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Accuracy of self-reported risk factors for hydroxychloroquine retinopathy

Published:February 16, 2021DOI:https://doi.org/10.1016/j.jcjo.2021.01.021
      Hydroxychloroquine (HCQ) is an effective and typically well-tolerated anti-inflammatory medication, but retinal toxicity is a potential side effect.
      • Marmor MF
      • Kellner U
      • Lai TY
      • Melles R
      • Mieler W.
      Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision).
      Current screening guidelines recommend baseline ophthalmic examination to rule out maculopathy and then yearly examination with visual field and optical coherence tomography after 5 years of HCQ use.
      • Marmor MF
      • Kellner U
      • Lai TY
      • Melles R
      • Mieler W.
      Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision).
      The presence of HCQ retinopathy risk factors,
      • Melles RB
      • Marmor MF.
      The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.
      such as HCQ duration ≥5 years, HCQ daily dose >5 mg/kg real body weight, tamoxifen use, or renal disease, should increase suspicion for retinopathy and may modify the retinopathy screening timeline.
      Identifying these risk factors requires taking a patient history or reviewing the electronic health record (EHR). With ever-increasing time demands, providers may rely solely on patient self-report of HCQ retinopathy risk factors. The primary goal of this study is to evaluate whether the patient interview accurately identifies HCQ retinopathy risk factors, and the secondary goal is to evaluate whether eye care providers accurately identify these risk factors.
      The study protocol was approved by the Minneapolis Veterans Affairs Health Care System Institutional Review Board (IRB)/Ethics Committee and adhered to the tenets of the Declaration of Helsinki. We utilized the Veterans Affairs Informatics and Computing Infrastructure (VINCI)
      VA Informatics and Computing Infrastructure (VINCI)
      VA HSR RES 13-457.
      to query Corporate Data Warehouse

      US Department of Veterans Affairs. 172VA10P2: VHA Corporate Data Warehouse – VA. 79 FR 4377. Accessed: March 12, 2020.

      data to identify patients currently taking HCQ and presenting for routine examinations in the Minneapolis Veterans Affairs Eye Clinic. After informed consent, all study subjects completed an in-person interview survey regarding HCQ retinopathy risk factors (Supplementary Table 1, available online). We reviewed the eye care provider note at the study visit and queried the EHR for HCQ retinopathy risk factors, cognitive diagnoses, and psychiatric diagnoses.
      A demographic and clinical summary of the 93 study participants appears in Table 1. After identifying subjects with HCQ retinopathy risk factors by EHR review, we determined whether the subject interview and eye care provider note identified these risk factors (Table 2). The presence of a cognitive or psychiatric diagnosis did not reduce self-reporting accuracy: 5/9 (56%) subjects with a cognitive disorder, 20/28 (71%) subjects with a psychiatric diagnosis, and 23/42 (55%) subjects with neither cognitive nor psychiatric diagnoses correctly reported all HCQ risk factors.
      Table 1Demographic and clinical characteristics of the study population
      CharacteristicResult (n = 93)
      Age, mean (range), years69 (33–88)
      Height, mean (range), cm172 (152–193)
      Real weight, mean (range), kg89 (44–146)
      BMI, mean (range), kg/m230 (21–37)
      Sex
       Female13 (14%)
       Male80 (86%)
      Cognitive diagnosis15 (16%)
      Psychiatric diagnosis28 (30%)
      No psychiatric or cognitive diagnosis56 (60%)
      HCQ duration based on EHR, mean (range), years5.6 (0.1–20.5)
      >6 month interruption in HCQ6 (6.5%)
      HCQ daily dose, mean (range), mg/kg/day3.9 (0.4–9.0)
      eGFR <60 mL/min/1.73m219 (20%)
      Tamoxifen use0
      BMI, body mass index; HCQ, hydroxychloroquine; EHR, electronic health record; eGFR, estimated glomerular filtration rate.
      Table 2Accuracy of hydroxychloroquine retinopathy risk factor reporting
      SituationnRisk factor(s) correctly reported by subject (%)Risk factor(s) correctly reported by provider (%)
      Any HCQ retinopathy risk factor6940 (58)33 (48)
      HCQ duration ≥5 years4735 (75)39 (83)
      HCQ dose >5 mg/kg/day105 (50)3 (30)
      Renal disease2911 (38)3 (10)
      HCQ, hydroxychloroquine.
      The patient interview identified HCQ duration ≥5 years in 75% of cases but was less successful at identifying HCQ daily dose >5 mg/kg and renal disease. Similarly, the eye care provider note identified HCQ duration ≥5 years but not HCQ daily dose >5 mg/kg or renal disease in most cases. Inconsistent self-report of HCQ retinopathy risk factors corresponds with previous studies showing variable accuracy in patient self-reported medication use.
      • Hafferty JD
      • Campbell AI
      • Navrady LB
      • et al.
      Self-reported medication use validated through record linkage to national prescribing data.
      Improving HCQ retinopathy screening by manual EHR review of risk factors can be time-consuming, but EHR templates may improve efficiency. Alternatively, if EHR confirmation is not feasible, we recommend communicating with the patient's HCQ prescribing provider, communicating with the patient's prescribing pharmacy, or requesting that the patient bring the medication bottle to the eye clinic to verify HCQ duration and dose. Other methods such as monitoring blood HCQ levels may improve HCQ retinopathy screening in the future,
      • Petri M
      • Elkhalifa M
      • Li J
      • Magder LS
      • Goldman DW.
      Hydroxychloroquine blood levels predict hydroxychloroquine retinopathy.
      but at present accurately assessing established HCQ retinopathy risk factors remains central in providing good patient care.
      One study limitation is that the older and more predominantly male population may affect generalizability. Although prior HCQ studies have predominantly female populations, male patients also take HCQ and develop HCQ retinopathy.
      • Melles RB
      • Marmor MF.
      The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.
      Additionally, with the potential for expanded clinical indications for HCQ treatment,
      • Nirk E
      • Reggiori F
      • Mauthe M.
      Hydroxychloroquine in rheumatic autoimmune disorders and beyond.
      the sex ratio of patients taking HCQ may change. The study is also limited by a small sample size.
      In conclusion, solely using the patient interview or prior eye care provider notes may not consistently identify HCQ retinopathy risk factors. Optimizing EHR use, with either manual review carried forward or automated templates, would improve quality of care in HCQ retinopathy screening.

      Acknowledgements

      The authors thank Ryan Hecker, VINCI data manager, for identifying potential subjects for this study.
      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This work was supported using resources and facilities at the Minneapolis Veterans Affairs Health Care System and the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. Neither the Minneapolis Veterans Affairs Health Care System nor VINCI had any role in the design or conduct of this research. The contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States government.

      Footnotes and Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

      Appendix. Supplementary materials

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