Background It is determined that riboflavin/ultraviolet A (UVA)-induced corneal collagen crosslinking is able to increase resistance of cornea against enzymatic digestion and has antimicrobial efficacy for various kinds of bacteria in vitro.However,its in vivo study is less now.Objective This study aimed to evaluate the efficacy of iontophoresis-mediated corneal collagen crosslinking combined with or without drugs for Staphylococcus aureus keratitis.Methods Bacterial keratitis models were induced by the interstromaly injection of Staphylococcus aureus suspension with concentration 2× 109/ml in the right eyes of 40 rabbits,and then the rabbits were randomly classified into the model group,gatifloxacin eye drops group,riboflavin/UVA corneal crosslinking group and drugs+ crosslinking group.The smearing of corneal surface was performed for the identification of bacteria 24 hours after injection.Iontophoresis-mediated riboflavin/UVA crosslinking was applied on the eyes of the riboflavin/UVA corneal crosslinking group and drugs+crosslinking group,and gatifloxacin eye drops was topically used 7 times per day on the eyes of the gatifloxacin eye drops group and drugs+crosslinking group.The corneal inflammation was examined and graded under the slit lamp biomicroscope before and after treatment.Ocular anterior segment optical coherence tomography(AS-OCT),corneal histopathology and ultrastructure were examined 14 days after treatment.The living environment of the experimental animals was maintained at 21 ℃ with a 12-hour light and dark cycle.Animals used in this study were treated in accordance with the Weifang Medical College Animal Experimentation Ethic Committee (AEEC) guidelines.The study protocol was approved by the AEEC.Results Corneal inflammation and ulcer were observed,but no significant difference was found in the inflammatory grade among the 4 groups 24 hours after injection (x2=0.293,P＞0.05).In the 14th day after injection,the corneal ulcer area was smaller and corneal edema was milder in the drugs+crosslinking group compared with the model group,gatifloxacin eye drops group and riboflavin/ UVA corneal crosslinking group,showing a significant difference in the inflammatory grade among them (x2 =38.710,P＜0.001).The cornea thickness values of ulcer zone were (428.1 ± 146.2) μm on the 14th postinjected day in the drugs+crosslinking group,which was evidently higher than those in the model group,gatifloxacin eye drops group and riboflavin/UVA corneal crosslinking group,with a significant difference among the 4 groups (F =8.310,P＜0.001).A lower degree of destruction of cornea collagen and less inflammatory cells were seen in the cornea tissue of the drugs+ crosslinking group by haematoxylin and eosin staining in comparison with other 3 groups,and normal keratocytes were much more in the drugs + crosslinking group than those in other treated groups.Conclusions Iontophoresismediated corneal collagen crosslinking can alleviate Staphylococcus aureus keratitis.The combination of crosslinking with drugs has a better effectiveness than the administration of gatifloxacin eye drops only or riboflavin/UVA corneal crosslinking only.