33

QUESTION

WHAT SYSTEMIC MEDICATIONS REQUIRE PERIODIC FUNDUS EVALUATION? WHAT AM I LOOKING FOR AND WHAT TESTS DO I DO?

Michael T. Andreoli, MD
William F. Mieler, MD

Every ophthalmologist should be familiar with medication-induced ocular side effects. There are 4 particular medications that are associated with well-described ocular effects even when used at “safe” daily dosages. These medications include hydroxychloroquine, thioridazine, tamoxifen, and sildenafil.

Plaquenil (hydroxychloroquine) is prescribed to treat connective tissue diseases. Although clinically identical to the retinopathy of chloroquine, the incidence is much lower since hydroxychloroquine does not as readily cross the blood-retinal barrier. Risk factors for the development of retinopathy include daily dosage exceeding 5 mg/kg/day, age greater than 60 years, liver or renal disease, concomitant retinal disease, concurrent tamoxifen use, treatment duration greater than 5 years, and obesity. Current guidelines recommend basing daily dosage on actual rather than ideal body weight. The American Academy of Ophthalmology guidelines suggest that a dilated fundus examination be performed at the commencement of hydroxychloroquine therapy. Annual optical coherence tomography (OCT), fundus autofluorescence, and perimetry (10-2 Humphrey visual field with white or red targets) are recommended starting at the fifth year of treatment or earlier.¹ Clinical examination may reveal retinal pigment epithelial mottling and atrophy, which may progress to a Bull’s eye maculopathy in cases of moderate to severe toxicity (Figure 33-1). Modern imaging should reveal minor structural alterations before gross abnormalities are apparent on fundus examination. Early OCT changes may include thinning of the outer nuclear layer, while later stages classically demonstrate a significant parafoveal atrophy of the outer retina with attenuation of the ellipsoid segment.² Autofluorescence may demonstrate paracentral hyper- or hypoautofluorescence, depending on the stage (Figure 33-2). Any visual field defect should be taken seriously. Multifocal electroretinography can be particularly helpful for confirming early toxicity and monitoring recovery, commonly exhibiting diminished wave amplitudes in the parafoveal region when toxicity is present. Retinal toxicity may occur in a more perifoveal than parafoveal distribution in Asian patients. If hydroxychloroquine toxicity is suspected, typically medication discontinuation is recommended; however, retinal changes may persist or even worsen after cessation of drug therapy.

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