Hydroxychloroquine
Retinal toxicity/Bulls-eye maculopathy
Estimates of risk of eye toxicity are higher than previously thought due to the availability of more sensitive screening methods. The risk of retinopathy also appears to increase with higher doses and a longer duration of therapy. In a retrospective case-control study including 2361 patients who used HCQ continuously for at least five years, the overall prevalence of HCQ retinopathy, using sensitive techniques (central visual field examination or spectral domain optical coherence imaging), was
7.5 percent. [1]
Recommended max dose = 5 mg per kg or 6.5 mg per kg.
Risk after 20 years =
Prognosis when drug is stopped? A "bull's eye" lesion, at this stage are generally not reversible and may include a dropout of letters from words when reading, photophobia, blurred distance vision, reduced night vision, visual field defects, and flashing lights. Severe retinopathy, including retinal pigment epithelium (RPE) damage, has been shown on SD-OCT to progress for at least three years following drug discontinuation; depigmentation and functional loss may continue for one year or more after the drug has been stopped. [1]
Calculate dose <5 mg per kg
| Weight (lbs) | Doses of 200 mg. Hydroxychloroquine per week |
| >169 | 14 |
| 158-169 | 13 |
| 145-157 | 12 |
| 133 -144 | 11 |
| 120 -132 | 10 |
| 95-119 | 8 |
| <95 | 7 |
Risk of eye toxicity from duration of use
| Duration of therapy | Odds of toxicity |
| 5 yrs | 2x |
| 10 yrs | 3.2x |
| 20 yrs | 20% |
Image from Melles RB, Marmor MF. The Risk of Toxic Retinopathy in Patients on Long-term Hydroxychloroquine Therapy. JAMA Ophthalmol. 2014;132(12):1453–1460
Routine eye examinations
Monitoring patients with routine eye exams is necessary to avoid permanent vision loss, although the incidence of retinal toxicity is reduced through the use of lower doses of medication. The purpose of screening is to detect retinal toxicity, if it develops, before the vision is affected. The primary screening tests
- automated visual fields
- spectral domain optical coherence tomography (SD-OCT).
Early OCT changes are almost always asymptomatic and may remain so if HCQ is discontinued. Image from Melles RB, Marmor MF. The Risk of Toxic Retinopathy in Patients on Long-term Hydroxychloroquine Therapy. JAMA Ophthalmol. 2014;132(12):1453–1460. doi:10.1001/jamaophthalmol.2014.3459
Baseline exam
Assess ocular health within a year of starting long-term antimalarial drug therapy. The baseline examination should include a fundus examination of the macula to rule out any underlying disease that may interfere with the interpretation of screening tests.[1]
Asians have more peripheral eye disease
Asian and Asian American patients tend to show early damage outside the central macula and can develop serious toxicity before it would be recognized by tests that focus only on the parafovea; thus, imaging studies in this population should examine beyond the central macula
Maintenance eye exams
The frequency of subsequent screening during the first five years of treatment may be individualized based upon assessment of risk. American Academey of Ophthalmology (AAO) has suggested that for patients with a normal baseline exam who do not have major risk factors for toxic retinopathy, follow-up examinations may be deferred until there have been five years of exposure.
Patients should be alert for any change in visual acuity and should seek medical attention promptly if any visual loss is noted. Antimalarials should be discontinued immediately if there is any suspicion of retinopathy.[1]
Major risk factors for toxic retinopathy
- a daily dose of HCQ greater than 5 mg/kg real body weight or a daily dose of chloroquine greater than 2.3 mg/kg real body weight
- antimalarial use for greater than five years
- the presence of renal disease
- concomitant tamoxifen use
- the presence of macular disease
Patients should be alert for any change in visual acuity and should seek medical attention promptly if any visual loss is noted. Antimalarials should be discontinued immediately if there is any suspicion of retinopathy. [1]Prognosis of eye disease
Indirect evidence from limited observational data suggest that early screening for HCQ toxicity can reduce the risk of losing visual acuity. A study of 22 patients with different degrees of HCQ retinopathy reported a range of changes during follow-up after cessation of HCQ whose magnitude correlated with retinopathy severity at the time of cessation. The eyes with the least severe retinopathy at the time of drug cessation demonstrated a low likelihood of progression and there was even some functional and structural improvement in some cases. Eyes with more severe retinopathy, however, demonstrated progressive deterioration of retinal structures and a decline in function even years after cessation of the drug. Another small study with 11 patients with different degrees of HCQ retinopathy also detected a similar pattern in which less severe retinopathy demonstrated little progression during the follow-up period, in contrast with more severe retinopathy that continued to progress during the three-year follow-up period. [1]
