Effects of selected repeated intravitreal chemotherapeutic agents

The toxic effects of repeated intravitreal injections of selected chemotherapeutic agents were studied in female albino rabbits. Three groups of eyes participated in each therapeutic regimen. Agents studied were doxorubicin (dox), 3 and 5ug; 5-fluorouracil (5-FU), 0.375 and 1.0 mg; bleomycin (bleo), 15 ug; thiotepa (thio), 12 ug; etoposide (VP-16), 150 ug; and methotrexate (MTX), 600 ug. Toxicity was evaluated using electroretinography (ERG) in 66% and histopathology in 100% of eyes 5 weeks following the initial injection and at least 2 weeks after the final injection of each series. Eyes receiving 2 doses of dox 3 ug showed no toxicity. Eyes receiving 3 or more doses of dox 3 ug and those treated with 2 or more doses of dox 5 demonstrated toxicity proportional to the number of doses received.Eyes treated with 5-FU 0.375 or 1.0 mg showed no toxic reaction. Successive intravitreal injections of 5-FU, 0.375 mg and dox 5 ug, and 5-FU, dox, and bleo produced no toxicity. Eyes treated with successive intravitreal injections of 5-FU, dox, bleo, and thio displayed decreased ERG response. The addition of VP-16 and MTX resulted in further loss of ERG response and more severe histologic retinal changes.