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Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease characterized by corneal endothelial cell (CEC) loss and guttae formation. Elevated levels of Transforming Growth Factor-Beta 1 and 2 (TGF-β1/-β2) have been reported in the aqueous humor (AH) of FECD patients and have been implicated with abnormal extracellular matrix (ECM) production, endothelial-to-mesenchymal transition (EndoMT), the unfolded protein response, and cell death. However, how TGF-β signaling affects cell migration in FECD remains to be elucidated. In this study, we found that TGF-β2 levels were significantly elevated in the AH of FECD patients compared to controls. We performed bulk RNA sequencing on FECD CECs treated with TGF-β1 or TGF-β2 and identified the epithelial-to-mesenchymal (EMT) pathway as one of the top dysregulated pathways. We found that TGF-β1 and TGF-β2 increased EMT markers, filamentous-actin (F-actin) expression and produced more EMT-like phenotype in FECD and control CECs. We also observed that TGF-β1 and TGF-β2 significantly increased FECD CEC migration speed as detected by scratch assay and individual cell tracking and promoted individual cellular migration behavior. This study provides novel insight into FECD pathogenesis and how increased TGF-β signaling promotes EndoMT and alters cellular migration in FECD CECs.

Objectives: Osteochondral lesions (OCLs) are commonly seen in the ankle and knee joints, and present difficult challenges for treatment. Evaluating the effectiveness of a treatment is dependent on how well constructed, content specific, reliable, and responsive the outcome measures used are. Currently, a considerable variety of outcome scores are used to assess the treatment effect of OCLs. The purpose of this study was to compare the frequency of validated outcome scores utilized in the ankle versus knee literature. Methods: A computerized search of multiple electronic databases was performed for all clinical studies from 2011 to 2020 assessing treatment outcome of ankle and knee OCLs. Eligible studies were independently screened by two reviewers. Outcome scores used in each eligible study were recorded and the overall frequency calculated. Correlation coefficients were used to determine if there was an association between use of validated outcome score with journal impact factor, publication year, or study level of evidence. Results: A total of 75 eligible ankle OCL studies were identified, with 27 different outcome scores utilized. The most frequently used scores were the American Orthopaedic Foot and Ankle Society (AOFAS) Clinical Rating Systems (47.7%), Visual Analog Scale (VAS) (34.4%), and Foot and Ankle Outcome Score (FAOS) (6.3%). Validated outcome scores were used in only 14.7% of all ankle OCL studies. There was no correlation between the use of validated outcome scores and journal impact factor (p=0.72), publication year (p=0.45), or level of evidence (p=0.66). A total of 239 eligible knee OCL studies were identified, with 34 different outcome scores utilized. The most frequently used scores were the International Knee Documentation Committee subjective knee forms (IKDC) (33.2%), Knee injury and Osteoarthritis Outcome Score (KOOS) (19.8%), and Tegner Activity Scale (TAS) (17.1%). Validated outcome scores were utilized in 87.4% of all knee OCL studies, compared to 14.7% in ankle OCL studies (p<0.001). There was no correlation between the use of validated outcome scores and journal impact factor (p=0.19), publication year (p=0.58), or level of evidence (p=0.62). Conclusions: Validated outcome scores were more frequently utilized in knee OCL studies compared to ankle OCL studies. Nearly half the ankle OCL studies utilized the AOFAS score despite the score not being shown to be valid or reliable. The extremely low frequency of validated scores used within the ankle literature may limit how well treatment effectiveness in ankle OCLs is appropriately evaluated.