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Covid-19: six million doses of hydroxychloroquine donated to US despite lack of evidence

BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m1166 (Published 23 March 2020) Cite this as: BMJ 2020;368:m1166

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Use of hydroxychloroquine for COVID-19: risk of ocular toxicity

Dear Editor,

Hydroxychloroquine causes ocular toxicity. It is not clear what role hydroxychloroquine plays in the management of COVID-19, and despite endorsement by the US President and surges in worldwide demand there remains a limited evidence base. What we do know is the damaging effect of hydroxychloroquine on vision, ranging from mild keratopathy to potentially blinding retinopathy.

There is a longstanding awareness of the damage caused by use of hydroxychloroquine; recent guidance from the UK Royal College of Ophthalmologists (RCOphth) suggests the incidence of retinal toxicity was previously significantly underestimated.[1] Risk factors for ocular toxicity include duration of use, dose (>5 mg/kg per day), pre-existing retinal disease, renal impairment and those taking Tamoxifen.[2]

The American Academy of Ophthalmology (AAO) and RCOphth recommend a maximum daily dose of 5 mg/kg (400 mg in an 80 kg person). Hydroxychloroquine is available in 200 or 400 mg film-coated tablets, and the usual maximum daily dose when treating various rheumatological and dermatological conditions is 400 mg. There has been ongoing concern that due to the inflexibility in dosing many have been incorrectly overprescribed medication.

Prolonged use of hydroxychloroquine at recommended doses increases your risk of ocular toxicity, however there is also evidence that high doses can lead to rapid changes to vision.[3,4] The recent studies linking hydroxychloroquine treatment to viral load reduction in COVID-19 patients did so with high dose treatment, either a 600 mg daily dose or 1000 mg daily dose.[5–7]

When hydroxychloroquine retinopathy results in noticeable vision loss, the damage to the retina is generally irreversible, and may progress even after cessation of therapy. The need to detect early pre-clinical signs of retinopathy has led to widespread screening campaigns. The AAO and RCOphth recommend a baseline examination and screening, including 10-2 Humphrey visual field testing and imaging with spectral domain optical coherence tomography (SD-OCT) and widefield fundus autofluorescence imaging (FAF).

A pandemic is an uncertain time; we have already seen the damaging effects misinformation brings. With hydroxychloroquine now at the centre of the media’s attention we must ensure people are fully informed to the risk of irreparable damage to vision. In addition, as optometrist services are reduced to halt the spread of infection and ophthalmology services are actively repurposed in preparation for the high volume of COVID-19 patients, we must ensure there are adequate screening services available for those that will inevitably take hydroxychloroquine at incorrect doses or with co-existing risk factors. These are difficult circumstances, but there are examples of hydroxychloroquine retinopathy screening services focused around virtual clinics and reviews that may be utilised during this viral pandemic.[8]

References

1 The Royal College of Ophthalmologists. Hydroxychloroquine and Chloroquine Retinopathy: Recommendations on Screening. February 2018. https://www.rcophth.ac.uk/2018/03/rcophth-guideline-hydroxychloroquine-a... [Accessed 25th March 2020].

2 The Royal College of Ophthalmologists. Hydroxychloroquine and Chloroquine Retinopathy: Recommendations on Monitoring. January 2020. https://www.rcophth.ac.uk/wp-content/uploads/2020/02/HCR-Recommendations... [Accessed 25th March 2020].

3 Navajas EV, Krema H, Hammoudi DS, et al. Retinal toxicity of high-dose hydroxychloroquine in patients with chronic graft-versus-host disease. Can J Ophthalmol 2015;50(6):442-50.

4 Leung LS, Neal JW, Wakelee HA, Sequist LV, Marmor MF. Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy. Am J Ophthalmol 2015;160(4):799–805e1.

5 Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020:105932. [Epub ahead of print]

6 Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020;14(1):72-73.

7 Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;105949. [Epub ahead of print]

8 Zaidi FH, Rennie CA, Drinkwater AK, Sahu D, Akyol E, Lotery AJ. How to set up a Hydroxychloroquine Retinopathy Screening Service. Eye (Lond) 2019;33(11):1679–1682.

Competing interests: No competing interests

25 March 2020
David McMaster
Medical Student
University of Nottingham
Queen's Medical Centre, Nottingham, UK, NG7 2UH