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Purpose: To investigate the potential of a combined assessment of clinical risk factors and biomarker profiling in the prediction of proliferative vitreoretinopathy (PVR) after retinal detachment surgery., Design: Retrospective case-control study., Methods: Multiplex bead-based immunoassays were used for the simultaneous measurement of 50 biomarkers in subretinal fluid samples obtained from patients who underwent scleral buckling surgery for primary rhegmatogenous retinal detachment (RRD). Of 306 samples that were collected and stored in our BioBank, we selected 21 samples from patients in whom a redetachment developed as a result of PVR within 3 months after reattachment surgery for primary RRD (PVR group). These were compared with age-, sex-, and storage time-matched RRD samples from 54 patients with an uncomplicated postoperative course after primary RRD repair (RRD group)., Results: Preoperative PVR was the only clinical variable that was an independent predictor of postoperative PVR development (P = .035) and resulted in an area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.51 to 0.83). The addition of the biomarkers chemokine (C-C motif) ligand 22, interleukin-3, and macrophage migration inhibitory factor improved the model significantly (P < .001) and resulted in an area under the receiver operating characteristic curve of 0.93 (95% confidence interval, 0.82 to 1.04). A sensitivity of 94.1% and a specificity of 94.2% were reached, using a cutoff value of 5%., Conclusions: In combination with preoperative PVR grade, the measurement of a single biomarker or a small multibiomarker panel shows great potential and may predict postoperative PVR development after primary RRD in a highly sensitive and specific manner., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Adipokines have recently emerged as a novel group of mediators with important roles in inflammatory and immune responses and in the process of wound healing. This study investigated the involvement of several adipokines in the future development of proliferative vitreoretinopathy (PVR) following reattachment surgery for rhegmatogenous retinal detachment (RRD). A multiplex immunoassay was used to measure 6 different adipokines in 75 subretinal fluid samples collected during reattachment surgery for primary RRD. Twenty-one patients who developed a redetachment due to postoperative PVR after scleral buckling surgery (PVR group) were compared with age-, sex-, and storage-time-matched RRD samples from 54 patients with an uncomplicated postoperative course (RRD group). Levels of adiponectin (P = 0.006), cathepsin S (P = 0.001), and leptin (P = 0.041) were significantly elevated in the PVR group as compared to the RRD group. Levels of tissue inhibitor of metalloproteinase (TIMP)-1 were significantly lower in the PVR group than in the RRD group (P = 0.044). After correction for diabetes, body mass index (BMI), macular involvement, and preoperative PVR, the association between postoperative PVR development and adiponectin, cathepsin S, and TIMP-1 remained statistically significant (P < 0.05), whereas the significant correlation between PVR and elevated leptin levels was lost (P = 0.068). There were no significant differences in levels of chemerin (P = 0.351) and adipsin (P = 0.915). Of all adipokines investigated, multivariate logistic regression analysis showed that adiponectin was the exclusive predictor of the development of postoperative PVR after scleral buckling surgery (P = 0.003). Our findings indicate that, at the time of surgery for primary RRD, an altered expression of certain adipokines is associated with the future development of postoperative PVR., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: In proliferative vitreoretinopathy (PVR), a nonangiogenic eye disease that is characterized by the formation of mainly avascular membranes, vascular endothelial growth factor (VEGF) levels are found to be upregulated. Recently, it was discovered that VEGF is alternatively spliced to form the angiogenic (VEGF xxx) and antiangiogenic (VEGF xxx b) family of isoforms. Previous studies on expression of VEGF in PVR samples have not distinguished between the two families of isoforms., Methods: We measured total VEGF and VEGF xxx b levels in subretinal fluid of patients with PVR (n = 10) and in patients with uncomplicated rhegmatogenous retinal detachment (n = 27) using enzyme-linked immunosorbent assay., Results: : We found total VEGF levels to be 2- to 3-fold elevated in the PVR group as compared with the rhegmatogenous retinal detachment group (P = 0.047). Antiangiogenic VEGF xxx b isoforms predominated (>60% of total VEGF) in the majority of rhegmatogenous retinal detachment and PVR samples investigated, although a wide variability of isoform ratios was observed within both groups., Conclusion: The absence of an increased ratio of VEGF xxx to VEGF xxx b in patients with PVR as compared with patients with uncomplicated rhegmatogenous retinal detachment may explain a lack of blood vessels in PVR membranes. Elevated VEGF levels indicate that this cytokine may play a role in the pathogenesis of PVR that is not related to angiogenesis.

Purpose: To investigate the influence of subfoveal fluid and foveal thickness on visual outcome in patients who underwent reattachment surgery for rhegmatogenous retinal detachment (RRD)., Methods: This prospective study included 53 patients who were undergoing successful scleral buckling surgery for primary RRD. A thorough ophthalmologic examination including best-corrected visual acuity, slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and optical coherence tomography scanning was performed preoperatively and during all subsequent follow-up visits at 1, 3, 6, 9, 12, and 24 months postoperatively., Results: Preoperative foveal thickness was significantly higher in the macula-off group (n = 38) compared with the macula-on group (n = 15) (P < 0.0001), whereas postoperative measurements were normal in both the groups. Linear mixed-model analysis revealed that persistent subfoveal fluid (P = 0.0004) was an independent predictor of a worse visual outcome after scleral buckling surgery for primary macula-off RRD, although the effect on visual outcome was small (0.1 logarithm of the minimal angle of resolution units). Moreover, increased preoperative foveal thickness was associated with a worse visual prognosis in macula-off RRD (P = 0.010)., Conclusion: Persistent subfoveal fluid and increased preoperative foveal thickness were associated with a worse visual prognosis in macula-off RRD patients, albeit the effect of persistent subfoveal fluid was small and temporary.

Purpose: To investigate the association between soluble apoptosis and adhesion molecules and the development of proliferative vitreoretinopathy (PVR) after reattachment surgery for rhegmatogenous retinal detachment (RRD)., Methods: A multiplex immunoassay was used to measure soluble Fas (sFas), sFas ligand (sFasL), soluble intercellular adhesion molecule (sICAM)-1, and soluble vascular cell adhesion molecule (sVCAM)-1 levels in 55 subretinal fluid samples collected during scleral buckling surgery for primary RRD. Seventeen patients who developed a redetachment due to postoperative PVR after reattachment surgery (PVR group) were compared with age-, sex-, and storage-time-matched RRD samples from 38 patients with an uncomplicated postoperative course (RRD group). Ten vitreous samples from patients with macular hole and ten vitreous samples from eye bank eyes served as additional controls., Results: A 2- to 3-fold increase in levels of sFas, sFasL, sICAM-1, and sVCAM-1 was found in the PVR group compared with those of the RRD group (P < 0.05 for all analytes), as well as a 5- to 20-fold increase in the PVR group compared with those of additional control groups (P < 0.001 for all analytes). Significant associations (P < 0.001) were found between sFas and both sICAM-1 (r = 0.84) and sVCAM-1 (r = 0.93) and between sFasL and both sICAM-1 (r = 0.82) and sVCAM-1 (r = 0.85). In addition, sFas, sFasL, and sVCAM-1 were significantly correlated (P < 0.05) with the extent and duration of retinal detachment., Conclusions: These findings indicate that an increased expression of soluble apoptosis and adhesion molecules at the time of primary retinal detachment surgery is associated with the future development of PVR.

Background: Rhegmatogenous retinal detachment (RRD) is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR), an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome., Methodology: A multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time-matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period., Findings: Levels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P<0.05) in patients who developed postoperative PVR after reattachment surgery than in patients with an uncomplicated postoperative course, whereas levels of IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-11, IL-12p70, IL-13, IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-25, IL-33, TNF-α, IFN-γ, IGF-1, bFGF, HGF, and NGF were not (P>0.05). Multivariate logistic regression analysis revealed that IL-3 (P = 0.001), IL-6 (P = 0.047), ICAM-1 (P = 0.010), and preoperative visual acuity (P = 0.026) were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005) and preoperative logMAR visual acuity (P = 0.001) were predictive of final visual outcome after primary RRD repair., Conclusions/significance: Our findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control.

Purpose: An increased mRNA expression of genes related to blood coagulation has been demonstrated in an experimental retinal detachment model but has not yet been confirmed in human clinical specimens. Tissue factor (TF), the initiating factor of blood coagulation, may be a determinant of the extent of tissue injury after rhegmatogenous retinal detachment (RRD). This study was conducted to determine whether subretinal fluid and vitreous fluid collected from patients with RRD have a procoagulant effect., Methods: Calibrated thrombin generation (CAT) was used to investigate the thrombogenic properties of 28 subretinal fluids collected during scleral buckling surgery for RRD. Further, the thrombogenic properties of vitreous fluids from RRD (n = 12), macular pucker (n = 5), macular hole (n = 6), and proliferative diabetic retinopathy (n = 5) were compared with the properties of eye bank eyes (n = 11), which served as control specimens. The procoagulant activity of TF was determined with Western blot analysis., Results: The addition of subretinal fluid from all RRD patients (28/28, 100%) induced thrombin generation in normal and severely factor (F)XII-deficient plasma. Contrary to the subretinal fluid, the addition of vitreous fluids from various ocular disorders evoked very little thrombin generation in normal and severely FXII-deficient plasma (4/12, 33% RRD; 1/5, 20% macular pucker; 0/6, 0% macular hole; 0/5, 0% proliferative diabetic retinopathy; and 2/11, 18% eye bank eyes). The procoagulant activity in subretinal fluid was almost completely neutralized by antibodies against human TF. The presence of TF in subretinal fluid was confirmed by Western blot., Conclusions: Subretinal fluid of patients with RRD induces high procoagulant activity, determined by measuring the level of tissue factor.

Purpose: Interleukin (IL)-6, a multifunctional cytokine with regulatory functions in wound healing, and several chemokines have been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD). The exact role of these chemokines, their correlation with IL-6 after primary RRD, and their association with the future development of PVR are not yet known., Methods: A multiplex immunoassay was used to determine levels of 15 different chemokines and IL-6 in subretinal fluid samples obtained during scleral buckling surgery for primary RRD. Samples from patients with preoperative uveitis, preoperative trauma, or preoperative vitreous hemorrhage were excluded. Patients who developed a redetachment due to postsurgical PVR within 2.5 months (n = 21) were compared with control subjects who had an uncomplicated retinal detachment during the overall follow-up period (n = 54). Control subjects were matched for sex, age, and storage time., Results: Levels of IL-6 (P = 0.001), MIF (P = 0.016), CCL2 (P = 0.041), CCL11 (P = 0.012), CCL17 (P = 0.003), CCL18 (P = 0.007), CCL19 (P < 0.001), CCL22 (P < 0.001), CXCL8 (P = 0.027), CXCL9 (P = 0.007), and CXCL10 (P = 0.002) were significantly higher in patients who developed postoperative PVR after primary RRD than in patients with uncomplicated retinal detachment. A significant positive correlation was observed between IL-6 and both CCL22 (r = 0.538; P < 0.0001) and CXCL8 (r = 0.645; P < 0.0001)., Conclusions: Various chemokines and IL-6 are upregulated in patients in whom fibrotic membranes develop after primary RRD repair and may therefore be involved in the future development of postoperative PVR.