Hydroxychloroquine Retinopathy Screening: Dose, Timing and Tests
Last updated: November 2026
Hydroxychloroquine is widely used for lupus, rheumatoid arthritis and other autoimmune diseases. It can cause an irreversible retinopathy that keeps progressing even after the drug is stopped, so the goal of screening is to catch it before the patient notices any change. Here is the current approach, based on the Royal College of Ophthalmologists (2020) and the American Academy of Ophthalmology (2016) recommendations.
The 5 × 5 rule
| Risk factor | Effect |
|---|---|
| Dose above 5 mg/kg/day (actual weight) | The main risk factor |
| Duration over 5 years | Risk rises with cumulative dose: under 2% in the first 10 years at recommended doses, about 20% after 20 years (Melles and Marmor 2014) |
| Reduced kidney function (eGFR below 60) | Less drug excretion |
| Tamoxifen | Increases retinal toxicity |
| Pre-existing macular disease | Makes screening harder to interpret |
Who, when and how
| Question | Answer (RCOphth 2020) |
|---|---|
| Baseline examination? | No longer recommended routinely in the UK. The AAO recommends a baseline fundus examination within the first year, with fields and OCT if maculopathy is present; many Indian units still record a baseline OCT. |
| When to start annual screening? | After 5 years of hydroxychloroquine; after 1 year if dose above 5 mg/kg/day, eGFR below 60, or on tamoxifen; after 1 year for chloroquine. |
| Which tests? | Spectral-domain OCT of the macula and widefield fundus autofluorescence (FAF) at each visit. Visual fields (10-2, and 24-2 or 30-2 in Asian patients) are used when imaging is abnormal or doubtful. |
| Who is responsible? | The prescriber refers the patient and acts on the result; the eye service reports normal, possible or definite retinopathy. |
What does toxicity look like?
- OCT: thinning or loss of the ellipsoid zone and outer nuclear layer, first in a parafoveal ring (the "flying saucer" sign of preserved central foveal tissue).
- Asian patients often show a pericentral pattern further out, along the arcades, which is why a wider field (24-2 or 30-2, and widefield FAF) is needed.
- FAF: a ring of increased then decreased autofluorescence.
- Late: bull's eye maculopathy, visible on examination, with permanent central field loss.
- Cornea: vortex keratopathy (verticillata) is harmless and not a reason to stop.
If retinopathy is found
- Definite retinopathy: inform the prescriber promptly; stopping the drug is the only intervention, and the decision is shared with the patient and rheumatologist.
- Possible retinopathy: repeat tests (often with fields and multifocal ERG) within a few months.
- Damage may progress for a while after stopping, so early detection matters.
Where residents slip
- Calculating the dose on ideal instead of actual body weight (the AAO 2016 change).
- Using only a 10-2 field in Asian patients and missing pericentral toxicity.
- Stopping the drug for vortex keratopathy.
- Relying on fundus examination alone: bull's eye maculopathy is a late sign.
Key sources
- Yusuf IH, et al. Hydroxychloroquine and chloroquine retinopathy: recommendations on monitoring. Royal College of Ophthalmologists; December 2020. rcophth.ac.uk
- Marmor MF, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123:1386-1394
- Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 2014;132:1453-1460
Related: Screening schedules, Ocular side effects of systemic drugs, OCT macula reference.
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