19664 Background: Perifosine is a novel, oral, alkylphospholipid with antiproliferative properties attributed to Akt inhibition. We describe the ocular findings in 5 patients enrolled in phase I/phase II trials of perifosine in combination with imatinib for treatment of advanced GIST. Methods: The medical records of 5 patients who developed peripheral ulcerative keratitis while receiving perifosine and imatinib were retrospectively reviewed. Results: 1 man and 4 women ranged in age from 43 to 72 (median, 57 years). The ocular symptoms included redness, irritation, tearing, photophobia and a gradual decrease in vision. Slit lamp biomicroscopy in each case revealed a peripheral, paralimbal, ring-shaped, superficial stromal infiltration and ulcerative keratitis (UK), reminiscent of the autoimmune keratitis in conditions such as rheumatoid arthritis. The best corrected visual acuity in the affected eye(s) ranged from 20/25 to 20/300 (median 20/70). The UK was unilateral in 3 and bilateral in 2 patients; it was NCI grade II in all. All 6 patients had imatinib-resistant metastatic GIST and had continued on the highest dose of imatinib tolerated and initiated therapy with perifosine 100 mg daily or 900 mg weekly. Time from start of perifosine therapy to diagnosis of UK ranged from 1 to 3 months (median, 2). A combination of topical steroids, topical antibiotics and lubricating drops were used to manage UK. In the first 3 patients, UK was initially treated with topical antibiotics without improvement, but subsequently improved significantly once topical steroids were added. In 5 of 6 patients, the visual acuity improved with this regimen. Conclusions: UK may occur as a side effect of perifosine and shares features of autoimmune forms of keratitis. It is possible that imatinib in combination with perifosine is contributing to this toxicity. Topical steroids improve the signs and symptoms of UK and early treatment with topical steroids may lessen the potential risk of permanent corneal scarring and visual loss. The visual loss associated with perifosine can be reversible with close monitoring and judicious use of topical steroids, topical antibiotic coverage, and lubrication. No significant financial relationships to disclose.