Intraocular complications of IFN-α and ribavirin therapy in patients with chronic viral hepatitis C

Table 1 Main characteristics and course of HCV-infected patients with VKH-like disease

	Case 1	Case 2	Case 3
Age (yr)	43	51	42
Sex	F	F	M
HCV genotype liver biopsy (Metavir)1	3	1	1
	A1F2	A1F2	A3F1
Anti-HCV therapy	PEG-IFN α-2b + Ribavirin	PEG-IFN α-2b + Ribavirin	PEG-IFN α-2b + Ribavirin
Interval before first ocular manifestations2	4 mo	3 mo	4 mo
Ocular manifestations	-Visual acuity 20/200 OS	-Bilateral vision loss	-Bilateral vision loss
	-Macular edema and a bilateral serous retinal detachment.	-Bilateral uveitis, major papillar and retinal edema	-Episcleritis and bilateral uveitis
Retinal fluorescein angiography	Pin-points and bilateral serous retinal and pigmented epithelium detachments, suggestive of a Vogt-Koyanagi-Harada like [VKH] disease
Therapeutic management	-PEG-IFN and ribavirin disruption	-PEG-IFN and ribavirin disruption	-PEG-IFN and ribavirin disruption
	-Methylprednisolone IV and per os	- Methylprednisolone IV and per os	- Methylprednisolone IV and per os
Course	-Complete recovery under low dose steroids (< 10 mg/d)	-Low improvement of ocular lesions	-Partial improvement of ocular lesions
	-Steroids were stopped after one year of treatment without ocular relapse.	-Cortico-dependency > 25 mg/d	-Cortico-dependency > 25 mg/d
		-Failure of cyclosporine course	-Re-introduction of PEG-IFN and ribavirin 5 mo later3
		-Introduction of azathioprine	-Full recovery of ocular manifestations 10 mo after IFN was reintroduced

¹Metavir scoring system for the appraisal of HCV-related liver disease.

²Time or interval between introduction of the anti-HCV therapy and the first ocular manifestations.

³Forcase 3, PEG-IFN and ribavirin was re-introduced because of the high level of cortico-dependency and based upon the reported efficacy of IFN in some cases of severe and refractory uveitis[14].

Table 2 Main features of HCV-infected patients with intraocular vascular complications under PEG-IFN and ribavirin treatment

Main features	Case 4	Case 5	Case 6	Case 7	Case 8
Age (yr)	51	70	55	40	40
Sex	M	M	F	M	M
HCV genotype		1	2
Liver biopsy (Metavir)	ND	F4	A2F1	A2F2	F4 (clinical cirrhosis)
Antecedents	Sarcoidosis	Arterial hypertension	-	Splenic lymphoma with villous lymphocytes	Hypertension with past hypertensive retinopathy
		Smoking		Mixed cryoglobulin- associated glomerulonephritis
				Severe arterial hypertension
				Dyslipidemia, smoking
Anti-HCV therapy	PEG-IFN α-2b + Ribavirin	PEG-IFN α-2b + Ribavirin	PEG-IFN α-2b + Ribavirin	Standard IFN α-2b + ribavirin	Standard IFN α-2b + Ribavirin
Interval before first ocular manifestations	7 mo	5 mo	6 mo	18 mo	6 mo
Ocular manifestations	-Initial visual acuity: OD (< 20/200), OS (20/20)	-OD vision loss (20/200 OD; 20/20 OS)	-Bilateral vision loss (20/400 OD, 20/80 OS)	-Visual acuity OS: 10/10; OD: < 20/200	-Bilateral vision loss (20/64 P2 OD, 20/200 OS)
	-Papillar edema, macular edema and retinal hemorrhages				-Bilateral macular edema and retinal hemorrhages
	-Cotton wool spots				-Cotton-wool spots (IFN-α-induced retinopathy) (Figure 1A and B)
Diagnosis	Central retinal vein occlusion OD	Central retinal vein occlusion OD	Acute anterior ischemic optic neuritis	Central retinal artery occlusion OD	Exsudative hypertensive and IFN -induced retinopathy
Treatment	-Withdrawal of PEG-IFN and ribavirin	-Withdrawal of PEG-IFN and ribavirin	-Withdrawal of PEG-IFN and ribavirin	-Withdrawal of standard IFN and ribavirin	-Withdrawal of standard IFN and ribavirin
	-Steroids and IV heparin	-Steroids, IV heparin and aspirin	-Steroids	-Steroids and IV heparin	-Better control of hypertension (nadolol, benazepril)
Course	-6 mo later, radiary neurotomy	-2 mo later, radiary neurotomy	-At the end of follow-up, severe visual impairment (< 20/400 OD; 20/80 OS)	-4 mo later, slow improvement (20/64 OD)	-2 mo later, significant improvement of the visual acuity (20/40 OD; 20/40 OS)
	-At the end of follow-up, definitive loss of vision OD (< 20/200)	-At the end of follow-up, definitive vision loss OD		-Died of severe sepsis 5 mo later	-Introduction of PEG- IFN α-2b and Ribavirin without recurrence after more than 1 yr follow-up