eMedicine Specialties > Ophthalmology > Unclassified Disorders

Chloroquine/Hydroxychloroquine Toxicity: Multimedia

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

Multimedia

Fluorescein angiogram of left macula in patient w...
(Enlarge Image)
Media file 1: Fluorescein angiogram of left macula in patient with hydroxychloroquine retinopathy. Reprinted from American Journal of Ophthalmology, Vol 104, Johnson and Vine, Hydroxychloroquine therapy in massive total doses without retinal toxicity, pages 139-144, Copyright 1987, with permission from Elsevier Science.
[ CLOSE WINDOW ]
Fluorescein angiogram of left macula in patient w...

Fluorescein angiogram of left macula in patient with hydroxychloroquine retinopathy. Reprinted from American Journal of Ophthalmology, Vol 104, Johnson and Vine, Hydroxychloroquine therapy in massive total doses without retinal toxicity, pages 139-144, Copyright 1987, with permission from Elsevier Science.

Membranous cytoplasmic bodies in ganglion cell of...
(Enlarge Image)
Media file 2: Membranous cytoplasmic bodies in ganglion cell of retina. (N=nucleus) (X12,500.) Reprinted from American Journal of Ophthalmology, Vol 67, Gleiser CA, Dukes TW, Lawwill T, Read WK, Bay WW, Brown RS. Ocular changes in swine associated with chloroquine toxicity, pages 399-405, Copyright 1969, with permission from Elsevier Science.
[ CLOSE WINDOW ]
Membranous cytoplasmic bodies in ganglion cell of...

Membranous cytoplasmic bodies in ganglion cell of retina. (N=nucleus) (X12,500.) Reprinted from American Journal of Ophthalmology, Vol 67, Gleiser CA, Dukes TW, Lawwill T, Read WK, Bay WW, Brown RS. Ocular changes in swine associated with chloroquine toxicity, pages 399-405, Copyright 1969, with permission from Elsevier Science.

Swollen ganglion cells with foamy cytoplasm (Hema...
(Enlarge Image)
Media file 3: Swollen ganglion cells with foamy cytoplasm (Hematoxylin-eosin, X500). Reprinted from American Journal of Ophthalmology, Vol 67, Gleiser CA, Dukes TW, Lawwill T, Read WK, Bay WW, Brown RS. Ocular changes in swine associated with chloroquine toxicity, pages 399-405, Copyright 1969, with permission from Elsevier Science.
[ CLOSE WINDOW ]
Swollen ganglion cells with foamy cytoplasm (Hema...

Swollen ganglion cells with foamy cytoplasm (Hematoxylin-eosin, X500). Reprinted from American Journal of Ophthalmology, Vol 67, Gleiser CA, Dukes TW, Lawwill T, Read WK, Bay WW, Brown RS. Ocular changes in swine associated with chloroquine toxicity, pages 399-405, Copyright 1969, with permission from Elsevier Science.

A 53-year-old female with a complaint of somethin...
(Enlarge Image)
Media file 4: A 53-year-old female with a complaint of something "funny" with her vision. The possibility of hydroxychloroquine toxicity was entertained, although clinical evidence was not found. Color vision testing and funduscopic examination were normal. A full field electroretinogram was normal, but foveal cone electroretinograms were reduced bilaterally. These findings prompted the question of possible early hydroxychloroquine retinopathy.
[ CLOSE WINDOW ]
A 53-year-old female with a complaint of somethin...

A 53-year-old female with a complaint of something "funny" with her vision. The possibility of hydroxychloroquine toxicity was entertained, although clinical evidence was not found. Color vision testing and funduscopic examination were normal. A full field electroretinogram was normal, but foveal cone electroretinograms were reduced bilaterally. These findings prompted the question of possible early hydroxychloroquine retinopathy.

The same patient as described in Media file 4 (ot...
(Enlarge Image)
Media file 5: The same patient as described in Media file 4 (other eye, left eye). The patient (with foveal cone electroretinogram reduction) had abnormal computerized acuity mapping of the macula results.
[ CLOSE WINDOW ]
The same patient as described in Media file 4 (ot...

The same patient as described in Media file 4 (other eye, left eye). The patient (with foveal cone electroretinogram reduction) had abnormal computerized acuity mapping of the macula results.

An Amsler grid is used to assess the central port...
(Enlarge Image)
Media file 6: An Amsler grid is used to assess the central portion of the macula. This simple test is helpful for patients to monitor their vision at home.
[ CLOSE WINDOW ]
An Amsler grid is used to assess the central port...

An Amsler grid is used to assess the central portion of the macula. This simple test is helpful for patients to monitor their vision at home.

More on Chloroquine/Hydroxychloroquine Toxicity

Overview: Chloroquine/Hydroxychloroquine Toxicity
Differential Diagnoses & Workup: Chloroquine/Hydroxychloroquine Toxicity
Treatment & Medication: Chloroquine/Hydroxychloroquine Toxicity
Follow-up: Chloroquine/Hydroxychloroquine Toxicity
Multimedia: Chloroquine/Hydroxychloroquine Toxicity
References
[ CLOSE WINDOW ]

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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

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

[ CLOSE WINDOW ]

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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.