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Objective: This study aimed to investigate the effects of orthosis, and additional nerve and tendon gliding exercises (NTGE) on median nerve morphology and functional status in patients with mild-to-moderate carpal tunnel syndrome (CTS) and to compare the effectiveness of proposed treatments. Methods: Twenty-seven wrists of19 patients with mild-to-moderate CTS were included in the study. They were randomized into three groups: neutral wrist orthosis alone (n=8), the combination of the orthosis with nerve gliding exercises (NGE) (n=10), and the combination of the orthosis with nerve/tendon gliding exercises (n=9). The cross-sectional area (CSA) of the median nerve (ultrasonography) and functional status (Boston carpal tunnel syndrome questionnaire and patient-specific functional scale) were evaluated at baseline and after six weeks of treatment. Results: While the functional status of all groups improved significantly (p<0.05), the CSA of the median nerve significantly decreased in the combination of the orthosis with NGE group (p<0.05). However, there were no significant differences between the treatment groups in relation to the improvement in the intraneural edema and the functional status (p<0.05). Conclusion: The 6-week orthotic treatment and additional NTGE could be effective in improving the patient's symptoms and functional status. However, the combination of a 6-week orthotic treatment and NGE could be effective in reducing intraneural edema. [ABSTRACT FROM AUTHOR]