Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Results of a prospective randomized placebo-controlled clinical trial. Pharmacological Therapy for Macular Degeneration Study Group

Arch Ophthalmol. 1997 Jul;115(7):865-72. doi: 10.1001/archopht.1997.01100160035005.


Background: Interferon alfa-2a has been shown to be effective as an antiangiogenic agent for several systemic human angiogenic disorders and has shown antiangiogenic activity in the laboratory.

Objective: To evaluate the safety and efficacy of interferon alfa-2a for the treatment of choroidal neovascularization secondary to age-related macular degeneration.

Methods: A randomized, placebo-controlled, parallel, multicenter double-blind trial was performed at 45 ophthalmic centers worldwide. Four hundred eighty-one patients were randomly assigned to 4 treatment groups: placebo or interferon alfa-2a (Roferon-A), 1.5, 3.0, or 6.0 million international units (MIU). Visual acuity testing, clinical examination, fluorescein angiography, and indocyanine green angiography were evaluated, with the primary end point being a comparison of the number of patients who experienced a loss of 3 lines or more of vision at 1 year.

Results: At 52 weeks, 40 (38%; 95% confidence interval, 29%-48%) of 105 placebo-treated patients had lost at least 3 lines of vision (with 12% unavailable for follow-up), compared with 142 (50%; 95% confidence interval, 44%-55%) of 286 in the 3 active treatment groups combined. The difference in proportions was not statistically significant. However, a pairwise comparison of these proportions for the placebo group vs the group that received interferon alfa-2a, 6 MIU (with 26% unavailable for follow-up), showed a statistically significant difference in favor of the placebo group (P = .02) and a nearly significant difference for the placebo vs the 1.5-MIU group (P = .05) (with 16% unavailable for follow-up), again favoring the placebo group. The 3-MIU group (with 22% unavailable for follow-up) did not show a statistically significant difference in pairwise comparison (P = .48), suggesting that a dose-response relationship was not evident.

Conclusion: Interferon alfa-2a provides no benefit as a treatment for choroidal neovascularization secondary to age-related macular degeneration and may be associated with a poorer visual outcome when given at a dose of 6 MIU. However, the absence of a clear dose-response relationship raises the possibility that the observed differences result from chance.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Choroid / blood supply*
  • Choroid Diseases / diagnosis
  • Choroid Diseases / etiology
  • Choroid Diseases / therapy*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Fundus Oculi
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Macular Degeneration / complications*
  • Macular Degeneration / diagnosis
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / diagnosis
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / therapy*
  • Recombinant Proteins
  • Safety
  • Treatment Outcome
  • Visual Acuity


  • Antineoplastic Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins