Intravitreal vascular endothelial growth factor and connective tissue growth factor levels and risk factors associated with vitreous hemorrhage in proliferative diabetic retinopathy after pan-retinal laser photocoagulation: a cross-sectional study

BACKGROUND: The study aimed to investigate the changes of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) concentrations in proliferative diabetic retinopathy (PDR) combined with vitreous hemorrhage (VH) patients after panretinal photocoagulation (PRP), and to explore the risk factors associated with the occurrence of VH. METHODS: This cross-sectional study included 46 eyes surgically treated with pars plana vitrectomy (PPV), divided into three groups: PRP group (18 eyes) – PDR combined with VH patients with previous PRP; no-PRP group (18 eyes) – PDR combined with VH patients without previous PRP; and control group (10 eyes) – PPV performed for idiopathic macular hole (IMH) without diabetes mellitus. Both PRP and no-PRP groups underwent surgery due to non-clearing VH. Vitreous samples were obtained during PPV, then VEGF and CTGF concentrations were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Intravitreal VEGF levels were significantly lower in the PRP group (1968.10[1423.96-2341.68] pg/mL) than in the no-PRP group (2815.71[2440.70-3395.52] pg/mL) (P = 0.015), but CTGF levels showed no statistical difference. The CTGF/VEGF ratio was significantly higher in the PRP group (0.27[0.13–0.34]) than in the no-PRP group (0.13[0.11–0.18]) (P = 0.002). Multiple linear regression analysis revealed that PRP treatment was independently associated with lower VEGF levels (P < 0.001) and a higher CTGF/VEGF ratio (P = 0.004). A positive correlation was observed between vitreous VEGF and CTGF levels in the no-PRP group (r = 0.486, P = 0.041), whereas no correlation was observed in the PRP group. CONCLUSION: PRP treatment was associated with an alteration in the relationship between VEGF and CTGF levels in PDR patients, characterized by an upregulation of the CTGF/VEGF ratio and a pro-fibrotic shift. Traction from microfibrous vascular membranes and the vitreous may represent key mechanisms contributing to VH in PDR patients after PRP treatment. TRIAL REGISTRATION: Trial registration number ChiCTR2400088011. Date of registration July 23, 2024.