Abstract
Purpose :
To determine the status of aqueous humor molecular factors that are associated with disease severity, progression, and response to treatments such as IOP lowering medications and trabeculectomy in patients with primary glaucoma (PG) patients.
Methods :
Aqueous humor (AH) was collected during trabeculectomy from PG patients (n=143; primary open angle glaucoma, POAG,n=85; primary angle closure glaucoma, PACG,n=58) and patient undergoing cataract surgery (n=89,controls). Severity grading was based on VFI (visual field index) grades (Non-severe,n=74, Severe,n=69). Progression status was determined based on clinical, perimetry and OCT findings at 1 year follow up (Stable,n=72; progressors,n=18). Response to anti-glaucoma medications (AGM) was determined based on IOP control (responders,n=66; non-responders,n=76) prior to surgery (responders,n=57; non-responders,n=31). Response to trabeculectomy was determined based on IOP control after the surgery. Secreted molecular factors (52) were measured in the AH by bead-based multiplex ELISA. 8 immune cell subsets proportions in AH were determined by immunophenotyping using flow cytometry.
Results :
Twenty-four factors were significantly altered in AH of PG patients compared to controls and PG type-specific alterations were also observed compared to controls. IL-6, IL-8, IL-18, IFNβ, IFNγ, HGF, VEGF-A, sICAM1, sL-selectin, sTNFRII, MMP9 and MMP9/TIMP1 levels were increased (P<0.05) in severe group compared with non-severe group. IL-6, IL-18, HGF & sICAM1 levels were increased (P≤0.05) in progressors compared with stables. IL-6, IL-8, IL-13, IL-18, IFNγ, MCP1, HGF, VEGF-A, MMP9, Perforins & sTNFRII levels were increased (P<0.05) in non-responders compared with responders to AGM. IL-1α, IL-12/23p40, IL-18, IFNβ, IFNγ, HGF, PDGF-BB, sICAM1 & Perforin levels were significantly altered in non-responders compared with responders to trabeculectomy. Levels of certain secreted factors correlated with clinical parameters and PG type-specific alterations. Proportions of neutrophils and natural killer cells were higher in the AH of POAG patients compared to controls.
Conclusions :
Distinct intraocular molecular pattern was observed in severe conditions, progressors and non-responders to treatment strategies. More specifically, HGF, IL-18, IL-6, sICAM1, and IFNγ are the factors that were significantly increased in majority of the study groups.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.