Purpose: To elucidate the clinical features which predict high-risk histopathological factors for subsequent metastatic disease as well as to report the incidence of these high-risk histopathological factors in a cohort of Asian patients with retinoblastoma.

Design: A retrospective and non-randomized sequential cases series.

Methods: A retrospective study was done on 334 eyes with retinoblastoma at Vietnam National Institute of Ophthalmology during a 10 year period (January 2004 – December 2013). All pathology specimens and medical records were reviewed and assessed for invasion and clinical signs.

Results: Among 334 eyes, 225 (67.4%) had high-risk retinoblastoma and 109 (22.6%) had non-high-risk features on histopathology. The high-risk histopathological features included anterior chamber seeding (48.2%), iris infiltration (14.7%), ciliary body involvement (14.1%), massive choroidal invasion (29.9 %), post-laminar optic nerve invasion (21.2%), invasion of optic nerve transection (9.6 %), combined choroidal and optic nerve invasion (9.6 %), scleral invasion (3.3%), and extra-scleral infiltration (11.4%). The significant clinical features in high-risk group versus non-high-risk group included hyphema (19.6% vs 3.7%, p < 0.001), pseudohypopyon (19.1% vs 6.4%, p = 0.001), iris neovascularization  (25.3% vs 5.5%, p < 0.001), vitreous seeding (72.4% vs 37.6%, p < 0.001), staphyloma (24% vs 4.6%, p < 0.001) and scleritis (20% vs 3.7%, p < 0.001).

Conclusions: Clinical signs including hyphema, pseudohypopyon, iris neovascularization, vitreous seeding, staphyloma, and scleritis were significantly associated with high-risk features on histopathology. Globe preserving methods should be used with caution in patients with these signs.