Over the past decade, the field of mesenchymal stem cell (MSC) therapy has exhibited rapid growth. Due to their regenerative, reparatory, and immunomodulatory capacities, MSCs have been widely investigated as therapeutic agents in the cell-based treatment of chronic ophthalmic pathologies. However, the applicability of MSC-based therapy is limited by suboptimal biocompatibility, penetration, and delivery to the target ocular tissues. An emerging body of research has elucidated the role of exosomes in the biological functions of MSCs, and that MSC-derived extracellular vesicles (EVs) possess anti-inflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties similar to MSCs. The recent advances in MSCs-derived exosomes can serve as solutions to the challenges faced by MSCs-therapy. Due to their nano-dimensions, MSC-derived exosomes can rapidly penetrate biological barriers and reach immune-privileged organs, allowing for efficient delivery of therapeutic factors such as trophic and immunomodulatory agents to ocular tissues that are typically challenging to target by conventional therapy and MSCs transplantation. In addition, the use of EVs minimizes the risks associated with mesenchymal stem cell transplantation. In this literature review, we focus on the studies published between 2017 and 2022, highlighting the characteristics of EVs derived from MSCs and their biological functions in treating anterior and posterior segment ocular diseases. Additionally, we discuss the potential use of EVs in clinical settings. Rapid advancements in regenerative medicine and exosome-based drug delivery, in conjunction with an increased understanding of ocular pathology and pharmacology, hold great promise for the treatment of ocular diseases. The potential of exosome-based therapies is exciting and can revolutionize the way we approach these ocular conditions.

Purpose: To evaluate long-term in vivo functionality of corneas regenerated using a cell-free, liquid hydrogel filler (LiQD Cornea) after deep corneal trauma in the feline model.Methods: Two healthy cats underwent 4 mm diameter stepwise 250/450 µm deep surgical corneal ablation with and without needle perforation. The filler comprising 10% (w/w) collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and 1% fibrinogen and crosslinked with 2% (w/w) 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), was applied to the wound bed previously coated with thrombin (250 U/ml). In situ gelation occurred within 5 min, and a temporary tarsorrhaphy was performed. Eyes were examined weekly for 1 month, then monthly over 12 months. Outcome parameters included slit-lamp, Scheimpflug tomography, optical coherence tomography, confocal and specular microscopy, and immunohistochemistry studies.Results: The gelled filler was seamlessly incorporated, supporting smooth corneal re-epithelialization. Progressive in-growth of keratocytes and nerves into the filler corresponding to the mild haze observed faded with time. The regenerated neo-cornea remained stably integrated throughout the 12 months, without swelling, inflammation, infection, neovascularization, or rejection. The surrounding host stroma and endothelium remained normal at all times. Tomography confirmed restoration of a smooth surface curvature.Conclusion: Biointegration of this hydrogel filler allowed stable restoration of corneal shape and transparency in the feline model, with less inflammation and no neovascularization compared to previous reports in the minipig and rabbit models. It offers a promising alternative to cyanoacrylate glue and corneal transplantation for ulcerated and traumatized corneas in human patients.