Skip to main content
Log in

Drug-Induced Uveitis

Incidence, Prevention and Treatment

  • Review Article
  • Pharmacoepidemiology
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rosenbaum JT, Holland GN. Uveitis and the Tower of Babel. Arch Ophthalmol 1996; 114: 604–5

    Article  PubMed  CAS  Google Scholar 

  2. Rodrigues A, Calonge M, Pedroza-Seres M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol 1996; 114: 593–9

    Article  Google Scholar 

  3. Rothova A, Buitenhuis HJ, Meenken C, et al. Uveitis and systemic disease. Br J Ophthalmol 1992; 76: 137–41

    Article  PubMed  CAS  Google Scholar 

  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: 2–6

    Article  Google Scholar 

  5. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239–45

    Article  PubMed  CAS  Google Scholar 

  6. Lea AP, Bryson HM. Cidofovir. Drugs 1996 Aug; 52(2): 225–30

    Article  PubMed  CAS  Google Scholar 

  7. Ambati J, Robinson MR, McCannel C, et al. Intravenous Vis-tide (cidofovir) induced uveitis. American Uveitis Society Meeting; 1997 May 10; Fort Lauderdale

  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): S914

    Google Scholar 

  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): 144–55

    Google Scholar 

  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): S914

    Google Scholar 

  11. Freeman WR. New developments in the treatment of CMV retinitis. Ophthalmol 1996; 103(7): 999–1000

    CAS  Google Scholar 

  12. Gilman AG, Goodman LS, Gilman A, editors. The pharmacological basis of therapeutics. 6th ed. New York: Macmillan, 1980: 1326–7

    Google Scholar 

  13. Rorsman H, Dahlquist I, Jacobsson S, et al. Tattoo granuloma and uveitis. Lancet 1969; II: 27–8

    Article  Google Scholar 

  14. Hawking F. Diethylcarbamazine and new compounds for treatment of filariasis. Adv Pharmacol Chemother 1979; 16: 129–94

    Article  PubMed  CAS  Google Scholar 

  15. Taylor HR, Greene BM. Ocular changes with oral and trans-epidermal diethylcarbamazepine therapy of onchocerciasis. Br J Ophthalmol 1981; 65: 494–502

    Article  PubMed  CAS  Google Scholar 

  16. Fleisch H. Biphosphonates: pharmacology and use in the treatment of tumour-induced hypercalcaemia and metastatic bone disease. Drugs 1991; 42: 919–44

    Article  PubMed  CAS  Google Scholar 

  17. Macarol V, Fraunfelder FT. Pamidronate disodium and possibleocular adverse drug reactions. Am J Ophthalmol 1994; 118: 220–4

    PubMed  CAS  Google Scholar 

  18. Siris ES. Biphosphonates and iritis. Lancet 1993; 342: 436–7

    Article  Google Scholar 

  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; Manchester

  20. De S, Meyer P, Crisp AJ. Pamidronate and uveitis [letter]. Br J Rheumatol 1995; 34(5): 479

    Article  PubMed  CAS  Google Scholar 

  21. Ghose K, Waterworth R, Trolove P, et al. Uveitis associated with pamidronate [letter]. Aust NZ J Med 1994; 24: 320

    Article  CAS  Google Scholar 

  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): 272–3

    Google Scholar 

  23. Wu WC-S, Mannion B, Stone RM, et al. Uveitis associated with interleukin-3 and interleukin-6 therapy. Arch Ophthalmol 1995; 113: 408–9

    Article  PubMed  CAS  Google Scholar 

  24. Murray PI, Hoekzema R, van Haren MAC, et al. Aqueous humor interleukin-6 levels in uveitis. Invest Ophthalmol Vis Sci 1990; 31: 917–20

    PubMed  CAS  Google Scholar 

  25. Hoekzema R, Murray PI, van Haren MAC, et al. Analysis of interleukin-6 in endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 1991; 32: 88–95

    PubMed  CAS  Google Scholar 

  26. Rosenbaum JT. Towards cytokine insight in sight. Br J Ophthalmol 1995; 79(11): 970–1

    Article  PubMed  CAS  Google Scholar 

  27. Davidson SI. Reported adverse effects of oral contraceptives on the eye. Trans Ophthalmol Soc UK 1971; 91: 561–74

    PubMed  CAS  Google Scholar 

  28. Walsh FB, Clark DB, Thompson RS, et al. Oral contraceptives and neuro-ophthalmic interest. AMA Arch Ophthalmol 1965; 74: 628–40

    Article  CAS  Google Scholar 

  29. Hustead JD. Granulomatous uveitis and quinidine hypersensitivity. Am J Ophthalmol 1991; 112(4): 461–2

    PubMed  CAS  Google Scholar 

  30. Spitzberg DH. Acute anterior uveitis secondary to quinidine sensitivity [letter]. Arch Ophthalmol 1979; 97: 1993

    Article  PubMed  CAS  Google Scholar 

  31. Caraco Y, Arnon R, Raveh D, et al. Quinidine-induced uveitis. Isr J Med Sci 1992; 28: 741–3

    PubMed  CAS  Google Scholar 

  32. Brogden RN, Fitton A. Rifabutin: a review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 47(6): 983–1009

    Article  PubMed  CAS  Google Scholar 

  33. Havlir D, Torriani F, Dube M. Uveitis associated with rifabutin prophylaxis. Ann Intern Med 1994; 121: 510–2

    PubMed  CAS  Google Scholar 

  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): 433–41

    Article  PubMed  CAS  Google Scholar 

  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): 438–9

    Article  PubMed  CAS  Google Scholar 

  36. Frank MO, Graham MB, Wispelway B. Rifabutin and uveitis [letter]. N Engl J Med 1994; 330(12): 868

    Article  PubMed  CAS  Google Scholar 

  37. Fuller JD, Stanfield LE, Craven DE. Rifabutin prophylaxis and uveitis [letter]. N Engl J Med 1994; 330(18): 1315–6

    Article  PubMed  CAS  Google Scholar 

  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: 1159–65

    Article  PubMed  CAS  Google Scholar 

  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, Glasgow

  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, Glasgow

  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: 716–22

    PubMed  CAS  Google Scholar 

  42. Chaknis MJ, Brooks SE, Mitchell KT, et al. Inflammatory opacities in the vitreous in rifabutin associated uveitis. Am J Ophthalmol 1996; 122(4): 580–2

    PubMed  CAS  Google Scholar 

  43. Dunn AM, Tizer K, Cervia JS. Rifabutin-associated uveitis in a pediatric patient. Pediatr Infect Dis J 1995 (14); 3: 246–7

    Google Scholar 

  44. Tseng AL, Walmsley SL. Rifabutin-associated uveitis. Ann Pharmacother 1995; 29: 1149–55

    PubMed  CAS  Google Scholar 

  45. Nichols CW. Mycobacterium avium complex infection, rifabutin, and uveitis: is there a connection? Clin Infect Dis 1996; 22Suppl. 1: S43–9

    Article  PubMed  CAS  Google Scholar 

  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: 77–8

    Google Scholar 

  47. Bell WR, Meek AG. Guidelines for the use of thrombolytic agents. N Engl J Med 1979; 301: 1266–70

    Article  PubMed  CAS  Google Scholar 

  48. Proctor BD, Joondeph BC. Bilateral uveitis: a feature of streptokinase-induced serum sickness. N Engl J Med 1994; 330: 576

    Article  PubMed  CAS  Google Scholar 

  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: 68–71

    Article  PubMed  CAS  Google Scholar 

  50. Gray MY, Lazarus JH. Iritis after treatment with streptokinase. BMJ 1994; 309: 97

    PubMed  CAS  Google Scholar 

  51. Kinshuck D. Bilateral hypopyon and streptokinase. BMJ 1992; 305: 1332

    Article  PubMed  CAS  Google Scholar 

  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: 603–32

    Google Scholar 

  53. Fujardo RV. Acute bilateral anterior uveitis caused by sulfa drugs. In: Saari KM, editor. Uveitis update. Princeton (NJ): Excerpta Medica, 1984: 115–8

    Google Scholar 

  54. Tilden ME, Rosenbaum JT, Fraunfelder FT. Systemic sulfonamides as a cause of bilateral, anterior uveitis. Arch Ophthalmol 1991; 1: 67–9

    Article  Google Scholar 

  55. Donaldson RC, Canaan SA, McLean RB, et al. Uveitis and vitiligo associated with BCG treatment for malignant melanoma. Surgery 1974; 76: 771–8

    PubMed  CAS  Google Scholar 

  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.): 2102

    Google Scholar 

  57. Donatini B, Goetz J, Hauptmann G. Uveitis and antineutrophil cytoplasmic antibody in immunoglobulin batches. Lancet 1992; 339: 1175–6

    Article  PubMed  CAS  Google Scholar 

  58. Grant WM, Schuman JS. Toxicology of the eye. Thomas CC, editor. 4th ed. Springfield (IL): Charles C Thomas Publishers Ltd, 1993: 1142–415

  59. Kass MA, Gieser DK, Hodapp E. et al. Corticosteroid-induced iridocyclitis in a family. Am J Ophthalmol. 1982; 93: 368–9

    PubMed  CAS  Google Scholar 

  60. Martins JC, Wilensky JT, Asseff CF, et al Corticosteroid-induced uveitis. Am J Ophthalmol 1974; 77: 433–7

    PubMed  CAS  Google Scholar 

  61. Krupin T, LeBlanc RP, Becker B, et al. Uveitis in association with topically administered corticosteroid. Am J Ophthalmol 1970; 70: 883–5

    PubMed  CAS  Google Scholar 

  62. Xalatan (latanoprost solution) sterile ophthalmic solution [package insert]. Kalamazoo, MI: Pharmacia Inc; 1996

  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: 929–932

    Article  PubMed  CAS  Google Scholar 

  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: 1916–24

    PubMed  CAS  Google Scholar 

  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: 601–15

    Article  PubMed  CAS  Google Scholar 

  66. Sorensen SJ, Abel SR. Comparison of the ocular beta-blockers. Ann Pharmacother 1996; 30: 43–53

    PubMed  CAS  Google Scholar 

  67. Melles RB. Metipranolol-associated granulomatous iritis. Am J Ophthalmol. 1994; 118: 712–5

    PubMed  CAS  Google Scholar 

  68. Schulz JS, Hoenig JA, Charles H. Possible bilateral anterior uveitis secondary to metipranolol therapy. Arch Ophthalmol. 1993; 111: 1606–1607

    Article  Google Scholar 

  69. Beck RW, Moke P, Blair RC, et al. Uveitis associated with topical beta-blockers. Arch Ophthalmol 1996; 114: 1181–2

    Article  PubMed  CAS  Google Scholar 

  70. Akingbehin T, Villada JR, Walley T. Metipranolol-induced adverse reactions. I. The rechallenge study. Eye 1992; 6: 277–9

    Article  PubMed  Google Scholar 

  71. Akingbehin T, Villada JR. Metipranolol-associated granulomatous anterior uveitis. Br J Ophthalmol 1991; 75: 519–23

    Article  PubMed  CAS  Google Scholar 

  72. Kebler C. Possible bilateral anterior uveitis secondary to metipranolol (optipranolol) therapy [letter]. Arch Ophthalmol 1994; 112: 1277

    Article  PubMed  CAS  Google Scholar 

  73. Kessler C, Christ T. Incidence of uveitis in glaucoma patients using metipranolol. J Glaucoma 1993; 2: 166–70

    Article  PubMed  CAS  Google Scholar 

  74. Kinshuck D. Glauline- (metipranolol) induced uveitis and increase in ocular pressure [letter]. Br J Ophthalmol 1991; 75: 575

    Article  PubMed  CAS  Google Scholar 

  75. Zimmerman TJ, Baumann JD, Hetherington J. Side effects of timolol. Surv Ophthalmol 1983; 28: 243–9

    Article  PubMed  Google Scholar 

  76. Van Buskirk EM. Adverse reactions from timolol administration. Ophthalmology 1980; 87: 447–50

    PubMed  Google Scholar 

  77. Jain S. Betaxolol-associated anterior uveitis. Eye 1994; 8: 708–9

    Article  PubMed  Google Scholar 

  78. Betagan (levobunolol Hcl) ophthalmic solution [package insert]. Irvine (CA): Allergan Inc; 1996

  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, 52–4

    Google Scholar 

  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, 447–50

    Google Scholar 

  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, 473–5

    Google Scholar 

  82. Appel GB. A decade of penicillin-related acute interstitial nephritis: more questions than answers. Clin Nephrol 1980; 13: 151–4

    PubMed  CAS  Google Scholar 

  83. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal anti-inflammatory drugs. N Engl J Med 1984; 310: 563–72

    Article  PubMed  CAS  Google Scholar 

  84. Rosenbaum JT. Bilateral anterior uveitis and interstitial nephritis. Am J Ophthalmol 1988; 105: 534–7

    PubMed  CAS  Google Scholar 

  85. Rosenbaum JT. An algorithm for the systemic evaluation of patients with uveitis: guidelines for the consultant. Semin Arthritis Rheum 1990; 19(4): 248–57

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James T. Rosenbaum.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fraunfelder, F.W., Rosenbaum, J.T. Drug-Induced Uveitis. Drug-Safety 17, 197–207 (1997). https://doi.org/10.2165/00002018-199717030-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199717030-00005

Keywords

Navigation