Malignancy risk in patients with inflammatory eye disease treated with systemic immunosuppressive therapy: a tertiary referral cohort study

Ophthalmology. 2015 Feb;122(2):265-73. doi: 10.1016/j.ophtha.2014.08.024. Epub 2014 Oct 11.


Objective: To ascertain whether patients on long-term systemic immunosuppressive therapy for inflammatory eye disease (IED) are at increased risk of malignancy.

Design: A single-center, retrospective cohort study.

Participants: We included 190 adults with IED treated with corticosteroids only (n = 58) or systemic immunosuppression (n = 132) for ≥6 months between 1985 and 2007. Immunosuppressed patients were treated with antimetabolites, T-cell inhibitors, and/or alkylating agents.

Methods: Incident malignancies were ascertained by self-report and confirmed by medical record review. Multiple malignancies in a single patient were counted, except for nonmelanoma skin cancer (NMSC), where only the first was counted. Standardized incidence ratios (SIRs) were calculated by malignancy type. Cox regression models were used to compare malignancy incidence by treatment type.

Main outcome measures: Risk of malignancy relative to the general population and within the cohort.

Results: During a median 7.34 years of follow-up, 25 malignancies were observed in 17 patients, namely, 2.10 per 100 person-years and 0.43 per 100 person-years in the immunosuppressed and corticosteroid only groups, respectively. In the immunosuppressed group, the most common malignancies were NMSC (n = 11) and non-Hodgkin's lymphoma (NHL; n = 4) and malignancy risk was significantly increased compared with the general population for any malignancy (SIR, 4.39; 95% CI, 2.78-6.59) and for any malignancy excluding NMSC (SIR, 4.16; 95% CI, 1.67-8.57). Significantly elevated SIRs were observed for NMSC and NHL in those treated with immunosuppressive agents. Compared with the corticosteroid treatment-only group, the immunosuppressed group was at an increased risk of any malignancy (adjusted hazard ratio, 4.36; 95% CI, 1.02-18.7), but not first malignancy (n = 17; adjusted hazard ratio, 2.56; 95% CI, 0.57-11.5). No cancer-related deaths were observed.

Conclusions: Our findings suggest that patients with IED treated with systemic immunosuppressive therapy are at increased risk of malignancy; however, the increase in absolute risk was modest. The types of malignancies observed at excess risk are similar to those observed in solid organ transplant recipients and patients with autoimmune diseases treated with systemic immunosuppression. Immunosuppressive therapy remains an important treatment modality in IED; however, patients may benefit from targeted malignancy-prevention strategies and long-term clinical follow-up. These findings require validation by a prospective, long-term, population-based cohort study.

MeSH terms

  • Adult
  • Alkylating Agents / adverse effects
  • Alkylating Agents / therapeutic use
  • Antimetabolites / adverse effects
  • Antimetabolites / therapeutic use
  • Cohort Studies
  • Female
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms / chemically induced*
  • Neoplasms / epidemiology
  • Pemphigoid, Benign Mucous Membrane / drug therapy*
  • Retrospective Studies
  • Risk Factors
  • Scleritis / drug therapy*
  • Tertiary Care Centers
  • Uveitis / drug therapy*
  • Young Adult


  • Alkylating Agents
  • Antimetabolites
  • Glucocorticoids
  • Immunosuppressive Agents