Levels of multiple inflammatory cytokines in the aqueous humor remain significantly elevated 3 to 12 years after cataract surgery, according to a new study.
Led by Caili Hao of the Department of Cellular Biology and Anatomy at the Medical College of Georgia at Augusta University, researchers analyzed 63 cytokines and growth factors using multiplex immunoassays in aqueous humor (AH) samples from 48 postmortem donors—23 with a history of bilateral phacoemulsification and 25 age- and sex-matched controls with no ocular disease history. The average time since surgery was 7.8 years. A total of 96 AH samples were assessed. Thirty-four proteins passed quality control and were included in final analyses.
To quantify overall inflammatory changes, researchers created a novel Post-Cataract Surgery Inflammation Index (PCSII) using ridge regression from the 34 protein markers. PCSII was significantly higher in postsurgery donors compared with controls, and patients in the highest PCSII tertile had an odds ratio of 27.83 for prior cataract surgery, compared with the lowest tertile. This index proved more sensitive for distinguishing postsurgical eyes than individual cytokine measurements.
Further univariate and multivariate analyses revealed several significant differences in specific cytokine levels:
Elevated in postsurgery donors:
- CD40L (fold change [FC] = 1.29, P=.043)
- IL-7 (FC = 1.30, P=.015)
- MIP-1α (FC = 1.39, P=.049)
- LIF (FC = 1.61, P=.036)
Decreased in postsurgery donors:
- IL-23 (FC = 0.44, P=.027)
- IL12p70 (FC = 0.66, P=.013)
- IFN-γ (FC = 0.70, P=.020)
- MIP-3α (FC = 0.71, P=.049)
- TRAIL (FC = 0.59, P=.046)
- SCF (FC = 0.86, P=.019)
These findings persisted after adjusting for age and sex in logistic regression models.
The researchers described how the decreased cytokines could be a sign of abnormal immune functioning and are often associated with chronic inflammatory or autoimmune diseases. In particular, they wrote, low IFN-γ levels can impair the tissue’s ability to combat pathogens and are implicated in tissue fibrosis.
The study explored several potential sources of persistent inflammation, including retained lens fragments, lens epithelial cells (LECs), and resident immune cells in the lens. Retained lens fragments can be immunogenic, and severe responses can lead to uveitis, the authors explained. A previous study found that the upregulation of several genes was detected in the lens epithelium, compared with controls. “This study strongly suggests that, similar to other epithelial tissues, LECs can modulate immune responses, likely serving as a key mechanism in chronic inflammation after cataract surgery. However, additional studies are required to determine whether human lens epithelial cells express certain cytokines and receptors, and if their expression is upregulated following cataract surgery,” they added.
Finally, while resident immune cells in the lens are thought to be essential in maintaining tissue homeostasis under normal conditions, the authors explained that they could become activated in response to injury or stress. “It is unclear whether these cells contribute to the sustained production of the cytokines identified in the current research,” they wrote. “Addressing these questions is critical to understanding the long-term immunological dynamics of the lens following surgical intervention.”
These findings raise additional important considerations, including long-term outcomes after cataract surgery and conditions such as corneal decompensation, diabetic macular edema, trabeculectomy failure, and posterior capsule opacification.
The authors had no interests to disclose.