What can visual caregivers expect with patients treated for SARS-CoV-2? An analysis of ongoing clinical trials and ocular side effects.

Within the COVID-19 pandemic context, the WHO has proposed a list of medicines to treat patients with severe acute respiratory syndrome (SARS-CoV-2). An analysis of their ocular side effects was performed. Only chloroquine and hydroxychloroquine were found to have an ocular impact in the medium and long-term. Detailed search strategies were performed in EMBASE, MEDLINE, SCOPUS and WOS Core Collection. Additionally, the worldwide ongoing clinical trials including chloroquine or hydroxychloroquine were evaluated, and their proposals of drug administration and exclusion criteria analyzed. In general, high maximum cumulative doses of chloroquine or hydroxychloroquine are being used for a short period in 135 currently underway clinical trials (to 21st April 2020). Typically, the doses were 2 to 5 times greater than the AAO recommendation (adjusted to weight) to avoid toxic retinopathy, the most undesirable ocular side effect. Maximum cumulative doses up to 12,000 mg for chloroquine and 18,000 mg for hydroxychloroquine were found. In prophylaxis clinical trials, 72,000 mg and 22,500 mg were the maximum cumulative doses for hydroxychloroquine and chloroquine respectively. Only 48% of the clinical trials considered retinal impairment as an exclusion criterion, and just one referred to an ophthalmic examination previous to study inclusion. How chloroquine and hydroxychloroquine treatment affect patients with a previous retinal condition is still poorly understood. A comprehensive ophthalmological examination 6 months after treatment is recommended in this subgroup. This review provides an overview of this topic and sheds light on the challenges visual caregivers may face regarding these repurposed drugs.

Hydroxychloroquine and chloroquine retinal safety concerns during COVID-19 outbreak.

PURPOSE: The current coronavirus disease 2019 (COVID-19) has been declared by the World Health Organization a global pandemic. Chloroquine (CQ) and hydroxychloroquine (HCQ) have been largely adopted in the clinical setting for the management of SARS-CoV-2 infection; however, their known retinal toxicity has raised some safety concerns, especially considering the higher-dosage employed for COVID-19 patients as compared with their suggested posology for their usual indications, including systemic lupus erythematosus and other rheumatic diseases. In this review, we will discuss the optimal dosages recommended for COVID-19 patients when treated with HCQ and CQ. METHODS: A comprehensive literature search was performed in PubMed, Cochrane library, Embase and Scopus, by using the following search terms: "chloroquine retinal toxicity" and "hydroxychloroquine retinal toxicity" alone or in combination with "coronavirus", "COVID-19", " SARS-CoV-2 infection " from inception to August 2020. RESULTS: Although there is still no consistent evidence about HCQ/CQ retinal toxicity in patients with COVID-19, these possible drug-related retinal adverse events may represent a major safety concern. For this reason, appropriate screening strategies, including telemedicine, should be developed in the near future. CONCLUSION: A possible future clinical perspective for patients with COVID-19 treated with HCQ/CQ could reside in the multidisciplinary collaboration between ophthalmologists monitoring the risk of HCQ/CQ-related retinal toxicity and those physicians treating COVID-19 infection.

Chloroquine and Hydroxychloroquine Retinal Toxicity Consideration in the Treatment of COVID-19.

The proposed doses of chloroquine (CQ) and hydroxychloroquine (HCQ) for treatment of COVID-19 (1000 mg/day for 10 days, CQ; 800 mg first day then 400 mg/day for 5 days, HCQ) in many guidelines worldwide, are considerably higher than the maximum recommended daily safe doses of both agents (≤2.3 mg/kg/day, CQ; ≤5.0 mg/kg/day, HCQ) for development of retinal toxicity. Irreversible retinal damage can occur if the exposure to the safe doses is >5 years. It is not known whether exposure to high doses over a short period of time can also cause the damage. We recommend that before prescribing CQ or HCQ, history of ocular disease should be obtained to avoid the prescription if appropriate. If either agent is to be used, routine baseline ocular examination is not absolutely necessary. Patients who do not have ocular disease should also be informed about the potential risk of retinal toxicity. Both agents, however, have not yet been proven to be beneficial to COVID-19.