{"doi":"10.1016/j.xops.2025.100898","title":"Supersaturated Oxygen Emulsion Mitigates Hypoxia-Driven Corneal Neovascularization after Alkali Burn","abstract":"Purpose: Alkali burn is a vision-threatening ocular emergency with no targeted acute therapy. We previously identified tissue hypoxia as a key driver and developed a perfluorodecalin-based supersaturated oxygen emulsion (SSOE) that delivers high levels of oxygen topically. In this study, we aim to investigate the role of hypoxia-inducible factor signaling in postburn sequalae and evaluate the therapeutic efficacy and timing of SSOE in treating ocular alkali burn. Design: Experimental animal study. Subjects: A total of 207 BALB/c mice were used in this study. Subjects were assigned to 6 experimental groups: naïve (n = 31), untreated or vehicle-treated controls (n = 75), and treatment groups receiving SSOE either immediately postinjury (n = 33), or with delayed initiation at 1 day (n = 26), 2 days (n = 21), or 5 days (n = 21) after alkali burn. Where possible, mice were used for multiple outcome assessments to reduce total animal use in accordance with ethical and institutional guidelines. Methods: Alkali burn was induced by applying 1M sodium hydroxide solution to the central cornea of BALB/c mice, followed by immediate or delayed (by 1, 2, or 5 days) topical application of SSOE or vehicle control daily for 14 days. Corneal opacity, neovascularization (NV), and cataract formation were assessed, and hypoxia-inducible factor 1-alpha (HIF-1α) and VEGF expression were measured. Main Outcome Measures: Corneal NV, anterior chamber (AC) inflammation, cataract formation, and HIF-1α or VEGF expression. Results: Alkali burn led to persistent HIF-1α activation in the cornea up to day 14 postinjury, which was strongly correlated with corneal NV. Immediate SSOE treatment significantly reduced corneal NV, edema, AC inflammation, cataract formation, and expression of HIF-1α and VEGF at days 14 and 28. Delayed SSOE application (up to 5 days postinjury) also improved corneal NV, edema, inflammation, and fibrosis but did not prevent cataract formation. Conclusions: Daily SSOE treatment mitigates hypoxia-driven corneal NV by inhibiting HIF-1α and VEGF signaling. Early administration offers the greatest benefit, though delayed treatment remains effective in reducing corneal damage. These findings support the potential of SSOE as a novel topical therapy for chemical eye injuries. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.","journal":"Ophthalmology Science","year":2025,"id":545932,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":474425,"name":"Elsayed Elbasiony","orcid":null,"position":1,"is_corresponding":false},{"id":1165080,"name":"Zhirong Lin","orcid":"0000-0002-8201-4902","position":2,"is_corresponding":false},{"id":1165079,"name":"Sheyda Najafi","orcid":"0000-0001-9334-6374","position":3,"is_corresponding":false},{"id":875404,"name":"Kathryn Pate","orcid":null,"position":4,"is_corresponding":false},{"id":295211,"name":"Jia Yin","orcid":"0000-0003-1340-6758","position":5,"is_corresponding":false},{"id":769108,"name":"Asmaa A. Zidan","orcid":"0000-0001-8248-8190","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:27.751050Z","pmid":"40933853","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":[]}