Hydroxychloroquine-induced Retinal Toxicity

Abstract

Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.

New proposal for a multimodal imaging approach for the subclinical detection of hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus

“…Modern imaging allows for more objective classification of retinopathy by severity and pattern, but variations in the interpretation of these tests still contribute to inconsistencies in toxicity definitions. 34 Allahdina et al proposed a new staging system based on OCT findings: stage 1 includes minor changes limited to the parafoveal region; stage 2 includes clear localised changes in the parafoveal region; stage 3 includes extensive parafoveal changes; and stage 4 includes foveal involvement. While this system is primarily applicable to eyes with parafoveal retinopathy, these stages have been functionally related to visual acuity, visual field test results or mfERG and are significantly associated with the degree of further progression.…”

Application of SS- OCTA to evaluate the effects of long- term hydroxychloroquine treatment on retinal structure and microcirculation in patients with systemic lupus erythematosus

“…Due to the presence of antiendothelial antibodies in systemic lupus erythematosus, complement-mediated cytotoxicity causes vascular endothelial cell damage, resulting in microvascular dysfunction that can affect blood vessels anywhere in the body [10]. Although HCQ has a favorable safety pro le as a rst-line agent for SLE at present, current studies have shown that 7.5 percent of all patients taking the drug long-term have retinopathy, and its prevalence increases with the duration of treatment and the increase in the dose per kilogram of body weight [11,12].…”

A Case of Hydroxychloroquine Toxicity as Evidenced by Visual Field Changes

“…It has immunomodulatory actions that reduce inflammation and immune activation [ 3 ]. The anti-inflammatory effect is likely due to a decrease in cytokine production through alteration of transcription, specifically interleukins IL-6 and IL1β [ 4 ]. In patients with lupus, hydroxychloroquine therapy reduces organ damage, the risk of infection, and the risk of thrombosis [ 3 ].…”

“…Other risk factors include age over 60 years old, kidney or liver disease, or an existing retinal disease [ 1 ]. Hydroxychloroquine retinopathy is typically described as bull’s eye maculopathy caused by parafoveal mottling of the retinal pigment epithelium (RPE) [ 4 ]. On optical coherence tomography (OCT) imaging, loss of photoreceptor layers beginning in the ellipsoid zone may be seen [ 4 ].…”

“…Hydroxychloroquine retinopathy is typically described as bull’s eye maculopathy caused by parafoveal mottling of the retinal pigment epithelium (RPE) [ 4 ]. On optical coherence tomography (OCT) imaging, loss of photoreceptor layers beginning in the ellipsoid zone may be seen [ 4 ]. In patients of Asian descent, the retinal toxicity may be outside of the macula initially [ 5 ].…”