Temporal changes in aqueous humor inflammatory cytokines of the contralateral eye after unilateral phacotrabeculectomy in rabbits

To determine whether unilateral phacotrabeculectomy induces detectable, time-dependent changes in the aqueous humor inflammatory cytokine profile of the contralateral unoperated eye, and to define the temporal fluctuation window. A unilateral phacotrabeculectomy model was established in New Zealand White rabbits. The contralateral unoperated eye was studied. Aqueous humor was collected at − 14 days preoperatively as baseline and serially at 3 days, 1 week, 2 weeks, 4 weeks, 8 weeks, and 12 weeks postoperatively from the same cohort (n = 10 rabbits). Concentrations of IL-6, IL-1β, TNF-α, MCP-1, MIP-1β, IP-10, IL-10, TGF-β2, and MMP-9 were quantified. Data are presented as mean ± SD. Each postoperative time point was compared with baseline using two-sided paired t-tests with Holm–Šidák correction for multiple comparisons. Multiple analytes in the contralateral aqueous humor showed a transient postoperative increase, predominantly in the early period. Proinflammatory and matrix remodeling–related markers (IL-6, TNF-α, IL-1β, and MMP-9) generally peaked at 3 days, and IL-6 remained significantly elevated through 2 weeks. The chemokines MCP-1 and MIP-1β most commonly peaked at 1 week; MCP-1 was significantly elevated primarily at 1 week, whereas MIP-1β showed significant upregulation from 3 days to 1 week. IP-10 peaked at 2 weeks and remained significantly elevated through 4 weeks. The immunoregulatory/repair-related cytokine IL-10 and the profibrotic factor TGF-β2 peaked at 2 weeks and remained elevated at selected time points through 4 weeks. Overall, most markers declined after the early postoperative rise, with some signals persisting to 4 weeks, and values approached stability/near-baseline levels by 8–12 weeks. Following unilateral phacotrabeculectomy, the contralateral unoperated eye showed modest, time-dependent fluctuations in aqueous humor cytokine levels, predominantly within 3 days to 2 weeks, with some signals extending to 4 weeks. Although the preliminary repeated-paracentesis control data suggest that serial aqueous humor sampling was unlikely to fully account for these patterns, subtle or very short-lived procedural effects cannot be completely excluded. These findings suggest that potential fellow-eye changes and their temporal window should be considered when designing and interpreting studies using early postoperative inflammation as an endpoint.