OBJECTIVE: The pathogenesis of retinal complications, such as retinal hemorrhage and cotton-wool spots formation, during interferon (IFN) therapy is unclear. We studied the relationship between the presence of retinal complications and levels of plasma-activated complement 5 (C5a), a known potent intravascular aggregator of granulocytes, during IFN-alpha therapy. METHODS: Forty-five patients with chronic hepatitis C but without diabetes mellitus and hypertension were studied. IFN-alpha was used 10 MU per day for 2 wk and 3 times weekly for an additional 22 wk. In 25 patients with IFN therapy, the optic fundi were examined before therapy began, every 4 wk thereafter, and whenever patients complained of visual symptoms. C5a levels were measured before, and during the 4th, 8th, 12th, and 24th wk, and at any time that a retinal complication was discovered. Twenty patients served as IFN-untreated controls. They had six optic fundi examinations, each 4 wk apart. C5a levels were measured three times, 4 wk apart, in 10 controls. RESULTS: No retinal hemorrhage or cotton-wool spots were detected before IFN-alpha therapy or in any of the controls. However, retinal hemorrhage occurred in six patients (24%) during IFN-alpha therapy. Five of six episodes occurred within the first 8 wk. Only three patients with retinal hemorrhage had visual symptoms. Cotton-wool spots developed in four patients with retinal hemorrhage. Retinal hemorrhage and cotton-wool spots resolved gradually despite continuous administration of IFN-alpha. Before IFN therapy and in controls, all C5a levels were <7 ng/ml. When retinal hemorrhage occurred, C5a was significantly increased (27.3+/-15.6 ng/ml,p < 0.01) relative to levels from the same patients before and after the hemorrhage (5.7+/-1.1 ng/ml), and also relative to levels in IFN-a-treated patients without retinal hemorrhage (5.7+/-1.1 ng/ml) and compared with levels in IFN-untreated controls (5.4+/-0.7 ng/ml). CONCLUSIONS: Retinal hemorrhage or cotton-wool spots often occur during IFN-alpha therapy for chronic hepatitis C. This study suggests that a high C5a level may be an important step in the pathogenesis of retinal capillary infarction, hemorrhage, and cotton-wool spots formation.
OBJECTIVE: The pathogenesis of retinal complications, such as retinal hemorrhage and cotton-wool spots formation, during interferon (IFN) therapy is unclear. We studied the relationship between the presence of retinal complications and levels of plasma-activated complement 5 (C5a), a known potent intravascular aggregator of granulocytes, during IFN-alpha therapy. METHODS: Forty-five patients with chronic hepatitis C but without diabetes mellitus and hypertension were studied. IFN-alpha was used 10 MU per day for 2 wk and 3 times weekly for an additional 22 wk. In 25 patients with IFN therapy, the optic fundi were examined before therapy began, every 4 wk thereafter, and whenever patients complained of visual symptoms. C5a levels were measured before, and during the 4th, 8th, 12th, and 24th wk, and at any time that a retinal complication was discovered. Twenty patients served as IFN-untreated controls. They had six optic fundi examinations, each 4 wk apart. C5a levels were measured three times, 4 wk apart, in 10 controls. RESULTS: No retinal hemorrhage or cotton-wool spots were detected before IFN-alpha therapy or in any of the controls. However, retinal hemorrhage occurred in six patients (24%) during IFN-alpha therapy. Five of six episodes occurred within the first 8 wk. Only three patients with retinal hemorrhage had visual symptoms. Cotton-wool spots developed in four patients with retinal hemorrhage. Retinal hemorrhage and cotton-wool spots resolved gradually despite continuous administration of IFN-alpha. Before IFN therapy and in controls, all C5a levels were <7 ng/ml. When retinal hemorrhage occurred, C5a was significantly increased (27.3+/-15.6 ng/ml,p < 0.01) relative to levels from the same patients before and after the hemorrhage (5.7+/-1.1 ng/ml), and also relative to levels in IFN-a-treated patients without retinal hemorrhage (5.7+/-1.1 ng/ml) and compared with levels in IFN-untreated controls (5.4+/-0.7 ng/ml). CONCLUSIONS:Retinal hemorrhage or cotton-wool spots often occur during IFN-alpha therapy for chronic hepatitis C. This study suggests that a high C5a level may be an important step in the pathogenesis of retinal capillary infarction, hemorrhage, and cotton-wool spots formation.