Changes in aqueous humor cytokines and metabolomics in contralateral eye after unilateral cataract surgery.

Background: For patients with bilateral age-related cataracts, sequential phacoemulsification and intraocular lens implantation is a common treatment. However, it remains unclear whether surgery on the first eye has an impact on the second eye, as current research results are inconsistent. This study will explore whether surgery on one eye affects the non-operated eye through aqueous humor cytokines and metabolomic analyses in the second eye.

Methods: A rabbit model of unilateral phacoemulsification and intraocular lens implantation was established. The experimental group consisted of 15 rabbits undergoing this procedure. Postoperatively, rabbits were divided into five subgroups (three rabbits per subgroup), and aqueous humor was collected from both the operated and non-operated eyes at 1 day, 3 days, 1 week, 2 weeks, and 3 weeks after surgery. Additionally, 5 rabbits were selected as a control group, from which aqueous humor was extracted. Levels of IL-1a, IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, TNF-α, MCP-1, and VEGF in the aqueous humor were compared. In the clinical study, preoperative aqueous humor samples were collected from 22 patients undergoing bilateral phacoemulsification and intraocular lens implantation. Among them, 11 patients were tested for the aforementioned 10 cytokines, while the other 11 patients underwent untargeted metabolomics research.

Results: In the animal experiment, levels of all 10 cytokines in the operated eyes were significantly higher compared to both the control and non-operated eyes groups (P < 0.05). In the non-operated eyes, IL-1β and IL-2 levels were also elevated compared to the control (P < 0.05); however, no statistically significant differences were observed between the non-operated eyes and the control group at postoperative time points of 1 day, 3 days, 1 week, 2 weeks, and 3 weeks. In the clinical study, no significant differences were found in cytokine levels between the two eyes. In the untargeted metabolomics analysis, 354 metabolites showed differential expression, 280 were upregulated and 74 were downregulated. Notably, Adenine and 2-Aminopurine were significantly downregulated, highlighting Purine metabolism as the most impacted pathway.

Conclusions: Animal experiments showed a significant increase in IL-1β and IL-2 levels in the non-operated eyes postoperatively, reflecting systemic and local inflammatory responses. In clinical experiments, although no significant changes in cytokines were observed in the aqueous humor of both eyes, differential expression of metabolites indicated metabolic adjustments in the non-operated eye following surgery on the first eye. These findings reveal that unilateral cataract surgery may affect the stability of the intraocular environment in the contralateral eye, suggesting that in staged bilateral surgeries, potential metabolic changes in the non-operated eye and their clinical significance should be considered. This result provides important reference value for optimizing postoperative management strategies, reducing complications, and determining the timing for bilateral surgeries, warranting further investigation.