A transient fellow-eye inflammatory window after unilateral trabeculectomy: an exploratory framework for staged bilateral filtration surgery

Staged bilateral trabeculectomy is common in glaucoma, yet the interval between first- and second-eye surgery is largely experience-based. Whether unilateral trabeculectomy induces a time-dependent inflammatory shift in the contralateral unoperated eye—potentially altering the perioperative milieu for second-eye surgery—remains unclear. We aimed to characterize the peak and recovery window of aqueous humor inflammatory mediators in the contralateral eye after unilateral trabeculectomy. Twelve New Zealand White rabbits (2.0 ± 0.25 kg; 6 males and 6 females) underwent unilateral trabeculectomy in the right eye; the left eye served as the fellow-eye control. Aqueous humor was collected bilaterally at baseline (Day − 14) and at 3 days, 1, 2, 4, 8, and 12 weeks postoperatively (50 µL/eye/time point; serial sampling). IL-6, IL-1β, TNF-α, MCP-1, MIP-1β, IP-10, IL-10, TGF-β2, and MMP-9 were quantified by commercial ELISA. Prespecified analyses compared each postoperative time point versus baseline in the control eye with multiplicity adjustment; operated-versus-control differences over time were evaluated in secondary analyses. The contralateral control eye showed a modest but measurable, predominantly subclinical inflammatory/chemotactic response after unilateral trabeculectomy, detectable primarily by aqueous humor biomarker analysis rather than by overt clinical signs, with multiplicity-adjusted elevations largely confined to an early postoperative interval (3 days–2 weeks) and an overall return toward baseline by ~ 4 weeks. IL-6 and MCP-1 exhibited the most consistent early increases, whereas IP-10 showed a relatively delayed normalization trend. The operated eye demonstrated substantially stronger and more sustained postoperative activation, with the largest inter-eye separation occurring during the early window. Unilateral trabeculectomy was associated with a short-lived contralateral aqueous humor inflammatory/chemotactic shift that peaked within 3 days–2 weeks and largely resolved by approximately 4 weeks in rabbits. In this experimental setting, these changes appeared to be predominantly subclinical and biomarker-detectable rather than clinically overt. These descriptive findings suggest a putative early fellow-eye “fluctuation window” but do not provide evidence to guide clinical timing of second-eye surgery. Whether a similar temporal pattern exists in patients, and whether it has clinical relevance, requires prospective validation.