Understanding corneal biomechanics is important to refractive or therapeutic corneal treatments. The authors studied the corneal response to variable intraocular pressure (IOP) in porcines eyes after UV collagen cross-linking (CXL), in comparison with untreated eyes.Twenty-three enucleated eyes were treated with standard CXL conditions (365 nm, 3 mW, 30 minutes), and 15 contralateral eyes served as control. Eyes (within a humidity- and temperature-monitored wet chamber) were measured by Scheimpflug corneal three-dimensional topographer. Images were obtained automatically while IOP either remained constant (14 eyes) or increased (24 eyes) by 40 mm Hg and then decreased (4-mm Hg steps). Measurements were performed immediately after treatment and 24 hours later. Corneal geometry was analyzed as a function of IOP, and whole globe stress-strain curves were calculated.Instillation of riboflavin-dextran solution reduced corneal thickness (by 281 +/- 5 microm). Cross-linking produced a 1.54x reduction in corneal thinning and 2.8x reduction in corneal apical rise with increased IOP. Anterior and posterior cornea flattened with increased IOP (less flattening in CXL eyes) and became steeper with decreased IOP. The horizontal meridian flattened significantly (P < 0.01) more than the vertical meridian. Young's modulus was higher in cross-linked eyes (1.096 +/- 0.30 kN/m(2)) than in non-cross-linked eyes (0.692 +/- 0.30 kN/m(2)). Hysteresis in nontreated eyes was also larger than in cross-linked eyes.Cross-linking stiffened porcine corneas significantly. Both experimental data and stress-strain analysis are valuable for finite element models to improve understanding of CXL and its predictability. Although differences are expected between human corneas in vivo and porcine corneas ex vivo, the results are consistent with clinical data found in patients. The apparent biomechanical anisotropy of pig corneas must be confirmed in humans.