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To compare cellular changes of donor corneal tissue after deep anterior lamellar keratoplasty (DALK) with those after penetrating keratoplasty (PKP) performed in patients with keratoconus using confocal microscopy.In this nonrandomized cross-sectional comparative study, 26 eyes received DALK and 19 eyes had PKP for moderate to advanced keratoconus. A normal age-matched group consisting of 28 eyes was considered as the control. After complete suture removal, keratocyte cell density at 3 different layers (anterior, mid stroma, and posterior), corneal thickness in the 3 groups, and the features of the interface in the DALK group were evaluated with confocal microscopy.Mean participant age was 32.4 ± 10.1, 28.5 ± 7.5, and 32.2 ± 6.4 years in the PKP, DALK, and normal groups, respectively (P = 0.15). Confocal microscopy was performed, on average, 24.6 ± 3.5 months after PKP and 19.0 ± 7.9 months after DALK (P = 0.32). The keratocyte density in the PKP group was comparable to those in the normal group in all 3 layers, whereas it was significantly reduced in the DALK group. Also, the normal reduction trend in keratocyte density from anterior to posterior stroma observed in the PKP and normal groups was not seen in the DALK group.The keratocyte density was significantly reduced, and their arrangement was profoundly altered after DALK. Such cellular changes of donor tissue after DALK can be contributed by some speculated mechanisms, including mechanical trauma to the tissue during the operation, transient dysfunction of the endothelial cells, and the presence of debris at the interface.