Drug Safety

, Volume 17, Issue 3, pp 197–207 | Cite as

Drug-Induced Uveitis

Incidence, Prevention and Treatment
  • Frederick W. Fraunfelder
  • James T. Rosenbaum
Review Article Pharmacoepidemiology


Drug-induced uveitis is a relatively rare occurrence. For example, the patient database at the tertiary referral Uveitis Clinic at the Casey Eye Institute, Oregon Health Sciences University records an incidence of less than 0.5%. Despite this, the frequency of uveitis secondary to rifabutin therapy in AIDS patients has brought greater recognition to the potential role of medications as a cause of intraocular inflammation.

A brief review of uveitis including its classification, causes, symptoms and signs is presented along with a review of systemic medications associated with uveitis. These medications include cidofovir, cobalt, diethylcarbamazepine, pamidronic acid (disodium pamidronate), interleukin-3 and interleukin-6, oral contraceptives, quinidine, rifabutin, streptokinase and sulfonamides. Other systemic medications may cause uveitis. Topical ocular medications such as β-blockers and corticosteroids as well as other topical ocular medications have been associated with uveitis. Cidofovir, pamidronic acid, sulfonamides, rifabutin and topical metipranolol can ‘probably’ cause uveitis. The remainder of the medications discussed have a ‘possible’ cause-and-effect relationship with uveitis.

Treatment begins with recognition of a drug-related event and usually subsequent avoidance of the drug. Therapy depends on the severity and likelihood of the reaction. Drug-induced uveitis is almost always reversible within weeks of discontinuation of the drug and treatment of the inflammation.


Uveitis Streptokinase Latanoprost Interstitial Nephritis Cidofovir 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Rosenbaum JT, Holland GN. Uveitis and the Tower of Babel. Arch Ophthalmol 1996; 114: 604–5PubMedCrossRefGoogle Scholar
  2. 2.
    Rodrigues A, Calonge M, Pedroza-Seres M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol 1996; 114: 593–9CrossRefGoogle Scholar
  3. 3.
    Rothova A, Buitenhuis HJ, Meenken C, et al. Uveitis and systemic disease. Br J Ophthalmol 1992; 76: 137–41PubMedCrossRefGoogle Scholar
  4. 4.
    Rothova A, Suttorp-van Schulten MS, Frits Treffers W, et al Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 1996; 80: 2–6CrossRefGoogle Scholar
  5. 5.
    Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239–45PubMedCrossRefGoogle Scholar
  6. 6.
    Lea AP, Bryson HM. Cidofovir. Drugs 1996 Aug; 52(2): 225–30PubMedCrossRefGoogle Scholar
  7. 7.
    Ambati J, Robinson MR, McCannel C, et al. Intravenous Vis-tide (cidofovir) induced uveitis. American Uveitis Society Meeting; 1997 May 10; Fort LauderdaleGoogle Scholar
  8. 8.
    McCannel CA, Ambati J, Moe A, et al. Clinical characteristics of uveitis associated with systemic administration of cidofovir for treatment of CMV retinitis. Invest Ophthalmol Vis Sci 1997; 38(4): S914Google Scholar
  9. 9.
    Rahhal FM, Arevalo JF, Chavez de la Paz E, et al. Treatment of cytomegalovirus retinitis with intravitreous cidofovir in patients with AIDS: a preliminary report. Ann Intern Med 1996 Jul 15; 125(3): 144–55Google Scholar
  10. 10.
    Macdonald JC, Taskintuna I, Rahhal FM, et al. Intravitreal cidofovir (HPMPC) for the treatment of CMV retinitis: a dose escalating clinical trial. Invest Ophthalmol Vis Sci 1997; 38(4): S914Google Scholar
  11. 11.
    Freeman WR. New developments in the treatment of CMV retinitis. Ophthalmol 1996; 103(7): 999–1000Google Scholar
  12. 12.
    Gilman AG, Goodman LS, Gilman A, editors. The pharmacological basis of therapeutics. 6th ed. New York: Macmillan, 1980: 1326–7Google Scholar
  13. 13.
    Rorsman H, Dahlquist I, Jacobsson S, et al. Tattoo granuloma and uveitis. Lancet 1969; II: 27–8CrossRefGoogle Scholar
  14. 14.
    Hawking F. Diethylcarbamazine and new compounds for treatment of filariasis. Adv Pharmacol Chemother 1979; 16: 129–94PubMedCrossRefGoogle Scholar
  15. 15.
    Taylor HR, Greene BM. Ocular changes with oral and trans-epidermal diethylcarbamazepine therapy of onchocerciasis. Br J Ophthalmol 1981; 65: 494–502PubMedCrossRefGoogle Scholar
  16. 16.
    Fleisch H. Biphosphonates: pharmacology and use in the treatment of tumour-induced hypercalcaemia and metastatic bone disease. Drugs 1991; 42: 919–44PubMedCrossRefGoogle Scholar
  17. 17.
    Macarol V, Fraunfelder FT. Pamidronate disodium and possibleocular adverse drug reactions. Am J Ophthalmol 1994; 118: 220–4PubMedGoogle Scholar
  18. 18.
    Siris ES. Biphosphonates and iritis. Lancet 1993; 342: 436–7CrossRefGoogle Scholar
  19. 19.
    Robinson J, Abood E, Durham B, et al. The use of intravenous disodium pamidronate for the treatment of Paget’s disease of bone [abstract no. 42]. First International Symposium on Paget’s Disease of Bone: 1992 Aug; ManchesterGoogle Scholar
  20. 20.
    De S, Meyer P, Crisp AJ. Pamidronate and uveitis [letter]. Br J Rheumatol 1995; 34(5): 479PubMedCrossRefGoogle Scholar
  21. 21.
    Ghose K, Waterworth R, Trolove P, et al. Uveitis associated with pamidronate [letter]. Aust NZ J Med 1994; 24: 320CrossRefGoogle Scholar
  22. 22.
    O’Donnel NP, Rao GP, Aguis-Fernandez A. Paget’s disease: ocular complications of disodium pamidronate treatment. Br J Clin Pract 1995; 49(5): 272–3Google Scholar
  23. 23.
    Wu WC-S, Mannion B, Stone RM, et al. Uveitis associated with interleukin-3 and interleukin-6 therapy. Arch Ophthalmol 1995; 113: 408–9PubMedCrossRefGoogle Scholar
  24. 24.
    Murray PI, Hoekzema R, van Haren MAC, et al. Aqueous humor interleukin-6 levels in uveitis. Invest Ophthalmol Vis Sci 1990; 31: 917–20PubMedGoogle Scholar
  25. 25.
    Hoekzema R, Murray PI, van Haren MAC, et al. Analysis of interleukin-6 in endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 1991; 32: 88–95PubMedGoogle Scholar
  26. 26.
    Rosenbaum JT. Towards cytokine insight in sight. Br J Ophthalmol 1995; 79(11): 970–1PubMedCrossRefGoogle Scholar
  27. 27.
    Davidson SI. Reported adverse effects of oral contraceptives on the eye. Trans Ophthalmol Soc UK 1971; 91: 561–74PubMedGoogle Scholar
  28. 28.
    Walsh FB, Clark DB, Thompson RS, et al. Oral contraceptives and neuro-ophthalmic interest. AMA Arch Ophthalmol 1965; 74: 628–40CrossRefGoogle Scholar
  29. 29.
    Hustead JD. Granulomatous uveitis and quinidine hypersensitivity. Am J Ophthalmol 1991; 112(4): 461–2PubMedGoogle Scholar
  30. 30.
    Spitzberg DH. Acute anterior uveitis secondary to quinidine sensitivity [letter]. Arch Ophthalmol 1979; 97: 1993PubMedCrossRefGoogle Scholar
  31. 31.
    Caraco Y, Arnon R, Raveh D, et al. Quinidine-induced uveitis. Isr J Med Sci 1992; 28: 741–3PubMedGoogle Scholar
  32. 32.
    Brogden RN, Fitton A. Rifabutin: a review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 47(6): 983–1009PubMedCrossRefGoogle Scholar
  33. 33.
    Havlir D, Torriani F, Dube M. Uveitis associated with rifabutin prophylaxis. Ann Intern Med 1994; 121: 510–2PubMedGoogle Scholar
  34. 34.
    Siegal FP, Eilbott D, Burger H, et al. Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis. AIDS 1990; 4(5): 433–41PubMedCrossRefGoogle Scholar
  35. 35.
    Shafran SD, Deschenes J, Miller M, et al. Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol [letter]. MAC Study Group of the Canadian HIV Trials Network. N Engl J Med 1994; 330(6): 438–9PubMedCrossRefGoogle Scholar
  36. 36.
    Frank MO, Graham MB, Wispelway B. Rifabutin and uveitis [letter]. N Engl J Med 1994; 330(12): 868PubMedCrossRefGoogle Scholar
  37. 37.
    Fuller JD, Stanfield LE, Craven DE. Rifabutin prophylaxis and uveitis [letter]. N Engl J Med 1994; 330(18): 1315–6PubMedCrossRefGoogle Scholar
  38. 38.
    Saran BR, Maguire AM, Nichols C, et al. Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin. Arch Ophthalmol 1994; 112: 1159–65PubMedCrossRefGoogle Scholar
  39. 39.
    Becker K, Vogt C, Armbrecht C. et al. Evidence for an association of rifabutin treatment with severe uveitis in HIV-in-fected patients [abstract]. 2nd International Congress on Drug Therapy in HIV Infection. 1994 Nov 10–22, GlasgowGoogle Scholar
  40. 40.
    Kelleher P, Helbert M, Anderson J, et al. Uveitis and rifabutin [abstract]. 2nd International Congress on Drug Therapy in HIV Infection. 1994 Nov 10–22, GlasgowGoogle Scholar
  41. 41.
    Jacobs DS, Piliero PJ, Kuperwaser MG, et al. Acute uveitis associated with rifabutin use in patients with HIV infection. Am J Ophthalmol 1994; 118: 716–22PubMedGoogle Scholar
  42. 42.
    Chaknis MJ, Brooks SE, Mitchell KT, et al. Inflammatory opacities in the vitreous in rifabutin associated uveitis. Am J Ophthalmol 1996; 122(4): 580–2PubMedGoogle Scholar
  43. 43.
    Dunn AM, Tizer K, Cervia JS. Rifabutin-associated uveitis in a pediatric patient. Pediatr Infect Dis J 1995 (14); 3: 246–7Google Scholar
  44. 44.
    Tseng AL, Walmsley SL. Rifabutin-associated uveitis. Ann Pharmacother 1995; 29: 1149–55PubMedGoogle Scholar
  45. 45.
    Nichols CW. Mycobacterium avium complex infection, rifabutin, and uveitis: is there a connection? Clin Infect Dis 1996; 22Suppl. 1: S43–9PubMedCrossRefGoogle Scholar
  46. 46.
    Fraunfelder FT, Grove JA. Antitubercular agents. In: Fraunfelder FT, Grove JA, editors. Drug-induced ocular side effects and drug interactions. Media, Pennsylvania: Williams and Wilkins, 1996: 77–8Google Scholar
  47. 47.
    Bell WR, Meek AG. Guidelines for the use of thrombolytic agents. N Engl J Med 1979; 301: 1266–70PubMedCrossRefGoogle Scholar
  48. 48.
    Proctor BD, Joondeph BC. Bilateral uveitis: a feature of streptokinase-induced serum sickness. N Engl J Med 1994; 330: 576PubMedCrossRefGoogle Scholar
  49. 49.
    Schweitzer DH, van der Wall EE, Bosker HA, et al. Serum sickness-like illness as a complication after streptokinase therapy for acute myocardial infarction. Cardiology 1991; 78: 68–71PubMedCrossRefGoogle Scholar
  50. 50.
    Gray MY, Lazarus JH. Iritis after treatment with streptokinase. BMJ 1994; 309: 97PubMedGoogle Scholar
  51. 51.
    Kinshuck D. Bilateral hypopyon and streptokinase. BMJ 1992; 305: 1332PubMedCrossRefGoogle Scholar
  52. 52.
    Hoigne R, Malinverni R, Schopfer K. Sulfonamides and miscellaneous antibacterial and antiviral drugs. In: Dukes MNG, editor. Meyler’s side effects of drugs. Amsterdam: Elsevier, 1988: 603–32Google Scholar
  53. 53.
    Fujardo RV. Acute bilateral anterior uveitis caused by sulfa drugs. In: Saari KM, editor. Uveitis update. Princeton (NJ): Excerpta Medica, 1984: 115–8Google Scholar
  54. 54.
    Tilden ME, Rosenbaum JT, Fraunfelder FT. Systemic sulfonamides as a cause of bilateral, anterior uveitis. Arch Ophthalmol 1991; 1: 67–9CrossRefGoogle Scholar
  55. 55.
    Donaldson RC, Canaan SA, McLean RB, et al. Uveitis and vitiligo associated with BCG treatment for malignant melanoma. Surgery 1974; 76: 771–8PubMedGoogle Scholar
  56. 56.
    Brezin AP, Boudin M, Massin-Korobelnik P, et al. Acute posterior multifocal placoid pigment epitheliopathy after immunization with recombinant hepatitis B vaccine. ARVO Abstracts. Invest Ophthalmol Vis Sci 1994; 35 (4 Suppl.): 2102Google Scholar
  57. 57.
    Donatini B, Goetz J, Hauptmann G. Uveitis and antineutrophil cytoplasmic antibody in immunoglobulin batches. Lancet 1992; 339: 1175–6PubMedCrossRefGoogle Scholar
  58. 58.
    Grant WM, Schuman JS. Toxicology of the eye. Thomas CC, editor. 4th ed. Springfield (IL): Charles C Thomas Publishers Ltd, 1993: 1142–415Google Scholar
  59. 59.
    Kass MA, Gieser DK, Hodapp E. et al. Corticosteroid-induced iridocyclitis in a family. Am J Ophthalmol. 1982; 93: 368–9PubMedGoogle Scholar
  60. 60.
    Martins JC, Wilensky JT, Asseff CF, et al Corticosteroid-induced uveitis. Am J Ophthalmol 1974; 77: 433–7PubMedGoogle Scholar
  61. 61.
    Krupin T, LeBlanc RP, Becker B, et al. Uveitis in association with topically administered corticosteroid. Am J Ophthalmol 1970; 70: 883–5PubMedGoogle Scholar
  62. 62.
    Xalatan (latanoprost solution) sterile ophthalmic solution [package insert]. Kalamazoo, MI: Pharmacia Inc; 1996Google Scholar
  63. 63.
    Mishima HK, Masuda K, Kitazawa Y, et al. A comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension. Arch Ophthalmol 1996; 114: 929–932PubMedCrossRefGoogle Scholar
  64. 64.
    Camras CB, Aim A, Watson P. Latanoprost, a prostaglandin analog, for glaucoma therapy: efficacy and safety after 1 year of treatment in 198 patients. Ophthalmology 1996; 103: 1916–24PubMedGoogle Scholar
  65. 65.
    Battershill PE, Sorkin EM. Ocular metipranolol: a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in glaucoma and ocular hypertension. Drugs 1988; 36: 601–15PubMedCrossRefGoogle Scholar
  66. 66.
    Sorensen SJ, Abel SR. Comparison of the ocular beta-blockers. Ann Pharmacother 1996; 30: 43–53PubMedGoogle Scholar
  67. 67.
    Melles RB. Metipranolol-associated granulomatous iritis. Am J Ophthalmol. 1994; 118: 712–5PubMedGoogle Scholar
  68. 68.
    Schulz JS, Hoenig JA, Charles H. Possible bilateral anterior uveitis secondary to metipranolol therapy. Arch Ophthalmol. 1993; 111: 1606–1607CrossRefGoogle Scholar
  69. 69.
    Beck RW, Moke P, Blair RC, et al. Uveitis associated with topical beta-blockers. Arch Ophthalmol 1996; 114: 1181–2PubMedCrossRefGoogle Scholar
  70. 70.
    Akingbehin T, Villada JR, Walley T. Metipranolol-induced adverse reactions. I. The rechallenge study. Eye 1992; 6: 277–9PubMedCrossRefGoogle Scholar
  71. 71.
    Akingbehin T, Villada JR. Metipranolol-associated granulomatous anterior uveitis. Br J Ophthalmol 1991; 75: 519–23PubMedCrossRefGoogle Scholar
  72. 72.
    Kebler C. Possible bilateral anterior uveitis secondary to metipranolol (optipranolol) therapy [letter]. Arch Ophthalmol 1994; 112: 1277PubMedCrossRefGoogle Scholar
  73. 73.
    Kessler C, Christ T. Incidence of uveitis in glaucoma patients using metipranolol. J Glaucoma 1993; 2: 166–70PubMedCrossRefGoogle Scholar
  74. 74.
    Kinshuck D. Glauline- (metipranolol) induced uveitis and increase in ocular pressure [letter]. Br J Ophthalmol 1991; 75: 575PubMedCrossRefGoogle Scholar
  75. 75.
    Zimmerman TJ, Baumann JD, Hetherington J. Side effects of timolol. Surv Ophthalmol 1983; 28: 243–9PubMedCrossRefGoogle Scholar
  76. 76.
    Van Buskirk EM. Adverse reactions from timolol administration. Ophthalmology 1980; 87: 447–50PubMedGoogle Scholar
  77. 77.
    Jain S. Betaxolol-associated anterior uveitis. Eye 1994; 8: 708–9PubMedCrossRefGoogle Scholar
  78. 78.
    Betagan (levobunolol Hcl) ophthalmic solution [package insert]. Irvine (CA): Allergan Inc; 1996Google Scholar
  79. 79.
    Fraunfelder FT, Grove JA. Antitubercular agents. In: Fraunfelder FT, Grove JA. editors. Drug-induced ocular side effects and drug interactions. Media, (PA): Williams and Wilkins; 1996, 52–4Google Scholar
  80. 80.
    Fraunfelder FT, Grove JA. Antitubercular agents. In: Fraunfelder FT, Grove JA, editors. Drug-induced ocular side effects and drug interactions. Media (PA): Williams and Wilkins; 1996, 447–50Google Scholar
  81. 81.
    Fraunfelder FT, Grove JA. Antitubercular agents. In: Fraunfelder FT, Grove JA, editors. Drug-induced ocular side effects and drug interactions. Media, (PA): Williams and Wilkins; 1996, 473–5Google Scholar
  82. 82.
    Appel GB. A decade of penicillin-related acute interstitial nephritis: more questions than answers. Clin Nephrol 1980; 13: 151–4PubMedGoogle Scholar
  83. 83.
    Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1984; 310: 563–72PubMedCrossRefGoogle Scholar
  84. 84.
    Rosenbaum JT. Bilateral anterior uveitis and interstitial nephritis. Am J Ophthalmol 1988; 105: 534–7PubMedGoogle Scholar
  85. 85.
    Rosenbaum JT. An algorithm for the systemic evaluation of patients with uveitis: guidelines for the consultant. Semin Arthritis Rheum 1990; 19(4): 248–57PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Frederick W. Fraunfelder
    • 1
  • James T. Rosenbaum
    • 1
  1. 1.Department of Ophthalmology, Casey Eye InstituteOregon Health Sciences UniversityPortlandUSA

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