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Diabetic retinopathy, an ocular complication of diabetes, is an important cause of blindness in adults. Puerarin is considered to have promising potential for clinical use in treating diabetic retinopathy. In this study, we designed a novel puerarin-loaded poly(lactic acid) sustained-release microspheres suitable for ocular administration, and we assessed itsin vitro and in vivo properties. The preparation of puerarin-loaded microspheres was optimized by Box-Behnken response surface design. The encapsulation efficiency and drug loading of microspheres were 35.71% and 3.85%, respectively. The microspheres exhibited good dispersion and high safety, making it suitable for ocular drug delivery. In vitro release demonstrated that microspheres had a well-sustained release effectiveness, and its release behavior complied with the zero-order kinetic characteristics. The results of ocular tissue distribution revealed that the C max andAUC 0-∞ of the microspheres group in the retina and choroid were considerably higher than those of the solution group and the intravenous injection group. This research revealed that intravitreal injection of microspheres can significantly prolong the half-life of puerarin in eye tissues and achieve sustained drug release. Therefore, intravitreal injection of microspheres has positive implications for the treatment of diabetic retinopathy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases. On intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina. In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells. The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases., Competing Interests: Competing interests: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives : Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods : The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results : The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA ( p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA ( p = 0.0050 and p = 0.0052, respectively). Conclusions : When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.