Chloroquine-Induced Retinal Gangliopathy: A Literature Review and Consideration of its Use as a Screening Procedure

1. Abraham, R. , and Hendy, R. J. : Irreversible Lysosomal Damage Induced by Chloroquine in the Retinae of Pigmented and Albino Rats. Exp. Mol. Pathol. 12: 185–200, 1970.

2. Abraham, R., and Hendy, R. J.: Retinal Lysosomal Changes in Pigmented and Albino Rats Treated with Chloroquine. Abstract No. 65, page 53, 9th Annual Meeting, Society of Toxicology, 1970.

2a. Abraham, R. , and Hendy, R. J. : Effects of Chronic Treatment on Lysosomes of Rat Liver Cells. Exp. Mol. Pathol. 12: 148–159, 1970.

3. Abraham, R. , Hendy, R. , and Grasso, P. : Formation of Myeloid Bodies in Rat Liver Lysosomes After Chloroquine Administration. Exp. Mol. Pathol. 9: 212–229, 1968.

4. Abraham, R. , Hume, M. , and Smith, J. A. : Histochemical Study of Lysosomal Enzymes in the Retina of the Rat. Histochemie 18: 195–201, 1969.

5. Alving, A. S. , Eichelberger, L. , Graige, B. Jr. , Jones, R. Jr. , Whorton, C. M. , and Pullman, T. N. : Studies on the Chronic Toxicity of Chloroquine (SN-7618). J. Clin. Invest. 27: 60–65, 1948.

6. Annotations , Eye Changes with Chloroquine. Brit. Med. J. 1: 812–813, 1966.

7. Baccino, F. M. : Lysosomal Involvement in Liver Cell Vacuolation by Hypoxia. Brit. J. Exp. Path. 50: 150–152, 1969.

8. Bagnall, A. W. : The Value of Chloroquine in Rheumatoid Disease. A Four-Year Study of Continuous Therapy. Can. Med. Assn. J. 77: 182–194, 1957.

9. Berato, J. , Commandre, F. , Albatro, J. , and Gilly, R. : A Propos d'une Observation de Syndrome Oculo-neuro-myopathique par Intoxication à la Chloroquine. Rhumatologie 21: 123–125, 1969.

10. Berliner, R. W. , Earle, E. P. Jr. , Taggert, J. V. , Zubrod, C. G. , Welch, W. J. , Cannon, N. J. , Bauman, E. , Scudder, S. T. , and Shannon, J. A. : Studies of the Chemotherapy of the Human Malarias. VI. The Physiological Disposition, Antimalarial Activity, and Toxicity of Several Derivatives of 4-Aminoquinoline. J. Clin. Invest. 27: Suppl. 98-107, 1948.

11. Bernstein, H. N. : Chloroquine Ocular Toxicity. Survey Ophthal. 12: 415–417, 1967.

12. Bernstein, H. N. : Chloroquine Ocular Toxicity. In Symposium on Ocular Pharmacology and Therapeutics. C. V. Mosby Co., St. Louis, pp. 164–189, 1970.

13. Bernstein, H. N. , and Ginsberg, J. : The Pathology of Chloroquine Retinopathy. Arch. Ophthal. 71: 238–245, 1964.

14. Bernstein, H. , Zvaifler, N. , Rubin, M. , and Mansour, A. : The Ocular Deposition of Chloroquine. Invest. Ophthal. 2: 384–392, 1963.

15. Calkins, L. L : Corneal Epithelial Changes Occurring During Chloroquine (Aralen) Therapy. Arch. Ophthal. 60: 981–988, 1958.

16. Cambiaggi, A. : Unusual Ocular Lesions in a Case of Systemic Lupus Erythematosus. Am. J. Ophthal. 57: 451–453, 1957.

17. Ciak, J. , and Hahn, F. : Chloroquine: Mode of Action. Science 151: 347–349, 1966.

18. Cogan, D. G. , and Kuwabara, T. : The Sphingolipidoses and the Eye. Arch. Ophthal. 79: 437–452. 1968.

19. Dale, A. J. D. , Parkill, E. M. , and Layton, D. D. : Studies in Chloroquine Retinopathy in Rabbits. JAMA. 193: 241–243, 1965.

20. Dame, L. R. : The Effects of Atabrine on the Human Visual System. Am. J. Ophthal. 29: 1432–1434, 1946.

21. Datta, A. , and Basu, U. : Studies on the Action of Antimalarial Drugs on Enzyme Systems: Part II. Some Quinoline-Containing Drugs on the Enzymes of the Tricarbolic Acid Cycle. J. Sci. Indust. Res. 146: 5–61, 1955.

22. Davidorf, F. H. : Ocular Toxicity of Systemic Drugs. Ohio State Med. J. 68: 1022–1026, 1972.

23. Dubois, E. L. : Systemic Lupus Erythematosus. Recent Advances in its Diagnosis and Treatment. Ann. Intern. Med. 45: 163–184, 1956.

24. Eadie, M. J. , and Ferrier, T. M. : Chloroquine Myopathy. J. Neurol Neurosurg. Psychiat. 29: 331–337, 1966.

25. Elfenbein, B. I. : Dystonie Juvenile Idiocy without Amaurosis: A New Syndrome Light-and Electron-Microscopic Observation of Cerebrum. John Hopkins Med. J. 123: 205–221, 1968.

26. Ellis, P. P. : Ocular Complications of Systemic Medications. Texas Med. 67: 70–73, 1971.

27. Ellsworth, R. J. , and Zeller, R. W. : Chloroquine-(Aralen-) Induced Retinal Damage. Arch. Ophthal. 66: 269–272, 1961.

28. Fedorko, M. : Effect of Chloroquine on Morphology of Cytoplasmic Granules in Maturing Human Leukocytes: An Ultrastructural Study. J. Clin. Invest. 46: 1932–1942, 1967.

29. Fedorko, M. E. : Effect of Chloroquine on Morphology of Leukocytes and Pancreatic Exocrine Cells from the Rat. Lab. Invest. 18: 27–37, 1968.

30. Fedorko, M. E. , Hirsch, J. G. , and Cohn, Z. A. : Autophagic Vacuoles Produced In Vitro. I. Studies on Cultured Macrophages Exposed to Chloroquine. J. Cell. Biol. 38: 377–391, 1968.

31. François, J. , De Rauck, A. , Cambie, E. , and De Laey, J. J. : Retinopathie Chloroquinique. Bull. Soc. Beige. Opthal. 160: 581–590, 1972.

32. François, J. , and Maudgal, M. C. : Experimental Chloroquine Retinopathy. Ophthalmologica, Basel. 148: 442–452, 1964.

33. François, J. , and Maudgal, M. C. : Experimental Chronic Chloroquine Intoxication. Med. Pharmac. Exp. 16: 579–590, 1967.

34. François, J. , and Maudgal, M. C. : Experimentally Induced Chloroquine Retinopathy in Rabbits. Am. J. Ophthal. 64: 886–893, 1967.

35. Fuhrmann, G. , and Koenig, K. : Untersuchungen über die Resorptions-und Ausscheidungs-Verhältnisse von Resortren, Resachin, und Yatren. Ztschr. Tropenmed. u. Parasitol. 4: 155–161, 1953.

36. Fuld, H. : Retinopathy Following Chloroquine Therapy. Lancet 2: 617–618, 1959.

37. Gleiser, C. A. , Bay, W. W. , Dukes, T. W. , Brown, R. S. , Read. W. K. , and Pierce, K. R. : Study of Chloroquine Toxicity and a Drug-Induced Cerebrospinal Lipodystrophy in Swine. Am. J. Path. 53: 27–45, 1968.

38. Gleiser, C. A. , Dukes, T. W. , Lawwill, T. , Read, W. K. , Bay, W. W. , and Brown, R. S. : Ocular Changes in Swine Associated with Chloroquine Toxicity. Amer. J. Ophthal. 67: 399–405, 1969.

39. Goldman, L. , Cole, D. P. , and Preston, R. H. : Chloroquine Diphosphate in Treatment of Discoid Lupus Erythematosus. JAMA. 152: 1428–1429, 1953.

40. Goldmann, L. , and Preston, R. H. : Reactions to Chloroquine Observed During the Treatment of Various Dermatologic Disorders. Am. J. Trop. Med. 6: 654–657, 1957.

41. Gonasun, L. M. , and Potts, A. M. : In Vitro Inhibition of Protein Synthesis in the Retinal Pigment Epithelium by Chloroquine. Invest. Ophthal. 13: 107–115, 1974.

42. Gregory, M. H. , Rutty, D. A. , and Wood, R. D. : Retinal Changes and Chloroquine. Brit. Med. J. 2: 428–429, 1968.

43. Gregory, M. H. , Rutty, D. A. , and Wood, R. D. : Differences in the Retinotoxic Action of Chloroquine and Phenothiazine Derivatives. J. Path. 102: 139–150, 1970.

44. Harcourt, R. B. , and Dobbs, R. H. : Ultrastructure of Retina in Tay-Sach's Disease. Brit. J. Ophthal. 52: 898–902, 1968.

45. Hendy, R. , Abraham, R. , and Grasso, P. : The Effect of Chloroquine on Rat Heart Lysosomes. J. Ultrastruct. Res. 29: 488–495, 1969.

46. Henkind, P. , Carr, R. E. , and Siegel, I. M. : Early Chloroquine Retinopathy, Clinical and Functional Findings. Arch. Ophthal. 71: 157–165, 1964.

47. Hobbs, H. E. , and Calnan, C. D. : Visual Disturbances with Antimalarial Drugs, with Particular Reference to Chloroquine Keratopathy. Arch. Derm. 80: 557–563, 1959.

48. Hobbs. H. E. , Eadie, S. P. , and Somerville, F. : Ocular Lesions after Treatment with Chloroquine. Brit. J. Ophthal. 45: 284–297,1961.

49. Hobbs. H. E. , Sorsby, A. , and Freeman, A. : Retinopathy Following Chloroquine Therapy. Lancet 2: 478–480, 1959.

50. Hodgkinson, J. B. , and Kolb, H. : A Preliminary Study of the Effect of Chloroquine on the Rat Retina. Arch. Ophthal. 84: 509–515,1970.

51. Holtzman, E. , Novikoff, A. B. , and Villaverde, H. : Lysosomes and Gerl in Normal and Chromatolytic Neurons of the Rat Ganglion Nodosum. J. Cell Biol. 33: 419–435, 1967.

52. Hori, Y. , Toda, K. , Pathak, M. A. , Clark, W. H. , and Fitzpatrick, T. B. : A Fine Structure Study of the Human Epidermal Melanosome Complex and its Acid Phosphatase Activity. J. Ultrastruct. Res. 25: 109–120, 1968.

53. Karbe, E. , and Schiefer, B. : Familial Amaurotic Idiocy in Male German Shorthair Pointers. Path, Vet. 4: 223–232, 1967.

54. Koppang, N. : Famileare Glykosphinolipoidose des Hundes (Juvenile Amaurotische Idiotie). Ergebn. Allg. Path. 47: 1–43, 1966.

55. Kurnick, M. , and Radcliffe, I. : Reaction Between DNA and Quinacrine and Other Antimalarials. J. Lab. Clin. Med. 54: 669–688, 1962.

56. Kuroda, K. : Detection and Distribution of Chloroquine Metabolites in Human Tissues. J. Pharmacol. Exper. Therap. 137: 156–161, 1962.

57. Lane, R. : The Treatment of Hepatic Amoebiasis with Chloroquine. I. Hepatic Amoebiasis. J. Trop. Med. 54: 198–206, 1951.

58. Lefler, C. F. , Lilja, H. S. , and Holbrook, D. J. Jr. : Inhibition of Aminoacylation and Polypeptide Synthesis by Chloroquine and Primaquine in Rat Liver In Vitro. Biochem. Pharmacol. 22: 715–728, 1973.

59. Mayer, W. : Chloroquine Retinopathy. Am. J. Ophthal. 53: 769–774, 1962.

60. McChesney, E. W. , Bank, W. F. Jr. , and Fabian, R. J. : Tissue Distribution of Chloroquine, Hydroxychloroquine, and Desethylchloroquine in the Rat. Toxicol. Appl. Pharmacol. 20: 501–513, 1967.

61. McChesney, E. W. , Bank, W. F. Jr. , and Sullivan, D. J. : Metabolism of Chloroquine and Hydroxychloroquine in Albino and Pigmented Rats. Toxicol. Appl. Pharmacol. 7: 627–635, 1965.

62. McChesney, E. W. , and McAuliff, J. P. : Laboratory Studies of the 4-Aminoquinoline Antimalarials. I. Some Biochemical Characteristics of Chloroquine Hydroxychloroquine, and SN-7718. Antibiotics Chemother. 11: 800–810, 1961.

63. Meier-Ruge, W. : Experimental Investigation of Morphogenesis of Chloroquine Retinopathy. Arch. Ophthal. 73: 540–544, 1965.

64. Meier-Ruge, W. : Die Morphologie der Experimentellen Chlorochinretinopathie des Kaninchens. Ophthalmologica 150: 127–137, 1965.

65. Meier-Ruge, W., and Cerletti, A.: Experimental Pathology of Chloroquine and Phenothiazine Retinopathy. Excerpta Med. Int. Congr. Ser. No. 146: Proc. XX Int. Ophthal. Congr. 1129-1136, 1966.

66. Mushinski, J. , Yielding, K. , and Munday, J. : A Comparison of the In Vitro Effect of Steroid Hormone and Certain Antimalarials. Arthritis Rheum. 5: 118, 1962.

67. Monahan, R. H. , and Horns, R. C. : The Pathology of Chloroquine in the Eye. Trans. Am. Acad. Ophthal. Otolaryng. 68: 40–44, 1964.

68. Nelson, A. A. , and Fitzhugh, O. : Chloroquine (SN-7618): Pathologic Changes Observed in Rats Which for Two Years Had Been Fed Various Proportions. Arch, Path. 45: 454–462, 1948.

69. Nylander, U. : Ocular Damage in Chloroquine Therapy. Acta Ophthalmol. 92: (Kobenhavn), Suppl.1-77, 1966.

70. Okun, E. , Gouras, P. , Bernstein, H. , and von Sallman, L. : Chloroquine Retinopathy. A Report of Eight Cases with ERG and Dark-Adaptation Findings. Arch. Ophthal. 69: 59–71,1963.

71. Pambor, R. , and Pambor, M. : Augenveränderungen bei Intermittierender Chlorochintherapie und Dermatologischer Indikation. Dtsch. Gesundheitsw. 25: 2091–2095, 1970.

72. Parker, F. S. , and Irvin, J. L. : The Interaction of Chloroquine with Nucleic Acids and Nucleoproteins. J. Biol. Chem. 199: 897–909, 1952.

73. Penner, R. , and Somers, K. : Bilateral Macular Degeneration Associated with Chloroquine Therapy. Am. J. Ophthal. 54: 381–385, 1962.

74. Percival, S. P. B. , and Behrman, J. : Ophthalmological Safety of Chloroquine. Brit. J. Ophthal. 53: 101–109, 1969.

75. Percival, S. P. B. , and Meancock, I. : Chloroquine Ophthalmological Safety, and Clinical Assessment in Rheumatoid Arthritis. Brit. Med. J. 3: 579–584, 1968.

76. Pinckers, A. : Oorspronkelijke Stukken Oogafivijkingen door Chloroquine en Hydroxychloroquine. Ned. T. Geneesk. 244: 631–636, 1970.

77. Potts. A. M. : Uveal Pigment and Phenothiazine Compounds. Tr. Am. Ophthol. Soc. 60: 517–652, 1962.

78. Potts. A. M. : Further Studies Concerning the Accumulation of Polycyclic Compounds on Uveal Melanin. Invest. Ophthal. 3: 399–404, 1964.

79. Potts. A. M. : The Reaction of Uveal Pigment in Vitro with Polycyclic Compounds. Invest. Ophthalmol. 3: 405–416, 1964.

80. Ramsey, M. S. , and Fine, B. S. : Chloroquine Toxicity in the Human Eye; Histopathologic Observations by Electron Microscopy. Am. J. Ophthal. 73: 229–235, 1972.

81. Read, W. K. , and Bay, W. W. : Basic Cellular Lesion in Chloroquine Toxicity, Lab. Invest. 24: 246–259,1971.

82. Rebello, D. J. A. : Ocular Reactions to Antimalarial Drugs. Arch. Dermatol. 83: 785–789, 1961.

83. Reinert, H., and Rutty, D. A.: Mechanisms of Chloroquine and Phenothiazine Retinopathies. Abstract 59, p. 47, 8th Annual Meeting, Society of Toxicology, 1969.

84. Richards, R. D. , and Wilson, W. R. : Retinopathy Associated with Chloroquine Phosphate Therapy. Am. J. Med. 32: 140–143, 1961.

85. Roskoski, R. Jr. , and Jaskunas, S. R. : Chloroquine and Primaquine Inhibition of Rat Liver Cell-Free Polynucleotide-Dependent Polypeptide Synthesis. Biochem. Pharmacol. 21: 391–399, 1972.

86. Rubin, M. , Bernstein, H. , and Zvaifler, N. : Studies on the Pharmacology of Chloroquine with Recommendations for Treatment of Chloroquine Retinopathy. A. M. A. Arch. Ophthol. 70: 474–481, 1963.

87. Rubin, M. , and Slonicki, A. : A Mechanism for the Toxicity of Chloroquine. Arthritis Rheumat. 9: 537, 1966,

88. Samuels, S. , Korey, S. R. , Gonatas, J. , Terry, R. D. , and Weiss, M. : Studies in Tay-Sach's Disease. J. Neuropath. Exp. Neurol. 22: 81–97, 1963.

89. Samuels, S. , Gonatas, N. K. , and Weiss, M. : Formation of the Membranous Cytoplasmic Bodies. J. Neuropath. Exp. Neurol. 24: 256–264, 1965.

90. Shearer, R. V. , and Dubois, E. L. : Ocular Changes Induced by Long-Term Hydroxychloroquine (Plaquenil) Therapy. Am. J. Ophthal. 64: 245–252,1967.

91. Smith, J. L : Chloroquine Macular Degeneration. Arch. Ophthal. 68: 186–190,1962.

92. Sternberg, T. H. , and Laden, E. : Discoid Lupus Erythematosus. Bilateral Macular Degeneration due to Chloroquine. Arch. Derm. 79: 116–118,1959.

93. Terry, R. D. , and Weiss, M. : Studies in Tay-Sach's Disease. II. Ultrastructure of the Cerebrum. J. Neuropath. Exp. Neurol. 22: 18–55, 1963.

94. Thompson, S. W. : Baker's Acid Hematin Test for Phospholipids with a Nuclear Red Counterstain. In Selected Histochemical and Histopathological Methods. Charles C. Thomas, Springfield, Illinois, pp. 345–347, 1966.

95. Ullberg, S. , Lindquist, N. G. , and Sjöstrand, S. E. : Accumulation of Chorio-Retinotoxic Drugs in the Foetal Eye. Nature 227: 1257–1258, 1970.

95a. Volk, B. W. , and Wallace, B. J. : The Liver in Lipidosis. An Electron-Microscopic and Histochemical Study. Am. J. Path. 49: 203–225, 1966.

96. Wallace, B. J. , Volk, B. W. , and Lazarus, S. S. : Fine Structural Localization of Acid Phosphatase Activity in Neurons in Tay-Sach's Disease. J. Neuropath. Exp. Neurol. 23: 676–691,1964.

97. Weissmann, G. : Lysosomesand Joint Disease. Arthritis. Rheumat. 9: 834–839, 1966.

98. Wetterholm, D. H. , and Winter, F. C : Histopathology of Chloroquine Retinal Toxicity. Arch. Ophthal. 71: 82–87, 1964.

99. Whisnant, J. P. , Espinosa, R. E. , Kierland, R. R. , and Lambert, E. G. : Chloroquine Neuromyopathy. Proc. Staff Meet. Mayo Clinic. 38: 501–513, 1963.

100. Whittem, J. H. , and Walker, D. : Neuropathy and Pseudolipidosis in Aberdeen-Angus Calves. J. Path. Bact. 74: 281–288,1957.

101. Wilson, W. : Retinopathy During Chloroquine Therapy. Brit. J. Ophthal. 45: 756–758, 1961.

102. Wright, C. , and Sabine, J. : Cholinesterases of Human Erythrocytes and Plasma and Their Inhibition by Antimalarial Drugs. J. Pharma. Exp. Ther. 93: 230–239, 1948.

103. Yanagisawa, Y. , and Takase, M. : Chloroquine Retinopathy, Societatis Ophthalmologicae Japonicae, Acta (Supplementum). 75: 609–618, 1971.

104. Zelter, R. W. , and Deering, D. : Corneal Complications of Chloroquine (Aral en) Phosphate Therapy. JAMA. 168: 2263–2264, 1958.

105. Zvaifler, N. J. : Antimalarial Treatment of Rheumatoid Arthritis. Med. Clin. N. Amer. 52: 759–764, 1968.