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Maculopathy associated with mefloquine (Lariam) therapy for malaria prophylaxis
Maculopathy associated with mefloquine (Lariam) therapy for malaria prophylaxis Randy A. Walker,* BSc; Kevin M. Colleaux,† MD, FRCSC ABSTRACT • RÉSUMÉ
Case report: We report maculopathy occurring in a patient after 18 months of weekly mefloquine for malaria prophylaxis. Macular retinal pigment epithelium changes bilaterally were visually insignificant, with the patient demonstrating 20/20 corrected visual acuity bilaterally. Comments: Retinal change as an adverse effect of mefloquine has not previously been reported. Observation : Présentation non signalée jusqu’ici d’une maculopathie survenue après 18 mois de traitement à la méfloquine en tant que prophylaxie de la malaria. Les changements bilatéraux de l’épithélium pigmentaire rétinien dans la macula étaient non significatifs visuellement chez des patients présentant une acuité visuelle corrigée de 20/20 bilatéralement. Commentaires : Les changements de la rétine n’ont jamais été signalés en tant qu’événement indésirable dû à la méfloquine.
T
he most commonly prescribed antimalarial drug is currently mefloquine (Lariam), a quinolone– methanol compound1 especially indicated in chloroquine-resistant areas.2 Retinopathy, typically described as a bulls-eye maculopathy, has been well documented with older generation antimalarials, including chloroquine, hydroxychloroquine, and quinacrine.3–5 Mefloquine has had many reported adverse effects, the most concerning being neurologic and psychiatric6,7; however, maculopathy has not previously been reported. We present a case of visually insignificant maculopathy, suspiciously associated with mefloquine treatment. CASE
REPORT
In June 2004, a 43-year-old man was seen on referral from an optometrist after bilateral macular changes were noted on routine eye examination. The patient spends 5 months each year working in Nigeria and accordingly receives malaria prophylaxis (250 mg of mefloquine weekly for approximately 1.5 years duration) during and From *the College of Medicine, University of Saskatchewan, and †the Department of Ophthalmology, Saskatoon City Hospital, University of Saskatchewan, Saskatoon, Sask. Originally received July 12, 2005 Accepted for publication May 30, 2006 Correspondence to: Randy Walker, MD, Department of Ophthalmology, Saskatoon City Hospital, 701 Queen St., Saskatoon SK S7K 0M7; [email protected] This article has been peer-reviewed. Cet article a été évalué par les pairs. Can J Ophthalmol 2007;42:125–6 doi:10.3129/can.j.ophthalmol.06-093
Mefloquine-associated maculopathy—Walker & Colleaux
before travel. On examination, corrected distance visual acuity was 20/20 bilaterally. Results of slit-lamp examination were unremarkable. Dilated fundus examination showed healthy discs with attenuated arterioles bilaterally and a sheathed sclerotic vein related to an old vascular occlusion extending superonasally in the right eye. Retinal pigment epithelium (RPE) changes were noted and a fluorescein angiogram showed some posterior pole transmission RPE changes in several discreet patches, the left more so than the right (Fig. 1). Subsequently, his medication was changed to doxycycline, and he was seen again for follow-up in January 2005. His corrected visual acuity remained 20/20 bilaterally and the RPE changes were stable. COMMENTS
The retinopathy that has been associated with the use of quinolones, perhaps now including mefloquine, is often attributed to the tendency of these drugs to accumulate in the RPE and exert toxic effects.3 In 1978, Rosenthal and associates suggested a different mechanism for quinolone retinopathy after their study on rhesus monkeys.8 Cytoplasmic granules were noted in the ganglion cell layer within 1 week of initiating chloroquine therapy (at a dosage much higher than typical human dosages). At 4 years of treatment, they described degeneration of half of the retinal ganglion cells, with reversibility upon treatment termination. Recent evidence suggests that antimalarial maculopathy is related to the amount of the daily or weekly dosage rather than the duration of therapy or total dose.9 In recent years, complications of antimalarial therapy have decreased because it has been possible to
125
Mefloquine-associated maculopathy—Walker & Colleaux
Fig. 1—Intravenous fluorescein angiogram demonstrates early parafoveal hyperfluorescence that persists in the late phase, left greater than right, without leakage.
decrease dosages while still maintaining efficacy of the treatments.10 Our patient showed asymptomatic RPE changes in both eyes, suspicious for antimalarial toxicity, although one cannot exclude the possibility of a previous inflammatory insult or bilateral central serous retinopathy, despite the absence of any previous history of visual disturbance. Although retinopathy has been relatively well documented in individuals taking older antimalarials, it has not been previously reported in patients using mefloquine. Because of the history of medications related to mefloquine causing maculopathy, one must be particularly suspicious of these changes and concerned about progression to a bull’s eye maculopathy. Patients should be informed about this possible adverse effect of mefloquine and its potential long-term sequelae. As mefloquine’s usage in malaria prophylaxis increases, further consideration and attention must be given to this potential complication of mefloquine therapy. REFERENCES 1. Borruat FX, Nater B, Robyn L, Genton B. Prolonged visual illusions induced by mefloquine (Lariam®). J Travel Med 2001;8:148–9. 2 Croft AMJ, Garner P. Mefloquine to prevent malaria: a sys-
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tematic review of trials. Br Med J 1997;36:1606–8. 3. Browning DJ. Bull’s-eye maculopathy associated with quinacrine therapy for malaria. Am J Ophthalmol 2004;137: 577–9. 4. Bertagnolio S, Tacconelli E, Camilli G, Tumbarello M. Case report: retinopathy after malaria prophylaxis with chloroquine. Am J Trop Med Hyg 2001;65:637–8. 5. Maturi RK, Folk JC, Nichols B, Oetting TT, Kardon RH. Hydroxychloroquine retinopathy. Arch Ophthalmol 1999; 117:1262–3. 6. Rendi-Wagner P, Noedl H, Wernsdorfer WH, Wiedermann G, Mikolasek A, Kollaritsch H. Unexpected frequency, duration, and spectrum of adverse events after therapeutic dose of mefloquine in healthy adults. Acta Tropica 2002;81:167–73. 7. Davis TME. Adverse effects of antimalarial prophylactic drugs: An important consideration in the risk-benefit equation. Ann Pharmacother 1998;32:1104–6. 8. Rosenthal AR, Kolb H, Bergsma D, Huxsoll D, Hopkins JL. Chloroquine retinopathy in the rhesus monkey. Invest Ophthalmol Vis Sci 1978;17:1158–75. 9. Ochsendorf FR, Runne U. Chloroquine: consideration of maximum daily dose (3.5 mg/kg ideal body weight) prevents retinopathy. Dermatology 1996;192:382–3. 10. Spalton DJ. Retinopathy and antimalarial drugs – the British experience. Lupus 1996;5(supp 1):S70–S72. Key words: mefloquine, maculopathy, antimalarial drugs, drug toxicity, malaria
Case report: We report maculopathy occurring in a patient after 18 months of weekly mefloquine for malaria prophylaxis. Macular retinal pigment epithelium changes bilaterally were visually insignificant, with the patient demonstrating 20/20 corrected visual acuity bilaterally. Comments: Retinal change as an adverse effect of mefloquine has not previously been reported. Observation : Présentation non signalée jusqu’ici d’une maculopathie survenue après 18 mois de traitement à la méfloquine en tant que prophylaxie de la malaria. Les changements bilatéraux de l’épithélium pigmentaire rétinien dans la macula étaient non significatifs visuellement chez des patients présentant une acuité visuelle corrigée de 20/20 bilatéralement. Commentaires : Les changements de la rétine n’ont jamais été signalés en tant qu’événement indésirable dû à la méfloquine.
T
he most commonly prescribed antimalarial drug is currently mefloquine (Lariam), a quinolone– methanol compound1 especially indicated in chloroquine-resistant areas.2 Retinopathy, typically described as a bulls-eye maculopathy, has been well documented with older generation antimalarials, including chloroquine, hydroxychloroquine, and quinacrine.3–5 Mefloquine has had many reported adverse effects, the most concerning being neurologic and psychiatric6,7; however, maculopathy has not previously been reported. We present a case of visually insignificant maculopathy, suspiciously associated with mefloquine treatment. CASE
REPORT
In June 2004, a 43-year-old man was seen on referral from an optometrist after bilateral macular changes were noted on routine eye examination. The patient spends 5 months each year working in Nigeria and accordingly receives malaria prophylaxis (250 mg of mefloquine weekly for approximately 1.5 years duration) during and From *the College of Medicine, University of Saskatchewan, and †the Department of Ophthalmology, Saskatoon City Hospital, University of Saskatchewan, Saskatoon, Sask. Originally received July 12, 2005 Accepted for publication May 30, 2006 Correspondence to: Randy Walker, MD, Department of Ophthalmology, Saskatoon City Hospital, 701 Queen St., Saskatoon SK S7K 0M7; [email protected] This article has been peer-reviewed. Cet article a été évalué par les pairs. Can J Ophthalmol 2007;42:125–6 doi:10.3129/can.j.ophthalmol.06-093
Mefloquine-associated maculopathy—Walker & Colleaux
before travel. On examination, corrected distance visual acuity was 20/20 bilaterally. Results of slit-lamp examination were unremarkable. Dilated fundus examination showed healthy discs with attenuated arterioles bilaterally and a sheathed sclerotic vein related to an old vascular occlusion extending superonasally in the right eye. Retinal pigment epithelium (RPE) changes were noted and a fluorescein angiogram showed some posterior pole transmission RPE changes in several discreet patches, the left more so than the right (Fig. 1). Subsequently, his medication was changed to doxycycline, and he was seen again for follow-up in January 2005. His corrected visual acuity remained 20/20 bilaterally and the RPE changes were stable. COMMENTS
The retinopathy that has been associated with the use of quinolones, perhaps now including mefloquine, is often attributed to the tendency of these drugs to accumulate in the RPE and exert toxic effects.3 In 1978, Rosenthal and associates suggested a different mechanism for quinolone retinopathy after their study on rhesus monkeys.8 Cytoplasmic granules were noted in the ganglion cell layer within 1 week of initiating chloroquine therapy (at a dosage much higher than typical human dosages). At 4 years of treatment, they described degeneration of half of the retinal ganglion cells, with reversibility upon treatment termination. Recent evidence suggests that antimalarial maculopathy is related to the amount of the daily or weekly dosage rather than the duration of therapy or total dose.9 In recent years, complications of antimalarial therapy have decreased because it has been possible to
125
Mefloquine-associated maculopathy—Walker & Colleaux
Fig. 1—Intravenous fluorescein angiogram demonstrates early parafoveal hyperfluorescence that persists in the late phase, left greater than right, without leakage.
decrease dosages while still maintaining efficacy of the treatments.10 Our patient showed asymptomatic RPE changes in both eyes, suspicious for antimalarial toxicity, although one cannot exclude the possibility of a previous inflammatory insult or bilateral central serous retinopathy, despite the absence of any previous history of visual disturbance. Although retinopathy has been relatively well documented in individuals taking older antimalarials, it has not been previously reported in patients using mefloquine. Because of the history of medications related to mefloquine causing maculopathy, one must be particularly suspicious of these changes and concerned about progression to a bull’s eye maculopathy. Patients should be informed about this possible adverse effect of mefloquine and its potential long-term sequelae. As mefloquine’s usage in malaria prophylaxis increases, further consideration and attention must be given to this potential complication of mefloquine therapy. REFERENCES 1. Borruat FX, Nater B, Robyn L, Genton B. Prolonged visual illusions induced by mefloquine (Lariam®). J Travel Med 2001;8:148–9. 2 Croft AMJ, Garner P. Mefloquine to prevent malaria: a sys-
126
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tematic review of trials. Br Med J 1997;36:1606–8. 3. Browning DJ. Bull’s-eye maculopathy associated with quinacrine therapy for malaria. Am J Ophthalmol 2004;137: 577–9. 4. Bertagnolio S, Tacconelli E, Camilli G, Tumbarello M. Case report: retinopathy after malaria prophylaxis with chloroquine. Am J Trop Med Hyg 2001;65:637–8. 5. Maturi RK, Folk JC, Nichols B, Oetting TT, Kardon RH. Hydroxychloroquine retinopathy. Arch Ophthalmol 1999; 117:1262–3. 6. Rendi-Wagner P, Noedl H, Wernsdorfer WH, Wiedermann G, Mikolasek A, Kollaritsch H. Unexpected frequency, duration, and spectrum of adverse events after therapeutic dose of mefloquine in healthy adults. Acta Tropica 2002;81:167–73. 7. Davis TME. Adverse effects of antimalarial prophylactic drugs: An important consideration in the risk-benefit equation. Ann Pharmacother 1998;32:1104–6. 8. Rosenthal AR, Kolb H, Bergsma D, Huxsoll D, Hopkins JL. Chloroquine retinopathy in the rhesus monkey. Invest Ophthalmol Vis Sci 1978;17:1158–75. 9. Ochsendorf FR, Runne U. Chloroquine: consideration of maximum daily dose (3.5 mg/kg ideal body weight) prevents retinopathy. Dermatology 1996;192:382–3. 10. Spalton DJ. Retinopathy and antimalarial drugs – the British experience. Lupus 1996;5(supp 1):S70–S72. Key words: mefloquine, maculopathy, antimalarial drugs, drug toxicity, malaria