Showing posts with label side effects-eyes. Show all posts
Showing posts with label side effects-eyes. Show all posts

Wednesday, January 22, 2014

Neutropenia-Lymphocyte count associated with infection risk during HCV interferon treatment

Lymphocyte count associated with infection risk during interferon treatment
Melia M. Clin Infect Dis. 2014;doi:10.1093/cid/ciu009.

Adults with hepatitis C who were treated with pegylated interferon and ribavirin for up to 48 weeks commonly experienced moderate, severe or life-threatening infections, according to a report in Clinical Infectious Diseases.

The nadir lymphocyte count, but not the nadir neutrophil count, was associated with the increased risk for infections in the Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) study.

“While the risk of infection associated with severe neutropenia due to chemotherapy among cancer patients and recipients of hematopoietic cell transplants is well-established, most studies have not demonstrated any increased risk among patients who develop neutropenia while receiving [pegylated interferon],” the researchers wrote. “Nevertheless, up to 23% of patients develop acute infections during HCV treatment.”

Patients in the IDEAL study were randomly assigned to varying doses of pegylated interferon with ribavirin for chronic HCV treatment. In this study, the investigators from evaluated the risk for infection among patients with myelosuppression, a common adverse effect of pegylated interferon treatment.

The IDEAL study included 3,070 treatment-naïve patients. Among those, 581 (19%) patients experienced moderate, severe or life-threatening infections, determined by the investigator. In a logistic regression model, female gender, history of depression and nadir on-treatment absolute lymphocyte count were associated with moderate, severe or life-threatening infections. After adjustment, pegylated interferon type (alfa-2a vs. alfa-2b) and nadir absolute neutrophil count were not associated with moderate, severe or life-threatening infections.

“This observation has important implications for the management of patients treated with [pegylated interferon/ribavirin] alone or in combination with other agents,” the researchers wrote. “While further research is needed to confirm this observation, clinicians should carefully monitor the [absolute lymphocyte count] in addition to the [absolute neutrophil count] for patients receiving HCV therapy with [pegylated interferon and/or ribavirin].”

Disclosure: See study manuscript for disclosure information.

New @ Healio

HCV testing rates low among IDUs in Thailand
January 22, 2014
Only one-third of Thai injection drug users reported getting tested for hepatitis C, according to study results published in the Journal of Public Health.
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Scoring system accurately predicted mortality among cirrhosis patients
January 21, 2014
Researchers focusing on nine specific comorbidities have developed a scoring system that can predict death or survival of cirrhosis patients with strong...
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HCV testing rates low among IDUs in Thailand
January 22, 2014
“Clinicians should be aware that although access to HIV testing has increased in most settings recently, rates of HCV testing among injection drug users (IDUs) remains low in some countries,” study researcher Thomas Kerr, PhD, co-director of the Urban Health Research Initiative at the British Columbia Centre for Excellence in HIV/AIDS, told Infectious Disease News. “It is important to ensure appropriate follow-up after testing for HCV is provided, including access to viral load testing and specialist care.”
Full Story »

Thursday, October 3, 2013

Telaprevir-induced retinopathy:Adverse effect during hepatitis C triple antiviral therapy

J Gastroenterol. 2013 Oct 1. [Epub ahead of print]

Telaprevir-induced, but not pegylated interferon-associated, retinopathy as a noteworthy adverse effect during triple antiviral therapy in patients with chronic hepatitis C.

Sugawara K, Inao M, Nakayama N, Mochida S.

Source
Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-Machi, Iruma-Gun, Saitama, 350-0495, Japan.

Abstract
BACKGROUND:
The significance of retinopathy during triple therapy with telaprevir is uncertain.

METHODS:
Ophthalmologic examination was done prospectively before and every month during the therapy in 95 CHC patients.

RESULTS:
Retinopathy was found in 46 (48.4 %), and the specialists recommended discontinuation of the therapy in 9 (9.5 %). Such lesions may develop as adverse effects by telaprevir, since the lesions disappeared following discontinuation of telaprevir in a 65-year-old man, in whom both pegylated-interferon (Peg-IFN) and ribavirin were continued, and reappeared when he took telaprevir again by his decision. Multivariate analysis revealed that interleukin 28B single-nucleotide polymorphism (IL28B SNP) and anemia development during the therapy were independent factors associating retinopathy.

CONCLUSION:
Ophthalmologic examinations should be done carefully during triple therapy, since the incidence was higher than that in previous Peg-IFN therapy, and lesions may develop as adverse effects by telaprevir, but not by Peg-IFN, especially in those showing preferable IL28B SNPs allele and/or anemia during the therapy.

Related On The Website
Aug 28 2013
Could interferon-based therapies for chronic hepatitis C cause retinopathy?
Interferon-Associated Retinopathy During HCV Therapy
To assess the incidence of retinopathy in patients with chronic hepatitis C being treated with interferon-based regimens and estimate the rate of resolution. A systematic literature search was performed to locate all relevant publications. Pooled
incidence of retinopathy was calculated in patients treated with interferon or pegylated interferon. We also estimated the rate of discontinuation of treatment and resolution after the treatment was stopped

Sunday, September 16, 2012

Retinopathy associated with interferon therapy in patients with hepatitis C virus

Retinopathy associated with interferon therapy in patients with hepatitis C virus

Mahmoud Abd El-Badie Mohamed1 Khaled Abd-El azeem Eed2
Ophthalmology Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt; Gastroentrology and Hepatology Department, Faculty of Medicine, Al-Azhar University, Assiut, Egypt

Full Text

This article was published in the following Dove Press journal:
Clinical Ophthalmology
17 August 2012

Purpose:
To evaluate retinopathy associated with interferon therapy in patients with chronic hepatitis C.

Methods:
One hundred patients with chronic hepatitis C undergoing interferon therapy were examined for the presence of cotton wool spots, retinal hemorrhages, cystoid macular edema, capillary non-perfusion, and arteriolar occlusion. Complete ophthalmological examination including indirect ophthalmoscopic fundus examination was carried out for all patients and colored fundus photography and fluorescein angiography were carried out for the patients with positive fundus findings. The follow-up period was 9 months.

Results:
Sixteen percent of patients developed retinopathy in the form of cotton wool spots, retinal hemorrhages, cystoid macular edema, and capillary non-perfusion.

Conclusion:
Interferon therapy can lead to retinopathy which is mostly reversible and dose related. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss.

 Keywords: retinopathy, interferon, hepatitis C, complications

Introduction
An estimated 170 million people worldwide have hepatitis C virus (HCV) infection and over 20,000 new cases emerge every year. HCV infection frequently persists and may cause cirrhosis and hepatocellular carcinoma. In the US and most developed nations, where the prevalence of infection is 1%–2%, HCV is the leading cause of chronic liver disease.

1- HCV infection is a serious public health problem in Egypt, and is the country with the highest HCV prevalence, where 10%–20% of the general population is infected.

2 - Interferons are a group of glycoproteins that modulate the activity of the immune system. Recombinant alpha-interferon (IFN) has recently been approved as a therapy for chronic hepatitis C, for its antiviral effects and inhibition of cell proliferation.

3 - Although interferon-based therapy is widely used for the treatment of chronic HCV, it is not without its disadvantages. Treatment duration lasts for months, and is often fraught with potentially dangerous side effects. Some of these side effects, such as influenza-like illness, myalgias, depression, and cytopenias can be intolerable resulting in premature treatment cessation, but have no lasting effects. Ocular complications are among the complications of interferon therapy and include retinal hemorrhages, cotton wool spots, loss of color vision, cataracts, glaucoma, and occasionally retinal artery or vein obstruction. Although the incidence of ophthalmological disorders while on interferon therapy is low, this can result in loss of vision.4–11

Patients and methods
In this prospective case series study, One hundred patients with chronic hepatitis-C under Interferon (INF) therapy were consecutively recruited from patients attending the outpatient ophthalmic clinic at the University Hospital, Faculty of Medicine, Al-Azhar University, Assuit. The research followed the tenets of declaration of Helsinki. The study protocol was approved by the Ethics Committee at Al-Azhar University Hospital. Written informed consent was obtained from all patients included in the study, and then in addition to the medical and laboratory examination, all patients were subjected to full ophthalmological assessment to evaluate the retinopathy associated interferon therapy. 

Inclusion criteria were: (1) seropositivity for anti-HCV antibodies determined using ELISA; (2) first use of interferon therapy.

Exclusion criteria were: (1) previous interferon therapy; (2) patients with hepatitis B; (3) patients with decompensated liver; (4) patients with renal failure; (5) patients with cardiovascular disorders such as coronary insufficiency, congestive heart failure, and ischemic stroke; (6) patients with a dense cataract, visual field abnormality, glaucoma, or any other ocular abnormalities. 

Evaluation before treatment:

A. History of visual loss, hazy vision, and ocular disease or ocular surgeries

B. Ophthalmological examination: (1) best corrected visual acuity (BCVA) measured using Landolt’s broken rings; (2) pupillary reaction (direct and consensual) and if there is afferent pupillary defect; (3) full slit-lamp examination; (4) intraocular pressure (IOP) measured by Goldmann’s applanation tonometer; (5) fundus biomicroscopy (carried out after maximum pupillary dilation by a combination of tropicamide 1% eye drops and phenylephrine 2.5% eye drops using both slit-lamp biomicroscopy with non-contact +90 D Volk lens and/or Goldmann contact lens); (6) examination of the retinal periphery using an indirect ophthalmoscope.

C. Medical examinations and abdominal ultrasonography.

 D. Investigations: (1) Ocular, both colored fundus photography and fundus fluorescein angiography (FFA); (2) Laboratory (including enzyme-linked immunosorbent assay (ELlSA) test for hepatitis surface Ag and Ab; polymerase chain reaction (PCR) for hepatitis C virus RNA; Full blood count;
prothrombin time; direct and indirect bilirubin; fasting blood sugar; serum creatinine; liver enzymes (serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase); alanine aminotransferase.

Treatment protocol

Patients were treated with pegylated interferon α-2a at a dose of 180 mcg injected subcutaneously once weekly for 48 weeks. Ribavirin was given orally 800–1200 mg/day according to body weight.

Follow-up

All patients underwent clinical and laboratory assessments, ophthalmic examination, at 15 days, 1 month, 2 months, 3 months, 6 months, 8 months, and 9 months after the start of IFN treatment.

Results

Initially, 120 patients fulfilled the criteria for IFN therapy, but 20 of them were excluded due to non-compliance with the follow-up visits and due to the presence of diabetic or hypertensive retinopathy. Also, two patients died during the study time, due to a disease not related to hepatitis, so these patients are not included.

 Therefore, a total of 100 patients (68 male and 32 female), with chronic HCV were selected. The mean age was 46 years.

After the start of interferon therapy, 16 out of 100 patients (16%) developed retinopathy which was bilateral in 12 (75%) patients and unilateral in 4 (25%) patients.

Retinopathy was initially diagnosed by the appearance of a cotton wool spot in 14 patients. In four of the 14 patients, retinal hemorrhage was also observed simultaneously or sequentially. Two of the 16 patients who developed retinopathy were diagnosed by retinal hemorrhage without cotton wool spots. One patient (not diabetic or hypertensive) had cystoid macular edema, this was the only patient who complained of the visual disturbance due to interferon.

All patients had BCVA of (6/6) during IFN treatment except for three patients: the one who had cystoid macular edema (BCVA was 6/12 and returned to 6/6 after cessation of treatment) and two patients with ametropic amblyopia.

No patient with diabetes had retinopathy before IFN treatment. In addition, we confirmed that all patients with hypertension had no retinopathy using the standard classification. To exclude the possibility of the development of diabetic or hypertension retinopathy after IFN treatment, we deleted the data obtained from patients who had diabetes or hypertension and any retinopathy 2 months after the cessation of IFN treatment.

Retinopathy was first diagnosed 2–14 weeks after the start of treatment and disappeared in 11 of the 16 patients despite the continuation of therapy. A few cotton wool spots, retinal hemorrhages, or both were observed in the remaining five patients at the end of treatment but resolved within 1 month after treatment was stopped.

Retinopathy did not recur in any patient after the IFN-induced retinopathy resolved. No other ocular complications (ie, cataracts, glaucoma, retinal artery, or vein obstruction) were observed.

The mean hemoglobin values, white blood cell, red blood cell, and platelet counts decreased significantly (P , 0.0001) during IFN treatment.

The clinical profiles and laboratory data of the patients are shown in Tables 1 and 2, respectively.




Discussion

Interferon-associated retinopathy was first recognized in 1990 when Ikebe and associates reported a 39-year-old patient who developed retinal hemorrhages and cotton wool spots following intravenous administration of interferon.

The underlying mechanisms of interferon-induced retinopathy are not completely understood. Guyer et al13 had proposed an immune complex deposition causing occlusion of retinal capillaries leading to cotton wool spot formation. On the other hand, an ischemic insult, similar to that seen in hypertensive and diabetic patients could be another potential mechanism by which these changes develop.14

Some studies15,16 have shown a relatively higher incidence of retinopathy (symptomatic or asymptomatic) ranging from 19% to 64% during treatment with interferon. Panetta and Gilani17 and Cuthbertson et al14 show relatively lower incidences of retinopathy (3.8% and 6.25%, respectively).

The incidence of retinopathy in our study was 16%.




Similar to other studies,4,5,9 our study also shows that retinal changes usually develop within the first 3 months of interferon treatment, a fact that may favor an immune etiology rather than a cumulative effect of interferon leading to the development of retinopathy.

Retinopathy developed by week 14 in most of the patients (13/16, 81.25%) after the start of therapy and disappeared in the majority of the patients (11/16, 68.75%) during the 4–8 week period in which the patients were receiving the treatment. This suggests that treatment can be continued despite the development of retinopathy in many patients. However, two patients who developed cotton wool spots early in the therapy (2 weeks) thereafter suffered from retinal hemorrhage in a prolonged manner. Therefore, patients who develop cotton wool spots early on during therapy should be carefully monitored.

However, as reported in previous studies,4,13,14 most of the patients with retinopathy in this study were asymptomatic. This study confirms previous reports that retinopathy is a temporary and asymptomatic complication of interferon therapy.

There is no classification for IFN-induced retinopathy, like diabetic retinopathy. Therefore there is no rule for suspending the use of interferon in patients who develop retinopathy or any other ocular side effects. It’s commonly agreed among authors that careful monitoring should be performed in the presence of any ocular sign, even without symptoms.

Conclusion
Interferon therapy can lead to retinopathy which is almost reversible and dose related. Periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss.

Figure 2
Cotton wool exudate and retinal hemorrhage after 12 weeks of treatment



Figure 3
The only case with cystoid macular in the study



Disclosure
The authors report no conflicts of interest in this work.

 References

1. World Health Organization. Hepatitis C.

Weekly Epidemiological Record. 1997;72:65–69.
2. Hassan MM, Zaghloul AS, El-Serag HB, et al. The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients.

J Clin Gastroenterol. 2001;33:123–126.
3. Tokai R, Ikeda T, Miyaura T, Sato K. Interferon-associated retinopathy and cystoid macular edema.

Arch Ophthalmol. 2001;119(7):1077–1079.
4. Hayasaka S, Fujii M, Yamamoto Y, Noda S, Kurome H, Sasaki M. Retinopathy and subconjunctival haemorrhage in patients with chronic viral hepatitis receiving interferon alfa.

Br J Ophthalmol. 1995;79:150–152.
5. Kawano T, Shigehira M, Uto H, et al. Retinal complications during interferon therapy for chronic hepatitis C.

Am J Gastroenterol. 1996;91: 309–313.
6. Kadayifcilar S, Boyacioglu S, Kart H, Gursoy M, Aydin P. Ocular complications with high-dose interferon alpha in chronic active hepatitis.

Eye (Lond). 1999;13:241–246.
7. Saito H, Ebinuma H, Nagata H, et al. Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.

Liver. 2001;21:192–197.
8. Nadir A, Amin A, Chalisa N, van Thiel DH. Retinal vein thrombosis associated with chronic hepatitis C: a case series and review of the literature.

J Viral Hepat. 2000;7:466–470.
9. Manesis EK, Moschos M, Brouzas D, et al. Neurovisual impairment: A frequent complication of alpha-interferon treatment in chronic viral hepatitis.

Hepatology. 1998;27:1421–1427.
10. Farel C, Suzman DL, McLaughlin M, et al. Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin.

AIDS. 2004;18:1805–1809.
11. Kwon YS, Choe YH, Chin HS. Development of glaucoma in the course of interferon alpha therapy for chronic hepatitis B.

Yonsei Med J. 2001;42:134–136.
12. Ikebe T, Nakatsuka K, Goto M. A case of retinopathy induced by intravenous administration of interferon.

Folia Ophthalmologica Japonica. 1990;41:2291–2296.
13. Guyer DR, Tiedeman J, Yannuzzi LA, et al. Interferon-associated retinopathy.

Arch Ophthalmol. 1993;111:350–356.
14. Cuthbertson FM, Davies M, McKibbin M. Is screening for interferon retinopathy in hepatitis C justified?

Br J Ophthalmol. 2004;88: 1518–1520.
15. Okuse C, Yotsuyanagi H, Nagase Y, et al. Risk factors for retinopathy associated with interferon alpha-2b and ribavirin combination therapy in patients with chronic hepatitis C.

World J Gastroenterol. 2006;12:3756–3759.
16. Nagaoka T, Sato E, Takahashi A, Yokohama S, Yoshida A. Retinal circulatory changes associated with interferon-induced retinopathy in patients with hepatitis C.

Invest Ophthalmol Vis Sci. 2007;48:368–375.
17. Panetta JD, Gilani N. Interferon-induced retinopathy and its risk in patients with diabetes and hypertension undergoing treatment for chronic hepatitis C virus infection.

Aliment Pharmacol Ther. 2009;30(6):597–602.

18. Hayasaka S, Nagaki Y, Matsumoto M, Sato S. Interferon associated retinopathy. Br J Ophthalmol. 1998;82(3):323–325.
Source

Friday, August 3, 2012

Hypertension ups retinopathy risk with HCV treatment

Hypertension ups retinopathy risk with HCV treatment

August 2, 2012

For patients with hepatitis C virus treated with pegylated interferon alpha and ribavirin, retinopathy occurs frequently, especially in those with hypertension, according to a study published in the August issue of Hepatology.

Stela Vujosevic, M.D., from IRCCS in Rome, and colleagues examined the frequency and clinical significance of retinopathy in 97 consecutive HCV patients treated with PegIFNα and ribavirin. Ophthalmologic examination was performed before therapy initiation (baseline), at three and six months (3T and 6T) of therapy, and three months after the end of therapy (3ET). The researchers found that 55.7 percent of patients were treated with PegIFNα 2a and 44.3 percent were treated with PegIFNα 2b. Retinopathy developed in 30.9 percent of patients. Age, metabolic syndrome, hypertension, cryoglobulinemia, and preexisting intraocular lesions at baseline were significantly associated with retinopathy during treatment. Hypertension was the only variable independently associated with PegIFNα-associated retinopathy on multivariate analysis (hazard ratio, 4.99).

Retinopathy was significantly more frequent in patients with hypertension versus those without hypertension, at all time points (18.5 versus 5.7 percent at baseline; 48.1 versus 15.7 percent at 3T; 68.0 versus 19.1 percent at 6T; 32.0 versus 6.2 percent at 3ET). Compared with thyroid-stimulating hormone screening, screening for PegIFNα-associated retinopathy was deemed cost-effective. "Retinopathy is frequent during treatment with PegIFNα and ribavirin, especially in hypertensive patients, who may develop serious complications," the authors write.

More information: Abstract Full Text (subscription or payment may be required)
Journal reference: Hepatology
Copyright © 2012 HealthDay. All rights reserved

Pegylated interferon-associated retinopathy is frequent in hepatitis C virus patients with hypertension and justifies ophthalmologic screening

Stela Vujosevic1

Hepatology
Volume 56, Issue 2, pages 455–463, August 2012

Abstract
Treatment with pegylated interferon alpha (PegIFNα) and ribavirin is still regarded as the standard of care for chronic hepatitis C virus (HCV). Retinopathy has been occasionally described but prospective, longitudinal data are lacking.

We investigated the frequency and clinical significance of retinopathy during therapy with PegIFNα and ribavirin in 97 consecutive HCV patients. In all, 54 (55.7%) and 43 (44.3%) patients were treated with PegIFNα 2a and PegIFNα 2b, respectively. Ophthalmologic examination was performed before therapy (baseline), at 3 and 6 months (3T and 6T, respectively) of therapy, and 3 months after the end of therapy (3ET).

All patients underwent the baseline and 3T examination, 95.9% and 90.7% of patients underwent 6T and 3ET examination, respectively. Overall, 30.9% of patients developed retinopathy, as defined by the presence of cotton wool spots and/or retinal hemorrhages. Variables significantly associated with retinopathy during treatment were age (P = 0.004), metabolic syndrome (P = 0.05), hypertension (P < 0.0001), cryoglobulinemia (P = 0.05), and preexisting intraocular lesions at baseline (P = 0.01). By multivariate analysis, the only variable independently associated with PegIFNα-associated retinopathy was hypertension (hazard ratio [HR] = 4.99, 95% confidence interval [CI] 2.29-10.89). The frequency of retinopathy was significantly higher in hypertensive patients versus those without hypertension at all timepoints (18.5% versus 5.7% at baseline, P = 0.05; 48.1% versus 15.7% at 3T, P = 0.0009; 68.0% versus 19.1% at 6T, P < 0.0001; 32.0% versus 6.2%, P = 0.0005 at 3ET). In one (1.1%) hypertensive patient, who developed bilateral branch retinal vein occlusion at 6T, the therapy was discontinued. A cost analysis showed that screening for PegIFNα-associated retinopathy was cost-effective as compared with thyroid-stimulating hormone screening.

Conclusion: Retinopathy is frequent during treatment with PegIFNα and ribavirin, especially in hypertensive patients, who may develop serious complications. Screening for PegIFNα-associated retinopathy should be recommended for HCV patients with hypertension. (HEPATOLOGY 2012)

 Read more at: http://medicalxpress.com/news/2012-08-hypertension-ups-retinopathy-hcv-treatment.html#jCp

Sunday, April 29, 2012

Interferon-Associated Retinopathy and Non-HCV Related Eye Conditions

Korean J Ophthalmol. 2012 Apr;26(2):147-150.
Published online 2012 March 22.
http://dx.doi.org/10.3341/kjo.2012.26.2.147
PMCID: PMC3325622
Copyright © 2012 The Korean Ophthalmological Society

Pegylated Interferon-Associated Severe Retinopathy in a Patient with Chronic Hepatitis

Hee Young Kang1 and Min Chul Shin21Konyang University Kim's Eye Hospital, Seoul, Korea.
2Department of Ophthalmology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea.
Corresponding author.Corresponding Author: Min Chul Shin, MD, PhD. Department of Ophthalmology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, #77 Sakju-ro, Chuncheon 200-704, Korea. Tel: 82-33-240-5176, Fax: 82-33-241-8063, Email: mcshin@hallym.ac.kr
Received May 19, 2008; Accepted August 4, 2010.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0 ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes. Pegylated interferon combination therapy was stopped, and the retinopathy of the patient was treated with intravitreal bevacizumab injections and panretinal photocoagulations. This case shows that pharmacokinetically improved pegylated interferon has ocular complications for patients with chronic hepatitis C. Accordingly, patients undergoing pegylated interferon treatment for hepatitis C need regular eye examinations for protection of their vision.

Keywords: Chronic hepatitis C, Interferon-associated retinopathy, Ocular vision, Pegyalted interferon

Interferon is a monotherapy or combination therapy antiviral drug for patients suffering from chronic hepatitis C. Certain ocular complications from interferon therapy have been reported, however, such as cotton wool spots [1-7], retinal hemorrhages [1-7], and optic neuropathy [8], among others. By pegylation of polyethylene glycol (PEG) to interferon, pharmacokinetially improved pegylated interferon has a larger molecular weight and a longer half life in the serum than non-pegylated interferon [3], which increases the efficacy of the drug for chronic hepatitis C patients. Non-pegylated interferon has a 12% to 16% clearance rate in the serum, whereas the 50% to 60% clearance rate of pegylated interferon makes it safer for long-term use by patients [3]. Even though pegyalted interferon is a more effective drug for chronic hepatitis C patients, to our knowledge there are no existing reports or studies about pegylated interferon-associated ocular complications such as interferon-associated retinopathy. To bring the issue to light, this study reports a case of pegylated interferon-associated acute and irreversible severe retinopathy in a patient with chronic hepatitis C.

Case Reports
A 32-year-old female was diagnosed with chronic hepatitis C (grade 3/4, stage 2/4, genotype 2a/c) in February of 2007. She underwent treatment with pegylated interferon-α2b 80 micrograms and ribavirin combination therapy for 5 months (from February of 2007 until July of 2007). She was also treated with subcutaneous insulin injections for a previous condition of pregnant diabetic mellitus diagnosed seven years before. She was first referred to ophthalmology in February of 2007 for a diabetic retinopathy examination. Her vision was 0.6 in both eyes, and intraocular pressure was 11 mmHg in the right eye and 12 mmHg in the left eye. Fundus examination found moderate nonproliferative diabetic retinopathy (NPDR) in the right eye and mild NPDR in the left eye. Accordingly, a follow-up visit to check her eyes was scheduled for six months later. She felt visual blurring two months later, and we referred to a past ophthalmologic exam in June of 2007. At that time, her best corrected visual acuity was 0.04 in both eyes. Previous fundoscopy revealed retinal hemorrhages, cotton wool spots, macular edema, and new vessels elsewhere (NVE) in both eyes (Fig. 1). The pegylated interferon and ribavirin combination therapy was stopped, and the patient was treated with intravitreal 0.05 mL bevacizumab (Avastin) injections. Panretinal photocoagulations were added.

Retinal hemorrhages, cotton wool spots, macular edema, and new vessels were found in both of the patient's eyes.


After completion of treatment, the patient's retinal hemorrhages, cotton wool spots, and macular edema improved (Fig. 2). The retinal non-perfusion areas (Figs. 3 and 4) and the best corrected visual acuity of the patient did not improve. As of June, we began regular ophthalmic examination of her eyes every other week.
(A,B) After intravitreal bevacizumab injections and panretinal photocoagulations, the cotton wool spots and retinal hemorrhages regressed, but the new vessels remained.
At the late arteriovenous phase (A,B), many microaneurys and new vessels were found. At the mid-venous phase, non-perfusion was more severe in the left eye (D) than in the right eye (C).
At the late arteriovenous phase (A,B) and mid-venous phase (C,D), new vessels and non-perfused areas progressed.


Discussion
Standard interferon therapy in chronic hepatitis C patients causes various ocular complications, including branch retinal vein occlusion [2], subconjunctival hemorrhages [5], visual blurring, papilledema [8], neovascular glaucoma, and retinal detachment [9], among others. The most common among the ocular complications are retinopathy-parapapillary retinal hemorrhages at the posterior pole, and cotton wool spots [1,2,4]. These features of retinopathy occur in approximately 18% to 86% of alpha interferon-treated chronic hepatitis C patients [1]. A study by Jain et al. [4] has reported that these features of retinopathy may occur between 4 to 12 weeks after the start of interferon and ribavirin combination therapy, and will regress within 4 to 12 weeks after therapy stops. The pathogenesis of these features of retinopathy is unknown, however, the hypothesis that interferon interferes with retinal microcirculations is persuasive [7]. In this respect, interferon treatment for patients with abnormal microcirculation diseases, such as diabetic mellitus or hypertension, has a very high risk of causing interferon-associated ocular complications [6,7].

The patient in this case, due to previous diagnosis of diabetic mellitus, belonged to a high-risk group for interferon-associated ocular complications. The patient presented with retinal hemorrhages, cotton wool spots, macular edema, and retinal ischemic changes in both of her eyes. These ocular complications progress more acutely and severely than the progression of complications in a state of pre-pegylated interferon treatment, and the patient's vision decreased irreversibly.

Usually, interferon-treated patients have reversible interferon-associated retinopathy [1-7]. Cases of severe, irreversible visual impairment are very rare [10]. Chronic hepatitis C patients must undergo examination of their eyes before interferon treatment begins, and they must follow up with a second exam within three months of starting treatment. Particularly for high-risk patients with hypertension or diabetes mellitus, not only are regular follow-up examinations very important, but also stopping the interferon treatment at the right time is critical. This report shows that patients treated with pegylated interferon combined with ribavirin may have irreversible and severe ocular complications. This study proposes that chronic hepatitis C patients treated with pharmacokinetically improved pegylated interferon must also be managed with regular and exact ophthalmic examinations on an ongoing basis.
References


HCV Related Eye Condition

 
 
Dry eye - The Schirmer test
HCV infection has been associated with several eye disorders, according to this 2009 study hepatitis C patients, especially those with advanced stages of fibrosis, were more likely to exhibit severe ocular surface damage and signs of dry eye. In another 2011 study researchers concluded that the hepatitis C virus infection causes dry eye. The data also showed - "There was no linear association between time of hepatitis C infection and intensity observed in dry eye tests." *patients in the study did not undergo therapy

Dry eye
A dry eye is caused by a disturbance in the tear film overlying the ocular surface. It may be the result of deficient aqueous production (eg, Sjogren syndrome, lacrimal gland dysfunction/obstruction) or increased evaporation (eg, contact lens use, allergies, Meibomian gland dysfunction, low blink rate). Patients may report burning, pain, foreign body sensation, photophobia, and blurred vision. Diagnosis is usually made based on the history and clinical examination, but a number of more objective tests are available.

 The Schirmer test
The Schirmer test uses filter paper to wick up tears and measure the amount of production, as shown in a patient with Sjogren syndrome. Treatment is initially supportive with artificial tears and the avoidance of offending medications or exposures. For patients with refractory cases, treatment of the underlying systemic illness or surgery may be required


Non-HCV Related Eye Conditions 
 
 
 
 
Blepharitis is an inflammation of the eyelash follicles, along the edge of the eyelid. The cause is overgrowth of the bacteria that is normally found on the skin.
Eyelids have the following symptoms:

Crusty
Reddened
Swollen
Itching
Burning

Blinking causes a granular sensation (like sand or dust in the eye)
Loss of eyelashes may occur

The primary treatment is careful daily cleansing of the edges of the eyelids, to remove the skin oils that the bacteria feed on. Your health care provider might recommend using baby shampoo or special cleansers. Antibiotic ointments may also be helpful in controlling bacteria on the lids.
If seborrheic dermatitis or rosacea are causing the problem, seek treatment for those conditions.

Causes
Blepharitis is usually caused by seborrheic dermatitis or a bacterial infection, and sometimes it is a combination of both. Allergies and eyelash infestation with lice may also cause blepharitis, although these causes are less common.

This condition is characterized by excess oil production in the glands near the eyelid. Too much oil creates an environment where the normal bacteria found on the skin can overgrow. The eyelids appear red and irritated, with scales that cling to the base of the eyelashes.

Blepharitis may be connected to repeated styes and chalazia. Risk factors are seborrheic dermatitis of the face or scalp, rosacea, lice, and allergies.

Tests & diagnosis
An examination of the eyelids during an eye examination is usually enough to diagnose blepharitis.

Prognosis
The likely outcome is good with treatment. Continued attention to lid cleanliness may be required to prevent repeated problems. Continued treatment will typically make the eyes less red and more comfortable.

Prevention
Cleaning eyelids carefully will help prevent blepharitis.
If a specific skin condition is present, it should be treated.

Complications
Styes
Chalazia

The image shown is from a patient with ocular rosacea and shows eyelid telangiectasias (yellow arrow) and inspissated meibomian glands (white arrow). Treatment consists of eyelid hygiene, lubricant eye drops, systemic antibiotics for refractory cases, and the discriminate use of steroids in case of ulcers or conjunctivitis



What is a sty?
A sty (sometimes spelled stye) is a tender, painful red bump located at the base of an eyelash or under or inside the eyelid. The medical term for a sty is hordeolum (plural, hordeola).
A sty results from an acute infection of the oil glands of the eyelid (meibomian glands) that occurs after these glands have become clogged. A sty also may arise from an infected hair follicle at the base of an eyelash. The bacterium Staphylococcus aureus is responsible for 90%-95% of cases of styes. Staph aureus is frequently found on the skin. A sty can develop as a complication of blepharitis (inflammation of the eyelid).
The term external hordeolum has been used to refer to a sty that develops at the base of an eyelash involving a hair follicle of the eyelid, whereas the term internal hordeolum refers to a sty arising due to an inflamed meibomian gland under the eyelid.
A sty is sometimes confused with a chalazion (see below), which is a cyst or a specific type of scarring (due to chronic inflammation) arising in the meibomian glands of the eyelid. In contrast to a sty, a chalazion is usually painless.

What are the signs and symptoms of a sty?
The first symptoms of a sty are generally redness, tenderness, and pain in the affected area. The eye may feel irritated or "scratchy." Later symptoms can include swelling, discomfort during blinking of the eye, watering of the eye, and sensitivity to light. A common sign of a sty is a small, yellowish spot at the center of the bump that develops as pus expands in the area.

Who is most susceptible to the development of a sty?
Styes are very common. People of all ages can develop a sty, and males and females are equally affected. There is a slight increase in incidence of styes during the third to fifth decades of life. People with certain chronic conditions (diabetes mellitus, chronic blepharitis [inflammation of the eyelid], seborrhea, and chronic debilitating illnesses) are more prone to developing styes than the general population. In many susceptible people, stress seems to trigger the development of a sty. Studies have shown that those who have high levels of blood lipids are more susceptible to blockages in the oil glands, including those of the eyelid and, therefore, are more likely to develop a sty.

What is the treatment for a sty?
Application of a warm compress or warm washcloth to the affected area for 10 minutes, four to six times a day, can speed rupture of the sty and aid in the relief of symptoms. A sty should not be pressed or squeezed to facilitate drainage, since this can spread or worsen the infection. If a sty persists for several days, a doctor may lance (drain) the infection under local anesthesia in his or her office. Children who require surgical drainage of a sty may need a general anesthetic. Antibiotic ointments and/or steroid ointments sometimes are prescribed to treat a sty. Rarely, systemic (oral) antibiotics are recommended for persistent or multiple styes. Over-the-counter pain medications may be used to alleviate pain and tenderness. Contact lenses and eye makeup should never be worn during treatment for a sty.

What is the prognosis (outcome) of a sty?
A sty is harmless in the majority of cases. In most cases, a sty ruptures on its own within a few days to a week, leading to relief from symptoms. Some people will require medical or surgical treatment of a sty, as described in the following section. A sty does not cause intraocular damage (damage to the eye). Styes often recur. Complications of styes are rare (see below).

Are there any potential complications resulting from a sty?
Complications of a sty are rare. The infection may spread to other eyelash follicles, leading to multiple styes. A chalazion (a form of scarring of the glands in the eyelid that may include the formation of cysts) is the most common complication that develops from a sty. Chalazia can be large enough to deform the cornea of the eye and interfere with vision, and they may cause a cosmetic problem. Other potential complications include a generalized infection (cellulitis) of the eyelid, and improper drainage of a sty may lead to deformity or disruption of eyelash growth. Progression of a sty to a systemic infection (spreading throughout the body) is extremely rare, and only a few instances of such spread have been recorded.

Can a sty be prevented?
While it is impossible to completely prevent the development of a sty, good hygienic practices, including proper hand washing, can help prevent all forms of infection, including a sty. Other measures that can help prevent styes include never sharing cosmetics or cosmetic eye tools (such as lash curlers or eyelash combs) with others, keeping eye tools clean, discarding old or contaminated eye makeup, keeping all cosmetics clean, and not touching the eye and surrounding areas.

Sty (Stye, Hordeolum) At A Glance
A sty (sometimes spelled stye and medically referred to as a hordeolum) is a tender, painful red bump located at the base of an eyelash or under or inside the eyelid.

Application of a warm compress or warm washcloth to the affected area for 10 minutes, four to six times a day, can speed rupture of the sty and aid in the relief of symptoms.
Styes are common and are generally harmless.
A chalazion (a form of scarring of the glands in the eyelid that may include the formation of cysts) is the most common complication that develops from a sty.



Chalazion
Conservative treatment for small, asymptomatic chalazions begins with lid massage, moist heat, and topical mild steroid drops. Firm pressure on the lid may express thick secretions. Oral tetracyclines will minimize the risk of infection. Surgical incision and curettage allows for drainage and is performed for large, symptomatic chalazions (shown). Biopsy of recurrent chalazions should be performed to rule out sebaceous cell carcinoma.



 Chalazion
A chalazion is a lump of the lid that is caused by obstruction of an oil gland within the upper or lower eyelid. This lump may increase in size over days to weeks and may occasionally become red, warm, or painful.

The gland involved in the formation of a chalazion is a modified oil gland that lies within the eyelid. There are about 40 of these glands within each of the upper and lower lids. These glands secrete oil into the tears. When one of these glands becomes blocked, it can increase in size and cause a visible lump.

Although a sty is also a lump in the eyelid caused by obstruction of an oil gland, a chalazion is not a sty. A sty, or hordeolum, represents an acute infection of the gland. A chalazion is not an infection but is an inflammation of the area. Inflammation is a process in which the body reacts to a condition and produces a swelling, redness, pain, or warmth. A sty is usually more painful than a chalazion and may look infected.

Chalazions are lipogranulomas of either a meibomian gland or a Zeis gland. They develop when lipid breakdown products leak into the surrounding tissues from either bacterial enzymes or retained sebaceous secretions and incite a granulomatous inflammatory reaction. On examination, chalazions appear as single, firm, nontender nodules deep within the lid or tarsal plate (shown). They are more common on the upper vs lower lid because of the increased number and length of meibomian glands on the upper lid. Eversion of the eyelid may show a dilated meibomian gland.



Basal cell carcinomas
Basal cell carcinomas are the most common form of skin cancer overall, and also the most common epithelial tumor of the eyelid. Patients may describe a nonhealing ulcer that bleeds with only mild trauma. On examination the tumor may have the following characteristics: painless nodule, shiny and waxy, indurated, firm and immobile, pearly, rolled border, and small telangiectatic vessels.

Treatment is surgical excision, radiation therapy, chemotherapy, or photodynamic therapy depending on the tumor size, location, and histologic type. The image shown is of a biopsy-proven basal cell carcinoma of the upper lid margin. Note the loss of cilia (madarosis) in the area of the tumor.



Conjunctivitis - Pinkeye

Conjunctivitis, also known as pinkeye, is an inflammation of the conjunctiva, the thin, clear tissue that lies over the white part of the eye and lines the inside of the eyelid.

What Causes Pinkeye?
Pinkeye has a number of different causes, including:
Viruses
Bacteria (such as
gonorrhea or chlamydia)
Irritants such as shampoos, dirt, smoke, and pool chlorine

Allergies, like dust, pollen, or a special type of allergy that affects some contact lens wearers
Pinkeye caused by some bacteria and viruses can spread easily from person to person, but are not a serious health risk if diagnosed promptly. Pinkeye in newborn babies, however, should be reported to a doctor immediately.

Viral conjunctivitis is an infection of the mucous membrane of the surface of the eye. The most common virus responsible is adenovirus, but other viruses have also been identified including herpes simplex, varicella-zoster, picorna, pox, and human immunodeficiency virus. Infections are usually self-limited, but compared to bacterial conjunctivitis they last longer (2-4 weeks), show less inflammation, do not have purulent discharge, and a preauricular lymph node may be palpable. Most patients report itching, foreign body sensation, tearing, redness, and photophobia.

Treatment is largely supportive with artificial tears, cold compresses, and good hand hygiene. Antiviral therapy is reserved for cases of varicella-zoster and herpes simplex infection. Patients in whom appropriate therapy fails or corneal involvement develops should be referred to an ophthalmologist.



Bacterial conjunctivitis

Types of Conjunctivitis Bacterial conjunctivitis is a common type of pink eye, caused by bacteria that infect the eye through various sources of contamination. The bacteria can be spread through contact with an infected individual, exposure to contaminated surfaces or through other means such as sinus or ear infections.

The most common types of bacteria that cause bacterial conjunctivitis include Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa. Bacterial conjunctivitis usually produces a thick discharge or pus and can affect one or both eyes.
As with any bacterial infection, antibiotics are required to eliminate the bacteria. Treatment of bacterial conjunctivitis is typically accomplished with topical antibiotic eye drops and/or eye ointments. The treatment usually takes from one to two weeks, depending on the severity of the infection.

Viral conjunctivitis is another common type of pink eye that is highly contagious, because airborne viruses can be spread through sneezing and coughing. Viral conjunctivitis also can accompany common viral upper respiratory infections such as measles, the flu or the common cold.
Viral conjunctivitis usually produces a watery discharge. Typically the infection starts in one eye and quickly spreads to the other eye.

Unlike with bacterial infections, antibiotics will not work against viruses. No eye drops or ointments are effective against the common viruses that cause viral conjunctivitis. But viral conjunctivitis is self-limited, which means it will go away by itself after a short time.

Typically with viral conjunctivitis, the third through the fifth days are the worst. After that, eyes begin to improve on their own. Treatment of viral conjunctivitis usually involves supportive therapies, such as eye drops, that help reduce the symptoms: for example, vasoconstrictors to whiten the eye, decongestants to reduce the surface swelling and antihistamines to reduce
occasional itching. Treatments are usually continued for one to two weeks, depending on the severity of the infection.

Gonococcal and chlamydial conjunctivitis are bacterial forms related to infections from sexually transmitted diseases including gonorrhea and chlamydia. Newborn babies may be exposed when they pass through the birth canal of an infected mother.

Trachoma is a form of chlamydial infection that causes scarring on the eye's surface. Trachoma is the world's leading cause of preventable blindness.

Neonatal conjunctivitis found in newborn babies can cause blindness when left untreated. Up to 10 percent of all pregnant women in the United States have a sexually transmitted chlamydial infection. If these infections are untreated in mothers, the possibility that a newborn infant will develop a related eye infection ranges from 10 percent to 20 percent.*

Another type of sexually transmitted disease related to the herpes simplex
virus type 2 found in the genital area can infect eyes of infants as they are born. Herpes simplex virus type 1, a cause of cold sores on the mouth, also can cause a type of eye herpes that results in pink eye.

If you are pregnant and suspect you may have a sexually transmitted disease, you need to be checked and possibly treated for any infection before the birth of your baby.

Allergic conjunctivitis caused by eye allergies is very common. Eye allergies, like other types, can be triggered by allergens including pollen, animal dander and dust mites.

The most common symptom of allergic conjunctivitis is itchy eyes, which may be relieved with special eye drops containing antihistamines to control allergic reactions. These eye drops are available both over the counter and by prescription.

Avoiding the allergen is also important in the treatment of allergic conjunctivitis. Allergic conjunctivitis can be seasonal or perennial (year-round), depending on the allergen causing the reaction.

Giant papillary conjunctivitis (GPC) usually involves both eyes and often affects soft contact lens wearers. This condition may cause contact lens intolerance, itching, a heavy discharge, tearing and red bumps on the underside of the eyelids.

Non-infectious conjunctivitis from eye irritation causing a pink eye can result from many sources, including smoke, diesel exhaust, perfumes and certain chemicals. Some forms of conjunctivitis also result from sensitivity to certain ingested substances, including herbs such as eyebright and turmeric.**

Certain forms of pink eye, including giant papillary conjunctivitis, can be caused by the eye's immune responses, such as a reaction to wearing contact lenses or ocular prosthetics (artificial eyes).
A reaction to preservatives in eye drops or ointments also can cause toxic conjunctivitis.

Bacterial conjunctivitis is a microbial infection involving the mucous membrane on the surface of the eye. It can be differentiated from viral conjunctivitis by the purulent discharge (shown). It is typically benign and self-limiting, but significant ocular morbidity may develop. In sexually active individuals, Neisseria gonorrhoeae and Chlamydia must be considered. If clinically suspicious, culture specimens and gram stains can be used to identify the specific etiologic agent. The mainstay of treatment is empiric topical antibiotic therapy with a broad-spectrum agent, with systemic antibiotics reserved for N gonorrhoeae and Chlamydia. Frequent handwashing and avoidance of shared linens can help prevent the spread of infection.



Pterygia
A pterygium is an elevated, superficial, external ocular mass that forms over the perilimbal conjunctiva and extends onto the corneal surface. Pterygia are caused by collagen degeneration and fibrovascular proliferation. Increased exposure to ultraviolet light is a risk factor. Clinically, patients may be asymptomatic, or complain of symptoms related to the elevation of the conjunctiva such as redness, itching, blurred vision, and irritation. Patients are typically observed without intervention unless there is significant discomfort or obstruction of the visual axis.



Corneal abrasion 
If the cornea (the membrane that covers the front of the eye) is damaged, the eye becomes inflamed and often very sensitive to light. Damage may occur as a result of an injury, often you get a scratch on your eye from a foreign object or from something else like if you walk through some tall bushes and get scratched in the eye by a branch. Or, if you fall in some dirt while rollerblading or cycling and your eye gets scratched by a pebble.
Call your health care provider right away if you do get a scratch like this on the surface of the eyeball. An infection can occur from the ulceration. You will be given prescription eye drops and sometimes oral medication to prevent infection. The eye can heal very quickly, but you must seek attention quickly with this kind of injury.

With the use of blue light, the fluorescein defect of a corneal abrasion may be more pronounced and will appear yellow-green (shown). Corneal abrasions typically heal without serious complications over time with supportive care: ice compresses and nonsteroidal anti-inflammatory eye drops. Prophylactic antibiotics are commonly prescribed, especially for traumatic or surgical abrasions. Close follow-up is necessary because of the risk of developing a corneal ulcer.




Subconjunctival hemorrhage



Subconjunctival hemorrhage is a bright red patch appearing in the white of the eye. This condition is also called red eye.

Symptoms
A bright red patch appears on the white of the eye. The patch does not cause pain and there is no discharge from the eye. Vision does not change.

Treatment
No treatment is needed. You should have your blood pressure regularly checked.

Causes
A subconjunctival hemorrhage occurs when a small blood vessel breaks open and bleeds near the surface of the white of the eye (bulbar conjunctiva). It may happen without injury, and is often first noticed when you wake up and look in a mirror.
Sudden increases in pressure such as violent sneezing or coughing can cause a subconjunctival hemorrhage. The hemorrhage may also occur in persons with high blood pressure or who take blood thinners.

A subconjunctival hemorrhage is common in newborn infants. In this case, the condition is thought to be caused by the pressure changes across the infant's body during childbirth.

Tests & diagnosis
The health care provider will perform a physical exam and look at your eyes.
Blood pressure should be tested. If you have other areas of bleeding or bruising, more specific tests may be needed.

Prognosis
A subconjunctival hemorrhage usually goes away on its own in about 1 week.

Prevention
There is no known prevention.

Complications
There are usually no complications.
The image shown is of a subconjunctival hemorrhage, a condition that can be easily managed with conservative treatment on an outpatient basis.

Images courtesy of Wikimedia Commons
Source

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Wednesday, December 14, 2011

Irreversible Anterior Ischemic Optic Neuropathy Complicating Interferon Alpha and Ribavirin Therapy


Journal List ; Int J Hepatol ; v.2011; 2011
Formats: Abstract
Full Text PDF (428K)

Int J Hepatol. 2011; 2011: 814242.

Published online 2010 December 19. doi: 10.4061/2011/814242
PMCID: PMC3170847
Copyright © 2011 Hassan Seddik et al.

Irreversible Anterior Ischemic Optic Neuropathy Complicating Interferon Alpha and Ribavirin Therapy

Hassan Seddik, 1 Mouna Tamzaourte, 1, 2 * Fadoua Rouibaa, 3 Maha Fadlouallah, 1 and Ahmed Benkirane 1
1Hepatogastroenterology 2 Unit, Mohamed V Military Hospital, Rabat, Morocco
219, Rue Oued El Makhazine No. 7, Agdal, Rabat, Morocco
3Hepatogastroenterology 1 Unit, Mohamed V Military Hospital, Rabat, Morocco

Abstract
Ophthalmologic complications with interferon therapy are rare and usually reversible. The anterior ischemic optic neuropathy is an uncommon complication of interferon treatment. A case of irreversible anterior ischemic optic neuropathy complicating interferon therapy for chronic hepatitis C is reported.

We suggest that periodic ophthalmological examinations, including visual acuity and fundus examinations, should be performed to patients with high risk of ocular complications after starting and during treatment. We also suggest that an ophthalmologist would be able to detect these complications. Antiviral treatment should be stopped immediately if severe ophthalmologic complications occur.

Ophthalmologic complications with interferon therapy are rare, usually mild and reversible, and do not require the withdrawal of antiviral treatment [1]. Ophthalmologic complications with interferon alpha therapy, such as retinopathy with cotton-wool spots, hemorrhages and macular edema, optic neuropathy, and thrombotic microangiopathy occur in less than 1% of treated patients. Individuals with diabetes, hypertension, dislipidemia, and hypercoagulable states are more prone to develop those changes.

In most cases, they are subclinical, mild, and reversible, not requiring the withdrawal of the treatment [2]. We report a case of a patient with chronic hepatitis C who developed irreversible anterior ischemic optic neuropathy during antiviral treatment by pegylated interferon combined with ribavirin.A 55-year-old man had chronic hepatitis C since 2008.

HCV genotype was 4, HCV-RNA level was 6,08·106equivalent/ml and the histological score of the liver biopsy was A2 F3 according to the METAVIR classification. Pegylated interferon (180μg/ week) combined with ribavirin (1000mg/day) was started in June 2008. HCV-RNA had been undetectable since week 12 of the therapy.

Five months after starting treatment, the patient presented with a sudden bilateral decreased vision. Visual acuity was 2/10 in the left eye and 4/10 in the right eye, while his visual acuity was previously normal. Fundus examination revealed bilateral disc edema.

Fluorescein angiography confirmed the bilateral anterior ischemic optic neuropathy. There was no response to the visual evoked potentials in the either eye. The complete blood count chemistry, sedimentation rate, C-reactive protein level, antinuclear antibodies, anti-DNA antibodies, and pANCA antibodies were normal. Cryoglobulinemia was negative as were magnetic resonance imaging of the head, echocardiogram, and carotid Doppler study. Antiviral treatment was discontinued, and the patient received methyl prednisolone 1g for 5 days.

An ophthalmologic examination one month later showed that visual acuity had not clearly improved the visual acuity was 3/10 for the left eye and 5/10 for the right one, while optic disc oedema was partially resolved. HCV- RNA was always undetectable six months and 1 year after interruption of treatment, suggesting a sustained virological response.

Ophthalmologic examination after 1 years showed a visual acuity of 3/10 for the left eye and 5/10 for the right one.Anterior ischemic optic neuropathy is an uncommon complication of interferon treatment which may dramatically impair visual function.

Few cases have been reported in the literature [3] during antiviral treatment for chronic hepatitis C [2] and also during interferon treatment of cancer (2 cases), treatment of primary thrombocytemia (1 case), treatment of malignant melanoma (1 case), and during treatment of amyotrophic lateral sclerosis [4]. Predisposing factors have not been clearly identified, except for classic vascular risk factors (diabetes, arterial hypertension, and dyslipidemia) [2].

In our patient's case, no vascular risk factors were found. Purvin and Col [5] has suggested involvement of the posterior ciliary arterius rather than the retinal vessels as a possible cause of anterior ischemic optic neuropathy [5]. Lohmann and Coll hypothesized that interferon could produce autoantibodies, and thus cause desposition of immune complexes in the small retinal or optic cytokines causing an inflammatory reaction of the blood vessels that could then lead to ischemia [6].

The favorable course is uncommon in anterior ischemic optic neuropathy with vascular causes suggesting another mechanism [4]. The absence of resolution of anterior ischemic optic neuropathy after discontinuation of interferon in our patient suggests probable vascular causes. In the literature, the course of anterior ischemic optic neuropathy occurring during interferon treatment for chronic hepatitis C was favorable in four cases [7], and not resolved in three cases [2, 4].

After interruption of the antiviral treatment, our patient received methyl prednisolone, a steroid drug prescribed by the ophthalmologists, without favorable course of visual function. In the literature, two patients received steroids after interferon treatment was discontinued, but there was no improvement in visual function [3]. Anterior ischemic optic neuropathy is uncommon unpredictable, and the frequency is unknown with interferon therapy.

Periodic ophthalmologic examinations before starting treatment and during treatment particularly in patients with vascular risk factors must be indicated. Therapy should be stopped immediately if severe ophthalmologic complications occur.

References
1. Gonçalves LL, Farias AQ, Gonçalves PL, D’Amico EA, Carrilho FJ. Branch retinal vein thrombosis and visual loss probably associated with pegylated interferon therapy of chronic hepatitis C. World Journal of Gastroenterology. 2006;12(28):4602–4603. [PubMed]
2. Sène D, Touitou V, Bodaghi B, et al. Intraocular complications of IFN-α and ribavirin therapy in patients with chronic viral hepatitis C. World Journal of Gastroenterology. 2007;13(22):3137–3140. [PubMed]
3. Willson RA. Visual side effects of pegylated interferon during therapy for chronic hepatitis C infection. Journal of Clinical Gastroenterology. 2004;38(8):717–722. [PubMed]
4. Kabbaj N, Sentissi S, Mohammadi M, Benaïssa A, Amrani N. Anterior ischemic optic neuropathy complicating interferon alpha and ribavirin therapy in patients with chronic hepatitis C. Gastroenterologie Clinique et Biologique. 2009;33(2):115–117. [PubMed]
5. Purvin VA. Anterior ischemic optic neuropathy secondary to interferon alfa. Archives of Ophthalmology. 1995;113(8):1041–1044. [PubMed]
6. Lohmann CP, Kroher G, Bogenrieder T, Spiegel D, Preuner J. Severe loss of vision during adjuvant interferon alfa-2b treatment for malignant melanoma. Lancet. 1999;353(9161):p. 1326.
7. Norcia F, Di Maria A, Prandini F, Redaelli C. Natural interferon therapy: optic nerve ischemic damage? Ophthalmologica. 1999;213(5):339–340. [PubMed]