Combination Therapy With Diquafosol Tetrasodium and Sodium Hyaluronate in Patients With Dry Eye After Laser In Situ Keratomileusis IKUKO TODA, TAKESHI IDE, TERUKI FUKUMOTO, YOSHIYUKI ICHIHASHI, AND KAZUO TSUBOTA  PURPOSE: To evaluate the possible advantages of com- bination therapy with diquafosol tetrasodium and sodium hyaluronate for dry eye after laser in situ keratomileusis (LASIK).  DESIGN: Prospective randomized comparative trial.  METHODS: A total of 206 eyes of 105 patients who underwent LASIK were enrolled in this study. Patients were randomly assigned to 1 of 4 treatment groups according to the postoperative treatment: artificial tears, sodium hyaluronate, diquafosol tetrasodium, and a com- bination of hyaluronate and diquafosol. Questionnaire responses reflecting subjective dry eye symptoms, uncorrected and corrected visual acuity, functional visual acuity, manifest refraction, tear break-up time, fluorescein corneal staining, Schirmer test, and corneal sensitivity were examined before and 1 week and 1 month after LASIK.  RESULTS: Distance uncorrected visual acuity was significantly better in the combination group than in the hyaluronate group 1 week and 1 month after LASIK. Near uncorrected visual acuity was signifi- cantly better in the combination group than in the artifi- cial tear and diquafosol groups 1 week and 1 month after LASIK. Distance functional visual acuity improved significantly only in the combination group 1 month after LASIK. The Schirmer value in the combination group was significantly higher than that in the hyaluro- nate group at 1 month after LASIK. Subjective dry eye symptoms in the combination group improved signifi- cantly compared with those in the other groups 1 week after surgery.  CONCLUSIONS: Our results suggest that hyaluronate and diquafosol combination therapy is beneficial for early stabilization of visual performance and improvement of sub- jective dry eye symptoms in patients after LASIK. (Am J Ophthalmol 2014;157:616–622. Ó 2014 by Elsevier Inc. All rights reserved.) L ASER IN SITU KERATOMILEUSIS (LASIK) HAS BEEN established as the most popular corneal refractive surgery in the world. Patient satisfaction is usually very high because LASIK provides a high quality of vision. However, most patients experience temporary worsening of dry eye symptoms during the early postoperative period. It is well known that LASIK affects the ocular surface and tear dynamics, and dry eye is one of the most common com- plications after the procedure. 1 Traditional therapies for post-LASIK dry eye are artifi- cial tears and sodium hyaluronate eye drops, which are use- ful for temporary relief of symptoms but may be insufficient in severe and/or longstanding cases. Punctal plugs and autologous serum eye drops 2 are effective in such cases, because they preserve and supply tear components including growth factors, hormones, and vitamins that exist in normal tears 3,4 and work to maintain a healthy ocular surface. However, punctal plug occlusion results in several adverse events, including spontaneous extrusion, 5 migration, 6 pyogenic granuloma, 7 biofilm formation, 8 and corneal ulceration. 9 Autologous serum eye drops are also effective for treating post-LASIK dry eye, 10 but they are inconvenient because patients are required to visit the hos- pital every 3 months. Protective glasses with side panels have been used in combination therapy, 11 but glasses may not be desired by patients after LASIK. A new eye drop, 3% diquafosol tetrasodium ophthalmic solution (DIQUAS ophthalmic solution 3%; Santen Phar- maceutical Co Ltd, Osaka, Japan), was launched in Japan for treating dry eye. 12 This eye drop is a purinergic P2Y 2 receptor agonist, which has a novel mechanism to stimulate water and mucin secretion from conjunctival epithelial cells and goblet cells. 13,14 Clinical trials in patients with dry eye show that topical application of 3% diquafosol ophthalmic solution significantly decreases ocular surface damage, as evaluated by fluorescein and rose bengal staining, and improves subjective dry eye symptoms. 15,16 In addition, combination therapy with diquafosol tetrasodium and hyaluronate is effective in improving objective and subjective symptoms in patients with dry eye. 17 The purpose of this study was to evaluate the possible advantage of combination therapy with 3% diquafosol ophthalmic solution and 0.3% sodium hyaluronate ophthalmic solution, in comparison with monotherapy with either agent for dry eye symptoms, signs, and visual performance after LASIK. Accepted for publication Nov 15, 2013. From Minamiaoyama Eye Clinic (I.T., T.I., T.F., Y.I.); and Keio University, School of Medicine (K.T.), Tokyo, Japan. Inquiries to Ikuko Toda, Minamiaoyama Eye Clinic, 3-3-11, Kitaaoyama, Renei Aoyama Building #4, Minato-ku, Tokyo, 107-0061 Japan; e-mail: ikuko@tka.att.ne.jp 616 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2013.11.017 Ó 2014 BY ELSEVIER INC.ALL RIGHTS RESERVED.