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Purpose: To use immunohistochemical staining to evaluate corneal inflammation and apoptosis induced after femtosecond laser incisions or manual incisions., Setting: Ophthalmology Clinic, University G. d'Annunzio, Chieti, Italy., Design: Experimental study., Methods: Ninety human cadaver corneas were cut manually or with the femtosecond laser at different energies and analyzed by immunohistochemistry after 5 minutes or 4 hours. The corneas were divided into 5 groups: untreated (Group 1), cut manually (Group 2), and treated with the femtosecond laser with increasing energies (Groups 3 to 5; 3.0 μJ, 6.0 μJ, and 15.0 μJ, respectively)., Results: At 5 minutes, increased expression of interleukin (IL)-18 was observed in the femtosecond laser groups compared with the manual group (P < .01). Interferon gamma (IFNγ) positivity was significantly higher in Groups 4 and 5 than in Group 2 and between Groups 3 and 4 (P < .05). The terminal uridine deoxynucleotidyl nick end-labeling (TUNEL) positivity increased with higher energy (Group 2 versus Group 4 and Group 2 versus Group 5; P < .05). After 4 hours, IFNγ positivity was higher in Group 5 than in Group 2 (P = .0021) and between Group 5 and Groups 3 and 4 (P < .05). No sign of IL-18 positivity was found after 4 hours in any sample. Group 5 showed significant higher TUNEL positivity than all other groups (P < .0001)., Conclusion: The femtosecond laser technique at high energies induced a higher corneal inflammatory response and a higher corneal cell apoptosis than the manual technique., Financial Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned., (Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)