Hyaluronic acid combined with mannitol to improve protection against free-radical endothelial damage: Experimental Model Jose ´ I. Belda, MD, PhD, Alberto Artola, MD, PhD, Marı ´a D. Garcı ´a-Manzanares, MD, PhD, Consuelo Ferrer, PhD, Hazem E. Haroun, MD, PhD, Ahmed Hassanein, MD, PhD, Vincent Baeyens, PhD, Gonzalo Munoz, MD, PhD, Jorge L. Alio ´, MD, PhD Purpose: To evaluate the protective properties of combined sodium hyaluronate 2% and mannitol 0.5% (Visiol) on the corneal endothelium in the presence of oxidative stress induced by hydrogen peroxide (H 2 O 2 ). Setting: Instituto Oftalmolo ´ gico de Alicante, Universidad Miguel Herna ´ ndez, Alicante, Spain. Methods: This was an exploratory randomized controlled parallel-group, masked- assessor study of 3 sodium hyaluronate-based ophthalmic viscosurgical devices (OVDs): Visiol, Healon (sodium hyaluronate 1%), and Viscoat (sodium hyaluronate 3%–chondroitin sodium 4%). The OVDs were tested for protective effects on the endothelium following oxidative stress induced by H 2 O 2 at increased concentrations: control (lactated Ringer’s solution), 1 mM, 10 mM, and 100 mM. Groups without OVD were used as controls at the same concentrations of peroxide. Each animal received the same treatment in both eyes (10 eyes per group). Endothelial cell lesion was assessed using the Janus green photometry absorbance technique. Results: At 10 mM peroxide concentration, the value of endothelial cell lesion was significantly lower in the Visiol (16.8%, P Z .0056), Healon (22.2%, P Z .0302), and Viscoat (21.6%, P Z .0336) groups than in the control group (29.4%, no OVD). There was a trend in favor of Visiol to more efficiently reduce cell lesions of the endothelium, than Healon (P Z .055) and Viscoat (P Z .1013). Values of endothelial cell lesion at peroxide concentrations of 1 mM and 100 mM showed the same trends than those observed at 10 mM. Conclusions: All of the OVDs tested efficiently reduced endothelial lesions against free radicals compared with the control group in which no OVD was used. The following sequence for the efficacy of endothelial cell protection was established: Visiol O Viscoat O Healon O no OVD. J Cataract Refract Surg 2005; 31:1213–1218 ª 2005 ASCRS and ESCRS C ataract surgery is currently the most frequently performed surgical procedure. Some of the most important conditions for a successful cataract operation, as judged by the surgeons, are to maintain a deep an- terior chamber, especially to facilitate the insertion of intraocular lens, and to protect the intraocular tissues from the surgical maneuvers. These conditions are essential for microsurgical manipulation in the spatially limited anterior eye segment and ultimately serve to protect the corneal endothelial cells. 1 During phacoemulsification, the tip of the probe oscillates at an ultrasonic frequency. The ultrasonic wavelengths pass through the aqueous humor, generat- ing tiny cavitation bubbles that expand and implode liberating energy and heat. 2 The energy and heat released lead to the formation of extremely reactive free radicals that may harm the cells of the corneal endothelium. 3–7 Hydrogen peroxide (H 2 O 2 ) is nor- mally found at extremely low levels in the aqueous humor (0.025 mM). However, it has been shown that ª 2005 ASCRS and ESCRS 0886-3350/05/$-see front matter Published by Elsevier Inc. doi:10.1016/j.jcrs.2004.11.055