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Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial

Sheppard, John D. Jr; Singh, Ruhi; McClellan, Andrew J.; Weikert, Mitchell P.; Scoper, Stephen V.; Joly, Thomas J.; Whitley, Walter O.; Kakkar, Ekta; Pflugfelder, Stephen C.

doi: 10.1097/ICO.0b013e318299549c
Clinical Science

Purpose: Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been found to decrease the production of disease-relevant inflammatory mediators that are implicated in the pathogenesis of chronic dry eye. This study evaluated the effect of a supplement containing both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe keratoconjunctivitis sicca in postmenopausal patients.

Methods: This multicenter, double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes) with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or placebo for 6 months. Disease parameters, including Ocular Surface Disease Index, Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green staining, and topographic corneal smoothness indexes (surface asymmetry index and surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks. The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured in conjunctival impression cytologies.

Results: The Ocular Surface Disease Index score improved with supplementation and was significantly lower than placebo (21 ± 4 vs. 34 ± 5) after 24 weeks (P = 0.05, n = 19 per group). The surface asymmetry index was significantly lower in supplement-treated subjects (0.37 ± 0.03, n = 15) than placebo (0.51 ± 0.03, n = 16) at 24 weeks (P = 0.005). Placebo treatment also significantly increased HLA-DR intensity by 36% ± 9% and CD11c by 34% ± 7% when compared with supplement treatment (n = 19 per group, P = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear breakup time, or corneal or conjunctival staining.

Conclusions: Supplemental GLA and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.

Clinical Trial Registration—URL: Unique identifier: NCT00883649.

Supplemental Digital Content is Available in the Text.

*Department of Ophthalmology and

Thomas R. Lee Center for Ocular Pharmacology, Eastern Virginia Medical School, Norfolk, VA;

Virginia Eye Consultants, Norfolk, VA;

§The Cullen Eye Institute,

Department of Ophthalmology, and

Ophthalmic-Ocular Surface Center, Baylor College of Medicine, Houston, TX.

Reprints: John D. Sheppard, Jr, EVMS, Department of Ophthalmology, Virginia Eye Consultants, 241 Corporate Blvd, Norfolk, VA 23502 (e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

Supported by an unrestricted research grant from ScienceBased Health and the Virginia Eye Foundation.

Presented at the Association for Research in Vision and Ophthalmology Meeting, May 6, 2012, Fort Lauderdale, FL.

J. D. Sheppard is a scientific advisor with Alcon (Fort Worth, TX), Allergan, Bausch + Lomb (Rochester, NY), Lux Biosciences (New Jersey), Merck (New Jersey), ScienceBased Health, and Vistakon (Jacksonville, FL). S. C. Pflugfelder is a consultant for Allergan, Alcon, Bausch & Lomb, GlaxoSmithKline, Mimetogen, and ScienceBased Health. He receives research funding from Allergan and Glaxo Smith Kline. R. Singh, A. J. McClellan, M. P. Weikert, S. V. Scoper, T. J. Joly, W. O. Whitley, and E. Kakkar have no financial interests related to the current study.

Received February 01, 2013

Accepted April 28, 2013

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.