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Hydroxychloroquine induced retinal toxicity

Chloroquine (CQ) and hydroxychloroquine (Plaquenil) (HCQ) have been used for many years, initially for the treatment of malaria but now more commonly for the treatment of inflammatory diseases such as rheumatoid arthritis and lupus . It is now considered for new disease applications in diabetes, heart disease and adjunct cancer therapies.

Ocular manifestations of hydroxychloroquine include corneal verticillata and retinal toxicity. Verticillata are cornea deposits of salts within the corneal epithelium.  This condition does not cause symptoms and is reversible with cessation of the medication. The finding of corneal verticillata bares no correlation with retinal toxicity and is not an indication to stop the medication . The hallmark of hydroxychloroquine toxicity is bilateral pigmentary retinopathy . Patients with early retinal findings are often asymptomatic despite having subtle paracentral scotomas. Later in the disease, patients can develop a bilateral bull's eye maculopathy, characterized by a ring of retinal pigment epithelium (RPE) depigmentation in the macula, sparing the fovea, which is often accompanied by paracentral and central scotomas . End stage hydroxychloroquine toxicity leads to widespread RPE and retinal atrophy with a loss of central vision, peripheral vision, and night vision.

The most important risk for toxicity is excessive daily dose by weight . Dosage >5.0mg/kg increases the risk of toxicity. Duration of use is also a critical risk factor. HCQ is cleared by the kidneys and thus renal disease increases the risk of toxicity. Tamoxifen (used in breast cancer treatment) increases the risk of toxicity approximately 5 fold. 

All patients should have a baseline Eye examination within the first year of initiating HCQ or CQ therapy with thorough risk factor assessment and fundus examination of the macula to rule out underlying disease. Baseline VFs and OCT are also recommended. Annual Exams are recommended as well.

Author
Paddy Kalish OD, JD and B.Arch

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