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Purpose: To evaluate continuous wear of a fluid-ventilated, gas-permeable scleral PROSE device using a standardized protocol as treatment for refractory persistent corneal epithelial defects in patients with severe ocular surface disease. Methods: Retrospective review of eight eyes of seven consecutive patients with persistent epithelial defects refractory to traditional therapies. The standardized treatment regimen consisted of: (1) 24-hour-a-day PROSE wear until re-epithelialization was achieved, (2) brief daily device removal, cleaning, disinfection, and reservoir fluid replacement, (3) addition of a benzalkonium chloride (BAK)-free fourth-generation fluoroquinolone antibiotic drop to the reservoir, and (4) transition to long-term, daytime PROSE wear upon re-epithelialization . Results: All eight eyes exhibited resolution of the persistent epithelial defect. No eyes developed microbial keratitis. Four eyes exhibited recurrences; all recurrences promptly responded to reinstitution of continuous wear. Conclusions: Continuous wear of a PROSE device, using a strictly standardized regimen, constitutes an effective, safe treatment option for refractory persistent epithelial defects. [ABSTRACT FROM AUTHOR]