Retinal Toxicity and Combination Therapy
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Retinal Toxicity During Pegylated Alfa Interferon Therapy for Chronic Hepatitis C
By Ronald Baker, PhD
There have been documented and anecdotal reports of ocular side effects during therapy with pegylated interferon and ribavirin. The aim of the current study was to evaluate the effect of therapy with pegylated interferon and ribavirin on the eyes of patients with chronic hepatitis C.
In this small study, 10 patients receiving peginterferon alfa-2a (Pegasys) and ribavirin and 10 healthy volunteers underwent full ophthalmic investigations and multifocal electroretinogram testing at baseline, and at regular intervals during treatment and post-treatment. The multifocal electroretinogram maps retinal function. Responses were compared with sequential recordings from healthy volunteers.
Results
All patients had normal clinical ophthalmic investigations at baseline. During therapy a single patient experienced central visual disturbance lasting 24 h with no prolonged ill effect.
No other patient was aware of any change in vision.
Fundal abnormalities [relating to the retinal area] appeared in five patients during treatment.
The multifocal electroretinogram showed reductions in retinal function in five patients.
Nine of 10 patients exhibited abnormalities on at least one multifocal electroretinogram or fundoscopic investigation.
The authors conclude, “Subclinical retinal toxicity during anti-viral therapy with pegylated alpha-interferon and ribavirin was frequent in this study and it suggests that patients should be warned of this risk and monitored during therapy.”
Department of Clinical Physics and Bioengineering, Gartnavel General Hospital, Glasgow, UK.
See also Is Screening for Peginterferon-related Retinopathy in Hepatitis C Justified? and
Treatment with Pegylated Interferon May Cause Eye Complications in Patients with Chronic Hepatitis C
Commentary
Serious ocular disorders do not appear to occur frequently among patients using standard interferon or the peginterferons plus ribavirin. However, such problems can occur. If vision problems develop, patients should immediately call their physician and set up an appointment to see an ophthalmologist for a complete eye examination.
The product information on the pegylated interferons contains a warning about potential ophthalmologic disorders. The following text is excerpted from the WARNINGS section of the Pegasys Product Information (9). There is a similar WARNING on potential ocular disorders associated with peginterferon alfa-2b in the Peg-Intron/Rebetol product information:
“Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, and papilledema are induced or aggregated by treatment with PEGASYS or other alpha interferons.
“All patients should receive an eye examination at baseline. Patients with preexisting opthalmologic disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic opthalmologic exams during interferon alpha treatment. Any patient who develops ocular symptoms should receive a prompt and complete eye examination.
“Pegasys treatment should be discontinued in patients who develop new or worsening ophthalmologic disorders.” [emphasis added]
Selected Excerpts from the Literature on Retinal Toxicity Related to Therapy with Standard Interferon and/or Pegylated Interferon:
“The incidence of serious ocular pathology associated with anti-HCV therapy may be very high and is probably associated with peg-IFN alpha-2b. Increased monitoring of patients treated with peg-IFN alpha-2b for retinal and visual changes is warranted.” C Farel et al (3).
“Although ocular toxicity is uncommon, it should be emphasized that it can occur any time after the start of interferon therapy, and physicians now treating chronic hepatitis C patients with pegylated interferon must be aware of this potentially serious adverse event.” RA Willson (8).
The multifocal electroretinogram can detect retinal dysfunction in chloroquine retinopathy even when the full-field electroretinogram is normal and retinal alterations are subtle. Kellner et al (5).
“This case report underlines the necessity of an EOG on patients with INF-alpha therapy. Until now, the pathogenesis of this retinal toxicity has been poorly understood. These results show that the retinal pigmented epithelium is probably implicated at an early stage in this retinal toxicity.” M Crochet et al (2)
“Subclinical retinal toxicity during anti-viral therapy with pegylated alpha-interferon and ribavirin was frequent in this study and it suggests that patients should be warned of this risk and monitored during therapy.” Chisolm et al (1)
‘Subclinical neurovisual impairment is a frequent, largely unrecognized complication of low-dose IFN therapy, and patients with chronic hepatitis B and older age appear to be most susceptible. This apparently innocuous complication is long lasting, possibly irreversible in some patients, with yet undetermined consequences on visual function.” Manesis et al (6)
“8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.” Jain et al (4)
“Although ocular toxicity is uncommon, it should be emphasized that it can occur any time after the start of interferon therapy, and physicians now treating chronic hepatitis C patients with pegylated interferon must be aware of this potentially serious adverse event.” Willson (8)
04/06/05
Citations
- J A Chisholm and others. Retinal toxicity during pegylated alpha-interferon therapy for chronic hepatitis C: a multifocal electroretinogram investigation. Alimentary Pharmacology & Therapeutics. 21(6): 23-32. March 15, 2005.
- M Crochet and others. Retinopathy caused by interferon alpha associated with ribavirin therapy and the importance of the electro-oculogram: a case report. Journal of French Ophthalmolology 27(3):257-262. March 2004.
- C Farel and others. Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin. AIDS 18(13):1805-9. September 3, 2004.
- K Jain and others. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin. British Journal of Ophthalmology 85(10):1171-3. October 2001.
- U Kellner, Kraus H, Foerster MH.. Multifocal ERG in chloroquine retinopathy: regional variance of retinal dysfunction. Graefe’s Archive for Clinical and Experimental Ophthalmology 238(1): 94-97. January 2000.
- E K Manesis and others. Neurovisual impairment: a frequent complication of alpha-interferon treatment in chronic viral hepatitis. Hepatology 27(5):1421-7. May 1998.
- A Tsolakos and N Zalatimo. Hepatitis C: a review of diagnosis, management, and ocular complications from treatment. Optometry 74(8): 517-23. August 2003.
- R A Willson. Visual side effects of pegylated interferon during therapy for chronic hepatitis C infection. Journal of Clinical Gastroenterology 38(8): 717-722. September 2004.
- Hoffman-La Roche. WARNINGS: Ophthalmologic Disorders. Pegasys Product Information. Page 10. January 2004.
