Table 1.

Summary of randomized clinical studies using fish oil for inflammatory eye diseases

Authors [ref.]	Study and participants' characteristics	n-3 fatty acids (EPA + DHA + DPA) dose and duration	Results
a Dry eye disease
Oleniket al.[12]	Randomized double-blinded placebo-controlled study (totaln = 61, M + F, mean age 54–58 y/o)	1.27 g/day for 3 months	Improvement in OSDI, TBUT, Schirmer's test, and lid margin inflammation
Bhargavaet al.[14]	Randomized double-blinded placebo-controlled study (totaln = 496, contact lens wearers with contact lens wearing time 1.4–4 years)	1.2 g/day for 6 months	Improvement in symptom score, lens wear comfort level, TBUT, Nelson grade in conjunctival cytology Only small increase in Schirmer's test
Bhargavaet al. [15]	Randomized double-blinded placebo-controlled study (totaln = 456, computer users more than 3 h/day, mean age 23–24 y/o)	1.2 g/day for 3 months	Improvement in symptoms, TBUT, Nelson grade in conjunctival cytology, goblet cell density, and Schirmer's test
Bhargava et al. [16]	Randomized double-blinded placebo-controlled study (totaln = 522, visual display terminal users, mean age 29–30 y/o)	2.4 g/day for 45 days	Improvement in symptoms, TBUT, Nelson grade in conjunctival cytology No significant change in Schirmer's test
Bhargava et al. [58]	Randomized double-blinded placebo-controlled study (totaln = 518, M + F, mean age 39–40 y/o)	1 g/day for 3 months	Improvement in symptoms, TBUT, and Schirmer's test
Kangari et al. [59]	Randomized double-blinded placebo-controlled study (totaln = 64, M + F, mean age 61–62 y/o)	0.6 g/day for 30 days	Improvement in OSDI, TBUT, and Schirmer's test
Kawakita et al. [60]	Randomized double-blinded placebo-controlled study (totaln = 27, M + F, mean age 52–53 y/o)	1.785 g/day for 12 weeks	Improvement in symptoms, TBUT, and Rose Bengal ocular surface staining score No change in Schirmer's test
Epitropoulos et al. [61]	Randomized double-blinded placebo-controlled study (totaln = 105, M + F, mean age 57 y/o)	2.24 g/day for 3 months	Improvement in tear osmolarity, TBUT, OSDI, MMP-9, and Omega-3 Index
Bhargava et al. [17]	Randomized double-blinded placebo-controlled study (totaln = 130, patients with rosacea, M + F, mean age 48–49 y/o)	2.4 g/day for 6 months	Improvement in symptoms, TBUT, MGS, and Schirmer's test
b Age-related macular degeneration
AREDS2 Research Group [33]	AREDS2, randomized double-blinded placebo-controlled study (totaln = 4,203, M + F, mean age 74 y/o)	1 g/day for 5 years in addition to AREDS formulation (as control)	Addition of DHA + EPA to the AREDS formulation did not further reduce risk of progression to advanced AMD
Dawczynski et al. [36]	LUTEGA, randomized double-blinded placebo-controlled study (totaln = 172, M + F, mean age 70 y/o)	0.13 g/day with lutein and zeaxanthin for 1 year	Improvement in macular pigment (MPOD) and visual acuity (BCVA)
NAT-2 study group [46, 51]	NAT-2, randomized double-blinded placebo-controlled study (totaln = 263, M + F, mean age 74 y/o)	1.11 g/day for 3 years	Overall, the treatment group has the same incidence of CNV as the placebo group; however, patients steadily achieving the highest tertile of EPA + DHA levels in RBCM had a significantly lower risk of CNV developing over 3 years
Rezende et al. [43]	Randomized open-label (totaln = 40, wet-AMD patients receiving anti-VEGF treatment)	0.6 mg/day for 6 months	n-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-a levels

EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; AMD, age-related macular degeneration; OSDI, ocular surface disease index; TBUT, tear breakup time; y/o, years old; MMP-9, matrix metalloproteinase-9; MGS, meibomian gland score; AREDS2, Age-Related Eye Disease Study 2; NAT-2, Nutritional AMD Treatment 2; MPOD, macular pigment optical density; BCVA, best-corrected visual acuity; RBCM, red blood cell membrane; CNV, choroidal neovascularization; VEGF, vascular endothelial growth factor.