A post-HSCT ocular surface “Window of Opportunity for Pre-emptive ocular treatment (WinOP)” shows early inflammatory activation and an oGVHD-like molecular subset

PURPOSE: To describe the early post-hematopoietic stem cell transplant (HSCT) "window of opportunity for pre-emptive ocular treatment" (WinOP) and assess whether WinOP patients show an ocular GVHD (oGVHD)-like profile before meeting criteria for definite oGVHD. METHODS: Observational case series including WinOP (≥2 early ocular findings but not definite oGVHD by ICCGVHD), ICCGVHD-defined definite oGVHD, and healthy controls. Ocular surface washings underwent 38-plex profiling; analytes were summarized into prespecified immune/trophic composite axes and an oGVHD-likeness score. RESULTS: Sixty-seven subjects were enrolled; 50 provided tear samples. WinOP onset was a median of 8 months post-HSCT and coincided with systemic chronic GVHD in 69%. At presentation, 25% were asymptomatic, and 25% had severe tear deficiency. With follow-up, definite oGVHD developed in 1/23 adherent versus 5/6 nonadherent WinOP patients. Innate/NFkB and myeloid-chemotaxis activity increased from Healthy to WinOP to oGVHD; the type I interferon composite was elevated in WinOP and similar to oGVHD, whereas trophic deficiency and PDGF isoform imbalance were preserved in WinOP but marked in definite oGVHD. WinOP was heterogeneous: 42% of WinOP samples were closer to oGVHD than healthy reference profile. CONCLUSIONS: These observational data substantiate WinOP as a conceptual construct: a plausible pre-definite oGVHD state in which tear inflammatory activity may precede trophic factor loss and PDGF imbalance in definite oGVHD. The findings do not establish treatment efficacy, but provide a framework for prospective testing of structured surveillance during the first 6-24 months post-HSCT, especially with systemic chronic GVHD, and early topical therapy when new symptoms and/or objective abnormalities develop.