American Journal of Clinical and Experimental Medicine
Volume 8, Issue 5, September 2020, Pages: 84-87
Received: Aug. 13, 2020;
Accepted: Aug. 31, 2020;
Published: Sep. 30, 2020
Views 109 Downloads 52
Daniel Choi, Department of Ophthalmology, University of Pennsylvania, Philadelphia, United States
Stephen Orlin, Department of Ophthalmology, University of Pennsylvania, Philadelphia, United States
Taylor Linaburg, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Vivian Lee, Department of Ophthalmology, University of Pennsylvania, Philadelphia, United States
The application of chloroquine has been expanded over time from the treatment of malaria to a variety of connective tissue, inflammatory, and dermatologic disorders. More recently, chloroquine and its derivative, hydroxychloroquine, have been investigated for its possible application against SARS-CoV-2 due to their antiviral properties. We present a case of a patient receiving chloroquine as adjuvant therapy for glioblastoma multiforme who developed significant keratopathy and review this overlooked entity in view of the resurgence of this enduring medication. A 48-year-old woman with a history of Marfan syndrome presented with a five-day history of pain and discomfort in her right eye. She had a history of glioblastoma multiforme that had been treated with surgical resection, radiation, and chemotherapy and was currently undergoing adjuvant treatment with chloroquine and cimetidine. Her exam was notable for decreased visual acuity, bilateral epithelial erosions, multiple subepithelial white dots in a whorl-like distribution, and decreased corneal sensation. These corneal changes reversed following cessation of chloroquine. While chloroquine related retinopathy is reported frequently in the literature, the corneal changes related to chloroquine have been less frequently discussed. With the resurgence of interest in using chloroquine and hydroxychloroquine as therapy for SARS-CoV-2 due to their promising in-vitro activity against the virus [1, 2], corneal toxicity is an important side effect to identify and monitor.
Case Report: Chloroquine Induced Keratopathy – Toxicity from Systemic Use, American Journal of Clinical and Experimental Medicine.
Vol. 8, No. 5,
2020, pp. 84-87.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30 (3): 269-71.
Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020; 6: 16.
Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LCP, Veiga VC, Avezum A, et al. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. N Engl J Med. 2020.
Arshad S, Kilgore P, Chaudhry ZS, Jacobsen G, Wang DD, Huitsing K, et al. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis. 2020; 97: 396-403.
Al-Bari MA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015; 70 (6): 1608-21.
Costedoat-Chalumeau N, Dunogue B, Leroux G, Morel N, Jallouli M, Le Guern V, et al. A Critical Review of the Effects of Hydroxychloroquine and Chloroquine on the Eye. Clin Rev Allergy Immunol. 2015; 49 (3): 317-26.
Hobbs HE, Sorsby A, Freedman A. Retinopathy following chloroquine therapy. Lancet. 1959; 2 (7101): 478-80.
Easterbrook M. Is corneal deposition of antimalarial any indication of retinal toxicity? Can J Ophthalmol. 1990; 25 (5): 249-51.
Wyler DJ. Landmark perspective: The ascent and decline of chloroquine. JAMA. 1984; 251 (18): 2420-2.
Calkins LL. Corneal epithelial changes occurring during chloroquine (aralen) therapy. AMA Arch Ophthalmol. 1958; 60 (6): 981-8.
Sotelo J, Briceno E, Lopez-Gonzalez MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2006; 144 (5): 337-43.
Bernstein HN. Chloroquine ocular toxicity. Surv Ophthalmol. 1967; 12 (5): 415-47.
Mason CG. Ocular accumulation and toxicity of certain systemically administered drugs. J Toxicol Environ Health. 1977; 2 (5): 977-95.
Percival SP, Meanock I. Chloroquine: ophthalmological safety, and clinical assessment in rheumatoid arthritis. Br Med J. 1968; 3 (5618): 579-84.
Slowik C, Somodi S, von Gruben C, Richter A, Guthoff R. [Detection of morphological corneal changes caused by chloroquine therapy using confocal in vivo microscopy]. Ophthalmologe. 1997; 94 (2): 147-51.
Ma X, He L, He D, Xu J. Chloroquine keratopathy of rheumatoid arthritis patients detected by in vivo confocal microscopy. Curr Eye Res. 2012; 37 (4): 293-9.
Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF, American Academy of O. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology. 2002; 109 (7): 1377-82.
Muller-Hocker J, Schmid H, Weiss M, Dendorfer U, Braun GS. Chloroquine-induced phospholipidosis of the kidney mimicking Fabry's disease: case report and review of the literature. Hum Pathol. 2003; 34 (3): 285-9.
Seiler KU, Thiel HJ, Wassermann O. [Chloroquine keratopathy as an example of drug-induced phospholipidosis (contribution to the pathogenesis of cornea verticillata) (author's transl)]. Klin Monbl Augenheilkd. 1977; 170 (1): 64-73.
Lefranc F, Yeaton P, Brotchi J, Kiss R. Cimetidine, an unexpected anti-tumor agent, and its potential for the treatment of glioblastoma (review). Int J Oncol. 2006; 28 (5): 1021-30.
Ette EI, Brown-Awala EA, Essien EE. Chloroquine elimination in humans: effect of low-dose cimetidine. J Clin Pharmacol. 1987; 27 (10): 813-6.
Krachmer JH, Mannis MJ, Holland EJ. Cornea: 2-Volume Set with DVD (Expert Consult: Online and Print), 3e. 3rd ed. Mosby; 2010.