Hydroxychloroquine Dose and Risk for Incident Retinopathy
Bibliographic record
Abstract
BACKGROUND: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus and is often used for other inflammatory conditions, but a critical long-term adverse effect is vision-threatening retinopathy. OBJECTIVE: To characterize the long-term risk for incident hydroxychloroquine retinopathy and examine the degree to which average hydroxychloroquine dose within the first 5 years of treatment predicts this risk. DESIGN: Cohort study. SETTING: U.S. integrated health network. PARTICIPANTS: All patients aged 18 years or older who received hydroxychloroquine for 5 or more years between 2004 and 2020 and had guideline-recommended serial retinopathy screening. MEASUREMENTS: Hydroxychloroquine dose was assessed from pharmacy dispensing records. Incident hydroxychloroquine retinopathy was assessed by central adjudication of spectral domain optical coherence tomography with severity assessment (mild, moderate, or severe). Risk for hydroxychloroquine retinopathy was estimated over 15 years of use according to hydroxychloroquine weight-based dose (>6, 5 to 6, or ≤5 mg/kg per day) using the Kaplan-Meier estimator. RESULTS: Among 3325 patients in the primary study population, 81 developed hydroxychloroquine retinopathy (56 mild, 17 moderate, and 8 severe), with overall cumulative incidences of 2.5% and 8.6% at 10 and 15 years, respectively. The cumulative incidences of retinopathy at 15 years were 21.6% for higher than 6 mg/kg per day, 11.4% for 5 to 6 mg/kg per day, and 2.7% for 5 mg/kg per day or lower. The corresponding risks for moderate to severe retinopathy at 15 years were 5.9%, 2.4%, and 1.1%, respectively. LIMITATION: Possible misclassifications of dose due to nonadherence to filled prescriptions. CONCLUSION: In this large, contemporary cohort with active surveillance retinopathy screening, the overall risk for hydroxychloroquine retinopathy was 8.6% after 15 years, and most cases were mild. Higher hydroxychloroquine dose was associated with progressively greater risk for incident retinopathy. PRIMARY FUNDING SOURCE: National Institutes of Health.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".