Yes-Associated Protein (YAP) Is Associated With Disease Severity and Visual Prognosis in Epiretinal Membrane

To investigate whether Yes-associated protein (YAP), a key mechanotransduction effector, is associated with disease severity, surgical difficulty, and postoperative outcomes in epiretinal membrane (ERM) and to explore its prognostic relevance.

This prospective study enrolled patients undergoing vitrectomy for ERM. Pre- and postoperative best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including ERM stage, central subfield thickness (CST), inner retinal irregularity index (IRII), and ellipsoid zone disruption (EZD), were evaluated. Surgical grading of internal limiting membrane (ILM) adherence (SGIA) was applied to assess ILM adhesion and surgical difficulty. ERMs were analyzed by immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR), and vitreous cytokines were also analyzed.

Among 152 patients with ERM stages ≥ 2, 26.3% were classified as stage 2, 42.1% as stage 3, and 31.6% as stage 4. Advancing ERM stage was significantly associated with poorer BCVA, higher SGIA grade, and worsening OCT parameters. YAP expression (by qPCR and IHC) and vitreous TGF-β1 levels progressively increased with ERM stage. YAP on IHC showed stronger associations with postoperative CST, postoperative IRII, and both pre- and postoperative EZD, whereas TGF-β1 was more strongly linked to preoperative CST and IRII. YAP also correlated independently with SGIA grade. Multivariate analysis identified YAP expression and SGIA grade as independent predictors of postoperative BCVA and visual improvement.

ILM adhesion and surgical difficulty increase with ERM progression. YAP expression reflects ERM stage, ILM adhesion-related surgical complexity, postoperative retinal remodeling, and visual outcomes, independent of TGF-β pathways. These findings highlight YAP-mediated mechanotransduction as a key contributor to ERM pathophysiology and prognosis.