Aqueous Humor Proteome in RVO-Associated Macular Edema: Analysis during Three Consecutive Conbercept Treatments

PURPOSE: This exploratory study aimed to assess the aqueous humor (AH) proteome in patients with retinal vein occlusion (RVO) and macular edema (ME) receiving three consecutive intravitreal injections of Conbercept, to identify potential molecular pathways, and to generate hypotheses. METHODS: Label-free quantitative liquid chromatography-tandem mass spectrometry was applied to analyze the AH of patients with RVO and ME who underwent three consecutive Conbercept intravitreal injections (IVI) and age-matched controls. The alterations in BCVA, central retinal thickness (CRT), and AH proteins were ascertained through a permutation-based calculation (the false discovery rate was set at 0.05). A repeated-measures analysis determined the most significantly changed protein in the AH (α = 0.05). RESULTS: Compared to controls, 45 proteins were regulated in the RVO cohort, with 19 and 48 proteins differentially expressed in the branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) subgroups, respectively. The plasma kallikrein (P = 0.0007, R = 0.775) and desmocollin-3 (P = 0.006, R = -0.673) levels were significantly correlated with CRT during treatment in the BRVO. SPARC (P = 0.007, R = -0.686), vasorin (P = 0.002, R = -0.759), desmocollin-2 (P = 0.008, R = -0.676), Neurotrimin (P = 0.007, R = -0.685), desmocollin-3 (P = 0.042, R = -0.549), fibulin-1 (P = 0.011, R = -0.656), and follistatin-related protein-1 (P = 0.048, R = -0.536) were significantly correlated with CRT during treatment, and desmocollin-2 (P = 0.025, R = -0.610), desmocollin-3 (P = 0.021, R = -0.610), plasma kallikrein (P = 0.0006, R = 0.8), and Neurotrimin (P = 0.017, R = -0.623) were significantly correlated with changes in patients' BCVA during treatment in the CRVO. CONCLUSIONS: This exploratory proteomic analysis identified distinct pathway alterations in early RVO pathogenesismetabolic in BRVO and inflammatory in CRVOand common treatment-related changes: plasma kallikrein was downregulated, while desmocollin-3 was up-regulated.