Vitreoretinal fibrosis is a hallmark pathological feature of proliferative vitreoretinopathy (PVR), which relies on invasive intraocular surgery, retinal detachment and ocular trauma in clinic. Upon initial data mining for depicting the key features of the vitreoretinal fibrosis microenvironment in both PVR patients and model mice, including elevated transforming growth factor β1 (TGFβ1) and M2 macrophage enrichment, we herein designed and engineered extracellular vesicles that conferred potent anti-fibrotic efficacy against PVR. These extracellular vesicles were derived from M1 macrophages (M1evs) and were conjugated with a TGFβ1 antibody (aT) through an MMP-cleavable linker (cl). Upon intravitreal injection into PVR model mice, we observed aT-cl-M1ev (ACE) selectively accumulated in the PVR lesions and aT was cleavably released. By neutralizing TGFβ1 and inhibiting M2 macrophage polarization, the microenvironment was effectively modulated and vitreoretinal fibrosis was diminished. Further incorporating a platelet derived growth factor receptor antibody via a cl linker, we developed aTP-cl-M1ev (ACEPlus) to treat PVR at an advanced stage and observed a potent benefit in preventing retinal detachment progression, which, notably, was validated with an innovative, patient-derived PVR membrane xenograft model. Our study thus demonstrated that therapeutic modulation of the vitreoretinal fibrosis microenvironment with the ACE platform was as an efficacious alternative to surgical interventions for PVR.