What is the incidence rate of Plaquenil (hydroxychloroquine) retinal toxicity?

From the Guidelines

The incidence rate of Plaquenil (hydroxychloroquine) retinal toxicity is less than 1% for the first 5 years of use, increasing to approximately 2% after 10 years, and rising to 20% after 20 years of continuous use at recommended doses (≤5 mg/kg real body weight per day) 1.

Key Points

• The risk of retinal toxicity increases with longer duration of use and higher dosing of hydroxychloroquine.
• Daily doses exceeding 5 mg/kg real body weight significantly increase the risk of retinopathy.
• Risk factors that increase toxicity include kidney disease, concurrent tamoxifen use, and pre-existing macular disease.
• Dosing based on actual body weight rather than ideal body weight is now recommended to reduce risk.
• Regular screening with visual field testing and spectral domain optical coherence tomography is essential, with baseline examination recommended within the first year of treatment and annual screening after 5 years of use (or sooner with risk factors) 1.

Screening and Monitoring

• Early detection is crucial as it allows for medication discontinuation before vision loss becomes significant.
• The American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology recommend widespread adoption of sensitive testing techniques, such as optical coherence tomography and automated visual fields, to detect early toxicity 1.
• Effective communication among prescribing physicians, patients, and eye care providers is essential to optimize the utility and safety of hydroxychloroquine 1.

From the FDA Drug Label

5.2 Retinal Toxicity Irreversible retinal damage was observed in some patients treated with hydroxychloroquine sulfate and it is related to cumulative dosage and treatment duration. In patients of Asian descent, retinal toxicity may first be noticed outside the macula Risk factors for retinal damage include daily hydroxychloroquine sulfate dosages ≥ 5 mg/kg of actual body weight, durations of use greater than five years, renal impairment, use of concomitant drug products such as tamoxifen citrate, and concurrent macular disease Within the first year of starting hydroxychloroquine sulfate, a baseline ocular examination is recommended including best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain ocular coherence tomography (SD-OCT) For patients at higher risk of retinal damage, monitoring should include annual examinations which include BCVA, VF and SD-OCT. For patients without significant risk factors, annual retinal exams can usually be deferred until five years of treatment. In patients of Asian descent, it is recommended that visual field testing be performed in the central 24 degrees instead of the central 10 degrees If ocular toxicity is suspected, discontinue hydroxychloroquine sulfate and monitor the patient closely given that retinal changes and visual disturbances may progress even after cessation of therapy.

The incidence rate of Plaquenil (hydroxychloroquine) retinal toxicity is not explicitly stated in the provided drug labels. However, it is mentioned that irreversible retinal damage was observed in some patients treated with hydroxychloroquine sulfate, and that the risk of retinal damage is related to cumulative dosage and treatment duration. Risk factors for retinal damage include:

• Daily hydroxychloroquine sulfate dosages ≥ 5 mg/kg of actual body weight
• Durations of use greater than five years
• Renal impairment
• Use of concomitant drug products such as tamoxifen citrate
• Concurrent macular disease 2, 2, 2

From the Research

Incidence Rate of Plaquenil (Hydroxychloroquine) Retinal Toxicity

• The incidence rate of Plaquenil retinal toxicity varies depending on the cumulative dose and duration of treatment 3.
• A study found that among patients who had taken a cumulative dose of less than 1,250 g, 10% showed a characteristic mfERG defect, while in patients with a cumulative dosage of 1,250 g or more, 41% showed one of these defects 3.
• Another study reported that 3 out of 12 patients (25%) developed retinal toxicity with scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, as well as abnormal mfERG, after a median duration of HCQ treatment of 22.8 months 4.
• A case report described a patient who developed bilateral bull's-eye retinopathy after taking a cumulative total of 19.8 g of HCQ, highlighting the potential for retinal toxicity even at lower cumulative doses 5.

Risk Factors for Retinal Toxicity

• Known major risk factors for HCQ retinal toxicity include drug loads >300 mg/day (5 mg/kg/day), use for >5 years, a cumulative dose >1,000 g, underlying retinal disease or retinopathy, tamoxifen use, and renal disease 5.
• High-dose HCQ in patients with chronic graft-versus-host disease was associated with a higher incidence and earlier development of retinal toxicity 4.

Detection and Monitoring of Retinal Toxicity

• Multifocal ERG ring ratios provide a sensitive and objective method to detect ocular toxicity in patients taking hydroxychloroquine (Plaquenil) 3, 6.
• SD-OCT and mfERG can detect toxic damage before prominent loss of the outer nuclear layer 7.
• Regular ophthalmologic examination and ancillary studies, including colour vision, Amsler grid, fundus photographs, Humphrey 10-2 automated perimetry, SD-OCT, and mfERG, are recommended to monitor patients on HCQ therapy 4.