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To identify the differences in the clinical and histopathologic features in eyes with advanced intraocular retinoblastoma in a developing country (India) versus a developed country (USA).Retrospective study.Of 524 patients with retinoblastoma who underwent primary enucleation, 331 were from India, and 193 were from the USA. Asian Indians were older at presentation (35 months vs. 29 months; P = 0.02), had thicker tumors (13.8 mm vs. 12.4 mm; P = 0.0001) compared with Americans. High-risk intraocular retinoblastoma was more common in Asian Indians with a 2-fold greater risk compared with Americans (35% vs. 23%; odds ratio = 1.83; P = 0.003). Statistically significant differences in the histopathologic features (Asian Indians vs. Americans) included massive (≥3 mm) choroidal infiltration (17% vs. 6%; P = 0.0003) and optic nerve infiltration (48% vs. 15%; P = 0.0001). Asian Indians had a 5-fold greater risk of having optic nerve invasion (odds ratio = 5.45; P < 0.0001) and 3-fold greater risk of massive choroidal invasion (odds ratio = 2.80; P < 0.0001) compared with Americans. With appropriate use of adjuvant systemic chemotherapy, the difference in the rates of systemic metastasis (5% vs. 2%, P = 0.67) and related death in both countries (5% vs. 0%, P = 0.14) were not statistically significant.High-risk intraocular retinoblastoma is more common in Asian Indians compared with Americans.