge, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, and colleagues aimed to identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy.

For this purpose, the researchers conducted a cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening following five years of use, from 1997 to 2020, with up to 15 years of follow-up.

Candidate risk factors included age at hydroxychloroquine initiation, race and ethnicity, sex, CKD, indications, diabetes, liver disease, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was evaluated from pharmacy dispensing records.

Incident hydroxychloroquine retinopathy was adjudicated from the masked review of guideline-recommended screening studies and categorized as a parafoveal or pericentral pattern. Potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation were assessed.

The study led to the following findings:

• Among 4677 long-term hydroxychloroquine users (mean age at initiation, 52.4 years; 82.9% women), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral).
• Older age at the time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 for those aged 45 to 54 years, 3.82 for those aged 55 to 64 years, and 5.68 for those aged 65 years or older compared with those younger than 45 years.
• Retinopathy risk was higher among females than males (HR, 3.83), among patients with CKD stage 3 or greater (HR, 1.95), and among individuals with tamoxifen use (HR, 3.43).
• There was a higher likelihood of pericentral retinopathy among Asian patients (HR, 15.02) and Black patients (HR, 5.51) compared with non-Hispanic White patients.

The findings suggest that female sex, increasing age, tamoxifen use, and CKD stage 3 or greater were associated with a higher risk of hydroxychloroquine retinopathy, whereas male sex and being younger than 45 years at hydroxychloroquine initiation were associated with a lower risk. Ethnicity and race were also associated with the pattern of retinopathy.

“These factors should be incorporated into hydroxychloroquine dosing decisions,” the researchers wrote.

In conclusion, the study on risk factors for hydroxychloroquine retinopathy and its subtypes represents a significant advancement in our understanding of this sight-threatening complication. As the medical community continues to refine strategies for optimizing HCQ therapy, personalized risk assessment and vigilant monitoring remain crucial pillars of patient care, ensuring that the benefits of treatment outweigh the risks to ocular health.

Reference:

Jorge AM, Melles RB, Marmor MF, Zhou B, Zhang Y, Choi HK. Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes. JAMA Netw Open. 2024;7(5):e2410677. doi:10.1001/jamanetworkopen.2024.10677