Recent Posts
Connect with:
Monday / July 15.
HomemipatientSaving Sally: A Case of Plaquenil Retinopathy

Saving Sally: A Case of Plaquenil Retinopathy

The anti-malarial drug plaquenil has anti-inflammatory properties and is commonly used for autoimmune conditions, however it can lead to retinal toxicity, resulting in irreversible vision loss.

Sally*, a 67-year-old female, presented to the practice for routine optometric management. She had been taking plaquenil (Hydroxychloroquine) for the past two years for lichen planopilaris (fibrosing alopecia). Her dosage was 400mg in the morning and 200mg in the evening. Sally is a petite woman weighing only 41kg.

Upon presentation, Sally’s unaided vision was R & L 6/7.5, correcting to R & L 6/6 with a mild hyperopic astigmatic correction.

…plaquenil can lead to retinal toxicity, resulting in irreversible vision loss

Figure 1 and 2. Fundus photographs revealing no abnormalities (right and left).

As Sally was on plaquenil, mydriatic fundus examination with optical coherence tomography (OCT) and central visual field examination was performed six monthly. She was also given an Amsler grid and was instructed to use it to test her vision at home daily.

After two years, or four years of cumulative 600mg daily dosage of plaquenil, Sally returned, distressed, having noted a defect in her Amsler grid. She reported reduced vision which produced a bull’s eye effect with a paracentral scotoma and clear centre in both eyes, L>R.

Vision unaided was R 6/9=.

Best corrected visual acuities were reduced to R & L 6/7.5.

Mydratic fundus examination revealed no abnormalities, with healthy optic nerves, maculae and blood vessels (Figures 1 and 2). OCT revealed paracentral thinning of the macula, L>R (Figure 3). Visual field examination revealed a mild central scotoma (Figure 4).

Figure 3. OCT showing paracentral thinning of the macula.

Plaquenil was ceased immediately, and Sally has continued to be monitored. Her visual field scotoma worsened at the next review (Figure 5), but fortunately over the past four years, there has been no progression in her visual field defect or changes in OCT.


Plaquenil is an anti-malarial drug belonging to a class of medications known as disease-modifying antirheumatic drugs. An immunomodulatory, it is used to manage a broad spectrum of autoimmune conditions including rheumatoid arthritis and systemic lupus erythematous. Recently, it has been studied for the treatment and prevention of COVID-19, with the likes of former US President Donald Trump famously advocating for its use to protect against COVID-19, however there is currently very limited data to support its effectiveness.1

Common side effects of plaquenil are nausea, diarrhoea and muscle weakness, however it may also adversely affect the eye, involving the cornea and the retina. Corneal manifestations result in deposits of salt within the corneal epithelium, resulting in cornea verticillata, or vortex keratopathy. These findings are normally innocuous, rarely affecting vision, and are reversible upon cessation of plaquenil.

Figure 4. Visual field examination – mild central scotoma.

More seriously, plaquenil can lead to retinal toxicity, resulting in irreversible vision loss. The mechanism of plaquenil toxicity is not completely understood, however it is thought that the drug molecule binds to the melanin in the retinal pigment epithelium (RPE) resulting in metabolic changes and toxic effects to the photoreceptors, outer nuclear and plexiform layer, but preserving the inner retina, and sparing the foveal centre. As the disease becomes more advanced, this will manifest as a ‘bull’s eye’ appearance at the macula.

In the early stages, patients are often asymptomatic, however as the toxicity progresses, patients may be symptomatic, with reduced vision, changes in colour perception and paracentral scotomas. As the toxicity is irreversible, it is crucial to detect toxicity early to limit the degree of visual loss.

This adverse effect has been considered rare, with an estimated occurrence in 0.5% – 2.0% of long-term users.3 However, more recent studies indicate that the risk is in fact much higher, with the most significant risk factors being dosage based on body weight and duration of treatment. The risk of toxicity is lower for patients on a dose less than 5.0mg/kg body weight. Patients taking a dose higher than 5.0mg/kg had a 10% risk of retinal toxicity within 10 years of treatment, and almost 40% risk after 20 years. Important to note is that there is no safe level of use, particularly after prolonged use. The annual risk for patients on a dosage of less than 5.0mg/kg is less than 1%, however increases to 4% after 20 years.4

Figure 5. Visual field – slight worsening of scotoma.

The risk of retinopathy increases with duration of use as plaquenil has a long halflife of 40 to 60 days and is cleared slowly from the body. It accumulates in the RPE cells leading to progressive retinopathy, even after its usage is ceased.3-4

Other risk factors for toxicity include renal disease, age, use of tamoxifen and co-existing macula disease. Plaquenil is mainly cleared by the kidneys, so impaired renal function will result in reduced clearance of the drug, leading to its greater concentration and subsequent toxicity. Older age and concurrent macular disease is believed to lead to susceptible or predamaged retinal cells.


The current recommendations for plaquenil dosage to reduce risk of toxicity is less than 5.0mg/kg per day. Sally, as mentioned, is a meagre 41 kilograms, which equates to a dosage of less than 205mg per day. She was on 600mg, i.e. almost three times more, or 14.6mg/kg, so it was not surprising that she experienced toxicity, even on a relatively short duration of treatment. Fortunately, as her disease was detected early with a relatively short duration of treatment, she has avoided severe visual loss, and a few years later, continues to remain stable.

*Patient name changed for anonymity. 

Jessica Chi is the director of Eyetech Optometrists, an independent speciality contact lens practice in Melbourne. She is the current Victorian, and a past national president of the Cornea and Contact Lens Society, and an invited speaker at meetings throughout Australia and beyond. She is a clinical supervisor at the University of Melbourne, a member of Optometry Victoria Optometric Sector Advisory Group and a Fellow of the Australian College of Optometry and the British Contact Lens Association. 


  1. Singh B, Ryan H et al. Chloroquin or hydroxychloroquine for prevention and treatment of COVID-19. Cochrane Database of Systematic Reviews 2021, 2:CD013587.
  2. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16:155-166.
  3. Wolfe F, Marmor MF.  Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus.  Arthritis Care Res (Hoboken). 2010;62(6):775-784.
  4. Melles, Ronald B, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 2014;12:1453–1460.