A 62 year old white female presented for a comprehensive eye exam. She reported good vision with her current glasses. Her medical history was relevant for chronic use of Plaquenil for the treatment of Lupus x 15 years. Retinal evaluation was unremarkable on her last visit 1 year ago. Our patient was treated with a daily dose of Plaquenil 200 mg BID throughout the years, however 2 years ago, her doctor decided to increase the dose to 400 mg BID. The patient weighs 175 pounds (79 Kg).

On examination, her BCVA was 20/20 OU, color vision was full OU and her fundus evaluation was unremarkable however, imaging showed subtle signs of maculopathy, see below.

Fundus autofluorescence shows a faint ring of hyper autofluorescence, which indicates RPE involvement.

OCT shows a classic flying saucer pattern with parafoveal fading and collapsing of outer retinal layers. Surprisingly, the en-face imaging highlighted some areas of defect as well.

Visual field shows non specific areas of defect in the right eye and a questionable ring-like pattern in the left eye.

Discussion:

Plaquenil (hydroxychloroquine) is a medication commonly used in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other connective tissue diseases. However, it’s essential to be aware of the risk of retinopathy associated with Plaquenil use.

Here are some key points regarding Plaquenil dosing and retinopathy risk:

  1. Use Real Body Weight:
    • The daily dose of Plaquenil should be 5.0 mg per kg or less, using real body weight. This represents a significant change from previous guidelines that recommended using ideal body weight.
    • Using real body weight helps avoid overdosing smaller individuals, especially since connective tissue diseases often affect women who may be slight in stature.
  2. Dose and Duration:
    • The risk of Plaquenil retinopathy depends on both the daily dose and the duration of use.
    • At recommended doses, the risk of toxicity is under 1% up to 5 years and under 2% up to 10 years. However, after 20 years of use, the risk increases to almost 20%.
    • Patients who have been taking Plaquenil for 5 or more years are at increased risk, even if they have no other risk factors.
  3. Screening Recommendations:
    • A baseline fundus examination should be performed before starting Plaquenil to rule out preexisting maculopathy.
    • Annual screening is recommended after 5 years for patients on acceptable doses and without major risk factors.
    • Screening tests include automated visual fields and OCT. These tests should look beyond the central macula, especially in Asian patients.
  4. Toxicity and Counseling:
    • Plaquenil retinopathy is not reversible, and there is no current therapy.
    • Early recognition (before any retinal pigment epithelium loss) is crucial to prevent central visual loss.
    • Patients and prescribing physicians should be informed about the risk of toxicity, proper dose levels, and the importance of regular annual screening.
  5. Take in consideration Kidney disease
    • Plaquenil is cleared by the kidneys, so renal disease can increase the risk of toxicity.
    • Patients with kidney disease may require adjusted dosages and more frequent screening due to the slower clearance of the medication.
  6. Tamoxifen Use:
    • Tamoxifen, a medication used for the long-term treatment of breast cancer, can significantly increase the risk of Plaquenil toxicity.
    • The risk is approximately 5-fold higher when tamoxifen is used concurrently with Plaquenil.
    • This may be due to tamoxifen being a retinal toxin itself, and there might be an adverse metabolic synergy between the two drugs.

Screening Recommendations

Plaquenil retinopathy cannot be reversed, proper screening is critical

  1. Baseline Fundus Examination:
    • Recommended to rule out pre existing maculopathy before starting Plaquenil therapy. Baseline visual fields and OCT are useful but not essential, unless abnormalities are present at baseline.
  2. Annual Screening:
    • Annual screening should begin after 5 years of therapy for patients on acceptable doses and without major risk factors.
  3. Screening Tests:
    • The primary screening tests are automated visual fields plus OCT.
    • These tests should look beyond the central macula, especially in Asian patients, due to the different pattern of damage that may occur.
  4. Additional Tests:
    • Multifocal electroretinogram (mfERG) and Fundus autofluorescence (FAF) can provide objective evidence to support visual fields and OCT findings.
  5. Screening asian patients:
    • Pattern of retinopathy in Asian patients is characterized by a pericentral rather than the patparafoveal (bull’s eye) pattern that is more commonly seen in other populations. Thus you should do both 10-2 and 24-2 fields.

Note: Fundus photos and direct examination are not sensitive enough for annual screening especially in early disease. Patient’s symptoms are also not a reliable indicator.

Back to our patient

This 79 Kg white female used to be on 200 mg BID for many years without showing signs of maculopathy however, her Doctor increased the dose to 400 mg BID. The recommended dosage shouldn’t exceed 5 mg per Kg, which corresponds to 397 mg for our patient based on her weight. Doubling the dose from 400 mg daily to 800 mg clearly exceeded the recommended amount and caused retinopathy. Our patient was also using Plaquenil for 15 years which is an additional risk factor that could have contributed to the onset of the  retinopathy. Coordination was made with her prescribing physician to discuss dosage adjustment.

Please note that Hydroxychloroquine is a remarkable drug in the management of patients with SLE, RA or other connective tissues disorders. It is a safe drug if used at recommended dosage and it is often safer compared to alternatives such as steroids or immunosuppressives.

I hope you guys enjoyed, and I’ll see you on the next one!

Case seen at Retina Consultants of Miami