Inflammatory and cytological effect of repeated application of povidone iodine in patients undergoing intravitreal injection

Objectives: The aim of this study is to investigate the effects of repeated povidone-iodine (PVI) administration on the tear film parameters and quality of life of patients who received intravitreal injection. In addition, by evaluating the inflammatory and cytological effects of repeated PVI exposure on the ocular surface, it is aimed to better understand the toxicity. Materials and Methods: Patients with age-related macular degeneration (AMD) who received unilateral intravitreal injection and healthy individuals were included in the study. The eyes of the patients with AMD who had at least 3 intravitreal injections in the last 1 year constituted the IVI group, and the fellow eyes of the patients who did not have the injection constituted the NIVI group. The control group consisted of one eye of healthy individuals. The ocular surface of all participants included in the study was examined with tear break-up time (BUT), Schirmer test and Oxford staining score during examination. Ocular surface-related complaints of the participants were evaluated with the ocular surface disease index (OSDI) questionnaire. In addition, samples were also taken for conjunctival impression cytology and analysis of inflammatory cytokines [interleukin (IL)-1β and IL-6] in tears. Results: The study included 104 eyes (52 IVI, 52 NIVI) of 52 AMD patients and 51 control eyes of 51 healthy subjects. BUT was found to be significantly lower in the IVI group compared to the IVI group and NIVI group (p=0.011, p=0.008, respectively), and the Oxford staining score was significantly higher (p=0.011, p=0.009, respectively). In the Schirmer test, the lowest result was observed in the IVI group (13.85 ± 10.56 mm), although there was no statistically significant difference between the groups (p=0.161). The OSDI score of the IVI group (36.81±19.49) was significantly higher than the control group (27.93 ± 15.4) (p=0.03). Although the OSDI score of the NIVI group (29.31 ± 17.5) was lower than the IVI group, there was no statistically significant difference between the groups (p=0.078). In the conjunctival impression cytology analysis, it was found that the IVI group had a significantly lower number of Goblet cells (p=0.027, p=<0.001, respectively) and a significantly higher Nelson staging result (p=<0.001, p=<0.001, respectively) compared to the NIVI and control groups. As a result of cytokine analysis in tears, IVI and NIVI groups had significantly higher IL-1β and IL-6 levels compared to the control group (p=˃0.05). There was no significant relationship between the number of injections and the injected drug molecule with the evaluated parameters (p=˃0.05). Conclusion: Repeated application of PVI causes cytotoxic damage to the ocular surface, resulting in goblet cell loss and squamous metaplasia of epithelial cells. As a result, it was observed that the stability of the tear film was impaired and symptoms related to the ocular surface developed in the patients. The results obtained from cytokine analysis in our study indicate that inflammatory mechanisms are involved in the pathogenesis of AMD. However, we think that the inflammatory effect of the PVI agent could not be demonstrated due to this inflammation due to caused by AMD. Keywords: Povidone iodine, Intravitreal injection, Impression cytology, Ocular surface, IL-1β, IL-6