Post-Travmatik Proliferatif Vitreoretinopati Üzerine Tirozin Kinaz İnhibitörü Nintedanib'in Etkisi

Abstract

Proliferative vitreoretinopathy (PVR) is the most common cause of rhegmatogenous retinal detachment surgery failure and is a serious complication of ocular trauma. It is characterized by growth and contraction of cellular membranes on both sides of the vitreous cavity and the retinal surface. Currently, the accepted standard treatment for PVR is surgery. However, despite the advances in surgical techniques, anatomical and visual results are unsatisfactory. In addition, there is no proven pharmacological agent for the treatment and prevention of PVR. In our study, it was aimed to demonstrate that intravitreal nintedanib prevents PVR formation on the PVR model induced in rabbit eyes by clinical observation, histological examination and immunohistochemistry. For this purpose, 12 rabbits were divided into two groups as control and nintedanib. Under general anesthesia, one eye of each rabbit was injured with a 23G needle, causing a puncture injury, and dispase solution was injected just above it. After the induction of the PVR animal model, phosphate buffered saline (PBS) was injected into the midvitreus of the rabbits in control group and 0.5% liposomal nintedanib was injected into the midvitreus of the rabbits in nintenib group. The rabbits were examined weekly for four weeks, and at the end of fourth week, the eyes were enucleated for histological and immunohistochemical assessment. After injecting 0.5% nintedanib into both eyes of 2 rabbits whose PVR model was not induced; Vitreous samples were taken on the 1st, 7th, 14th and 35th days and the drug level in the vitreous was determined by HPLC method. As a result, although the PVR stages determined in nintedanib group were low, there was no significant difference between nintedanib and control group (p=0,108). In histological evaluation, it was observed that epiretinal membrane formations were less common in nintedanib treated group, without any significant toxic effect. Additionally, immunohistochemistry revealed that the intensity and CTCF (Corrected Total Cell Fluorescence) values measured for collagen-1 expression were found significantly lower in nintedanib group compared to the control group (p=0,004, p=0,004). The CTCF/area value was lower in nintedanib group, which could be considered borderline significant (p=0,065). It was determined that nintedanib loaded liposome formulation gave about half of them to the vitreous part in the first 7 days, but it took longer than 25 days to release all of them. According to these findings, it was shown that nintedanib could prevent PVR formation without any significant side effects. This study shows that nintedanib is a potential drug that can be used in the treatment and prophylaxis of PVR.