title: Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial.
abstract: OBJECTIVE
  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.
authors.affiliation: *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.
authors.forename: John D
authors.initials: JD
authors.lastname: Sheppard
authors.forename: Ruhi
authors.initials: R
authors.lastname: Singh
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McClellan
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Weikert
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Scoper
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Joly
authors.forename: Walter O
authors.initials: WO
authors.lastname: Whitley
authors.forename: Ekta
authors.initials: E
authors.lastname: Kakkar
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D039521:CD11c Antigen / Q000378:metabolism; D003228:Conjunctiva / Q000502:physiology; D019781:Corneal Topography; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019793:Fluorescein / Q000737:chemistry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007638:Keratoconjunctivitis Sicca / Q000188:drug therapy* / Q000378:metabolism; D008086:Lissamine Green Dyes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D010349:Patient Compliance; D013194:Staining and Labeling / Q000379:methods; D013666:Tears / Q000502:physiology; D014792:Visual Acuity / Q000502:physiology; D017965:gamma-Linolenic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D039521:CD11c Antigen; D015525:Fatty Acids, Omega-3; D006684:HLA-DR Antigens; D008086:Lissamine Green Dyes; D009883:Ophthalmic Solutions; D017965:gamma-Linolenic Acid; D019793:Fluorescein