GLA & EPA / DHA Blend Reduces Inflammatory Marker in Dry Eye

Dry Eye Syndrome (DES) and Fatty Acids

A wide range of anti-inflammatory therapies have been investigated to reduce DES, including the use of supplements containing the omega-6 fatty acid gamma linolenic acid (GLA), and the omega-3 fatty acids eicosapentaenoic and docosahexaenoic (EPA and DHA).

Supplements providing GLA have been shown to increase the concentration of anti-inflammatory prostaglandin E1 in tears, and to reduce inflammation of the ocular surface as shown by a significant decrease in the inflammatory marker human leukocyte antigen-DR (HLA-DR) in conjunctival epithelial cells. HLA-DR class II antigen is usually expressed by antigen-presenting cells with major histocompatibility complex (MHC) on their surfaces such as dendritic cells and macrophages.

The fatty acids EPA and DHA also have anti-inflammatory action believed to result from the synthesis of prostaglandin E3 and leukotriene B5. Leukotriene B5 inhibits the conversion of arachidonic acid to potentially harmful inflammatory mediators, prostaglandin E2 and leukotriene B4.

Combining GLA and EPA/DHA in DES

The efficacy of combining GLA and EPA/DHA has been reported in an animal model of DES, where only the combined fatty acids (versus GLA or EPA/DHA alone) reduced the expression of MHC II and inhibited the production of inflammatory cytokines (1). In a pilot trial, 3-months of treatment with the fatty acid combination suggested a beneficial effect on the clinical signs of ocular dryness (2).

The objectives of the present controlled trial were to investigate the effect of omega-6 and omega-3 supplementation on HLA-DR inflammatory marker in conjunctival cells, and to determine the impact on signs and symptoms in patients with DES.

Study Design

138 eligible adult patients with mild to moderate DES were randomized to receive placebo or treatment supplement containing omega-3 and omega-6 fatty acids, vitamins and zinc 3 times daily for 3 months. Impression cytology was performed at baseline and 3 months to assess the percentage of cells expressing

HLA-DR and to evaluate fluorescence intensity, an alternate measure of HLA-DR. Signs of dry eye (Schirmer, TBUT, fluorescein and lissamine staining) were evaluated; Symptoms were evaluated via a quality of life questionnaire. Statistical analyses were performed on the full analysis set, and on those patients who completed the trial (per-protocol set or PPS).

Results

Of the patients randomized, 121 with available impression cytology were included in the full analysis set. Of those 121 patients, 106 with no major protocol deviations comprised the PPS.

In the PPS, there was a significant reduction the % of HLA-DR positive cells in the fatty acids group compared to placebo (p = 0.021). Expression of HLA-DR as measured by fluorescence intensity was also reduced in the fatty acids group of the full analysis set (p = 0.041) and in the PPS compared to placebo (p = 0.017). No significant difference between groups was found in signs and symptoms, though there was a tendency toward improvement in the fatty acids group.

Comments

The authors conclude that this supplemental fatty acid combination can reduce expression of conjunctival inflammatory markers.

A discrepancy between signs and symptoms and a biological marker is very common in ocular surface disease, and highlights the need for objective endpoints like inflammatory marker assessment for an earlier and reliable evaluation of ocular surface inflammation.

References

1. Viau S, et al. Efficacy of a 2-month dietary supple-mentation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model. Graefes Arch Clin Exp Ophthalmol 247:1039–50, 2009.
2. Creuzot C, et al. Improvement of dry eye symptoms with polyunsaturated fatty acids. J Fr Ophtalmol 29:868–73, 2006.
3. Brignole-Baudouin F et al. A multicenter, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 on a conjunctival inflammatory marker in dry eye patients. Acta Ophthalmol 89:591-7, 2011.