Updated project metadata. In contrast to neovascular age-related macular degeneration (nAMD), no treatment option exists for dry AMD. The identification of specific biomarkers is required to facilitate diagnosis and therapy of dry AMD. We thus measured the proteome of 34 vitreous humor samples (dry AMD: n = 6, nAMD: n = 10, PDR: n = 9, ERM: n = 9). Samples were immunodepleted for high abundant blood proteins and analyzed by LC-MS/MS with a shotgun approach. Data from dry AMD, nAMD and PDR were compared to the ERM patient group, which was used as reference group. A bioinformatic pipeline was used for label-free relative quantification of proteins and to perform cluster analysis, gene ontology classification and gene set enrichment analysis. A selection of differentially regulated proteins was validated by ELISA. A total of 677 proteins were identified and relatively quantified in the four patient groups. Different clusters of regulated proteins for each patient group were identified and showed characteristic enrichment of specific pathways, like ‘oxidative stress’ for dry AMD, ‘focal adhesion’ for nAMD and ‘complement and coagulation cascade’ for PDR patients. We’ve identified CHLE to be specifically upregulated in dry AMD and RNAS1 together with CPVL to be upregulated in both forms of AMD. The description of pathways specific for the different patient groups and the identification of differentially regulated proteins provide a first step towards the definition of biomarkers for dry AMD. To validate these data and to unravel the mechanistic connection of identified proteins to dry AMD, larger patient cohorts need to be investigated.