Introduction: Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of a wide variety of malignancies. The toxic effects of ICIs can manifest themselves in a variety of organs, including the cornea.
Aim of the Work: The current research aimed to analyze the corneal adverse impacts of pembrolizumab and the efficacy of topically applied axitinib alone or with albumin.
Materials and Methods: Rats were classified into four groups: control group, pembrolizumab treated group (3mg/kg, i.p, 3 days per week for 4 weeks), Pembrolizumab +Axitinib (0.5 mg/ml two drops every 8 h for 4 weeks) and Pembrolizumab +Axitinib+ albumin (5 % of serum albumin). Animals were anesthetized and sacrificed at the end of experiment. Both animal eyes were removed for histological, immunohistochemistry, electron microscopic analyses and morphometric studies.
Results: Pembrolizumab treatment resulted in epithelium loss, desquamation, as well as vacuolated cytoplasm with pyknotic nuclei and a significant apparent decrease in epithelial and total corneal thickness. The area percentage of irregular collagen was declined, with spacing, neovascularization, and cellular infiltration, as well as an uneven damaged endothelium surface. Ultra structural changes in the corneal epithelium revealed damaged mitochondria with pyknotic nuclei and cytoplasmic vacuoles. Desmosomal connections were disrupted in the majority of cells, resulting in an increase in intercellular space. Collagen fibers were found to be extensively separated from keratocytes containing shrunken nuclei and vacuolated cytoplasm. Infiltration of eosinophils, mast cells, and lymphocytes, as well as stromal neovascularization was observed. Endothelial cells had mitochondrial degeneration and a thin Descemet's membrane. A substantial positive caspase-3, TNF-α, and VEGF immune response was observed in corneal epithelium, keratocytes, and corneal endothelial cells. Axitinib alleviated the ocular histological changes caused by pembrolizumab. Co-administration of albumin with axitinib enhanced results.
Conclusion: Although axitinib was demonstrated to attenuate immune-related corneal damage associated with pembrolizumab, albumin co-administration enhanced this response.