Retinal vascular complications associated with interferon-ribavirin therapy for chronic hepatitis C: A population-based study

Pharmacoepidemiol Drug Saf. 2018 Feb;27(2):191-198. doi: 10.1002/pds.4363. Epub 2017 Dec 6.


Purpose: To investigate the incidence of retinal vascular complications and risk factors in patients with chronic hepatitis C receiving interferon-ribavirin therapy in Taiwan.

Methods: By using the Taiwan National Health Insurance Research Database, we compared the incidence of retinal vascular complications between patients receiving and not receiving interferon-ribavirin treatment. The exposure and nonexposure groups were randomly 1:1 frequency-matched according to age, sex, income, urbanization level, hypertension, and diabetes. Incidence of each retinal vascular complication and hazard ratios were assessed in the follow-up evaluation.

Results: Of the sample of 4736 patients, a total of 182 patients (3.84%) developed retinopathy during the follow-up period, of which 110 patients (4.65%) received interferon-ribavirin therapy and 72 patients (3.04%) did not receive interferon-ribavirin therapy. After multivariate adjustments, the risk of retinopathy during the follow-up period was 1.533 (95% confidence interval [CI], 1.139-2.064; P = .0048) times higher in patients receiving interferon-ribavirin therapy than in those in the comparison cohort not receiving the therapy. Patients with hypertension compared with those without it (adjusted hazard ratio, 1.530; 95% CI, 1.069-2.135; P = .0125) also had an increased risk of retinopathy.

Conclusions: Interferon-ribavirin therapy was associated with a 53.3% increased risk of retinal vascular complications compared with not receiving the therapy. Regular ophthalmologic examination is essential for patients receiving interferon-ribavirin, particularly those with hypertension.

Keywords: cotton-wool spots; hepatitis C virus; interferon; pharmacoepidemiology; retinal hemorrhage; retinal vascular complication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Comorbidity
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / epidemiology
  • Humans
  • Hypertension / epidemiology
  • Incidence
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects*
  • Male
  • Middle Aged
  • Retina / drug effects
  • Retinal Diseases / chemically induced
  • Retinal Diseases / epidemiology*
  • Retinal Vessels / drug effects
  • Retrospective Studies
  • Ribavirin / administration & dosage
  • Ribavirin / adverse effects*
  • Risk Factors
  • Taiwan / epidemiology


  • Antiviral Agents
  • Interferon-alpha
  • Ribavirin