Comparison of Collagen Cross‐Linking Alone to 1% Povidone–Iodine Treatment of Refractory Corneal Ulcers: A Randomized Clinical Trial

<b>Background:</b> Corneal ulcer is one of the most common causes of corneal opacities. This study compared the effects of topical 1% povidone-iodine (PI) and corneal collagen cross-linking in patients with therapy-resistant corneal ulcers. <b>Methods:</b> This single-blind randomized clinical trial included patients referred to Al-Zahra Ophthalmology Hospital in Zahedan, Iran, from 2022 to 2024, who had corneal ulcers resistant to standard therapy. Participants were divided into two groups using stratified permuted block randomization method: one group received 1% PI and the other underwent corneal collagen cross-linking. Signs and symptoms were recorded before treatment and on days 1, 3, 7, and 28 posttreatment. Statistical analysis was performed using generalized estimating equations and repeated measures analysis of variance (ANOVA). <b>Results:</b> Thirty patients, with a mean age of 52.23 ± 2.34 years, participated in this study. Both corneal collagen cross-linking and 1% PI treatments significantly reduced the wound area, stromal infiltration, hypopyon, corneal edema, eye itching, eye burning, and eye pain (<i>p</i> < 0.05). However, no statistically significant differences were observed between the two treatments (<i>p</i> > 0.09). The improvement rate was 73.3% in the 1% PI group and 60% in the corneal collagen cross-linking group. <b>Conclusions:</b> Corneal collagen cross-linking and 1% PI demonstrated comparable efficacy in promoting healing of refractory corneal ulcers. Therefore, both methods may be considered for managing corneal ulcers that are resistant to standard therapy. <b>Trial Registration:</b> Iranian Registry of Clinical Trials (IRCT): IRCT20221230056988N1.