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

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: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.