OBJECTIVE: To evaluate the pattern of anterior segment indocyanine green (ICG) angiography in episcleritis and scleritis. DESIGN: Prospective comparative (paired-eye) observational case series. PARTICIPANTS: Twenty subjects presenting clinical diseases compatible with episcleritis or scleritis. METHODS: Anterior segment ICG angiography was performed according to a standard protocol in subjects presenting either episcleritis or scleritis. Photographs of the anterior segment were taken in the early phase (up to 3 minutes after dye injection), intermediate phase (10-12 minutes) and late phase (30-45 minutes). The inflamed zones were compared with the same regions of the controlateral eye. The amount of protein ICG exudation was scored by a masked observer as follows: zero for no exudation, one for slight exudation, two for moderate exudation, and three for severe exudation. MAIN OUTCOME MEASURES: Evaluation of dye leakage, which reflects protein exudation, with anterior segment ICG angiography in episcleritis and scleritis. RESULTS: Twenty subjects with a mean age of 43 +/- 15 years (7 male, 13 female) were enrolled in the study. Thirteen subjects had anterior scleritis (7 nodular, 5 diffuse, and 1 scleromalacia perforans), and 7 subjects had episcleritis. Only 1 out of 7 subjects with episcleritis showed a slight ICG leakage (a score of one), whereas all subjects with scleritis had ICG leakage scores of one or more (P = 0.0005, Fisher exact test). CONCLUSIONS: ICG angiography of the anterior segment of the eye is a good clinical test to differentiate episcleritis from scleritis.