Skip to main content

Advertisement

Log in

Retinal disorders in northern Brazilian patients treated with chloroquine assessed by multifocal ERG

  • Original Research Article
  • Published:
Documenta Ophthalmologica Aims and scope Submit manuscript

Abstract

The effects of chloroquine intake on the retinal function in a Brazilian population of patients were assessed by multifocal electroretinography. Twenty-four randomly chosen eyes of patients treated with chloroquine for rheumatoid arthritis and systemic lupus erythematosus were examined using multifocal electroretinography (mfERG). Control measurements were acquired from 21 randomly chosen eyes of age-matched healthy subjects. None of the study participants had an inherited retinal disease or a Snellen visual acuity reduced to less than 20/40. In patients and control subjects, cumulative chloroquine dose, total daily dose, duration of treatment, retinal examination, visual field defects, visual acuity, and the mfERG were assessed. The average amplitudes and implicit times of the N1, P1, and P2 components of the mfERGs were measured in the central hexagon (R1) and in five rings (R2–R6). The values measured in patients and normal subjects were compared. The P1 amplitudes in R2 were significantly decreased in the patients. In addition, the amplitudes of N1 and N2 in R1 were significantly smaller in the patients. The implicit times of none of the components were significantly different between patients and controls. The response amplitude was not significantly correlated with cumulative dose and duration of intake. There was no correlation with retinal appearance, visual field, and visual acuity. In agreement with earlier data, the central mfERG amplitudes were decreased in chloroquine patients indicating functional alterations in the retina. These changes are also present in a Brazilian population suggesting that the effects of chloroquine are general and that genetic background and life circumstances probably have, if at all, only little effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Tzekov R (2005) Ocular toxicity due to chloroquine and hydroxychloroquine: electrophysiological and visual function correlates. Doc Ophthalmol 110:111–120

    Article  PubMed  Google Scholar 

  2. Ministerió da Saúde B (2001) Ministerió da Saúde. Manual de terapêutica da malária, Brasil

  3. Scherbel AL, Harrison JW, Atdjian M (1958) Further observations on the use of 4-aminoquinoline compounds in patients with rheumatoid arthritis or related diseases. Clevel Clin Q 25:95–111

    CAS  Google Scholar 

  4. McChesney EW (1983) Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med 75:11–18

    Article  PubMed  CAS  Google Scholar 

  5. Ministerió da Saúde B (2010) Ministerió da Saúde Brasil Secretaria de vigilância em saúde Departamento de vigilância epidemiológica. Guia prático de tratamento da malária no Brasil

  6. Wellems TE, Plowe CV (2001) Chloroquine resistant malaria. J Infect Dis 184:770–776

    Article  PubMed  CAS  Google Scholar 

  7. Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV (2006) Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 355:1959–1966

    Article  PubMed  CAS  Google Scholar 

  8. Plowe CV (2005) Antimalarial drug resistance in Africa: strategies for monitoring and deterrence. In: Compans RW, Cooper MD, Honjo T, Koprowski H, Melchers F, Oldstone MBA, Olsnes S, Potter M, Vogt PK, Wagner H, Sullivan DJ, Krishna S (eds) Current topics in microbiology and immunology. WHO Technical Report Series, pp 55–79

  9. Kellner U, Kraus H, Foerster MH (2000) Multifocal ERG in chloroquine retinopathy: regional variance of retinal dysfunction. Graefes Arch Clin Exp Ophthalmol 238:94–97

    Article  PubMed  CAS  Google Scholar 

  10. Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF (2002) Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology 109:1377–1382

    Article  PubMed  Google Scholar 

  11. Shearer RV, Dubois EL (1967) Ocular changes induced by long-term hydroxychloroquine (plaquenil) therapy. Am J Ophthalmol 64:245–252

    PubMed  CAS  Google Scholar 

  12. Tobin R, Krobel GB, Ryners RI (1982) Hydroxychloroquine: seven years experience. Arch Ophthalmol 100:81–83

    PubMed  CAS  Google Scholar 

  13. Nylander U (1966) Ocular damage in chloroquine therapy. Acta Ophthalmol (Copenh) 44:335–348

    Article  CAS  Google Scholar 

  14. Mackenzie AH (1983) Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med 75(Suppl):40–45

    Article  PubMed  CAS  Google Scholar 

  15. Mavrikakis M, Papazoglou S, Sfikakis PP, Vaiopoulos G, Rougas K (1996) Retinal toxicity in long term hydroxychloroquine treatment. Ann Rheum Dis 55:187–189

    Article  PubMed  CAS  Google Scholar 

  16. Weisinger HS, Pesudovs K, Collin HB (2000) Management of patients undergoing hydroxychloroquine (Plaquenil) therapy. Clin Exp Optom 83:32–36

    Article  PubMed  Google Scholar 

  17. Johnson MW, Vine AK (1987) Hydroxychloroquine therapy in massive total doses without retinal toxicity. Am J Ophthalmol 104:139–144

    PubMed  CAS  Google Scholar 

  18. Easterbrook M (1988) Ocular effects and safety of antimalarial agents. Am J Med 85:23–29

    Article  PubMed  CAS  Google Scholar 

  19. Kellner U, Renner AB, Tillack H (2006) Fundus autofluorescence and mfERG for early detection of retinal alterations in patients using chloroquine/hydroxychloroquine. Invest Ophthalmol Vis Sci 47:3531–3538

    Article  PubMed  Google Scholar 

  20. So SC, Hedges TR, Schuman JS, Quireza ML (2003) Evaluation of hydroxychloroquine retinopathy with multifocal electroretinography. Ophthalmic Surg Lasers Imaging 34:251–258

    PubMed  Google Scholar 

  21. Maturi RK, Yu M, Weleber R (2004) Multifocal electroretinographic evaluation of long-term hydroxychloroquine users. Arch Ophthalmol 122:973–981

    Article  PubMed  CAS  Google Scholar 

  22. Penrose PJ, Tzekov R, Sutter EE, Fu AD, Allen AW Jr, Fung W, Oxford KW (2003) Multifocal electroretinography evaluation for early detection of retinal dysfunction in patients taking hydroxychloroquine. Retina 23:503–512

    Article  PubMed  Google Scholar 

  23. Kellner U, Kellner S, Weinitz S (2008) Chloroquine retinopathy: lipofuscin- and melanin-related fundus autofluorescence, optical coherence tomography and multifocal electroretinography. Doc Ophthalmol 116:119–127

    Article  PubMed  Google Scholar 

  24. Sutter EE, Tran D (1992) The field topography of ERG components in man-I. The photopic luminance response. Vis Res 32:433–446

    Article  PubMed  CAS  Google Scholar 

  25. Tzekov RT, Serrato A, Marmor MF (2004) ERG findings in patients using hydroxychloroquine. Doc Ophthalmol 108:87–97

    Article  PubMed  Google Scholar 

  26. Moschos MN, Moschos MM, Apostolopoulos M, Mallias JA, Bouros C, Theodossiadis GP (2004) Assessing hydroxychloroquine toxicity by the multifocal ERG. Doc Ophthalmol 108:47–53

    Article  PubMed  Google Scholar 

  27. Neubauer AS, Stiefelmeyer S, Berninger TA, Arden G, Rudolph G (2004) The multifocal pattern electroretinogram in chloroquine retinopathy. Ophthalmic Res 36:106–113

    Article  PubMed  Google Scholar 

  28. Kertes PJ, Coupland SE, Leonard BC, Bhargava SK (2003) Multifocal ERG changes secondary to chloroquine and plaquenil toxicity. Invest Ophthalmol Vis Sci 44: E-Abstract 2701

    Google Scholar 

  29. Ruther K, Foerster J, Berndt S, Schroeter J (2007) Chloroquine/hydroxychloroquine: variability of retinotoxic cumulative doses. Ophthalmologe 104:875–879

    Article  PubMed  CAS  Google Scholar 

  30. Marmor MF, Hood DC, Keating D, Kondo M, Seeliger MW, Miyake Y (2003) Guidelines for basic multifocal electroretinography (mfERG). Doc Ophthalmol 106:105–115

    Article  PubMed  Google Scholar 

  31. Lyons JS, Severns ML (2007) Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of multifocal electroretinography. Am J Ophthalmol 143:801–809

    Article  PubMed  CAS  Google Scholar 

  32. Bearse MA Jr, Sutter EE (1996) Imaging localized retinal dysfunction with the multifocal electroretinogram. J Opt Soc Am A Opt Image Sci Vis 13:634–640

    Article  PubMed  Google Scholar 

  33. Rodrigues AR, Da Silva Filho M, Silveira LC, Kremers J (2010) Spatial distributions of on- and off-responses determined with the multifocal ERG. Doc Ophthalmol 120:145–158

    Article  PubMed  Google Scholar 

  34. Hood DC, Frishman LJ, Saszik S, Viswanathan S (2002) Retinal origins of the primate multifocal ERG: implications for the human response. Invest Ophthalmol Vis Sci 43:1673–1685

    PubMed  Google Scholar 

  35. Thorne JE, Jabs DA (2006) Rheumatic disease. In: Ryan SJ, Schachat AP (eds) Retina. Mosby, St. Louis

    Google Scholar 

  36. Lessel S (1979) The neuro-ophthalmology of systemic lupus erythematosus. Doc Ophthalmol 47:13–42

    Article  Google Scholar 

  37. Bernstein HN, Ginsberg J (1964) The pathology of chloroquine retinopathy. Arch Ophthalmol 71:238–245

    PubMed  CAS  Google Scholar 

  38. Wetterholm DH, Winter FC (1964) Histopathology of chloroquine retinal toxicity. Arch Ophthalmol 71:82–87

    PubMed  CAS  Google Scholar 

  39. Rosenthal AR, Kolb H, Bergsma D, Huxsoll D, Hopkins JL (1978) Chloroquine retinopathy in the rhesus monkey. Invest Ophthalmol Vis Sci 17:1158–1175

    PubMed  CAS  Google Scholar 

  40. Shroyer NF, Lewis RA, Lupski JR (2001) Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease? Am J Ophthalmol 131:761–766

    Article  PubMed  CAS  Google Scholar 

  41. Tsybovsky Y, Molday RS, Palczewski K (2010) The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease. Adv Exp Med Biol 703:105–125

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work was supported by CAPES-DAAD PROBRAL #182/2007; BMBF/CNPq BRA 09/010/#490857/2008-6; FINEP IBN-Net #01.06.0842-00; CNPq #550671/2007-2; CNPq #620037/2008-3. JK is Fellow in the Excellence Program of the Hertie Foundation. LCLS is a CNPq research fellow. MGL receives a CAPES-PROF fellowship for graduate students.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Kremers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Raster, M., Horn, F., Jünemann, A. et al. Retinal disorders in northern Brazilian patients treated with chloroquine assessed by multifocal ERG. Doc Ophthalmol 122, 77–86 (2011). https://doi.org/10.1007/s10633-011-9262-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10633-011-9262-5

Keywords

Navigation