BACKGROUND Peripheral ulcerative keratitis is one of the ocular complications associated with chronic inflammatory immune-mediated diseases, such as rheumatoid arthritis, in which inflammatory reactions and infections can be recurrent. Suspected infections are treated with topical antibiotics that, in some cases, may promote selection of resistant microbes. Povidone iodine is known for its rapid broad-spectrum activity against all kinds of microbes and biofilms, lack of microbial resistance, ability to counteract excessive inflammation, and efficacy in wound healing, along with an optimum safety and tolerability profile. The purpose of this case report is to show the resolution of a peripheral ulcerative keratitis case by means of treatment with 0.66% povidone iodine. CASE REPORT An 89-year-old woman with rheumatoid arthritis, 1 eye, and a superior descemetic corneal ulcer was treated with amniotic membrane, topical antibiotics, and antiviral drugs without any control of clinical signs and symptoms. Therefore, all anti-infective treatments were replaced with 0.66% povidone iodine (3 times/day) given alone for 5 weeks and then associated with serum eyedrops. When a clear regression of the ulcer was observed, the patient was maintained with serum eyedrops only. CONCLUSIONS Unusual treatment with povidone iodine 0.66% (used for the first time in an autoimmune patient), alone and in association with serum eyedrops, probably contributed to alleviate the signs and symptoms of a case of peripheral ulcerative keratitis not responding to conventional treatments. Although its regular use warrants further investigation, povidone iodine seems a useful therapeutic tool for the treatment of corneal ulcers associated with chronic immune-mediated inflammatory diseases.