The risk of toxicity is low for individuals without complicating conditions during the first 5 years of treatment using less than 6.5 mg/kg/day of hydroxychloroquine or 3 mg/kg/day of chloroquine, and/or cumulative doses of less than 1000 gram and 460 gram, respectively. Some physicians suggest that lean body weight is more accurate when calculating daily dosage. Most patients are routinely given 400 mg of hydroxychloroquine daily. This dose is considered acceptable.
Early stage
The earliest signs of toxicity include bilateral paracentral visual field changes and a subtle granular depigmentation of the paracentral RPE.
Advanced stage
With continued drug exposure, there is progressive development of a bilateral atrophic bull's-eye maculopathy and paracentral scotomata, which may in severe cases ultimately spread over the entire fundus, causing widespread retinal atrophy and visual loss.
Pathophysiology
Both agents bind to melanin pigment in the RPE, and this may serve to concentrate the drugs or to prolong their adverse effects.
Diagnosis
Patients and their primary care physicians must be made fully aware of the ophthalmic risks and the need for regular screening examinations to detect retinal toxicity at an early stage. Baseline evaluation for patients beginning treatment with a chloroquine derivative should include a complete eye examination by an eye care professional, retinal photography for follow-up comparisons, and Visual field testing with a white pattern. Central visual field assessment should test the central 10° of vision with a white test target. In patients at risk or those with unclear presentation, optical coherence tomography, fundus autofluorescence, and multifocal electroretinography may be obtained. Profound abnormalities detected with visual field and multifocal electroretinography testing can be observed in the presence of a normal retinal appearance. Retinal examinations are advised for documentation, but visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at an earlier stage. Annual screening should begin after 5 years.
Treatment
Cessation of the drug at the first sign of toxicity is recommended. No treatment exists as yet for this disorder, so it is imperative that patients and their ophthalmologists be aware of the best practices for minimizing toxic damage.
Prognosis
Associated visual loss rarely recovers and may even progress after the drug is discontinued.
