Pegylated Interferon for HCV Linked to Increased Risk for Retinal Hemorrhage

Patients with subjective vision changes should be referred for fundus examination.

Hepatitis C

Findings from a new study demonstrated that pegylated interferon (PegIFN) therapy for hepatitis c (HCV) significantly increased risk for retinal hemorrhage.

Nonetheless, patients treated with PegIFN therapy and non-treated patients had similar risk for retinal vascular occlusions.

The retrospective cohort study was led by Chia-Min Wu, Department of Ophthalmology, Taipei Medical University, Tawain, and incorporated data from the Taiwan Longitudinal Health Insurance Database.

“Because retinopathy might be caused by HCV infection or induced by therapy, we compared patients receiving treatment for HCV (HCV-treated cohort), those not receiving treatments for HCV (HCV-untreated cohort), and those without HCV (non-HCV cohort),” the investigators wrote.

They excluded those who were <18 years of age, those with chronic HBV infection, HIV, progressive high myopia, and any retinal vascular events prior to initiation of first antiviral treatment.

Interferon Therapy and Ocular Events

Overall, a total of 21,944 patients were assessed. Of this population, 1688 individuals were HCV patients treated with PegIFN plus ribavirin therapy, 3376 were HCV patients who did not undergo treatment, and 16,880 did not have HCV.

All patients were frequency-matched by age, sex, and index (initiation) date and followed up through 2013.

“The 2-year cumulative incidence of any retinopathy was approximately 0.89% in the HCV-treated cohort, 0.15% in the HCV-untreated cohort, and 0.19% in the non-HCV cohort,” Wu and colleagues wrote.

According to Cox proportional hazard regression models, the HCV-treated cohort had a greater risk of developing retinopathy—as compared with the non-HCV cohort (hazard ratio [HR], 4.98; 95% CI, 2.02-12.3).

Furthermore, risk was higher for retinal hemorrhage (HR, 12.7; 95% CI, 3.78-42.9) in the treated cohort than the non-HCV cohort.

When compared with the HCV-untreated group, risk for retinopathy in the treated group increased to an HR of 9.02 (95% CI, 3.04-26.8), and risk for retinal hemorrhage increased to 32.3 (95% CI, 3.94-265).

The investigators reported that the retinal hemorrhage subtype accounted for 73% of (11/15) of IFN-associated retinopathy cases in the HCV-treated group, while it accounted for 38% (12/32) and 20% (1/5) of cases in the non-HCV and HCV-untreated cohorts, respectively.

In terms of additional, non-ocular side effects, both HCV-treated and untreated cohorts had higher risks for anemia and thrombocytopenia—with the HCV-treated group demonstrating comparably greater risks for both events.

Nevertheless, the investigators considered the difference in thrombocytopenia risk between HCV cohorts to be nonsignificant.


“We observed a comparable incidence of more advanced events, such as retinal venous or arterial occlusions, in the non-HCV, HCV-untreated, and HCV-treated cohorts, and a significantly higher incidence of the less advanced retinal hemorrhage subtype in the HCV-treated cohort,” Wu and team wrote.

They indicated it is acceptable only to refer patients with subjective vision changes to ophthalmologists for fundus examination—considering that retinal hemorrhage and other typical IFN-associated retinal findings are benign and reversible.

Nonetheless, they acknowledge various limitations with their study, including their reliance on ICD-9-CM diagnostic codes and retrospective/observational data.

“These limitations may have resulted in the underestimation of the true incidence of PegIFN/RBV-associated retinopathy, particularly that of asymptomatic retinal hemorrhage and cotton wool spots,” they wrote.

The study, “Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin,” was published online in Viruses.

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