# The Protective Effect of Polyunsaturated Fatty Acids against Dry Eye Disease: A Literature Review
## 3 PUFAS Supplementation and DED
### Oral Supplementation of \(\omega 3\) PUFAs for DED  
[PERSON] et al. [21] reported that oral supplementation with fish oil (EPA + DHA) and flaxseed oil for 90 days resulted in increased tear production, although there was no significant influence on the tear evaporation rate or meibum lipid composition. [PERSON] et al. [20]. also showed that the supplementation of EPA and DHA in the form of fish oil for 12 weeks improved dry eye symptoms, corneal staining score and TBUT. [PERSON] et al. [19] revealed that short-term (for 30 days) administration of EPA and DHA resulted in the improvement of symptoms of DED and tear film stability [19]. [PERSON] [53] reported that the intake of EPA and DHA for 12 weeks led to the improvement of ocular surface symptoms and contact lens tolerance [53]. [PERSON] et al. [23] also showed that oral supplementation of EPA and DHA for 6 months improved symptoms of DED, contact lens discomfort, and conjunctival epithelial metaplasia associated with contact lens wear [23]. Oral supplementation with EPA and DHA for 3 months was helpful for improving symptoms of DED, increasing tear stability, and restoring conjunctival metaplasia in patients with DED associated with visual display terminal (VDT) use [25]. Short-term (45 days) supplementation with EPA and DHA also resulted in improved dry eye symptoms, tear stability and conjunctival epithelial changes in patients with VDT-associated DED [24]. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Study** & **Design** & **Level (of Evidence) * & **Sample Size** & **Daily Dose** & **Duration** & **Objective and Subjective Study Outcomes** \\ \hline \begin{tabular}{c} [PERSON] et al. \\ [51] (2003) \\ (RCT) \\ [17] (2005) \\ (2008) \\ \end{tabular} & Randomized & I & 26 & \begin{tabular}{c} 57 mg LA + \\ 30 mg GLA \\ \end{tabular} & 45 days & Reduced ocular surface inflammation, \\ \begin{tabular}{c} [PERSON] et al. \\ [17] (2005) \\ \end{tabular} & RCT & I & 40 & \
\begin{tabular}{c} 224 mg LA + \\ 30 mg GLA \\ \end{tabular} & 30 days & Increased tear PGE1 levels, Improved \\
\begin{tabular}{c} [PERSON] et al. [18] \\ (2008) \\ \end{tabular} & RCT & I & 76 & 300 mg GLA & 6 months & Improved contact lens comfort \\ \hline \hline \end{tabular}
* The level of evidence was rated according to the guidelines of the American Academy of Ophthalmology, based on the scale introduced by the Oxford Centre for Evidence-Based Medicine [52].  
\end{table} 
Table 1: Summary of the studies on the efficacy of \(\omega 6\) PUFAs on DED. [PERSON] et al. [54] revealed that oral administration of EPA and DHA for 90 days provided neuroprotection for the corneal sub-basal nerve plexus in correlation with a restoration of tear homeostasis [54]. For DED associated with type 2 diabetes mellitus, oral \(\omega\)3 PUFA supplementation improved the symptoms of DED, Schirmer score, TBUT, and restored conjunctival epithelial metaplasia [55]. In comparison between two forms of \(\omega\)3 supplements, [PERSON] et al. [56] revealed that the phospholipid form (krill oil) might be more advantageous than the triacylglycerlyceride form (fish oil) with additional improvements in ocular surface symptoms and the reduction of tear inflammatory cytokine IL-17\(\alpha\) levels, although both forms resulted in improved tear osmolarity and stability [56]. [PERSON] et al. [57] reported that oral \(\omega\)3 supplementation (1.2 g of a triglyceride formulation) improved the Schirmer score in DED after laser in situ keratomileusis. The intake of \(\omega\)3 PUFAs also accelerated epithelial healing, improved TBUT, and facilitated visual recovery after photorefractive keratectomy [58]. Oral supplementation of \(\omega\)3 PUFAs was associated with additional improvements in tear stability and osmolarity as well as symptoms associated with DED after phacoemulsification surgery [59]. [PERSON] et al. [60] demonstrated that oral supplementation of EPA and DHA for 2 months might improve ocular surface symptoms and inflammation, rather than tear secretion, in DED after cataract surgery.