Ophthalmologic complications of antiviral therapy in hepatitis C treatment

Table 1 Incidence of interferon-associated retinopathy in observational studies during which more than half of the patients are treated with interferon-α based regimens for chronic hepatitis C

Study	IAR incidence	Country	Timing of examinations	Comment
Nagaoka et al[17]	22 of 36 (61%)	Japan	Baseline, 2, 4, 8, 16 and 24 wk	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. Age was a risk factor for the development of IAR. HTN and DM were not. Atypical adverse events: nil reported.
d’Alteroche et al[18]	36 of 144 (25%)1	France	Baseline and then 3 monthly	IAR: No reduced VA in eyes that developed IAR. No dose reduction for management of IAR. HTN (9 of 11), receiving PEG-IFNα and older age were more likely to develop retinopathy. Insufficient numbers with DM (n = 1). Atypical adverse events: nil reported.
Okuse et al[19]	14 of 73 (19%)	Japan	Baseline, 2, 4, 12 and 24 wk	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. HTN significantly associated with development of IAR (5 of 15), T2DM not (1 of 2). Atypical adverse events: nil reported.
Schulman et al[20]	27 of 42 (64%)	United States	Baseline and then 2-3 monthly for 4-20 mo	IAR: therapy discontinued in two patients with multiple CWS, one with mild decrease in VA. All other patients with IAR continued with treatment. High doses of interferon used, up to 5MIU/d. HTN was not predictive of the development of IAR. Insufficient eyes for analysis of DM as risk factor (n = 2). Atypical adverse events: permanent peripheral monocular scotoma in 1 patient. Disc edema in 1 patient with a background of rheumatoid arthritis; no long term vision loss.
Jain et al[21]	8 of 19 (42%)	Canada	Baseline and then monthly	IAR: no change in VA in any patient with retinopathy. IAR resolved during study period in all but one patient. No dose reduction for management of IAR. Atypical adverse events: nil reported.
Saito et al[22]	28 of 81 (35%)	Japan	Baseline and then 2 weekly	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. IAR was more likely in older patients and those with DM and/or HTN. Atypical adverse events: nil reported.
Kadayifcilar et al[23]	7 of 20 (35%)2	Turkey	Baseline, monthly during treatment and 1 yr after completing treatment.	IAR: one of 7 with CWS at the macular had dose reduction by 1/2 for decreased VA. Full resolution in 4 wk. Otherwise no dose reduction for IAR. 16 of 20 patients had backgrounds of chronic renal failure. Atypical adverse events: unilateral BRVO in 1 patient with a background of CRF resulting in normal visual acuity at 12 mo but residual upper quadrantanopia.
Sugano et al[24]	6 of 25 (24%)	Japan	Baseline and then 4 weekly	IAR: not available. Atypical adverse events: not available.
Kawano et al[25]	36 of 63 (57%)	Japan	Baseline, 1, 2 and 4 wk and then 4 weekly until 6 mo after completing treatment	IAR: no dose reduction for 35 of 36 patients with IAR. Significantly higher incidence of retinopathy in patients with diabetes (11 of 12) and HTN (4 of 5). Atypical adverse events: severe RH in 1 patient with a background of DM; no long term vision loss.
Hayasaka et al[26]	14 of 40 (35%)3	Japan	1 mo prior to starting treatment and 2 weekly during treatment.	IAR: no reduced VA in eyes that developed IAR Not clear, but seems that interferon was ceased if developed IAR. Three patients with retinopathy at baseline all showed progression. Atypical adverse events: nil reported.

¹Twelve patients treated for chronic hepatitis B infection were excluded from the incidence data shown;

²Sixteen patients treated for chronic hepatitis B infection were excluded from the incidence data shown;

³Three patients that had baseline diabetic retinopathy were excluded from the incidence data shown. BRVO: Branch retinal vein occlusion; CRF: Chronic renal failure; CWS: Cotton wool spots; DM: Diabetes; HTN: Hypertension; IAR: Interferon-associated retinopathy; MIU: Million international units; PEG: Pegylated; IFN: Interferon; RBV: Ribavirin; RH: Retinal hemorrhage; VA: Visual acuity; VEGF: Vascular endothelial growth factor.

Table 2 Incidence of interferon-associated retinopathy in observational studies during which more than half of the patients were treated with pegylated interferon-α based regimens for chronic hepatitis C

Study	IAR incidence	Country	Timing of examinations	Comments
Mousa et al[27]	8 of 98 (8%)	Egypt	Baseline, 2, 4, 8, 12 and 24 wk then every 3 mo	IAR: seven of 8 patients with IAR had no reduction in VA. No dose reduction for management of IAR. Combined DM and HTN gave relative risk of 6.5 of developing IAR. Atypical adverse events: vitreous hemorrhage from retinal tears with retinal detachment requiring vitrectomy in 1 patient, final visual outcomes were not described.
Fouad et al[28]	22 of 84 (26%)	Egypt	Baseline, 12, 24 and 48 wk and 1 mo after completing treatment	IAR: no reduced VA in eyes that developed IAR. Three patients with IAR developed retinal hemorrhages and treatment was ceased. Logistic regression found HTN (9 of 12) and DM (13 of 16) to be predictors of developing IAR. Atypical adverse events: NAION in 2 patients and optic neuritis in 1 patient, final visual outcomes for these patients were not described.
Vujosevic et al[29]	21 of 97 (22%)1	Canada	Baseline, 3 and 6 mo and 3 mo after completing treatment	IAR: all patients with pre-existing retinopathy, 9 patients, had worsening of retinopathy during treatment. Factors associated with developing IAR were age, metabolic syndrome, HTN, cryoglobulinemia and pre-existing intraocular lesions. Using multivariate analysis only HTN was a significant predictor of developing IAR. Insufficient number of patients with DM (n = 5). Atypical adverse events: bilateral BRVO in one patient with a background of HTN resulting in irreversible vision loss in the left eye only.
Lim et al[30]	5 of 10 (50%)2	Korea	Baseline and then 3 weekly for 6 mo	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. Atypical adverse events: unilateral CRVO in 1 patient with a background of DM resulting in irreversible vision loss.
Mehta et al[31]	18 of 64 (28%)3	United States	Baseline, 3 and 6 mo	IAR: no reduced VA in eyes that developed IAR. 1 of 88 ceased treatment for asymptomatic IAR. Male only cohort. HTN and DM not significant predictor of developing IAR. Poor follow up rates - 69% had an eye exam within the first 12 weeks of starting treatment. Atypical adverse events: nil reported.
Kim et al[32]	11 of 32 (34%)	Korea	Baseline, 4, 8, 12, 16, 24, 36 wk	IAR: no reduced VA in eyes that developed IAR alone. No dose reduction for management of IAR. All retinal lesions spontaneously resolved. 91% of retinopathy developed within 2 mo, but 1 occurred at 4 mo. HTN significantly associated with development of IAR (6 of 10), T2DM not (1 of 2). Atypical adverse events: unilateral BRVO in 1 patient with background of HTN resulting in irreversible vision loss.
Panetta et al[33]	7 of 183 (4%)	United States	Baseline and repeat examination when visually symptomatic	IAR: three patients ceased treatment. Two with visual symptoms associated with IAR. 46% of patients had HTN and 16% had DM - neither predictive of developing IAR. Atypical adverse events: nil reported.
Malik et al[34]	3 or 38 (8%)	United Kingdom	Baseline, 3 and 6 mo. Low follow up rates	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. Atypical adverse events: nil reported.
Andrade et al[35]	5 of 34 (15%)	Spain	Baseline, at cessation of treatment and when visually symptomatic	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. Higher serum VEGF in patients with retinopathy and/or subconjunctival hemorrhage. Atypical adverse events: cystoid macular edema in 1 patient, final visual outcomes were not described.
Ogata et al[36]	25 of 69 (36%)	Japan	Baseline and then regularly for 6 months	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. 46% (13 of 28) treated with IFNα developed IAR compared to 29% (12 of 41) treated with PEG-IFNα. Atypical adverse events: no details.
Chisholm et al[37]	5 of 10 (50%)	United Kingdom	Baseline, 2, 4, 8, 12 and 24 wk and 12 wk after completing treatment	IAR: no dose reduction for management of IAR. Atypical adverse events: nil reported.
Cuthbertson et al[38]	4 of 25 (16%)	United Kingdom	3 mo after starting treatment or when visually symptomatic	IAR: no reduced VA in eyes that developed IAR. No dose reduction for management of IAR. Atypical adverse events: nil reported.

¹Nine patients that had baseline retinopathy were excluded from the incidence data shown. All 9 had progression of retinopathy;

²Thirty-six of the 46 patients treated for chronic hepatitis B infection were excluded from the incidence data shown;

³Ten patients that had baseline diabetic retinopathy were excluded from the incidence data shown. Five of these had resolution of retinopathy on subsequent eye exams. BRVO: Branch retinal vein occlusion; CRVO: Central retinal vein occlusion; DM: Diabetes; HTN: Hypertension; IAR: Interferon-associated retinopathy; NAION: Non-arteritic anterior ischemic optic neuropathy; PEG: Pegylated; IFN: Interferon; RBV: Ribavirin; VA: Visual acuity; VEGF: Vascular endothelial growth factor.