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A Statement on Hydroxychloroquine

 

The drug Hydroxychloroquine has been in the news as a possible treatment under consideration for COVID-19.

”Hydroxychloroquine has been used for many years for autoimmune diseases such as rheumatoid arthritis and lupus. The vast majority of patients who take it never have any eye problems from it. Vision problems from retinal toxicity may occur in some patients after several years of continuous use. The potential protective benefit of hydroxychloroquine in the coronavirus outbreak remains unproven pending ongoing clinical trials. If a person’s doctor suggests that he or she use it to treat COVID-19, there is likely minimal risk of vision loss as a result of taking it for several months. However, the drug should ONLY be taken after careful discussion with a medical doctor and discussion of potential systemic side effects. The risk of any toxicity may be increased by concurrent medical conditions such as kidney or liver disease and by alcohol consumption.“

Sunir J. Garg, MD and James P. Dunn, MD on behalf of the Wills Eye Retina Service.

COMMENTARY

Hydroxychloroquine: Possible COVID Drug Can Be Toxic to Retinas

Brianne N. Hobbs, OD; Kaila M. Osmotherly, OD

DISCLOSURES

April 02, 2020

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Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

As we await evidence from multiple ongoing trials of hydroxychloroquine (HCQ) for the treatment of COVID-19, clinicians have had to make do with conflicting reports regarding its potential efficacy. Although HCQ is one of the safest drugs used for chronic rheumatic and autoimmune disorders, the current lack of a consensus regarding its optimal dosage for COVID-19 has also made it difficult to quantify the risk for adverse effects. There is an existing body of knowledge around the potential toxic effects of HCQ, however, especially to the retina, that every clinician should keep in mind if it becomes widely used in the treatment of COVID-19.

Greater Retinal Toxicity Risks With Higher Dosages, Longer Durations

The most significant risk factors for the development of HCQ-related retinal toxicity are a high dose relative to real weight and duration of use. The current recommendation for the treatment of chronic rheumatic disease is a maximum daily HCQ dosage of ≤ 5.0 mg/kg/day. A typical dosage for inflammatory disease is 200 mg twice daily; at this dose, a patient should weigh at least 176 pounds to not exceed the recommended maximum.

In terms of duration, patients who did not exceed the maximum daily dose had a < 1% risk for toxicity following 5 years of treatment. However, limited studies assessing higher doses of HCQ (up to 20 mg/kg/day) for non–small cell lung cancer and chronic graft-versus-host disease showed an increased incidence of retinopathy within 1-2 years, and previous data suggest that a lifetime cumulative dose of 1000 g increased the risk for macular toxicity.

There is no current consensus on the appropriate dosage of HCQ in the treatment of COVID-19, but early reports suggest that a higher dose (600-800 mg/day) for a short period of time (typically not lasting more than 10 days) may be optimal. Although the dosage will probably exceed the recommended 5.0 mg/kg/day for most patients, given the brief duration of treatment it is unlikely that patients will develop retinal toxicity.

Comorbidities Increase Likelihood of Retinal Toxicity

While a detailed patient history may be impossible to obtain if HCQ is used in the treatment of COVID-19, certain comorbidities do place patients at an increased risk for retinal toxicity. HCQ is excreted through renal clearance, so the dosage should be reduced in those with compromised kidney function to minimize the risk for toxicity. The presence of macular disease, such as age-related macular degeneration, has also been demonstrated to be a risk factor for the development of toxic maculopathy. The concurrent use of tamoxifen also increases the risk for retinal toxicity. Tamoxifen itself may deposit in the retina and make the macula more susceptible to the potentially toxic effects of HCQ.

Early Detection of Retinal Toxicity Is Critical

It is estimated that the prevalence of retinal toxicity due to HCQ is 7.5% with long-term use of the drug. Monitoring patients for its development is important, as the damage is irreversible. Progression continues following discontinuation of the medication but can be limited if toxicity is detected early.

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