Aqueous Cytokine Levels Are Associated With Progression of Peripheral Anterior Synechiae After Descemet Stripping Automated Endothelial Keratoplasty

Abstract

Purpose To evaluate the association between total protein and cytokine levels in aqueous humor (AqH) and the progression of peripheral anterior synechiae (PAS) after Descemet stripping automated endothelial keratoplasty (DSAEK). Methods This prospective study included 146 consecutive patients who underwent DSAEK. Preoperative levels of total protein and 20 cytokines in AqH were measured. Using three-dimensional anterior segment optical coherence tomography, we assessed the iridotrabecular contact (ITC) area before and at 3, 6, and 12 months after DSAEK. Correlations between the total protein and cytokine levels in the AqH and ITC area were analyzed. Results ITC was observed in 47 eyes (32.2%) after DSAEK. The ITC area increased from 2.00 ± 4.42 mm 2 preoperatively to 3.00 ± 6.85 mm 2 at 12 months. The total protein level in AqH was significantly higher in eyes with ITC progression than in those without (1.45 ± 1.03 mg/mL vs. 1.00 ± 0.57; P = 0.04) and was significantly positively correlated with the progression of ITC area after DSAEK (at 6 months, r = 0.311 and P = 0.005; at 12 months, r = 0.342 and P = 0.0004). The ITC area at 12 months was significantly correlated with the preoperative AqH levels of interleukin-8 ( r = 0.252; P = 0.021), interferon-γ ( r = 0.318; P = 0.009), and soluble intercellular adhesion molecule-1 ( r = 0.292; P = 0.004). Multivariate analyses showed that the total protein levels in AqH and the presence of preoperative ITC were significant risk factors for increased ITC area after DSAEK (β = 0.193–0.574; all P < 0.02). Conclusions Higher preoperative total protein and specific cytokine levels in AqH were associated with ITC formation after DSAEK. Translational Relevance Our findings indicate that chronic pathological changes in AqH can cause PAS progression and glaucoma after DSAEK.

Elevated Cytokine Levels in Aqueous Humor Are Associated with Peripheral Anterior Synechiae after Penetrating Keratoplasty

“…PAS did not progress in 12 eyes (13.8%) with preoperative PAS. To evaluate PAS severity, we measured the degree, height and area of irido-trabecular contact (ITC) using three-dimensional AS-OCT, as previously reported [24]. The ITC indices (ITC %degree, maximal height and area) gradually increased after PKP; however, all ITC indices significantly increased at 12 months after PKP, compared to the preoperative values (Table 1, p < 0.03).…”

“…Recent advances in anterior segment optical coherence tomography (AS-OCT) have enabled the non-invasive and accurate quantification of PAS [13][14][15][19][20][21][22][23]. Using stateof-the-art AS-OCT, we have demonstrated that the elevated levels of specific cytokines in the aqueous humor (AqH) were significantly correlated with the development of PAS after EK [24]. This suggests that the inflammatory microenvironment in AqH leads to PAS development and refractory glaucoma after corneal transplantation.…”

“…Our recent study demonstrated a positive correlation between PAS formation and cytokine levels after EK [24]. In the current study, we first sought to quantify PAS after PKP in our hospital.…”

“…Next, to identify the clinical factors associated with PAS progression, we conducted multivariate analysis (Table S2). We selected the progression of the ITC area as it represented a threedimensional alteration of ITC and was the most reliable PAS index [24]. It showed that only the presence of preoperative ITC was significantly associated with the progression of ITC area (β = 2.30, p < 0.0001), whereas preoperative total protein levels, axial length, graft size and patient age were not.…”

“…Inflammation in the AqH plays a pivotal role in PAS formation, leading to an IOP increase after corneal transplantation [24]. Since specific cytokine levels were found to be significantly correlated with PAS formation after EK [24], we compared the inflammatory cytokine levels in the AqH between the eyes with and without PAS after PKP (Table 3), which demonstrated that the levels of interleukin (IL)-6, IL-8, IL-10, IL-12p70, monocyte chemotactic protein (MCP)-1, P-selectin and interferon-gamma inducible protein (IP)-10 were significantly higher in eyes with postoperative PAS than in those without postoperative PAS (p ≤ 0.041). We further evaluated the correlation between cytokine levels in the AqH and ITC areas (Table 4).…”