{"doi":"10.3389/fopht.2024.1356957","title":"Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy","abstract":"Introduction: Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD. Methods: We examined plasma levels of TNF-α and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-α and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers. Results: There were 97 GA, 199 iAMD patients and 139 controls. TNF-α was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p<0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p<0.01. There was a significant positive correlation between TNF-α and VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and VEGF in any group. Discussion: These findings suggest TNF-α and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and VEGF may function as systemic biomarkers for disease development.","journal":"Frontiers in Ophthalmology","year":2024,"id":462950,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":351431,"name":"Brandie D. Wagner","orcid":"0000-0002-2745-0103","position":1,"is_corresponding":false},{"id":714165,"name":"Jennifer L. Patnaik","orcid":"0000-0002-0375-0187","position":2,"is_corresponding":false},{"id":749862,"name":"Naresh Mandava","orcid":"0000-0003-3251-6469","position":3,"is_corresponding":false},{"id":750519,"name":"Marc T. Mathias","orcid":null,"position":4,"is_corresponding":false},{"id":913430,"name":"Niranjan Manoharan","orcid":"0000-0001-5746-6854","position":5,"is_corresponding":false},{"id":1112811,"name":"Talisa E. de Carlo","orcid":"0000-0001-7289-1509","position":6,"is_corresponding":false},{"id":1112812,"name":"Ramya Gnanaraj","orcid":"0000-0002-8559-7963","position":7,"is_corresponding":false},{"id":311040,"name":"Anne M. Lynch","orcid":"0000-0001-6508-8136","position":8,"is_corresponding":false},{"id":672414,"name":"Alan G. Palestine","orcid":"0000-0001-6361-6767","position":9,"is_corresponding":false},{"id":1112810,"name":"Vivian Rajeswaren","orcid":"0000-0001-7654-0984","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:04:24.680035Z","pmid":"38984140","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}