Interferon-associated Retinopathy Research Articles

Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin.

This retrospective cohort study aims to investigate interferon (IFN)-associated retinopathy incidence in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon (PegIFN) plus ribavirin (RBV). We selected 1688 patients undergoing PegIFN/RBV therapy for HCV (HCV-treated cohort), 3376 patients not receiving HCV treatment (HCV-untreated cohort) and 16,880 controls without HCV (non-HCV cohort) from the Taiwan Longitudinal Health Insurance Database. The patients were frequency-matched by age, sex, and index date at a 1:2:10 ratio, and followed up until the end of 2013. Cox proportional hazard regression models were used to compare the incidences of any retinal vascular events, including subtypes, among the three cohorts. Compared with the non-HCV cohort, the HCV-treated cohort had a significantly increased risk of retinopathy (hazard ratio (HR) = 4.98, 95% confidence interval (CI): 2.02–12.3). The risk was particularly prominent for retinal hemorrhage (HR = 12.7, 95% CI: 3.78–42.9). When the HCV-untreated cohort was used as the reference, the aforementioned HRs increased to 9.02 (95% CI: 3.04–26.8) and 32.3 (95% CI: 3.94–265), respectively. This study suggested that PegIFN/RBV therapy significantly increased the risk of retinal hemorrhage but not retinal vascular occlusions in the HCV-treated cohort.

Retinal Lesions and Renal Impairment Associated with Interferon β1α Therapy for Multiple Sclerosis: A Case Report

Background: Recombinant interferon β is now the mainstay of maintenance therapy for multiple sclerosis in many countries. Retinal lesions are rarely related with subcutaneous interferon β1α in multiple sclerosis. Interferon nephrotoxicity is also an extremely rare side effect. We report a case of interferon-associated retinopathy and nephropathy in a patient with multiple sclerosis receiving subcutaneous interferon β1α. Case report: A 42 years old Caucasian female with a history of multiple sclerosis on continuous treatment with interferon β1α, presented with anemia, thrombocytopenia, albuminouria, mild elevation of liver enzymes, renal impairment and sudden hypertension without visual disorders. Ocular fundus exam showed several retinal cotton wool spots indicating interferon-retinopathy and the drug was discontinued. Biochemical and immunological analyses were negative for autoimmune renal diseases. The retinopathy disappeared without specific therapy 2 months after discontinuing interferon β1α and kidney function restored. Interferon β1α resumed 16 weeks after stopping treatment due to multiple sclerosis relapse. On an iterative fundus exam 3 months after resumption of interferon β1α, no further cotton wool spots have recurred. 6 and 12 months later, with the patient on interferon β1α treatment, the ocular fundus was free of lesions and kidney function was within normal range. Conclusions: In our patient, both complications resolved after drug cessation and the diagnosis of interferon β1α retinopathy and nephropathy was retained due to the lack of any other etiology.

Proliferative retinopathy in a diabetic on interferon therapy: A diagnostic dilemma

Hepatitis C virus (HCV) is a blood-borne RNA virus that causes hepatitis C, chronic liver disease, and hepatocellular carcinoma. Patients with HCV infection are now treated with a combination of interferon alpha, which has antiviral and immunomodulatory properties, and ribavirin, an antiviral medication included in the family of nucleoside analogs. Recently, a long acting form of interferon alpha (pegylated interferon) has been developed, which has a more sustained antiviral response. One of the ocular side effects of interferon alpha is proliferative retinopathy related to ischemia. Interferon-associated retinopathy is usually mild and resolves completely, but occasionally, it can become severe.

Transient Visual Loss in a Hepatitis C Patient Treated With Pegylated Interferon Alfa-2a and Ribavirin

Introduction:Patients with Hepatitis C are commonly treated with combination of Pegylated Interferon alfa-2a and Ribavirin. Less than 1% of patients receiving this treatment experience very uncommon ophthalmological side effects such as optic neuropathy and vision disorder, which are usually subclinical, mild and reversible, not requiring the withdrawal of the treatment. Retinopathy is the most commonly reported ocular side effect of interferon use, usually presenting with cotton wool spots and retinal hemorrhages.Case Presentation:We represent a case of severe retinopathy and optic neuropathy in a patient with chronic hepatitis C genotype 3a infection, treated with the combination of PEG-IFN alfa-2a (180 mkg once weekly) and Ribavirin (1200 mg daily). Bilateral visual loss of both eyes developed at 11th week of therapy and changes in retina and optic nerve were observed. Fluorescein angiography and optical coherence tomography showed bilateral anterior ischemic optic neuropathy and macular edema. Visual acuity improved 1 month and fundoscopic changes were no longer present 6 months after the urgent permanent discontinuation of PEG-IFN treatment and the pulse steroid therapy followed by a 2 week course of oral prednisone.Discussion:In case of interferon-associated retinopathy discontinuation of the therapy and treatment with high dose steroids can be beneficial. The prognosis of interferon-associated opthalmological side effects remains uncertain: in some patients visual acuity improves, other continues with poor visual outcome. Considering that, all patients should undergo ophthalmologic examination before treatment with interferon and their ophthalmological status should be monitored regularly while receiving this therapy.

Interferon-associated retinopathy risk in patients with diabetes and hypertensive hepatitis C.

To investigate the association of hypertension and diabetes mellitus (DM) with interferon-associated retinopathy (IAR) risk in chronic hepatitis C (CHC). Two investigators independently searched PubMed and Embase for eligible articles published prior to December 2013; additional studies were identified by reviewing the bibliographies. Only case-control or cohort studies that evaluated the association between hypertension and/or DM and IAR incidence in CHC patients were included. IAR was characterized by the presence of cotton-wool spots and/or retinal hemorrhage, and was defined as the primary efficacy measure. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were estimated using data extracted from papers based on random-effects models. Eight eligible studies were included in the present meta-analysis. The outcomes showed that patients with CHC and hypertension were at higher risk of IAR (48/189 vs 96/455, RR = 1.90; 95%CI: 1.15-3.15, P < 0.05). Patients with DM receiving interferon (IFN)-based therapy for CHC infection may be at higher risk for IAR (18/72 vs 60/256, RR = 1.56, 95%CI: 1.11-2.20, P < 0.05); however, the outcome was not stable. There was no significant difference in IAR risk between genotype-1-infected patients and non-genotype-1-infected patients (RR = 1.09, 95%CI: 0.64-1.87, P > 0.05). Comparable incidences of IAR were also found between patients treated with pegylated interferon (PIFN) α-2a and those treated with PIFN α-2b (RR = 0.84, 95%CI: 0.56-1.24, P > 0.05) and between patients treated with IFN α and those treated with PIFN α (RR = 1.04, 95%CI: 0.72-1.50, P > 0.05). Patients with hypertension have a higher risk of retinopathy when receiving IFN-based therapy for CHC.

Interferon-associated retinopathy in a patient with metastatic melanoma.

We present the unusual case of a 35 year-old woman with stage IV melanoma and widespread metastases, who was undergoing treatment with interferon alpha-2b and who presented with interferon-associated retinopathy. The patient, who had been taking interferon treatment for three months, complained of a sudden loss of visual acuity in the left eye. An ocular examination revealed multiple cotton wool spots along the retina and macular involvement. Interferon treatment was suspended. Although rare, retinopathy represents a potentially serious adverse effect of interferon treatment. Although normally patients are asymptomatic, complications derived of its use may arise, which can lead to significant visual impairment. We therefore suggest that before initiating treatment with this drug, patients should be informed of its potential ocular risks, and that regular eye examinations are conducted along with the treatment.

Ophthalmologic complications of antiviral therapy in hepatitis C treatment

Antiviral therapy consisting of interferon-alpha and ribavirin for chronic hepatitis C infection is associated with multi-system side-effects. Ophthalmologic complications are common and can be classified into two groups: interferon-associated retinopathy and atypical adverse events. Interferon-associated retinopathy has been investigated by multiple observational studies that have found widely divergent results. The clinical importance of this complication is, consequently, controversial. This review examines the literature with the specific goal of identifying the most important ophthalmologic issues facing the hepatologist prescribing antiviral therapy. Accordingly, it assesses the incidence of interferon-associated retinopathy, as well as its risk factors, pathogenesis, clinical manifestations and options for management using data from the observational studies. The likely benefit of a screening program, especially one targeting patients with the highest risk of developing interferon-associated retinopathy, is analysed. Atypical ophthalmologic adverse events occur less frequently than interferon-associated retinopathy during antiviral therapy for chronic hepatitis C infection. They often, however, lead to irreversible vision loss. We examine the reports of these adverse events - in individual case reports or case series and in the observational studies investigating interferon-associated retinopathy - to describe the spectrum of these adverse events, the likely outcome for patients and to highlight the most important areas of future clinical research.

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

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. 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.

Retinopathy Associated with Adjuvant High-Dose Interferon-α2b in a Patient with Resected Melanoma: A Case Report and Review of the Literature

Interferon is the only accepted adjuvant treatment for patients with melanoma; hence, oncologists should be aware of the possibility of retinal abnormalities resulting from its use. Interferon-associated retinopathy in patients being treated for resected melanoma is a rare phenomenon with a proposed immunological basis. Patients are usually asymptomatic or have mild visual impairments, with cotton wool infarcts and hemorrhages. These symptoms and signs usually resolve with the discontinuation of interferon, but in a few severe presentations the visual impairments and retinal changes can be irreversible.

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

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.

Hepatitis C and interferon-associated retinopathy: A case report

Background Hepatitis C is a common virus affecting approximately 170 million people worldwide. The main ocular manifestations of hepatitis C virus include a Sjögren-type of dry eye syndrome and an ischemic retinopathy secondary to treatment with interferon or a result of a systemic vasculitis induced by the infection itself. Current treatment for hepatitis C is a combination therapy using pegylated (long-lasting) interferon and ribavirin. This treatment, however, is not without ocular sequelae. Interferon-associated retinopathy is present in > 50% of patients taking the drug and is mainly characterized by cotton wool spots and retinal hemorrhages. The pathogenesis of this disorder is not specifically known. Fortunately, many patients remain asymptomatic, and the retinal changes are usually reversible. Case Report A 48-year-old black man presented to the clinic complaining of decreased vision in both eyes for the previous few weeks. His medical history was positive for hypertension and hepatitis C for which he was being treated. At his examination, he had interferon retinopathy diagnosed. Soon thereafter, his treatment for hepatitis C was discontinued, and when he returned for follow-up 4 months later, his retinal findings had resolved. Conclusions An overview of hepatitis C and its recommended therapy and possible ocular side effects are reviewed, as well as the differential diagnosis of interferon-associated retinopathy, 1 of the main side effects of treatment.

INTERFERON-β-ASSOCIATED RETINOPATHY.

Interferon-associated retinopathy is a rare complication of interferon treatment. It has been well described with the use of interferon-α. This study reports a retrospective case series of interferon-β-associated retinopathy in three patients that were being treated for multiple sclerosis. All cases were characterized by cotton-wool spots or peripheral microaneurysms. One central retinal artery occlusion was observed associated with interferon-β treatment. Findings improved spontaneously in two of three cases; all three patients elected to continue interferon treatment. Patients being treated with interferon-β should have periodic fundus examinations to determine if they have evidence of interferon-associated retinopathy.

Pegylated Interferon Associated Retinopathy in Chronic Hepatitis Patients

Purpose: To investigate clinical features of pegylated interferon‐associated retinopathy in chronic hepatitis patients. Methods: The present study was a consecutive case series of 46 patients who were treated with pegylated interferon for chronic hepatitis C or B from October 2007 to September 2008 in our hospital. The patients had a regular ophthalmologic examination every 3 weeks for 6 months after treatment. Results: Out of 46 patients, 10 patients (21.73%) developed retinal abnormality. Pegylated interferon‐associated retinopathy occurred at 7.2510.28 weeks after the treatment with cotton‐wool spots and retinal hemorrhage. All cases except one mild nonproliferative diabetic retinopathy case presenting broad perimacular non‐perfusion recovered without cessation of the treatment. Conclusions: Pegylated interferon‐associated retinopathy in chronic hepatitis patients was reversible and had a recovery without visual complication. However, a single case did present with irreversible visual impairment. Pegylated interferon‐associated retinopathy is usually asymptomatic and clinicians should observe patients closely for 3 months after treatment.

Continued Treatment of Chronic Hepatitis C Despite Development of Interferon-Associated Retinopathy

Continued Treatment of Chronic Hepatitis C Despite Development of Interferon-Associated Retinopathy

Patients with Hypertension and Diabetes Mellitus Undergoing Interferon Therapy for Treatment of HCV Are Not at Higher Risk To Develop Ophthalmologic Complications

Purpose: To determine the frequency and risk factors related to interferon-associated ophthalmologic complications during treatment for hepatitis C. Methods: Review of records from a cohort of patients undergoing HCV treatment between January 2005 and May 2007. Patients were treated with ribavirin in addition to either pegylated INF α-2a, α-2b or consensus INF. A mandatory, baseline ophthalmologic examination was performed on each patient prior to initiation of treatment. Data recorded included genotype, treatment duration, type of INF used, presence of prior eye disease/complaints, presence of DM / HTN, visual complaints during treatment and findings at baseline and follow-up eye exams. Any visual complaints during therapy prompted immediate evaluation by an eye specialist. Results: A total of 183 patients treated for HCV were included in the study cohort. Seventy-one (38.7%) received interferon α-2a, 100 α-2b (54.6%) and 12 (6.5%) consensus INF. Treatment duration was 1 to 48 weeks (mean = 27.6). Age range was 31 to 72 years (mean = 52.9) and 95% were men. Twenty-nine (15.8%) had DM, 85 (46.2%) HTN and twenty-one (12.5%) had both DM and HTN. One patient with DM + HTN had retinopathy (cotton wool spots) at baseline exam. During treatment 16 (8.7%) had visual complaints, but only 3/16 (18.75%) found to have retinal changes. In addition 4 (2.2%) asymptomatic patients had retinopthay on routine follow-up examinations. Overall 7 (3.82%), (6 during treatment) had documented retinal changes (6 CWS, 1 optic neuritis). Of 7 with retinal changes, 1 (14.2%) had DM, 3 (42.8%) HTN and 1 (14.2%) had both. Of these, 5 were on α-2b and 2 on α-2a. Three patients required treatment discontinuation 44, 20 and 2 weeks earlier than scheduled. These included asymptomatic worsening CWS(1), symptomatic CWS(1) and symptomatic optic neuritis (1). Conclusion: In our study, both the incidence of symptomatic retinopathy and resultant treatment discontinuation rate appears very low 3/183 (1.63%) during treatment with PEG INF/ribavirin. The majority of patients who experienced visual symptoms during treatment had no evidence of retinopathy (81%). Diabetes and hypertension do not appear to be predictors for the development of clinically significant interferon-associated retinopathy.

Interferon-Associated Retinopathy - a Case Report

Interferon alpha is used for treatment in oncology and for chronic hepatitis C. Interferon-associated retinopathy is not infrequent and typically includes cotton wool spots, haemorrhages, rarely macular or papillary oedema, capillary non-perfusion and sometimes retinal or even choroidal vascular occlusion. The latter may be irreversible, while uncomplicated forms are usually reversible. We report an atypical case of interferon-associated retinopathy, associated with microaneurysms, Roth spots, and retinal pigment changes. A 63-year-old asymptomatic patient presented with partially white centred, flame-shaped haemorrhages, some cotton wool spots and microaneurysms on both fundi. In addition, the left eye presented chronic pigment epithelium abnormalities surrounding the fovea without signs of exudation, most likely secondary to a previous central retinal exudative detachment combined with choroidal hypoperfusion. Interferon alpha 2a therapy for chronic hepatitis C had been given for 6 months. He was known for arterial hypertension (risk factor), mild microcytic anaemia and mild glucose intolerance, which may be responsible for some unusual features of the retinopathy. The patient was closely followed, while the interferon therapy was continued on reduced dosage. No vision-threatening complication was observed. Interferon-associated retinopathy may show atypical features. Early diagnosis and careful follow-up are recommended in order to avoid progression to irreversible changes. Dose-reduction or even interruption of interferon treatment needs to be considered in cases of interferon-associated retinopathy.

Interferon löst okuläre Ischämien aus

Reports of interferon-associated retinopathy mainly originate from Japanese working groups. Only a few cases have been described in Europe. We have performed a retrospective analysis of the patients who were examined in the University Eye Clinic in Mainz complaining of visual loss associated with systemic interferon therapy in the time span between January 2001 and December 2003. 12 patients (age 35 - 67 years), undergoing treatment with interferon alpha for hepatitis C, metastatic renal cell carcinoma, leukaemia and malignant melanoma of the skin, complained of blurred vision 2 - 10 weeks after the start of interferon therapy. Fundus examination revealed retinal haemorrhages and cotton-wool spots in all eyes. Additionally in some eyes macular edema, retinal arteriolar occlusion or anterior ischemic optic neuropathy was seen. As underlying risk factors we found diabetes mellitus (6 x) and systemic hypertension (3 x). After interruption (10 x) or dose reduction (2 x) of interferon therapy in all eyes the ischemic changes disappeared rapidly. Permanent visual loss or visual field defects remained in 3 out of 24 eyes. Patients under interferon therapy should be monitored closely by an ophthalmologist, especially those with systemic vascular risk factors. In the case of development of ischemic microangiopathy of the retina or optic nerve, interferon therapy should be stopped or dose reduction is recommended.

Pegylated Interferon-Associated Retinopathy in Chronic Hepatitis C Patients

Pegylated Interferon-Associated Retinopathy in Chronic Hepatitis C Patients

Retinopatia em paciente portador de hepatite C tratado com interferon peguilado e ribavirina: relato de caso

Interferon is an immunomodulating cytokine used to treat patients with different diseases, such as hepatitis C chronic infection. Pegylated interferon is a new type of interferon, developed to increase the half-life of the drug. Many side effects have been related to its use, including ocular toxicity and retinopathy. The most reported ocular findings are cotton-wool spots and hemorrhages located at the posterior pole and surrounding optic nerve head. We describe one case of pegylated interferon-associated retinopathy with visual loss. The patient had visual acuity improvement four weeks after discontinuation of the medication and the ocular findings became much more subtle.

Clinical Course of Macular Edema in Two Cases of Interferon-Associated Retinopathy Observed by Optical Coherence Tomography

Interferon (IFN)-associated retinopathy is typically characterized by retinal hemorrhages and cotton wool spots at the posterior fundus, but visual function is usually maintained. With the use of optical coherence tomography (OCT), two patients with IFN-associated retinopathy who had developed macular edema and reduced visual acuity during the clinical course of IFN therapy were observed. A 37-year-old man with chronic hepatitis C and a 59-year-old man with chronic myeloid leukemia, both of whom had received IFN therapy, were referred to our outpatient clinic. The former patient had complained once that his visual acuity had decreased after the termination of IFN therapy, and the latter patient complained twice during IFN therapy that his visual acuity had decreased. In both patients, at the time of the visual disturbances, macular edema was clearly observed by OCT. Hypoalbuminemia and thrombocytopenia were observed at this time also. After the remission of the hypoalbuminemia and thrombocytopenia, the macular edema observed by OCT disappeared and visual acuity returned to normal. During and after IFN therapy, OCT is a useful examination technique for revealing macular edema in patients who have decreased vision. Ophthalmologists should be aware of the ocular side effects of IFN therapy and carefully monitor patients for the possible occurrence of hypoalbuminemia and thrombocytopenia. Jpn J Ophthalmol 2005;49:231-234 (c) Japanese Ophthalmological Society 2005.