There have been reports of unexplained visual loss following intra-ocular silicone oil (SiO) tamponade in retinal detachment patients, yet the underlying mechanism is unknown. In the present study, we identified differentially expressed proteins in the vitreous humor of four groups (each group, n=3): pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RD group), SiO removal after successful retinal reattachment (SO group), cataract surgery after successful retinal reattachment with sterilized air tamponade (FA group), and PPV for epiretinal membrane (ERM group). DIA was combined with two-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS) to find expression changes in the proteome of vitreous.