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Documenta Ophthalmologica

, Volume 132, Issue 1, pp 75–81 | Cite as

A possible early sign of hydroxychloroquine macular toxicity

  • Livia M. Brandao
  • Anja M. Palmowski-Wolfe
Clinical Case Report

Abstract

Purpose

Hydroxychloroquine (HCQ) has a low risk of retinal toxicity which increases dramatically with a cumulative dose of >1000 g. Here we report a case of HCQ macular toxicity presentation in a young patient with a cumulative dose of 438 g.

Methods

A 15-year-old female started attending annual consultations for retinal toxicity screening in our clinic after 3 years of HCQ treatment for juvenile idiopathic dermatomyositis. She had been diagnosed at age 12 and had been on hydroxychloroquine 200 mg/day, cyclosporin 150 mg/day and vitamin D3 since. Screening consultations included: complete ophthalmologic examination, automated perimetry (AP, M Standard, Octopus 101, Haag-Streit), multifocal electroretinogram (VERIS 6.06™, FMSIII), optical coherence tomography (OCT, fast macular protocol, Cirrus SD-OCT, Carl Zeiss), fundus autofluorescence imaging (Spectralis OCT, Heidelberg Engineering Inc.) and color testing (Farnsworth-Panel-D-15).

Results

After 5 years of treatment, AP demonstrated reduced sensibility in only one extra-foveal point in each eye (p < 0.2). Even though other exams showed no alteration and the cumulative dose was only around 353 g, consultations were increased to every 6 months. After 2-year follow-up, that is, 7 years of HCQ, a bilateral paracentral macula thinning was evident on OCT, suggestive of bull’s eye maculopathy. However, the retinal pigmented epithelium appeared intact and AP was completely normal in both eyes. Further evaluation with ganglion cell analysis (GCA = ganglion cell + inner plexiform layer, Cirrus SD-OCT, Carl Zeiss) showed a concentric thinning of this layer in the same area. Although daily and cumulative doses were still under the high toxicity risk parameters, HCQ was suspended. At a follow-up 1 year later, visual acuity was 20/16 without any further changes in OCT or on any other exam.

Conclusions

This may be the first case report of insidious bull’s eye maculopathy exclusively identified using OCT thickness analysis, in a patient in whom both cumulative and daily dosages were under the high-risk parameters for screening and the averages reported in studies. As ganglion cell analysis has only recently become available, further studies are needed to understand toxicity mechanisms and maybe review screening recommendations.

Keywords

Hydroxychloroquine Maculopathy Multifocal electroretinogram Bull’s eye Optical coherence tomography Ganglion cell layer 

Notes

Acknowledgments

This work was financially supported by Swiss National Science Foundation (SNF NMS 1823), LHW Stiftung Liechtenstein.

Compliance with ethical standards

Conflict of interest

All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

For this type of retrospective study a prior former consent is not required. This chapter does not contain any studies with animals performed by any of the authors.

Informed consent

The patient has consented to the submission of the case report for submission to the journal.

References

  1. 1.
    Wolfe F, Marmor MF (2010) Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res 62(6):775–784. doi: 10.1002/acr.20133 CrossRefGoogle Scholar
  2. 2.
    Marmor MF, Melles RB (2015) Hydroxychloroquine and the retina. Jama 313(8):847–848. doi: 10.1001/jama.2014.14558 CrossRefPubMedGoogle Scholar
  3. 3.
    Rosenthal AR, Kolb H, Bergsma D, Huxsoll D, Hopkins JL (1978) Chloroquine retinopathy in the rhesus monkey. Invest Ophthalmol Vis Sci 17(12):1158–1175PubMedGoogle Scholar
  4. 4.
    Hallberg A, Naeser P, Andersson A (1990) Effects of long-term chloroquine exposure on the phospholipid metabolism in retina and pigment epithelium of the mouse. Acta Ophthalmol (Copenh) 68(2):125–130CrossRefGoogle Scholar
  5. 5.
    Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF (2011) Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology 118(2):415–422. doi: 10.1016/j.ophtha.2010.11.017 CrossRefPubMedGoogle Scholar
  6. 6.
    Pasadhika S, Fishman GA (2010) Effects of chronic exposure to hydroxychloroquine or chloroquine on inner retinal structures. Eye 24(2):340–346. doi: 10.1038/eye.2009.65 CrossRefPubMedGoogle Scholar
  7. 7.
    Pasadhika S, Fishman GA, Choi D, Shahidi M (2010) Selective thinning of the perifoveal inner retina as an early sign of hydroxychloroquine retinal toxicity. Eye 24(5):756–762. doi: 10.1038/eye.2010.21 quiz 763 PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Lee MG, Kim SJ, Ham DI, Kang SW, Kee C, Lee J, Cha HS, Koh EM (2015) Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy. Invest Ophthalmol Vis Sci 56(1):396–402. doi: 10.1167/iovs.14-15138 CrossRefGoogle Scholar
  9. 9.
    Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS, Marmor MF, McCulloch DL, Palmowski-Wolfe AM (2012) ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124(1):1–13. doi: 10.1007/s10633-011-9296-8 PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Fung AE, Samy CN, Rosenfeld PJ (2007) Optical coherence tomography findings in hydroxychloroquine and chloroquine-associated maculopathy. Retin Cases Brief Rep 1(3):128–130. doi: 10.1097/01.iae.0000226540.61840.d7 CrossRefPubMedGoogle Scholar
  11. 11.
    Korah S, Kuriakose T (2008) Optical coherence tomography in a patient with chloroquine-induced maculopathy. Indian J Ophthalmol 56(6):511–513PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Ruther K, Foerster J, Berndt S, Schroeter J (2007) Chloroquine/hydroxychloroquine: variability of retinotoxic cumulative doses. Ophthalmologe 104(10):875–879. doi: 10.1007/s00347-007-1560-7 CrossRefPubMedGoogle Scholar
  13. 13.
    Chiang E, Jampol LM, Fawzi AA (2014) Retinal toxicity found in a patient with systemic lupus erythematosus prior to 5 years of treatment with hydroxychloroquine. Rheumatology 53(11):2001. doi: 10.1093/rheumatology/keu317 CrossRefPubMedGoogle Scholar
  14. 14.
    Phillips BN, Chun DW (2014) Hydroxychloroquine retinopathy after short-term therapy. Retin Cases Brief Rep 8(1):67–69. doi: 10.1097/icb.0000000000000006 CrossRefPubMedGoogle Scholar
  15. 15.
    Kellner S, Weinitz S, Kellner U (2009) Spectral domain optical coherence tomography detects early stages of chloroquine retinopathy similar to multifocal electroretinography, fundus autofluorescence and near-infrared autofluorescence. Br J Ophthalmol 93(11):1444–1447. doi: 10.1136/bjo.2008.157198 CrossRefPubMedGoogle Scholar
  16. 16.
    Cukras C, Huynh N, Vitale S, Wong WT, Ferris FL 3rd, Sieving PA (2015) Subjective and objective screening tests for hydroxychloroquine toxicity. Ophthalmology 122(2):356–366. doi: 10.1016/j.ophtha.2014.07.056 CrossRefPubMedGoogle Scholar
  17. 17.
    Tsang AC, Ahmadi Pirshahid S, Virgili G, Gottlieb CC, Hamilton J, Coupland SG (2015) Hydroxychloroquine and chloroquine retinopathy: a systematic review evaluating the multifocal electroretinogram as a screening test. Ophthalmology 122(6):1239–1251. doi: 10.1016/j.ophtha.2015.02.011 (e1234) CrossRefPubMedGoogle Scholar
  18. 18.
    Melles RB, Marmor MF (2015) Pericentral retinopathy and racial differences in hydroxychloroquine toxicity. Ophthalmology 122(1):110–116. doi: 10.1016/j.ophtha.2014.07.018 CrossRefPubMedGoogle Scholar
  19. 19.
    Lyons JS, Severns ML (2009) Using multifocal ERG ring ratios to detect and follow Plaquenil retinal toxicity: a review: review of mfERG ring ratios in Plaquenil toxicity. Doc Ophthalmol 118(1):29–36. doi: 10.1007/s10633-008-9130-0 CrossRefPubMedGoogle Scholar
  20. 20.
    Yulek F, Ugurlu N, Akcay E, Kocamis SI, Gerceker S, Erten S, Midillioglu I, Simsek S (2013) Early retinal and retinal nerve fiber layer effects of hydroxychloroquine: a follow up study by sdOCT. Cutan Ocul Toxicol 32(3):204–209. doi: 10.3109/15569527.2012.751602 CrossRefPubMedGoogle Scholar
  21. 21.
    Michaelides M, Stover NB, Francis PJ, Weleber RG (2011) Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy. Arch Ophthalmol 129(1):30–39. doi: 10.1001/archophthalmol.2010.321 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Eye HospitalUniversity of BaselBaselSwitzerland

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