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Plaquenil Toxicity

Hydroxychloroquine (Plaquenil) is utilized systemically as

prophylaxis for malaria and also to treat dermatological and rheumatological inflammatory conditions like systemic lupus erythematosus and rheumatoid arthritis.

The exact mechanism of action of hydroxycholorquine is unknown, however, it is thought to have an impact on the following conditions by:

  • Malaria Treatment – hydrochloroquinine inhibits hemozoin biocrystallization, which leads to the accumulation of cytotoxic heme which builds up in the malaria parasite causing their deaths.

  • Anti-inflammatory – Hydroxychloroquine increases lysosomal pH (more basic) in antigen-presenting cells and blocks toll-like receptors on plasmacytoid dendritic cells, which leads to a reduced activation of the dendritic cells and a reduction in inflammatory process. ![endif]--

In early stages of hydroxychloroquine retinopathy, patients are asymptomatic. When vision is impacted it can include:

  • paracentral scotoma (early)

  • decreased color vision (early)

  • reduced acuity (late)

  • reduced peripheral vision (late)

  • reduced night vision (late)


The classic sign of hydroxychloroquine retinopathy is bilateral “bull’s-eye” appearance of the macula due to disruption of the retinal pigmented epithelium. However, this finding occurs late in the toxicity and once it occurs the likelihood of permanent vision loss is significant so it is not useful as a screening tool.

Medication Dosage

Studies show that cumulative dose may be more important that daily dosage but since a higher daily dose will lead to a higher cumulative dose more rapidly than a lower daily dose.

It is difficult to predict exactly which patients will develop retinal toxicity, however, high-risk characteristics include the following:

  • daily dose greater than 400 mg

  • a daily dosage over 6.5 mg/kg ideal body weight

  • In patients who weigh < 135lbs daily dose should be adjusted

  • total cumulative dose of more than 1,000 g

  • medication use longer than five years

  • concomitant renal or liver disease (because the drug is cleared by both routes)

  • underlying retinal disease or maculopathy

  • age greater than 60 years

Monitoring Guidelines

Updated guidelines state that due to sensitivity, specificity and reliability issues, the following tests are NOT recommended to be utilized as screening tools:

  • Amsler grid testing

  • Color vision testing

  • Fundus examination (including photos)

  • Full-field electroretinogram (ffERG)

  • Electrooculogram (EOG)

Current Guidelines Recommend:

A baseline examination at the initiation of treatment to include:

  1. Thorough ocular examination documenting any preexisting conditions and baseline fundus photos,

  2. Humphrey visual field central 10-2 white-on-white pattern

  3. At least one of the following objective tests:

  • Fundus autofluorescence (FAF)

  • Multifocal electroretinogram (mfERG) or

  • Spectral domain OCT (SD-OCT)

Have a great week! ~ Chris

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