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.
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References
Tzekov R (2005) Ocular toxicity due to chloroquine and hydroxychloroquine: electrophysiological and visual function correlates. Doc Ophthalmol 110:111–120
Ministerió da Saúde B (2001) Ministerió da Saúde. Manual de terapêutica da malária, Brasil
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
McChesney EW (1983) Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med 75:11–18
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
Wellems TE, Plowe CV (2001) Chloroquine resistant malaria. J Infect Dis 184:770–776
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
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
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
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
Shearer RV, Dubois EL (1967) Ocular changes induced by long-term hydroxychloroquine (plaquenil) therapy. Am J Ophthalmol 64:245–252
Tobin R, Krobel GB, Ryners RI (1982) Hydroxychloroquine: seven years experience. Arch Ophthalmol 100:81–83
Nylander U (1966) Ocular damage in chloroquine therapy. Acta Ophthalmol (Copenh) 44:335–348
Mackenzie AH (1983) Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med 75(Suppl):40–45
Mavrikakis M, Papazoglou S, Sfikakis PP, Vaiopoulos G, Rougas K (1996) Retinal toxicity in long term hydroxychloroquine treatment. Ann Rheum Dis 55:187–189
Weisinger HS, Pesudovs K, Collin HB (2000) Management of patients undergoing hydroxychloroquine (Plaquenil) therapy. Clin Exp Optom 83:32–36
Johnson MW, Vine AK (1987) Hydroxychloroquine therapy in massive total doses without retinal toxicity. Am J Ophthalmol 104:139–144
Easterbrook M (1988) Ocular effects and safety of antimalarial agents. Am J Med 85:23–29
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
So SC, Hedges TR, Schuman JS, Quireza ML (2003) Evaluation of hydroxychloroquine retinopathy with multifocal electroretinography. Ophthalmic Surg Lasers Imaging 34:251–258
Maturi RK, Yu M, Weleber R (2004) Multifocal electroretinographic evaluation of long-term hydroxychloroquine users. Arch Ophthalmol 122:973–981
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
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
Sutter EE, Tran D (1992) The field topography of ERG components in man-I. The photopic luminance response. Vis Res 32:433–446
Tzekov RT, Serrato A, Marmor MF (2004) ERG findings in patients using hydroxychloroquine. Doc Ophthalmol 108:87–97
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
Neubauer AS, Stiefelmeyer S, Berninger TA, Arden G, Rudolph G (2004) The multifocal pattern electroretinogram in chloroquine retinopathy. Ophthalmic Res 36:106–113
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
Ruther K, Foerster J, Berndt S, Schroeter J (2007) Chloroquine/hydroxychloroquine: variability of retinotoxic cumulative doses. Ophthalmologe 104:875–879
Marmor MF, Hood DC, Keating D, Kondo M, Seeliger MW, Miyake Y (2003) Guidelines for basic multifocal electroretinography (mfERG). Doc Ophthalmol 106:105–115
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
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
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
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
Thorne JE, Jabs DA (2006) Rheumatic disease. In: Ryan SJ, Schachat AP (eds) Retina. Mosby, St. Louis
Lessel S (1979) The neuro-ophthalmology of systemic lupus erythematosus. Doc Ophthalmol 47:13–42
Bernstein HN, Ginsberg J (1964) The pathology of chloroquine retinopathy. Arch Ophthalmol 71:238–245
Wetterholm DH, Winter FC (1964) Histopathology of chloroquine retinal toxicity. Arch Ophthalmol 71:82–87
Rosenthal AR, Kolb H, Bergsma D, Huxsoll D, Hopkins JL (1978) Chloroquine retinopathy in the rhesus monkey. Invest Ophthalmol Vis Sci 17:1158–1175
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
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
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.
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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
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DOI: https://doi.org/10.1007/s10633-011-9262-5