In Glaucoma, Aqueous Humor Cytokines May Play Pathophysiologic Role

Cytokines may have possible roles in the pathogenesis and development of primary open-angle glaucoma.

In glaucoma, aqueous humor cytokine levels are significantly elevated in patients with more severe disease, according to research published in BMC Ophthalmology. The findings suggest cytokines may have possible roles in the pathogenesis and development of primary open-angle glaucoma (POAG).

Researchers investigated the possible effects of cytokine levels on clinical characteristics and postoperative outcomes in glaucoma. They simultaneously compared the levels of cytokines in serum and aqueous humor of patients with POAG and patients with cataracts. 

The study included 38 patients with POAG (mean age, 57.8±8.0 years; 58% men, 42% women), divided according to the severity of visual field defects (mean deviation cutoff point of -12 dB), and 26 patients with cataract (mean age, 58.5±7.2 years; 46% men and 54% women). All patients underwent a complete ophthalmic examination, peripheral blood collection, and aqueous humor collection during cataract or glaucoma surgery. 

The investigators assayed levels of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta2 (TGF-β2) and IL-4 in aqueous humor and peripheral blood in both groups and recorded postoperative intraocular pressures (IOPs) of POAG patients during the follow-up period (mean ± SD, 7.4±0.9 months).

In patients with glaucoma, aqueous humor cytokines TNF-α and TGF-β2 were present in higher levels than in the cataract group (mean TNF-α level, 2.68 vs 1.91 pg/mL; P <.001; mean TGF-β2 level, 311.3 vs 239.2 pg/mL; P =.001, respectively). 

Within POAG group, the researchers found that preoperative IOPs were positively correlated with levels of TNF-α (r2=0.129; P =.027) and TGF-β2 (r2=0.273; P =.001) in the aqueous humor. They also found that levels of TGF-β2 in the aqueous humor were significantly higher in both patients with POAG with mean deviation (MD) of the visual field was greater than -12 dB (mean, 2.57 pg/mL) and those with POAG with mean deviation of the visual field of -12 dB or less (mean, 2.96 pg/mL) than those with cataract (mean, 1.91 pg/ml; P =.002 for both).

A regression analysis revealed aqueous humor levels of TNF-α were positively associated with IOP reduction after trabeculectomy (P=0.025). The study did not find a relationship between levels of cytokines in the aqueous humor and peripheral blood and long-term success of trabeculectomy.

“TNF-α and TGF-β2 levels might be correlated with elevated preoperative IOP and IOP reductions after trabeculectomy in POAG patients and play roles in POAG pathophysiologic progression,” explain the study authors. “TGF-β2 may serve as biomarkers for assessing the severity of glaucomatous neuropathy.”

Limitations of the study included significant differences in the numbers of men and women between the groups, inability to obtain the aqueous humor after surgery, inability to analyze the relationship between real-time aqueous humor levels of cytokines and postoperative IOP after surgery, and the potential effect of medications to manage glaucoma on aqueous humor cytokines.


Yin Z, Gao Y, Tang Y, Tian X, Zheng Y, Han Q. Aqueous humor cytokine levels are associated with the severity of visual field defects in patients with primary open-angle glaucoma. BMC Ophthalmol. 2023;23(1):141. Published 2023 Apr 5. doi:10.1186/s12886-023-02875-8