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

ABSTRACT: Peripheral anterior synechiae (PAS) after corneal transplantation leads to refractory glaucoma and permanent loss of vision. However, the exact mechanism remains elusive. This study aimed to evaluate the association between cytokine levels in the aqueous humor (AqH) and the progression of PAS after penetrating keratoplasty (PKP). We measured 20 cytokine levels in AqH and assessed the correlation with PAS progression after PKP in 85 consecutive patients who underwent PKP. We also evaluated age-dependent alterations in PAS and cytokine levels in DBA2J mice. PAS developed in 38 (44.7%) of 85 eyes after PKP. The incidence of intraocular pressure increase after PKP was significantly greater in eyes with PAS (26.3%) than in those without PAS (2%, p = 0.0009). The PAS area at 12 months after PKP was significantly positively correlated with the preoperative levels of interleukin (IL)-6, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1 (p ≤ 0.049). In the DBA2J mice, an experimental glaucoma model that developed PAS at 50 weeks, the AqH levels of IL-2, IL-6, IL-10, IFN-γ, tumor necrosis factor-α, MCP-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased at 50 weeks compared to 8 weeks (p ≤ 0.021). In conclusion, inflammatory alterations in the AqH microenvironment, such as high preoperative specific cytokine levels, can lead to PAS formation and glaucoma.

SUBMITTER: Kusano Y

PROVIDER: S-EPMC8618311 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy.To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response.In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up.Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1.Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME.Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, -190.88; interquartile range [IQR], -634.20 to -26.54; P < .001), VEGF (median change, -639.45; IQR, -1040.61 to -502.61; P < .001), placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; P < .001), IL-6 (median change, -38.61; IQR, -166.72 to -2.80; P < .001), and monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998).Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.

Project description:PurposeTo evaluate difference in therapeutic outcomes between deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PKP) for the clinical treatment of keratoconus.MethodsA comprehensive search was conducted in Pubmed, EMBASE, Cochrane Library, and Web of science. Eligible studies should include at least one of the following factors: best corrected visual acuity (BCVA), postoperative spherical equivalent (SE), postoperative astigmatism and endothelial cell count (ECC), central corneal thickness (CCT), graft rejection and graft failure, of which BCVA, graft rejection and graft failure were used as the primary outcome measures, and postoperative SE, astigmatism, CCT and ECC as the secondary outcome measures. Given the lack of randomized clinical trials (RCTs), cohort studies and prospective studies were considered eligible.ResultsSixteen clinical trials involving 6625 eyes were included in this review, including 1185 eyes in DALK group, and 5440 eyes in PKP group. The outcomes were analyzed using Cochrane Review Manager (RevMan) version 5.0 software. The postoperative BCVA in DALK group was significantly better than that in PKP group (OR = 0.48; 95%CI 0.39 to 0.60; p<0.001). There were fewer cases of graft rejection in DALK group than those in PKP group (OR = 0.28; 95%CI 0.15 to 0.50; p<0.001). Nevertheless the rate of graft failure was similar between DALK and PKP groups (OR = 1.05; 95%CI 0.81 to 1.36; p = 0.73). There were no significant differences in the secondary outcomes of SE (p = 0.70), astigmatism (p = 0.14) and CCT (p = 0.58) between DALK and PKP groups. And ECC in DALK group was significantly higher than PKP group (p<0.001). The postoperative complications, high intraocular pressure (high-IOP) and cataract were analyzed, fewer cases of complications occurred in DALK group than those in PKP group (high-IOP, OR 0.22, 95% CI 0.11-0.44, P<0.001) (cataract, OR 0.22; 95% CI 0.08-0.61, P = 0.004). And no cases of expulsive hemorrhage and endophthalmitis were reported.ConclusionThe visual outcomes for DALK were not equivalent to PKP. The rate of graft failure was similar between DALK and PKP. Fewer postoperative complications occurred in DALK group, indicating that compared with PKP, DALK has lower efficacy but higher safety.

Project description:PurposeTo theoretically compare corneal displacement and the von Mises (VM) stress distribution of deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) for keratoconus (KC) and to evaluate the effects of residual stromal thickness (RST) and intraocular pressure (IOP) on postoperative corneal biomechanics.MethodsWe performed DALK and PK simulations using Ansys by employing anisotropic nonlinear hyperelastic corneal material properties. We analyzed corneal displacement and VM stress in DALK and PK models under IOPs of 10, 15, 20, and 25 mmHg. We established two DALK models: The ideal-type DALK ensured that postoperative central corneal thickness was constant at 560 µm and the corneal graft thickness varied with RST. The clinical-type DALK ensured that corneal grafts had the same thickness (500 µm) regardless of RST. Then we analyzed the effects of RST and IOP on postoperative corneal displacement and VM stress.ResultsCorneal displacement and VM stress were lower in the DALK than in the PK model. In the ideal-type DALK model, an increase in RST was associated with increased deformation and decreased VM stress in the healing zone, except for a RST of 0 µm. In the clinical-type DALK model, deformation and VM stress in the healing zone decreased with an increase in RST, except for a RST of 0 µm.ConclusionsDALK showed more stability than PK. For the ideal-type DALK model, an increase in RST resulted in decreased postoperative corneal biomechanics in the healing zone. For the clinical-type DALK model, corneal deformation and VM stress decreased with an increase in RST, which provides numerical evidence for the design of corneal transplantation for patients with KC.Translational relevanceIn this computational modeling study, we first theoretically compared corneal biomechanics between DALK and PK for KC. Then, the effects of RST and IOP on postoperative corneal biomechanics were investigated. Our findings provide novel insights into the optimal design for corneal transplantation for patients with KC.

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

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