Copyright restrictions may apply JAMA Ophthalmology Journal Club Slides: Chloroquine and Hydroxychloroquine Use Maculopathy Nika M, Blachley TS, Edwards P, Lee PP, Stein JD. Regular examinations for toxic maculopathy in long-term chloroquine or hydroxychloroquine users. JAMA Ophthalmol. Published online June 26, doi: /jamaophthalmol

Copyright restrictions may apply Introduction Chloroquine (CQ) and hydroxychloroquine sulfate (HCQ) are medications commonly used to treat rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and other rheumatological conditions. A known adverse effect associated with long-term use of these medications is vision loss resulting from irreversible retinal toxic effects. Guidelines put forth by the American Academy of Ophthalmology recommend screening patients who have long-term exposure to these medications to check for signs of retinopathy. Screening tests include a dilated eye examination, perimetry, Amsler grid testing, fundus photography, fluorescein angiography, multifocal electroretinography, and optical coherence tomography. Objective: To determine whether enrollees in a large US managed care network with RA or SLE taking CQ or HCQ are regularly visiting eye care providers and being screened for maculopathy.

Copyright restrictions may apply Data Source –Clinformatics database: health care claims database of beneficiaries in a large managed care network who had any form of eye care from –Database contains: Claims for all ocular and nonocular medical conditions. International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and Current Procedural Terminology billing codes. Sociodemographic information for each enrollee. Records of all outpatient medications prescribed. –Data were linked by a unique identifier, allowing enrollees to be followed up longitudinally over time. Sample Selection –All persons diagnosed as having RA or SLE who were continuously enrolled in the medical plan for ≥ 5 years after their first RA or SLE diagnosis were identified. Those with noncontinuous enrollment were excluded, as were enrollees with <5 years of follow-up after first RA or SLE diagnosis. Methods

Copyright restrictions may apply Quantifying CQ or HCQ use: none, >0 to 5 years. Identifying persons at highest risk for maculopathy: patients with >1 year of CQ or HCQ use with concomitant renal or hepatic disease, retinal disease, or ≥60 years of age. Identifying persons with greatest use of CQ or HCQ: patients with use of CQ or HCQ for ≥4 years of the 5-year study period. Multivariable logistic regression: –Determined factors affecting the odds of visiting an eye care provider regularly (eye examinations in ≥3 of the 5 years) among those at highest risk for maculopathy, among the greatest users of CQ or HCQ, and overall. –CQ or HCQ use was the key predictor of interest in the model. –Other covariates in models: age, sex, race, education, income, diabetes, hypertension, depression, patients whose SLE or RA is managed by a rheumatologist, and long-term oral steroid use. Methods

Copyright restrictions may apply Total eligible enrollees. Medication use: –6339 enrollees (35.1%) had any CQ or HCQ use during the 5 years. –8% of enrollees were prescribed CQ or HCQ for ≥4 years Visits to eye care providers: –77% of enrollees had ≥1 visit to an eye care provider in 5-year study period. –Highest CQ or HCQ users: 66%-72% visited an eye care provider ≥1 time in a given year; 8% had no visits to eye care providers during the 5-year study period. –Highest risk for maculopathy: 68%-73% visited an eye care provider ≥1 time in a given year; 6% had no visits to eye care providers during the 5-year study period. Diagnostic testing for maculopathy –Highest CQ or HCQ users: 64% had ≥1 diagnostic test during the 5 years. –Highest maculopathy risk: 66% had ≥1 diagnostic test during the 5 years. –Few underwent diagnostic testing annually. Results

Copyright restrictions may apply Eye Care Visits and Diagnostic Testing Based on the Amount of CQ or HCQ Use Results

Copyright restrictions may apply Eye Care Visits and Diagnostic Testing Among Low-Risk and High-Risk Patients Results

Copyright restrictions may apply Results Odds of Seeking Regular Eye Care in All Patients

Copyright restrictions may apply Results Odds of Seeking Regular Eye Care in High-Risk Patients

Copyright restrictions may apply Key Findings –Despite all of the enrollees possessing health insurance, a large number of persons with long-term CQ or HCQ therapy are not undergoing annual eye examinations or screening tests as recommended by expert guidelines. –Among those enrollees at high risk for maculopathy, 6% had no eye care visits during the entire 5 years, only 57% had visits to eye care providers in ≥4 of the 5 years, and 34% had no record of any diagnostic testing (visual field, optical coherence tomography, etc) during the 5 years. –Odds of receiving regular eye care are statistically significantly greater for those taking CQ or HCQ relative to others. Factors associated with increased odds of receiving regular eye care: –Older age, female sex, education higher than high school level, end- organ damage from diabetes or hypertension, and patients whose RA or SLE was being managed by a rheumatologist. Comment

Copyright restrictions may apply Study Strengths: Large sample size, nationwide cohort with good geographic diversity, longitudinal data (not cross-sectional); all enrollees have medical insurance and thus access to eye care providers, and testing should not be an issue; diversity of health care providers practicing in an array of settings. Study Limitations: Inability to link eye care visits and testing captured in the database to outcomes (eg, loss of best-corrected visual acuity); data were extracted from billing records (inability to access clinical records); limited ability to identify high-risk patients based on billing codes alone; inability to quantify CQ or HCQ use before plan entry or cumulative exposure to these medications (only exposure during time in plan). Conclusions: Many CQ or HCQ users, including patients at high risk for retinal toxic effects and long-term users over multiple years, are not undergoing regular visits to eye care providers and diagnostic testing to check for maculopathy, as recommended by the American Academy of Ophthalmology. Future studies will hopefully identify reasons for nonadherence to the recommendations and ways of improving adherence. Comment

Copyright restrictions may apply If you have questions, please contact the corresponding author: –Joshua D. Stein, MD, MS, W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, 1000 Wall St, Ann Arbor, MI Funding/Support This study was supported by K23 Mentored Clinician Scientist Award 1K23EY from the National Eye Institute (Dr Stein), by the Blue Cross Blue Shield of Michigan Foundation (Dr Stein), and by a Physician Scientist Award from Research to Prevent Blindness (Dr Stein). Conflict of Interest Disclosures None reported. Contact Information