eMedicine Specialties > Ophthalmology > Unclassified Disorders

Chloroquine/Hydroxychloroquine Toxicity: Follow-up

Author: Manolette R Roque, MD, MBA, DPBO, FPAO, President and CEO, Chief of Service, Ocular Immunology and Uveitis, Consulting Staff, Cornea and Refractive Surgery, Eye Republic Ophthalmology Clinic; General Manager, Ophthalmic Consultants Philippines Co; Consulting Staff, CME Liaison, Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center
Coauthor(s): Barbara L Roque, MD, Full Partner, Ophthalmic Consultants Philippines Co, Chief of Service, Pediatric Ophthalmology and Strabismus, Consulting Staff, Orbit and Eye Plastics, EYE REPUBLIC Ophthalmology Clinic; C Stephen Foster, MD, FACS, FACR, FAAO, Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution
Contributor Information and Disclosures

Updated: Apr 1, 2008

Follow-up

Further Outpatient Care

  • Once retinal toxicity is identified, the drug is discontinued; the patient is administered other immunosuppressive agents. Chloroquine and/or hydroxychloroquine clear very slowly from the body, so the full effects may not manifest for 3–6 months. Slow, continued deterioration of visual function may occur even after the drug is discontinued. The authors recommend that patients be reevaluated 3 months after a diagnosis of toxicity is made, even after discontinuation of drug use. Annual examinations are recommended until the findings are clearly stable.
    • Distance and near acuity
    • Color vision
    • Visual field examination (red pin and red Amsler grid)
    • Slit lamp biomicroscopic examination of the cornea
    • Dilated examination of the retina
    • Electroretinogram (full field and multifocal)
    • Perimetry (Humphrey 10-2)
    • Fundus photography
    • Fluorescein angiography

Inpatient & Outpatient Medications

  • Discontinue use of quinolones.

Deterrence/Prevention

  • The recommended safe threshold dose has been reported as 3.5 mg/kg/d for chloroquine and 6.5 mg/kg/d for hydroxychloroquine.
    • These dosages are based on lean body weight.
    • A body mass index calculator used by endocrinologists is helpful in calculating the recommended dose.

Complications

Prognosis

  • If the maximum daily dosage recommendations are followed, then the likelihood of toxicity is small.
  • If diagnosed early, toxicity (eg, corneal epithelial changes, loss of normal foveal reflex) is reversible.
  • Once the appearance of a bull's eye maculopathy is noted, disturbances associated with this condition are irreversible.

Patient Education

  • Monitor patients on an annual basis. Record visual symptomatology, visual acuity, and Amsler grid testing.
  • Advise patients to discontinue treatment and to seek consultation with an ophthalmologist if changes in visual acuity or blurred vision occur while on treatment.
  • See Deterrence/Prevention.

Miscellaneous

Medicolegal Pitfalls

  • The most important factor in avoiding toxicity with long-term therapy appears to be the daily dose. If the daily dose is below the stated threshold levels, then the chance of encountering any retinopathy is small. However, it is essential that the early symptoms of toxicity are discussed with the patient. A high index of suspicion of toxicity would justify the performance of expensive ancillary procedures to detect possible retinopathy.
  • In addition to following the guidelines for the safe administration of chloroquine/hydroxychloroquine therapy, dose adjustments should be made in consideration of lean body weight and renal and hepatic insufficiency.

Special Concerns

  • Pediatric: Use of quinolones in children should be monitored closely.
  • Geriatric: Elderly patients should be considered part of a high-risk group; therefore, they should be monitored closely.
  • Renal insufficiency: Dose adjustments should be made in patients with renal impairment.
  • Hepatic insufficiency: Dose adjustments should be made in patients with hepatic impairment.
 


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References
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References

  1. Bernstein HN. Chloroquine ocular toxicity. Surv Ophthalmol. Oct 1967;12(5):415-47. [Medline].

  2. Alarcón GS. How frequently and how soon should we screen our patients for the presence of antimalarial retinopathy?. Arthritis Rheum. Feb 2002;46(2):561. [Medline].

  3. Almony A, Garg S, Peters RK, Mamet R, Tsong J, Shibuya B, et al. Threshold Amsler grid as a screening tool for asymptomatic patients on hydroxychloroquine therapy. Br J Ophthalmol. May 2005;89(5):569-74. [Medline].

  4. Aylward JM. Hydroxychloroquine and chloroquine: assessing the risk of retinal toxicity. J Am Optom Assoc. Nov 1993;64(11):787-97. [Medline].

  5. Bernatsky S, Pineau C, Joseph L, Clarke A. Adherence to ophthalmologic monitoring for antimalarial toxicity in a lupus cohort. J Rheumatol. Aug 2003;30(8):1756-60. [Medline].

  6. Bernstein HN. Ocular safety of hydroxychloroquine. Ann Ophthalmol. Aug 1991;23(8):292-6. [Medline].

  7. Bernstein HN, Ginsberg J. The pathology of chloroquine retinopathy. Arch Ophthalmol. Feb 1964;71:238-45. [Medline].

  8. Bienfang D, Coblyn JS, Liang MH, Corzillius M. Hydroxychloroquine retinopathy despite regular ophthalmologic evaluation: a consecutive series. J Rheumatol. Nov 2000;27(11):2703-6. [Medline].

  9. Block JA. Hydroxychloroquine and retinal safety. Lancet. Mar 14 1998;351(9105):771. [Medline].

  10. Blomquist PH, Chundru RK. Screening for hydroxychloroquine toxicity by Texas ophthalmologists. J Rheumatol. Aug 2002;29(8):1665-70. [Medline].

  11. Blyth C, Lane C. Hydroxychloroquine retinopathy: is screening necessary?. BMJ. Mar 7 1998;316(7133):716-7. [Medline].

  12. Browning DJ. Hydroxychloroquine and chloroquine retinopathy: screening for drug toxicity. Am J Ophthalmol. May 2002;133(5):649-56. [Medline].

  13. Calkins LL. Corneal epithelial changes occurring during chloroquine (aralen) therapy. AMA Arch Ophthalmol. Dec 1958;60(6):981-8. [Medline].

  14. Cox NH, Paterson WD. Ocular toxicity of antimalarials in dermatology: a survey of current practice. Br J Dermatol. Dec 1994;131(6):878-82. [Medline].

  15. Coyle JT. Hydroxychloroquine retinopathy. Ophthalmology. Feb 2001;108(2):243-4. [Medline].

  16. Cruess AF, Schachat AP, Nicholl J, Augsburger JJ. Chloroquine retinopathy. Is fluorescein angiography necessary?. Ophthalmology. Aug 1985;92(8):1127-9. [Medline].

  17. Duncker G, Bredehorn T. Chloroquine-induced lipidosis in the rat retina: functional and morphological changes after withdrawal of the drug. Graefes Arch Clin Exp Ophthalmol. Jun 1996;234(6):378-81. [Medline].

  18. Easterbrook M. An ophthalmological view on the efficacy and safety of chloroquine versus hydroxychloroquine. J Rheumatol. Sep 1999;26(9):1866-8. [Medline].

  19. Easterbrook M. Detection and prevention of maculopathy associated with antimalarial agents. Int Ophthalmol Clin. 1999;39(2):49-57. [Medline].

  20. Easterbrook M. Hydroxychloroquine retinopathy. Ophthalmology. Dec 2001;108(12):2158-9. [Medline].

  21. Easterbrook M. Is corneal deposition of antimalarial any indication of retinal toxicity?. Can J Ophthalmol. Aug 1990;25(5):249-51. [Medline].

  22. Easterbrook M. Screening for antimalarial toxicity: current concepts. Can J Ophthalmol. Oct 2002;37(6):325-8, 331-4. [Medline].

  23. Falcone PM, Paolini L, Lou PL. Hydroxychloroquine toxicity despite normal dose therapy. Ann Ophthalmol. Oct 1993;25(10):385-8. [Medline].

  24. Fielder A, Graham E, Jones S, Silman A, Tullo A. Royal College of Ophthalmologists guidelines: ocular toxicity and hydroxychloroquine. Eye. 1998;12 (Pt 6):907-9. [Medline].

  25. Fraenkel L, Felson DT. Rheumatologists' attitudes toward routine screening for hydroxychloroquine retinopathy. J Rheumatol. Jun 2001;28(6):1218-21. [Medline].

  26. Gleiser CA, Dukes TW, Lawwill T, Read WK, Bay WW, Brown RS. Ocular changes in swine associated with chloroquine toxicity. Am J Ophthalmol. Mar 1969;67(3):399-405. [Medline].

  27. Grierson DJ. Hydroxychloroquine and visual screening in a rheumatology outpatient clinic. Ann Rheum Dis. Mar 1997;56(3):188-90. [Medline].

  28. Halfeld Furtado de Mendonca R, Oliveira Maia Junior O, Yukihiko Takahashi W. Electrophysiologic findings in chloroquine maculopathy. Doc Ophthalmol. Sep 2007;115(2):117-9. [Medline].

  29. Herman K, Leys A, Spileers W. (Hydroxy)-chloroquine retinal toxicity: two case reports and safety guidelines. Bull Soc Belge Ophtalmol. 2002;(284):21-9. [Medline].

  30. Johnson MW, Vine AK. Hydroxychloroquine therapy in massive total doses without retinal toxicity. Am J Ophthalmol. Aug 15 1987;104(2):139-44. [Medline].

  31. Klinger G, Morad Y, Westall CA, Laskin C, Spitzer KA, Koren G, et al. Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet. Sep 8 2001;358(9284):813-4. [Medline].

  32. Lee AG. Hydroxychloroquine screening. Br J Ophthalmol. May 2005;89(5):521-2. [Medline].

  33. Levy GD, Munz SJ, Paschal J, Cohen HB, Pince KJ, Peterson T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis Rheum. Aug 1997;40(8):1482-6. [Medline].

  34. Lozier JR, Friedlander MH. Complications of antimalarial therapy. Intl Ophthalmology. 1985;29(3):172-8.

  35. Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med. Jul 18 1983;75(1A):40-5. [Medline].

  36. Marmor MF. New American Academy of Ophthalmology recommendations on screening for hydroxychloroquine retinopathy. Arthritis Rheum. Jun 2003;48(6):1764. [Medline].

  37. Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology. Jul 2002;109(7):1377-82. [Medline].

  38. Maturi RK, Yu M, Weleber RG. Multifocal electroretinographic evaluation of long-term hydroxychloroquine users. Arch Ophthalmol. Jul 2004;122(7):973-81. [Medline].

  39. Mavrikakis I, Sfikakis PP, Mavrikakis E, Rougas K, Nikolaou A, Kostopoulos C, et al. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. Ophthalmology. Jul 2003;110(7):1321-6. [Medline].

  40. Mavrikakis M, Papazoglou S, Sfikakis PP, Vaiopoulos G, Rougas K. Retinal toxicity in long term hydroxychloroquine treatment. Ann Rheum Dis. Mar 1996;55(3):187-9. [Medline].

  41. May K, Metcalf T, Gough A. Screening for hydroxychloroquine retinopathy. Screening should be selective. BMJ. Nov 14 1998;317(7169):1388-9. [Medline].

  42. Medical Economics Company. Physicians' Desk Reference (PDR). Montvale, NJ: Thomson Healthcare; 1999.

  43. Mills PV, Beck M, Power BJ. Assessment of the retinal toxicity of hydroxychloroquine. Trans Ophthalmol Soc U K. 1981;101(1):109-13. [Medline].

  44. Moorthy RS, Valluri S. Ocular toxicity associated with systemic drug therapy. Curr Opin Ophthalmol. Dec 1999;10(6):438-46. [Medline].

  45. Morsman CD, Livesey SJ, Richards IM, Jessop JD, Mills PV. Screening for hydroxychloroquine retinal toxicity: is it necessary?. Eye. 1990;4 (Pt 4):572-6. [Medline].

  46. Moschos MN, Moschos MM, Apostolopoulos M, Mallias JA, Bouros C, Theodossiadis GP. Assessing hydroxychloroquine toxicity by the multifocal ERG. Doc Ophthalmol. Jan 2004;108(1):47-53. [Medline].

  47. Neumann R, Foster CS. Corticosteroid-sparing strategies in the treatment of retinal vasculitis in systemic lupus erythematosus. Retina. 1995;15(3):201-12. [Medline].

  48. Penrose PJ, Tzekov RT, Sutter EE, Fu AD, Allen AW Jr, Fung WE, et al. Multifocal electroretinography evaluation for early detection of retinal dysfunction in patients taking hydroxychloroquine. Retina. Aug 2003;23(4):503-12. [Medline].

  49. Percival SPB. The ocular toxicity of chloroquine. Trans Oph UK. 1967;87:355-9.

  50. Petrohelos MA. Chloroquine-induced ocular toxicity. Ann Ophthalmol. Jun 1974;6(6):615-8. [Medline].

  51. Raines MF, Bhargava SK, Rosen ES. The blood-retinal barrier in chloroquine retinopathy. Invest Ophthalmol Vis Sci. Aug 1989;30(8):1726-31. [Medline].

  52. Ramsey MS, Fine BS. Chloroquine toxicity in the human eye. Histopathologic observations by electron microscopy. Am J Ophthalmol. Feb 1972;73(2):229-35. [Medline].

  53. Razeghinejad MR, Torkaman F, Amini H. Blue-yellow perimetry can be an early detector of hydroxychloroquine and chloroquine retinopathy. Med Hypotheses. 2005;65(3):629-30. [Medline].

  54. Rivett K. Chloroquine-induced retinal toxicity. S Afr Med J. Jan 2004;94(1):41. [Medline].

  55. Rubin M, Bernstein HN, Zvaifler NJ. Studies on the pharmacology of chloroquine. Recommendations for The treatment of Chloroquine Retinopathy. Arch Ophthalmol. Oct 1963;70:474-81. [Medline].

  56. Ruiz RS, Saatci OA. Chloroquine and hydroxychloroquine retinopathy: how to follow affected patients. Ann Ophthalmol. Aug 1991;23(8):290-1. [Medline].

  57. Rynes RI. Ophthalmologic considerations in using antimalarials in the United States. Lupus. Jun 1996;5 Suppl 1:S73-4. [Medline].

  58. Sfikakis PP, Mavrikakis M. Ophthalmologic monitoring for antimalarial toxicity. J Rheumatol. May 2004;31(5):1011-2; author reply 1012. [Medline].

  59. Shipley M, Silman A. Should patients on hydroxychloroquine have their eyes examined regularly?. Br J Rheumatol. May 1997;36(5):514-5. [Medline].

  60. Silman A, Shipley M. Ophthalmological monitoring for hydroxychloroquine toxicity: a scientific review of available data. Br J Rheumatol. May 1997;36(5):599-601. [Medline].

  61. So SC, Hedges TR, Schuman JS, Quireza ML. Evaluation of hydroxychloroquine retinopathy with multifocal electroretinography. Ophthalmic Surg Lasers Imaging. May-Jun 2003;34(3):251-8. [Medline].

  62. Spalton DJ. Retinopathy and antimalarial drugs--the British experience. Lupus. Jun 1996;5 Suppl 1:S70-2. [Medline].

  63. Spalton DJ, Verdon Roe GM, Hughes GR. Hydroxychloroquine, dosage parameters and retinopathy. Lupus. Dec 1993;2(6):355-8. [Medline].

  64. Thorne JE, Maguire AM. Retinopathy after long term, standard doses of hydroxychloroquine. Br J Ophthalmol. Oct 1999;83(10):1201-2. [Medline].

  65. Tobin DR, Krohel G, Rynes RI. Hydroxychloroquine. Seven-year experience. Arch Ophthalmol. Jan 1982;100(1):81-3. [Medline].

  66. Toimela T, Tähti H, Salminen L. Retinal pigment epithelium cell culture as a model for evaluation of the toxicity of tamoxifen and chloroquine. Ophthalmic Res. 1995;27 Suppl 1:150-3. [Medline].

  67. Tzekov RT, Serrato A, Marmor MF. ERG findings in patients using hydroxychloroquine. Doc Ophthalmol. Jan 2004;108(1):87-97. [Medline].

  68. Warner AE. Early hydroxychloroquine macular toxicity. Arthritis Rheum. Aug 2001;44(8):1959-61. [Medline].

  69. Wei LC, Chen SN, Ho CL, Kuo YH, Ho JD. Progression of hydroxychloroquine retinopathy after discontinuation of therapy: case report. Chang Gung Med J. May 2001;24(5):329-34. [Medline].

  70. Weiner A, Sandberg MA, Gaudio AR, Kini MM, Berson EL. Hydroxychloroquine retinopathy. Am J Ophthalmol. Nov 15 1991;112(5):528-34. [Medline].

  71. Weise EE, Yannuzzi LA. Ring maculopathies mimicking chloroquine retinopathy. Am J Ophthalmol. Aug 1974;78(2):204-10. [Medline].

  72. Whitelaw D, Jessop S. Chloroquine-induced retinal toxicity. S Afr Med J. Feb 2005;95(2):72. [Medline].

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Further Reading

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Keywords

chloroquine, hydroxychloroquine, Aralen, Plaquenil, bull's eye maculopathy, toxicity

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Contributor Information and Disclosures

Author

Manolette R Roque, MD, MBA, DPBO, FPAO, President and CEO, Chief of Service, Ocular Immunology and Uveitis, Consulting Staff, Cornea and Refractive Surgery, Eye Republic Ophthalmology Clinic; General Manager, Ophthalmic Consultants Philippines Co; Consulting Staff, CME Liaison, Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center
Manolette R Roque, MD, MBA, DPBO, FPAO is a member of the following medical societies: American Academy of Ophthalmic Executives, American Society of Cataract and Refractive Surgery, American Society of Ophthalmic Administrators, American Uveitis Society, International Ocular Inflammation Society, Philippine Medical Association, Philippine Ocular Inflammation Society, and Philippine Society of Cataract and Refractive Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Barbara L Roque, MD, Full Partner, Ophthalmic Consultants Philippines Co, Chief of Service, Pediatric Ophthalmology and Strabismus, Consulting Staff, Orbit and Eye Plastics, EYE REPUBLIC Ophthalmology Clinic
Disclosure: Nothing to disclose.

C Stephen Foster, MD, FACS, FACR, FAAO, Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution
C Stephen Foster, MD, FACS, FACR, FAAO is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Association of Immunologists, American College of Rheumatology, American College of Surgeons, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, American Uveitis Society, Association for Research in Vision and Ophthalmology, Massachusetts Medical Society, Royal Society of Medicine, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Kilbourn Gordon III, MD, FACEP, Urgent Care Physician, Primary Medical, Huntington Walk-In and Greenwich Convenient Medical Center
Kilbourn Gordon III, MD, FACEP is a member of the following medical societies: American Academy of Ophthalmology and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

J James Rowsey, MD, Former Director of Corneal Services, St Luke's Cataract and Laser Institute, Florida
J James Rowsey, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American Medical Association, Association for Research in Vision and Ophthalmology, Florida Medical Association, Pan-American Association of Ophthalmology, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
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