Patients with cyclops syndrome exhibit elevated synovial fluid interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels and disorganized collagen remodelling within the lesion: A histological and molecular study.

Purpose: Cyclops syndrome is a clinically relevant complication of anterior cruciate ligament (ACL) reconstruction characterized by the formation of a fibrotic nodule (cyclops lesion) that causes extension loss and often requires a revision surgery. Biological mechanisms underlying lesion formation remain poorly understood. The purpose of this study is to characterize the tissue architecture, cellular composition, inflammatory profile and single-cell cytokine secretion patterns of patient-derived biopsies to gain mechanistic insight into disease pathogenesis. Methods: This prospective observational comparative study included three patient groups: patients undergoing revision surgery for cyclops syndrome ( Results: Histological analyses demonstrated that cyclops lesions exhibited disorganized collagen architecture, neovascularization and infiltration of immune cells. Flow cytometry identified activated FAP Conclusions: Our preliminary data from a small patient cohort show that cyclops syndrome may be observed as an active fibro-inflammatory process rather than a purely mechanical post-operative complication. Patient-derived samples revealed persistent inflammatory activity characterized by immune cell infiltration, elevated levels of pro-inflammatory mediators, and sustained activation of fibroblasts. The absence of detectable TGF-β secretion despite established fibrosis suggests that lesion persistence may be maintained through alternative fibrotic pathways (non-TGF-β/non-canonical pathways), which requires further investigation. Level of Evidence: N/A.