International Journal of Ophthalmic PathologyISSN: 2324-8599

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Case Report, Int J Ophthalmic Pathol Vol: 3 Issue: 3

Interferon Associated Retinopathy in Chronic Hepatitis C: Two Cases Report

Hachicha F1*, Lajmi H2, Zahaf A2, Brour J1, Hammami A2, Cheour M1 and Kraiem A1
1Department of Ophtalmologie of Habib Thameur Hospital-Tunis
2University Tunis El Manar, Faculty of medicine of Tunis, Tunisia
Corresponding author : Hachicha Firas
Department of Ophtalmologie of Habib Thameur Hospital-Tunis
Tel: (00216) 22387310
E-mail: [email protected]
Received: July 02, 2014 Accepted: August 11, 2014 Published: August 14, 2014
Citation: Hachicha F, Lajmi H, Zahaf A, Brour J, Hammami A, et al. (2014) Interferon Associated Retinopathy in Chronic Hepatitis C: Two Cases Report. J Ophthalmic Pathol 3:3. doi:10.4172/2324-8599.1000142

Abstract

Alpha interferons have been used widely to treat chronic hepatitis C virus infection. A wide array of adverse effects of alpha interferon has been described. Ocular complications are infrequent. We report through two cases report the signs, the risk factors and the management of retinopathy associated with interferon therapy in patients with hepatitis C virus.

Keywords: Hepatitis C; Interferon α; Ribavirin; Ischemic retinopathy

Keywords

Hepatitis C; Interferon α; Ribavirin; Ischemic retinopathy

Introduction

Interferons are a group of glycoproteins that modulate the activity of the immune system. Recombinant alpha-interferon has recently been approved as a therapy for chronic hepatitis C, for its antiviral effects and inhibition of cell proliferation. Although interferon-based therapy is widely used for the treatment of chronic Hepatitis C, it is not without its disadvantages. Indeed, a wide array of systemic adverse effects of alpha interferon has been described. Ocular complications are infrequent and the most typical one is ischemic retinopathy with cotton-like exudates, retinal hemorrhages in the posterior pole and micro aneurysms. We report through two cases report the signs, the risk factors and the management of retinopathy associated with interferon therapy in patients with hepatitis C virus.

Case Report

Case 1
A 69 year old woman, with no systemic vascular involvement, treated since 2 months with interferon alpha (IFN α) and Ribavirin for chronic hepatitis C, was referred to us to evaluate her ocular state. The patient did not use anti-hypertensive pills.
Treatment was established with pegylated IFN α (180 g/week) together with Ribavirin (800 mg/day) and it was stopped for iatrogenic medullar aplasia. Visual acuity in the right eye was of 8/10 with a normal anterior segment. Fundus examination revealed multiple cotton wool spots respecting the macular area, as well as some superficial micro hemorrhages in the posterior pole. There were no signs of inflammation, vasculitis or arteriosclerosis (Figure 1). Blood pressure was balanced and the patient did not use anti-hypertensive pills. Examination of the left eye showed a visual acuity of light perceptions due to a complete cataract and the fundus examination was impossible. Fluoreceine retinal angiography showed the hypo fluorescence of hemorrhage and cotton wool spots (Figure 2). This retinopathy disappeared spontaneously 4 weeks after stopping treatment (Figure 3).
Figure 1: Multiple cotton wool spots respecting the macular area, as well as some superficial micro hemorrhages in the posterior pole with no signs of inflammation, vasculitis or arteriosclerosis.
Figure 2: Fluorescein angiography showed the hypofluorescence of hemorrhage and cotton wool spots with no vasculitis.
Figure 3: Interferon associated retinopathy disappeared spontaneously four weeks after stopping treatment.
Case 2
A 64 years old woman with history of diabetes mellitus, ischemic cardiopathy and no other systemic vascular involvement, was diagnosed with chronic hepatitis C and treated with Interferon IFN α. Blood pressure was balanced and the patient did not use antihypertensive pills.
Treatment was established with pegylated IFN α (150 g/week) together with ribavirin (1 g/day). Three months after beginning the treatment the patient was referred to us in order to evaluate her ocular state. The ophthalmological examination revealed in both eyes a visual acuity of 7/10 and some cotton wool spots with superficial hemorrhage in the posterior pole (Figure 4).
Figure 4: Some cotton wool spots with superficial hemorrhage in the posterior pole of both eyes.
There were no signs of inflammation, vasculitis or arteriosclerosis. The diagnosis retained was interferon associated retinopathy and the treatment was suspended. Successive controls showed an improvement of the visual acuity (10/10) and almost complete resolution of the retinal lesions 2 months after stopping treatment. (Figure 5).
Figure 5: Almost complete resolution of the retinal lesions in both eyes 2 months after stopping treatment.

Discussion

General side effects of interferon include flu-like symptoms such as mild fever and chills, fatigue, myalgia, nausea, loss of appetite and psychiatric symptoms such as depression, suicidal ideation, irritability, nervousness and insomnia. The less common ones are hematopoietic suppression, reversible hair loss, hearing loss, dermatitis, seizures, the development or exacerbation of autoimmune diseases such as thyroid dysfunction, rheumatoid arthritis, arteritis, cryoglobulinemia, sarcoidosis, systemic lupus erythematosus, vitiligo, type 1 diabetes and myasthenia gravis [1,2].
Ocular complications are infrequent and the most typical one is ischemic retinopathy with cotton-like exudates, retinal hemorrhages in the posterior pole and microaneurysms [3]. Retinopathy, secondary to the use of IFN, is known since 1990, with a prevalence which varies according to each series between 18% and 86% [4]. Many risk factors of retinopathy associated with interferon therapy in patients with hepatitis C virus have been reported.
There is a relationship between the dosage and duration of the treatment [4]. Indeed, the retinopathy associated with interferon therapy rarely appears before 8 weeks after beginning the treatment [3]. Association with Ribavirin as our two patients, may aggravate this situation because of its synergic action in combination with IFN; that is why in some studies Interferon monotherapy was associated with a prevalence of retinopathy of 24-58%, while interferon-ribavirin combination with a prevalence of 16%-64% [5].
IFN pegylation is also an important risk factor [3]. During pegylation a polyethylene glycol molecule is attached to a protein in order to increase its molecular weight and the half-life of serum elimination. This process increases the antiviral effect and enables to use interferon once weekly, but a number of side effects such as retinopathy increases too [2,3].
Diabetes, hypertension and anemia have been described as risk factors for the development and progression of retinopathy [6]. The physiopathology of these lesions are complex, but many authors speculates that IFN α therapy may cause deposition of immune complexes in the retinal vasculature leading to retinal ischemia, hemorrhage and cotton wool spots formation. It increases also leukocyte adherence to the vascular endothelium, trapping these cells in the retinal capillaries. These activated leukocytes and the toxic substances generated result in the capillary infarction observed during interferon associated retinopathy [5].
Interferon associated retinopathy is normally asymptomatic and is associated to good visual acuity as the case of our two patients. It could disappear spontaneously in the course of the treatment or rapidly if IFN is suspended, in the majority of cases without visual sequels [3,4]. Adults develop the retinopathy at a mean of 12 weeks that will regress within 4 to 12 weeks after therapy stops [2].
However other described manifestations may leads to serious complication and even visual loss such as retinal vascular occlusions, ischemic optic neuropathy (20% of patients), macular edema, Vogt- Koyanagi-Harada like, choroidal neovascularization, vessel spasms and neovascular glaucoma [3,5,7,8].
The main differential diagnoses are hypertensive retinopathy and Purtscher’s retinopathy. Besides the clinical context in which the acute changes in visual acuity occurred, fundoscopic examination is the most important clue for the diagnosis of Purtscher retinopathy. Typical acute lesions include Purtscher flecken and cotton-wool spots, although macular edema, optic disk swelling and retinal hemorrhages may also be present. The loss of vision is often bilateral, acute, deep and can persist in 50% of cases [9].
Treatment was withdrawn in our two patients but there is no good evidence to guide whether interferon therapy should be modified or discontinued when interferon associated retinopathy has been diagnosed. In fact, although suspending the treatment is advisable with reduced visual acuity and the appearance of intense retinal ischemia; it is, well established that dose reduction of interferon increases the risk of treatment failure. Interferon treatment may usually be continued in asymptomatic patients as long as there is careful fundoscopic examination even if there is evidence of retinopathy [2,5,10].
Some studies propose that patients on interferon therapy should be examined before the initiation of therapy, during and after the end of treatment including visual acuity, color vision examination, slit lamp microscopy and ophthalmoscopy. For some others, screening is not pertinent and ophthalmologic examination should be reserved for patients complaining of visual symptoms or for those with predisposing factors such as diabetes mellitus [5-10].
We recommend examination of the eye fundus before treatment especially in patients with diabetes and arterial hypertension and during interferon treatment. If typical retinal changes are found (cotton wool spots and/or retinal hemorrhages), visual acuity supervising is recommended. In case of vision deterioration and sever retinal lesions with optic disc or macular edema, discontinuation of antiviral drugs should be considered.

Conclusion

Interferon associated retinopathy is an uncommon condition. It is mostly benign but sometimes may lead to a serious visual deterioration. Visual acuity and ocular funduscopy should be made before beginning treatment and at 3-month intervals especially in patients with risk factors. If retinopathy is determined, monitoring should be more frequent and made up to full resolution of lesions.

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