The authors report on the safety and efficacy of 90 µg/0.18 cc of intravitreal topotecan for recurrent solid retinal tumors in retinoblastoma. Topotecan 90 µg was injected intravitreally in three retinoblastoma cases that progressed after prior therapy. Safety was monitored with retinal examinations under anesthesia and 30-Hz flicker electroretinograms. There was complete disappearance of recurrent retinal tumors with only one injection of 90 µg of intravitreal topotecan without any toxicity. Intravitreal 90 µg caused prompt regression of retinal tumors in three children who had progression of their retinoblastoma after prior therapy. No toxicity was seen. This is the first report of intravitreal 90 µg in humans and the first report of responses of retinal tumors from intravitreal topotrecan. [J Pediatr Ophthalmol Strabismus. 2023;60(2):e16-e18.].