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Chloroquine Retinopathy

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.


Presentation

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 [1] [2]. 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 [2] [3] [4] [5]. Its affinity for pigmented tissues [5], 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 [1] [5], 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 [5]. 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 [2] [3] [5] [6] [7]. 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 [2].

Physician
  • Patients and their primary care physicians must be made fully aware of the ophthalmic risks and the need for regular screening examinations to detect retinal toxicity at an early stage.[en.wikipedia.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[symptoma.com]
  • All cases arose because of failure by physicians to avoid dosing above published safe levels. Five cases developed despite accepted ophthalmologic patterns of screening for toxicity.[ncbi.nlm.nih.gov]
  • This book is a “must-have” resource for physicians who use these drugs.[books.google.com]
Fishing
  • 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]
Aspiration
  • 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]
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]
  • 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[symptoma.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]
  • 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[symptoma.com]
Central Scotoma
  • scotoma in both eyes.[doi.org]
  • Paracentral scotomas typically manifest first, affecting saccades in reading. 5 Central scotomas and a decrease in acuity can also result if toxicity spreads towards the fovea. 5,6 Spectral domain ocular coherence tomography (SD-OCT), multifocal electroretinogram[optometry.org.au]
  • Humphrey 10-2 visual fields can demonstrate (para)central scotomas [1] . Multifocal electroretinogram may show “moat around a small hill” appearance [4] .[eyewiki.aao.org]
  • It is marked by paracentral and central scotoma and decreased color vision.[journalretinavitreous.biomedcentral.com]
  • Patients usually complain about blurred vision, with visual acuity from 0.8 to 0.3 (right eye) and 0.4 (left eye), a central scotoma is present and fundus-examination shows a typical bull's-eye maculopathy.[ispub.com]
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]
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]
Suggestibility
  • 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]
Fear
  • 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.[symptoma.com]

Workup

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 [2] [3] [4] [8]. 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 [2] [3]. 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 [4] [8] [9].

Plasmodium Falciparum
  • Return of widespread chloroquine-sensitive Plasmodium falciparum to Malawi. J Infect Dis 2014; 210 (7): 1110–1114.[nature.com]
Central Scotoma
  • scotoma in both eyes.[doi.org]
  • Paracentral scotomas typically manifest first, affecting saccades in reading. 5 Central scotomas and a decrease in acuity can also result if toxicity spreads towards the fovea. 5,6 Spectral domain ocular coherence tomography (SD-OCT), multifocal electroretinogram[optometry.org.au]
  • Humphrey 10-2 visual fields can demonstrate (para)central scotomas [1] . Multifocal electroretinogram may show “moat around a small hill” appearance [4] .[eyewiki.aao.org]
  • It is marked by paracentral and central scotoma and decreased color vision.[journalretinavitreous.biomedcentral.com]
  • Patients usually complain about blurred vision, with visual acuity from 0.8 to 0.3 (right eye) and 0.4 (left eye), a central scotoma is present and fundus-examination shows a typical bull's-eye maculopathy.[ispub.com]

Treatment

  • No treatment exists as yet for this disorder, so it is imperative that patients and their ophthalmologists be aware of the best practices for minimizing toxic damage.[en.wikipedia.org]
  • Its value in the control of chloroquine treatment is still doubted, but the method will become better if an EOG is made before treatment is started. EOGs made during the treatment can then be compared with those made earlier.[ncbi.nlm.nih.gov]

Prognosis

  • […] encyclopedic reference this atlas provides an up-to-date clinical overview of all the major areas of ophthalmology including, epidemiology and etiology, history, physical examination, differential diagnosis, laboratory and special examinations, diagnosis, prognosis[books.google.com]
  • Figure 4: Multifocal electroretinography in the same patient showing paracentral amplitude reductions Click here to view Treatment and Prognosis There is no treatment to reverse HCQ toxicity.[kjophthal.com]
  • The prognosis thus depends on the extent of the retinopathy at the time the drug is stopped. Most of the clinically serious cases are iatrogenic, arising from overdosing (based on ideal body weight) or missed screening.[academic.oup.com]
  • The visual prognosis of retinopathy is excellent if the diagnosis is made at an early stage of the disease.[uwo.ca]
  • Expected results Nonproliferative retinopathy has a better prognosis than proliferative retinopathy. Prognosis depends upon the extent of the retinopathy, the cause, and promptness of treatment.[encyclopedia.com]

Etiology

  • […] 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[symptoma.com]
  • Written to be a "go-to" field manual rather than an encyclopedic reference this atlas provides an up-to-date clinical overview of all the major areas of ophthalmology including, epidemiology and etiology, history, physical examination, differential diagnosis[books.google.com]
  • Patients should be advised that HCQ retinopathy may progress despite discontinuation of medication, and the etiology of this progression is poorly understood.[ijo.in]
  • Patients should be advised that toxicity may progress despite discontinuation of medication, and the etiology of this progression is poorly understood.[kjophthal.com]
  • Etiology and Pathogenesis Choroquine retinopathy is caused by the ingestion of chloroquine or its related sulfates and disulphates of over 250 mg per day to a total exceeding 500 mg.[ispub.com]

Epidemiology

  • Goodman, Division of Epidemiology and Ophthalmology, Stellenbosch University, South Africa Ari Ziskind, Division of Ophthalmology, Stellenbosch University, South Africa Full Text: HTML EPUB XML PDF (1MB) Share this article Abstract Purpose: To determine[avehjournal.org]
  • Written to be a "go-to" field manual rather than an encyclopedic reference this atlas provides an up-to-date clinical overview of all the major areas of ophthalmology including, epidemiology and etiology, history, physical examination, differential diagnosis[books.google.com]
  • These findings suggest that the currently widely accepted risk factors may not be applicable to all patients and that there may be risk factors previously not reported that may play a role in the development of toxicity. [5] Epidemiology Despite variability[emedicine.medscape.com]
  • The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum 2013; 43: 77–95. doi: 10.1016/j.semarthrit.2012.12.002. PubMed Singal AK, Kormos-Hallberg C, Lee C, et al.[dermnetnz.org]
Sex distribution
Age distribution

Pathophysiology

  • Patterns of FAF and NIA indicate different stages of pathophysiologic processes involving lipofuscin and melanin in the RPE.[ncbi.nlm.nih.gov]
  • Comprehensively updated to reflect everything you need to know regarding retinal diagnosis, treatment, development, structure, function, and pathophysiology, this monumental ophthalmology reference work equips you with expert answers to virtually any[books.google.com]
  • Pathophysiology Hydroxychloroquine binds to melanin, accumulates in the RPE, and remains there for long periods of time. It is directly toxic to the RPE, causing cellular damage and atrophy [2] .[eyewiki.aao.org]
  • Pathophysiology The mechanism of chloroquine and hydroxychloroquine toxicity is not well understood. Chloroquine has an affinity for pigmented (melanin-containing) structures, which may explain its toxic properties in the eye.[emedicine.medscape.com]
  • When observed, coexisting mfERG or SD-OCT abnormalities have also been concomitantly detected, suggesting a pathophysiologic basis for the FAF finding. 7,18 Despite this, evidence supporting the usefulness of FAF in detecting early subclinical toxicity[reviewofophthalmology.com]

Prevention

  • Using this criterion, we think the EOG to be a valuable tool in preventing chloroquine retinopathy, although it is not yet certain if static perimetry with red light is still a better method.[ncbi.nlm.nih.gov]
  • Even stoppage of the drug does not prevent progression of retinopathy, although this is typically mild if the toxicity is recognized before there is RPE damage.[aao.org]
  • This may not prevent HCQ retinopathy but would prevent vision loss or significant visual impairment.[ijo.in]
  • “Screening can be viewed as a means of helping patients to continue HCQ or CQ (by not stopping the drugs for certain findings) as much as a means of preventing serious retinal damage (by the early recognition of definitive findings),” they wrote.[the-rheumatologist.org]

References

Article

  1. 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.
  2. 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.
  3. Oluleye TS, Babalola Y, Ijaduola M. Chloroquine retinopathy: pattern of presentation in Ibadan, Sub-Sahara Africa. Eye (Lond). 2016;30(1):64-67.
  4. Kazi MS, Saurabh K, Rishi P, Rishi E. Delayed Onset Chloroquine Retinopathy Presenting 10 Years after Long-Term Usage of Chloroquine. Middle East Afr J Ophthalmol. 2013;20(1):89-91.
  5. 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.
  6. 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.
  7. Mavrikakis M, Papazoglou S, Sfikakis PP, et al. Retinal toxicity in long term hydroxychloroquine treatment. Ann Rheum Dis. 1996;55:187–189.
  8. 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.
  9. 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.

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Last updated: 2019-06-28 10:33