Nonleaking Cystoid Macular Edema as a Presentation of Hydroxychloroquine Retinal Toxicity

Parikh, Vishal S.; Modi, Yasha S.; Au, Adrian; Ehlers, Justis P.; Srivastava, Sunil K.; Schachat, Andrew P.; Singh, Rishi P.

doi:10.1016/j.ophtha.2015.09.011

Cited by 20 publications

(22 citation statements)

References 5 publications

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“…Despite the fact that a series of studies and case reports [ 79 – 86 ] have found that HCQ could increase the risk of retinopathy, this review has demonstrated that the pooled incidence of ophthalmic AEs occurring in the HCQ group was not significantly increased compared with the control group and only two specified retinopathies [ 51 , 62 ] were reported in the eligible studies. This observation might be accounted for by the fact that the follow-up periods of the randomized studies included in this review were not long enough.…”

Section: Discussionmentioning

confidence: 85%

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

Chen

Pan

et al. 2020

Eur J Clin Pharmacol

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Introduction Many concerns still exist regarding the safety of hydroxychloroquine (HCQ) in the treatment of Coronavirus Disease 2019 (COVID-19). Objectives The purpose of this study was to evaluate the safety of HCQ in the treatment of COVID-19 and other diseases by performing a systematic review and meta-analysis. Methods Randomized controlled trials (RCTs) reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved starting from the establishment of the database till June 5, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. Results We identified 53 eligible studies involving 5496 patients. The meta-analysis indicated that the risk of adverse effects (AEs) in the HCQ group was significantly increased compared with that in the control group (RD 0.05, 95%CI, 0.02 to 0.07, P = 0.0002), and the difference was also statistically significant in the COVID-19 subgroup (RD 0.15, 95%CI, 0.07 to 0.23, P = 0.0002) as well as in the subgroup for other diseases (RD 0.03, 95%CI, 0.01 to 0.04, P = 0.003). Conclusions HCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population. Given the small number of COVID-19 participants included, we should be cautious regarding the conclusion stating that HCQ is linked with an increase incidence of AEs in patients with COVID-19, which we hope to confirm in the future through well-designed and larger sample size studies. Electronic supplementary material The online version of this article (10.1007/s00228-020-02962-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 85%

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

Chen

Pan

et al. 2020

Eur J Clin Pharmacol

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“…Intracellular swelling of the retina may occur primarily with certain kinds of intoxication and in the margins of hypoxic/ischemic damage, where breakdown of the BRB is a secondary event [15] . Vasogenic edemas, which are by far the most frequent, are those in which the primary defect is in the BRB, leading to abnormal accumulation of extracellular fluid.…”

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confidence: 99%

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture

Cunha-Vaz

2017

Ophthalmologica

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Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels. A major role of active transport processes was also identified. Today, the BRB is understood to play a fundamental role in retinal function in both health and disease. Retinal edema, an ubiquitous manifestation of retinal disease, is directly associated with breakdown of the BRB and with vision loss. In its most common form (i.e., vasogenic edema), due to breakdown of the BRB, Starling's law of capillary filtration may be used to interpret the mechanisms of fluid accumulation in the retina. The main factors involved in the development of retinal edema are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. In the clinical environment, breakdown of the BRB has been identified by fluorescein angiography and vitreous fluorometry, requiring the intravenous administration of fluorescein. An OCT-based method, OCT-Leakage, recently introduced by our group is capable of noninvasively identifying and quantifying sites of alteration of the BRB by mapping areas of lower-than-normal optical reflectivity, thus reflecting changes in the retinal extracellular fluid. We found good correspondence between the location of increased areas of low optical reflectivity identified by OCT-Leakage and the main sites of leakage on fluorescein angiography. Furthermore, with OCT-Leakage the areas of abnormal fluid accumulation can be identified in specific retinal layers, clearly offering more information than previously obtained with fluorescein angiography. OCT angiography has become available, replacing much of the information yielded by fluorescein angiography in a noninvasive manner. However, OCT angiography cannot visualize the leakage, i.e., the alteration of the BRB. OCT-Leakage is able to identify the locations of increases in extracellular fluid in the different layers of the retina. The complementarity of these 2 methods is of potential great interest for the diagnosis and management of several retinal diseases in which the presence and amount of fluid, as a marker of severity and activity, is paramount to treatment and management decisions in clinical practice.

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“…It is associated with various forms of retinopathy including photoreceptor damage, bull's eye maculopathy via RPE damage, and even diffuse retinal atrophy; these effects are related to dosage and duration of treatment 19 , 20 . HCQ has also been reported to be associated with leaking 21 as well as non-leaking 22 CME with 12 cases reported. Although the mechanism of HCQ-induced CME is not well understood, it may be by inducing Increased RPE permeability subsequently causing partial loss of blood retinal barrier (BRB) but without affecting tight junction molecules expression 23 .…”

Section: Discussionmentioning

confidence: 99%

Docetaxel-induced maculopathy possibly potentiated by concurrent hydroxychloroquine use

Elhusseiny

Relhan

Smiddy

2019

American Journal of Ophthalmology Case Reports

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PurposeTo report a case of bilateral non-leaking cystoid macular degeneration induced by docetaxel, possibly potentiated by hydroxychloroquine.ObservationsA 63-year-old female patient with a long-term history of rheumatoid arthritis controlled on hydroxychloroquine for 33 years with no evidence of retinopathy developed bilateral loss of vision after having been on docetaxel chemotherapy for breast cancer. Optical coherence tomography showed bilateral cystic maculopathy with no angiographic evidence of leakage on fluorescein angiography. The patient was treated conservatively with no further interventions. Marked improvement of the macular degeneration occurred over the subsequent 9 months, but without visual improvement, although a cataract likely confounded final visual acuity measurement.Conclusions and importanceDocetaxel-induced maculopathy has been previously reported, but with only four case reports in literature, and most often in conjunction with concurrent therapies or conditions also known to cause macular edema. This is the first case report of docetaxel-induced maculopathy in a setting of hydroxychloroquine therapy which may possibly has potentiated the effect of docetaxel to induce maculopathy. Impaired transcellular retinal pigment epithelial transport might be the cause of non-leaking cystic maculopathy.

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Nonleaking Cystoid Macular Edema as a Presentation of Hydroxychloroquine Retinal Toxicity

Cited by 20 publications

References 5 publications

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials

The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture

Docetaxel-induced maculopathy possibly potentiated by concurrent hydroxychloroquine use

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