Chloroquine is a potent drug used for the treatment of various diseases, including malaria and a range of connective tissue disorders. Chloroquine retinopathy is an important complication that may appear even years after cessation of the drug, presenting with impaired visual acuity, central vision loss and progressive damage that could result in irreversible blindness. A detailed patient history that confirms chloroquine use is essential, while advanced ophthalmologic methods must be employed to assess the status of the retina.
Chloroquine (and hydroxychloroquine) are drugs with still incompletely understood mechanisms of action, but their ability to alter intracellular pH, suppress CD4+ T-cells activity and promote the activation of CD8+ T-cells makes them useful in an array of disorders of different etiologies  . In the tropical parts of the world, chloroquine is a potent antimalarial agent (both in therapy and in prophylaxis), whereas autoimmune connective tissue diseases, such as systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), and Sjogren's syndrome are also treated with chloroquine, primarily to achieve long-term suppression    . Its affinity for pigmented tissues , however, is the principal reason why chloroquine retinopathy is one of the most important, but also most feared complications when using this drug. As a consequence of progressive chloroquine accumulation in the retinal pigment epithelium and the retinal neurons  , where it exerts its toxic effects, various visual symptoms may be encountered even years after cessation of drug use, as the body excretes chloroquine through urine for a long period of time . The "bull's eye" maculopathy is considered to be a pathognomonic finding of chloroquine retinopathy, manifesting as loss of central vision, while night blindness, reduced visual acuity, photoaversion, reading difficulties, and other visual deficits (eg. color blindness, scotomas) are some of the most frequent symptoms reported in chloroquine retinopathy     . In a significant proportion of individuals who develop this complication, progression toward blindness in an irreversible fashion can be observed, due to the severe damage of photoreceptors and the retinal epithelium .
Entire Body System
Chen E, Brown DM, Benz MS, Fish RH, Wong TP, Kim RY, et al. Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the “flying saucer” sign). Clin Ophthalmol 2010;4:1151-8. 16. [kjophthal.com]
Chen E, Brown DM, Benz MS, Fish RH, Wong TP, Kim RY, et al. Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign). Clin Ophthalmol 2010;4:1151-8. 12. [ijo.in]
- Short Stature
While most rheumatologists are now routinely prescribing their patients 400 mg of HCQ (or 250 mg CQ) daily for the management of conditions like systemic lupus erythematosus and rheumatoid arthritis, individuals of short stature often have their dosage [newgradoptometry.com]
stature, as these doses may be too great and will elevate the risk for maculopathy. 5 In these situations, the correct dose should be calculated based on height and ideal weight, with 6.5 mg/kg/day being the cut-off for HCQ, and 3.0 mg/kg/day for CQ. [optometry.org.au]
We aspire that larger clinical studies will be performed, focusing on various SD-OCT indices, in order to better evaluate earlier detection methods for HCQ retinopathy. [ijo.in]
Buffer was immediately aspirated. Cells from each well were rinsed twice with 1 ml of ice-cold buffer containing unlabeled thiamine, digested with 0.25 ml of 1 N NaOH for 2 hours, and neutralized with 0.25 ml of 1 N HCl. [journals.plos.org]
- Heart Block
Patients with heart block of unknown cause should have their fundi examined so that signs of chloroquine retinopathy may be sought. [ncbi.nlm.nih.gov]
Chloroquine abuse and heart block in Africans. Aust N Z J Med 1989; 19 (1): 17–21. 6. Ezedinachi EN, Ejezie GC, Emeribe AO. Problems of chloroquine-resistant P. falciparum in Nigeria: one antimalaria drugs' utilisation in metropolitan Calabar. [nature.com]
block, conduction disorders [ Ref ] Electrocardiographic changes observed included prolongation of the QRS interval and, rarely, complete heart block. [drugs.com]
- Retinal Pigmentation
The major retinal findings are those of macular retinal pigment epithelial changes, narrowed retinal vessels, and scotomatous visual field defects. [ncbi.nlm.nih.gov]
- Background Retinopathy
retinopathy and retinal vascular changes 2016 2017 2018 2019 Non-Billable/Non-Specific Code Code Also any associated hypertension ( I10.- ) Background retinopathy and retinal vascular changes Approximate Synonyms Bilateral hydroxychloroquine retinopathy [icd10data.com]
Abstract A survey of Canadian ophthalmologists and rheumatologists suggests that there is a significant incidence of definite chloroquine retinopathy in their patients. [ncbi.nlm.nih.gov]
Some physicians suggest that lean body weight is more accurate when calculating daily dosage.Most patients are routinely given 400 mg of hydroxychloroquine daily (or 250 mg chloroquine). This dose is considered acceptable. [en.wikipedia.org]
The purpose of this consultation is to obtain suggestions of additional sources of evidence which the GDG may wish to consider, or alternative interpretation of the evidence leading to a rephrasing or amendment of the recommendations. [rcophth.ac.uk]
There have been suggestions that some patients have a genetic predisposition to HCQ toxicity (e.g., from abnormalities in the ABCA4 gene), 23 but a new report suggests that some nonpathogenic ABCA 4 polymorphisms actually may be protective. 24 Polymorphisms [aao.org]
Because chloroquine retinopathy might result in blindness without proper monitoring and follow-up, the appearance of visual complaints must alert the physician to conduct a detailed patient history to confirm either current or previous use of chloroquine, regardless of the underlying etiology. Furthermore, many reports have stressed the need for continuous follow-ups and screening of individuals who are taking chloroquine with several ophthalmologic procedures    . Firstly, a meticulous physical examination that includes visual field and acuity testing, together with anterior fundoscopy, should be the first step in workup, where typical findings of chloroquine retinopathy (pigmentary changes, bull's eye maculopathy, retinal degeneration, atrophy of the optic nerve) may be initially seen  . Once a presumptive diagnosis is made, various specialized procedures are used for confirming the clinical suspicion. Spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinography, and fundus autofluorescence (FAF) are recommended for screening and detection of retinal changes associated with chloroquine retinopathy   .
- Mahon GJ, Anderson HR, Gardiner TA, McFarlane S, Archer DB, Stitt AW. Chloroquine causes lysosomal dysfunction in neural retina and RPE: implications for retinopathy. Curr Eye Res. 2004;28(4):277-284.
- Tangtavorn N, Yospaiboon Y, Ratanapakorn T, et al. Incidence of and risk factors for chloroquine and hydroxychloroquine retinopathy in Thai rheumatologic patients. Clin Ophthalmol. 2016;10:2179-2185.
- Oluleye TS, Babalola Y, Ijaduola M. Chloroquine retinopathy: pattern of presentation in Ibadan, Sub-Sahara Africa. Eye (Lond). 2016;30(1):64-67.
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- Bae EJ, Kim KR, Tsang SH, Park SP, Chang S. Retinal Damage in Chloroquine Maculopathy, Revealed by High Resolution Imaging: A Case Report Utilizing Adaptive Optics Scanning Laser Ophthalmoscopy. Korean J Ophthalmol. 2014;28(1):100-107.
- Michaelides M, Stover NB, Francis PJ, Weleber RG. Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy. Arch Ophthalmol. 2011;129(1):30-39.
- Mavrikakis M, Papazoglou S, Sfikakis PP, et al. Retinal toxicity in long term hydroxychloroquine treatment. Ann Rheum Dis. 1996;55:187–189.
- Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016;123(6):1386-1394.
- Tsang AC, Ahmadi Pirshahid S, Virgili G, Gottlieb CC, Hamilton J, Coupland SG. Hydroxychloroquine and chloroquine retinopathy: a systematic review evaluating the multifocal electroretinogram as a screening test. Ophthalmology. 2015;122(6):1239-1251.e4.