Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown promise in promoting nerve regeneration in ocular diseases. In particular, EVs derived from MSCs have been demonstrated to promote axonal regeneration and functional recovery in various animal models of optic nerve injury and glaucoma. EVs contain various neurotrophic factors and cytokines that can enhance neuronal survival and regeneration, promote angiogenesis, and modulate inflammation in the retina and optic nerve. Additionally, in experimental models, the application of EVs as a delivery platform for therapeutic molecules has revealed great promise in the treatment of ocular disorders. However, the clinical translation of EV-based therapies faces several challenges, and further preclinical and clinical studies are needed to fully explore the therapeutic potential of EVs in ocular disorders and to address the challenges for their successful clinical translation. In this review, we will provide an overview of different types of EVs and their cargo, as well as the techniques used for their isolation and characterization. We will then review the preclinical and clinical studies that have explored the role of EVs in the treatment of ocular disorders, highlighting their therapeutic potential and the challenges that need to be addressed for their clinical translation. Finally, we will discuss the future directions of EV-based therapeutics in ocular disorders. Overall, this review aims to provide a comprehensive overview of the current state of the art of EV-based therapeutics in ophthalmic disorders, with a focus on their potential for nerve regeneration in ocular diseases.

Background To assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab. Methods Patients with pDME on chronic anti-vascular endothelial growth factor therapy that were switched to faricimab and received at least three injections at our institution between April 2022 and May 2023 were included in this study. Patients were excluded if they had complete response to previous treatment but were switched to extend treatment intervals if they had steroid or laser treatment for DME within 6 months prior to switch. Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT) and Snellen visual acuity (VA) were obtained before and after three intravitreal faricimab injections. Generalised estimating equations were used to analyse the change in CFT and VA. Result During the study period, 69 eyes of 53 patients met inclusion criteria. The mean age was 68.6±9.0 years. The mean number of injections prior to switch was 18.1±16.0. Pre-switch mean logarithm of the minimal angle of resolution VA was 0.40±0.30 (Snellen equivalent 20/50) and 0.38±0.27 (Snellen equivalent 20/48) after three faricimab injections (p=0.397). Mean CFT improved from 380±155 microns to 323±147 microns (p<0.001). No ophthalmic or systemic adverse events occurred during the study period. Conclusions Intravitreal faricimab can improve anatomic outcomes while maintaining visual acuity in eyes with pDME previously treated with anti-VEGF therapy.

Purpose: To characterize real-world use of intravitreal aflibercept 8 mg across 22 US retina practices. Methods: A retrospective review was performed of patients who received at least 1 intravitreal aflibercept 8 mg injection for treatment of neovascular age-related macular degeneration, diabetic macular edema, or diabetic retinopathy through April 1, 2024. Data from health records were collected retrospectively, including best-corrected visual acuity (BCVA), interval between treatments, and adverse events. Results: A total of 8323 eyes of 6271 patients received 20 385 intravitreal aflibercept 8 mg injections. A total of 669 eyes (8.0%) were not previously treated. Among treatment-naive eyes, mean logMAR BCVA improved from 0.57 (Snellen equivalent ~20/80) at the time of the first intravitreal aflibercept 8 mg injection, to 0.47 (Snellen equivalent ~20/60) ( P < .001), 0.46 (Snellen equivalent ~20/60) ( P < .001), and 0.48 (Snellen equivalent ~20/60) ( P = .012) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Among previously treated eyes, mean logMAR BCVA improved from 0.46 (Snellen equivalent ~20/60) at the time of the first intravitreal aflibercept 8 mg injection, to 0.42 (Snellen equivalent ~20/50) ( P < .001), 0.43 (Snellen equivalent ~20/50) ( P < .001), and 0.45 (Snellen equivalent ~20/60) ( P = .70) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Treatment intervals to time of second, third, and fourth intravitreal aflibercept 8 mg injections increased compared with baseline intervals, by a mean of 2.2 days ( P < .001), 2.5 days ( P < .001), and 13.5 days ( P < .001), respectively. Intraocular inflammation was observed in 11 eyes (1 in 1853 injections). Nine eyes (1 in 2265 injections) developed suspected endophthalmitis. Conclusions: In this real-world clinical setting, intravitreal aflibercept 8 mg treatment demonstrated improvements in BCVA outcomes, with increased intervals between injections. Rates of intraocular inflammation and endophthalmitis were low.