Dataset Information

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study.

ABSTRACT: Purpose: Large-scale protein analysis may bring important insights into molecular changes following branch retinal vein occlusion (BRVO). Using proteomic techniques this study compared aqueous humor samples from patients with BRVO to age-matched controls.

Methods: Aqueous humor samples from treatment naive patients with BRVO complicated by macular edema (n = 19) and age-matched controls (n = 18) were analyzed with label-free quantification nano liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). The severity of macular edema was measured as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Proteins were filtered by requiring quantification in at least 50% of the samples in each group without imputation of missing values. Significantly changed proteins were identified with a permutation-based calculation with a false discovery rate at 0.05.

Results: In BRVO, 52 proteins were differentially expressed. Regulated proteins were involved in cell adhesion, coagulation, and acute-phase response. Apolipoprotein C-III, complement C3, complement C5, complement factor H, fibronectin, and fibrinogen chains were increased in BRVO and correlated with CRT. Fibronectin also correlated with best corrected visual acuity (BCVA) and vascular endothelial growth factor (VEGF). Monocyte differentiation antigen CD14 (CD14) and lipopolysaccharide-binding protein (LBP) were upregulated in BRVO. Contactin-1 and alpha-enolase were downregulated in BRVO and correlated negatively with CRT.

Conclusions: Multiple proteins, including complement factors, fibrinogen chains, and apolipoprotein C-III, correlated with CRT, indicating a multifactorial response. Fibronectin correlated with BCVA, CRT, and VEGF. Fibronectin may reflect the severity of BRVO. The proinflammatory proteins CD14 and LBP were upregulated in BRVO.

SUBMITTER: Cehofski LJ

PROVIDER: S-EPMC7718822 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study.

Cehofski Lasse Jørgensen LJ Kojima Kentaro K Terao Nobuhiro N Kitazawa Koji K Thineshkumar Sasikala S Grauslund Jakob J Vorum Henrik H Honoré Bent B

Investigative ophthalmology & visual science 20201201 14

<h4>Purpose</h4>Large-scale protein analysis may bring important insights into molecular changes following branch retinal vein occlusion (BRVO). Using proteomic techniques this study compared aqueous humor samples from patients with BRVO to age-matched controls.<h4>Methods</h4>Aqueous humor samples from treatment naive patients with BRVO complicated by macular edema (n = 19) and age-matched controls (n = 18) were analyzed with label-free quantification nano liquid chromatography - tandem mass sp ...[more]

PMID: 33270842

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Project description:BackgroundBranch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach.MethodsWe detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses.ResultsIn total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group.ConclusionsOur study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.

Project description:PurposeTo assess the relationship between best-corrected visual acuity (BCVA) and anatomic features in patients with macular edema (ME) related to retinal vein occlusion (RVO).DesignPost hoc analysis of 3 clinical trials, which included verified diagnoses, protocol refractions, and the assessment of OCT and fluorescein angiography (FA) images at a masked reading center.ParticipantsPatients diagnosed with RVO-ME.MethodsCorrelation analyses were performed to determine the correlation between BCVA and macular anatomy at baseline and at 12 and 24 weeks and between changes from baseline to 12 and 24 weeks.Main outcome measuresThe correlations between BCVA and central subfield thickness (CST), ellipsoid zone (EZ) integrity, intraretinal fluid (IRF), subretinal fluid, central leakage, and ischemia were assessed.ResultsIn a total of 828 eyes with RVO-ME, the mean age, BCVA, and CST at baseline was 64.7 years, 51.1 letters, and 656.9 μm, respectively. At baseline, a moderate negative correlation was observed between BCVA and CST (r = - 0.56, P < 0.001). At weeks 12 and 24, the mean BCVA of eyes with definitely abnormal (absent) EZ was statistically significantly worse than that of eyes with normal EZ. At week 12, a moderate negative correlation was observed between changes in BCVA and changes in CST (r = - 0.35, P < 0.001), with a similar degree of association noted at week 24 (r = - 0.35, P < 0.001). At weeks 12 and 24, eyes that showed any improvement in central IRF showed a greater improvement in BCVA than eyes that showed no improvement worsening (week 12: 463 eyes, 18.3 letters vs. 177 eyes, 13.0 letters, respectively, P < 0.001) and (week 24: 332 eyes, 20.2 letters vs. 131 eyes, 13.3 letters, respectively, P < 0.001). With respect to the correlation between baseline BCVA and fluorescein leakage or capillary nonperfusion, the Pearson correlation coefficients were - 0.41 (P < 0.001) and - 0.16 (P = 0.060), respectively.ConclusionsIn addition to CST, there are important clinically relevant relationships between BCVA and both OCT and FA anatomic features in patients with RVO-ME.

Project description:Macular edema (ME) is the main cause of visual impairment in patients with retinal vein occlusion (RVO). The degree of ME affects the prognosis of RVO patients, while it lacks objective laboratory biomarkers. We aimed to compare aqueous humor samples from 28 patients with retinal vein occlusion macular edema (RVO-ME) to 27 age- and sex-matched controls by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry, so as to identify the key biomarkers and to increase the understanding of the mechanism of RVO-ME at the molecular level. Through univariate and multivariate statistical analyses, we identified 60 metabolites between RVO-ME patients and controls and 40 differential metabolites in mild RVO-ME [300 μm ≤ central retinal thickness (CRT) < 400 μm] patients compared with severe RVO-ME (CRT ≥ 400 μm). Pathway enrichment analysis showed that valine, leucine, and isoleucine biosynthesis; ascorbate and aldarate metabolism; and pantothenate and coenzyme A biosynthesis were significantly altered in RVO-ME in comparison with controls. Compared with mild RVO-ME, degradation and biosynthesis of valine, leucine, and isoleucine; histidine metabolism; beta-alanine metabolism; and pantothenate and coenzyme A biosynthesis were significantly changed in severe RVO-ME. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that adenosine, threonic acid, pyruvic acid, and pyro-L-glutaminyl-l-glutamine could differentiate RVO-ME from controls with an area under the curve (AUC) of >0.813. Urocanic acid, diethanolamine, 8-butanoylneosolaniol, niacinamide, paraldehyde, phytosphingosine, 4-aminobutyraldehyde, dihydrolipoate, and 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide had an AUC of >0.848 for distinguishing mild RVO-ME from severe RVO-ME. Our study expanded the understanding of metabolomic changes in RVO-ME, which could help us to have a good understanding of the pathogenesis of RVO-ME.

Project description:IntroductionRanibizumab and aflibercept are anti-vascular endothelial growth factor agents licensed for the treatment of visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). The aim of this study was to estimate, from a UK healthcare payer's perspective, the cost-effectiveness of ranibizumab versus aflibercept in this indication.MethodsA Markov model was used to simulate the outcomes and costs of treating BRVO. Patient baseline characteristics and efficacy data for ranibizumab were obtained from the BRAVO trial. The relative efficacy of aflibercept was derived from a published network meta-analysis. Injection frequencies were derived from ranibizumab and aflibercept studies included in the network meta-analysis. Health states were defined by increments of 10 letters in best corrected visual acuity (BCVA). Patients could gain or lose a maximum of two health states between cycles. The first cycle was 6 months, followed by monthly cycles. Different utility values were assigned to the better-seeing and worse-seeing eyes based on BCVA. A 2-year treatment time frame and a lifetime time horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to test the robustness of the model.ResultsThe lifetime cost per patient treated was £15,273 with ranibizumab and £17,347 with aflibercept. Ranibizumab was dominant over aflibercept, producing incremental health gains of 0.0120 quality-adjusted life-years (QALYs) and cost savings of £2074. Net monetary benefit for ranibizumab at a willingness-to-pay threshold of £20,000/QALY was £2314. Sensitivity analyses showed that the results were robust to variations in model parameters.ConclusionsRanibizumab provides greater health gains at a lower overall cost than aflibercept in the treatment of visual impairment due to macular edema secondary to BRVO. Ranibizumab is therefore cost-effective from a UK healthcare payer's perspective.FundingNovartis Pharma AG, Basel, Switzerland.

Dataset Information

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study.

Publications

Aqueous Fibronectin Correlates With Severity of Macular Edema and Visual Acuity in Patients With Branch Retinal Vein Occlusion: A Proteome Study.

Similar Datasets

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