***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A ( VEGF-A ) levels in patients with exudative age-related macular degeneration ( wet AMD ) receiving intravitreal anti-VEGF treatment .  DESIGN Prospect i ve , r and omized , open-label , single-center , clinical trial , consecutive interventional case series . METHODS The study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole . Twenty wet AMD patients being treated with anti-VEGF  were r and omized to daily supplementation of antioxidants , zinc , and carotenoids with omega-3 fatty acids ( docosahexaenoic acid and eicosapentaenoic acid ; group 1 , n = 10 ) or without omega-3 fatty acids ( group 2 , n = 10 ) . They were compared with an anti-VEGF treatment-naïve wet AMD group ( group 3 , n = 10 ) and an epiretinal membrane or macular hole group ( group 4 , n = 10 ) . Primary outcome was vitreal VEGF-A levels ( at the time of anti-VEGF injection ) . Secondary outcomes were plasma VEGF-A and central foveal thickness .  Patients with new  submacular hemorrhage  or any other treatment within 3 months were excluded . Final analyses included 9 , 6 , 7 , and 8 patients in groups 1 through 4 , respectively . RESULTS Patients receiving omega-3s ( group 1 ) had significantly lower levels of vitreal VEGF-A ( 141.11 ± 61.89 pg/mL ) when compared with group 2 ( 626.09 ± 279.27 pg/mL ; P = .036 ) and group 3 ( 735.48 ± 216.43 pg/mL ; P = .013 ) , but similar levels to group 4 ( 235.81 ± 33.99 pg/mL ; P=.215 ) . All groups showed similar values for plasma VEGF-A and central foveal thickness measurements . CONCLUSIONS This study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more IMPORTANCE It has been shown that the functionality of the macula lutea depends on the nutritional uptake of lutein and zeaxanthin and that it is inversely associated with the risk of age-related macular degeneration ( AMD ) . Additionally , ω-3 long-chain polyunsaturated fatty acids ( LC-PUFAs ) may also be protective . OBJECTIVE To investigate the effect of a 12-month intervention with macular xanthophylls and ω-3 LC-PUFAs on xanthophylls and fatty acids in plasma , antioxidant capacity , and optical density of the macular pigment of patients with nonexudative AMD . DESIGN The LUTEGA study was a r and omized , double-blind , placebo-controlled , parallel clinical trial that was conducted for 12 months . SETTING University Eye Hospital and Institute of Nutrition , Friedrich Schiller University Jena , Germany . PARTICIPANTS A total of 172 individuals with nonexudative AMD . INTERVENTION Individuals were enrolled and r and omly divided as follows : placebo group , group 1 ( a capsule containing 10 mg of lutein , 1 mg of zeaxanthin , 100 mg of docosahexaenoic acid , and 30 mg of eicosapentaenoic acid administered each day ) , and group 2 ( same substances but twice the dose used in group 1 ) . One hundred forty-five participants completed the study successfully . MAIN OUTCOME MEASURES Plasma xanthophyll concentrations and fatty acid profiles , optical density of the macular pigment , and antioxidant capacity in plasma ( 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [ Trolox ] equivalent antioxidant capacity and photochemiluminescence ) . RESULTS The concentrations of the administered carotenoids in plasma as well as the optical density of the macular pigment increased significantly in the groups r and omized to receive supplementary macular xanthophylls and ω-3 LC-PUFAs after 1 month of intervention and remained at this level through the end of the study . Use of the double dose result ed in a beneficial alteration of the fatty acid profile in the plasma of patients with AMD in comparison with the dose in group 1 . The lipophilic antioxidant capacity in plasma was significantly elevated with the intervention . CONCLUSIONS AND RELEVANCE A supplement containing a fixed combination of lutein , zeaxanthin , and ω-3 LC-PUFAs during 12 months significantly improved plasma antioxidant capacity , circulating macular xanthophyll levels , and the optical density of the macular pigment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00763659 OBJECTIVE To examine the association of dietary omega-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration ( AMD ) and central geographic atrophy ( CGA ) . METHODS Multicenter clinic-based prospect i ve cohort study from a clinical trial including Age-Related Eye Disease Study ( AREDS ) participants with bilateral drusen at enrollment . Main outcome measures were incident neovascular AMD and CGA , ascertained from annual stereoscopic color fundus photographs ( median follow-up , 6.3 years ) . We estimated nutrient and food intake from a vali date d food frequency question naire ( FFQ ) at baseline , with intake of docosahexaenoic acid ( DHA ) , eicosapentaenoic acid ( EPA ) , combined EPA and DHA , and fish as primary exposures . RESULTS After controlling for known covariates , we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA ( odds ratio [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.23 - 0.87 ) and EPA+DHA ( OR , 0.45 ; 95 % CI , 0.23 - 0.90 ) consumption . Levels of DHA  were associated with CGA in age- , sex- , and calorie-adjusted models ( OR , 0.51 ; 95 % CI , 0.26 - 1.00 ) ; however , this statistical relationship did not persist in multivariable models . CONCLUSIONS Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD . Our findings suggest that dietary omega-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA OBJECTIVE To examine whether intake of ω-3 fatty acids and fish affects incidence of age-related macular degeneration ( AMD ) in women . DESIGN A detailed food-frequency question naire was administered at baseline among 39 876 female health professionals ( mean [ SD ] age : 54.6 [ 7.0 ] years ) . A total of 38 022 women completed the question naire and were free of a diagnosis of AMD . The main outcome measure was incident AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review . RESULTS A total of 235 cases of AMD , most characterized by some combination of drusen and retinal pigment epithelial changes , were confirmed during an average of 10 years of follow-up . Women in the highest tertile of intake for docosahexaenoic acid , compared with those in the lowest , had a multivariate-adjusted relative risk of AMD of 0.62 ( 95 % confidence interval , 0.44 - 0.87 ) . For eicosapentaenoic acid , women in the highest tertile of intake had a relative risk of 0.66 ( 95 % confidence interval , 0.48 - 0.92 ) . Consistent with the findings for docosahexaenoic acid and eicosapentaenoic acid , women who consumed 1 or more servings of fish per week , compared with those who consumed less than 1 serving per month , had a relative risk of AMD of 0.58 ( 95 % confidence interval , 0.38 - 0.87 ) . CONCLUSION These prospect i ve data from a large cohort of female health professionals without a diagnosis of AMD at baseline indicate that regular consumption of docosahexaenoic acid and eicosapentaenoic acid and fish was associated with a significantly decreased risk of incident AMD and may be of benefit in primary prevention of AMD IMPORTANCE Oral supplementation with the Age-Related Eye Disease Study ( AREDS ) formulation ( antioxidant vitamins C and E , beta carotene , and zinc ) has been shown to reduce the risk of progression to advanced age-related macular degeneration ( AMD ) . Observational data suggest that increased dietary intake of lutein + zeaxanthin ( carotenoids ) , omega-3 long-chain polyunsaturated fatty acids ( docosahexaenoic acid [ DHA ] + eicosapentaenoic acid [ EPA ] ) , or both might further reduce this risk . OBJECTIVES To determine whether adding lutein + zeaxanthin , DHA + EPA , or both to the AREDS formulation decreases the risk of developing advanced AMD and to evaluate the effect of eliminating beta carotene , lowering zinc doses , or both in the AREDS formulation . DESIGN , SETTING , AND PARTICIPANTS The Age-Related Eye Disease Study 2 ( AREDS2 ) , a multicenter , r and omized , double-masked , placebo-controlled  phase 3 study with a 2 × 2 factorial design , conducted in 2006 - 2012 and enrolling 4203 participants aged 50 to 85 years at risk for progression to advanced AMD with bilateral large drusen or large drusen in 1 eye and advanced AMD in the fellow eye . INTERVENTIONS Participants were r and omized to receive lutein ( 10 mg ) + zeaxanthin ( 2 mg ) , DHA ( 350 mg ) + EPA ( 650 mg ) , lutein + zeaxanthin and DHA + EPA , or placebo . All participants were also asked to take the original AREDS formulation or accept a secondary r and omization to 4 variations of the AREDS formulation , including elimination of beta carotene , lowering of zinc dose , or both . MAIN OUTCOMES AND MEASURES Development of advanced AMD . The unit of analyses used was by eye . RESULTS Median follow-up was 5 years , with 1940 study eyes ( 1608 participants ) progressing to advanced AMD . Kaplan-Meier probabilities of progression to advanced AMD by 5 years were 31 % ( 493 eyes [ 406 participants ] ) for placebo , 29 % ( 468 eyes [ 399 participants ] ) for lutein + zeaxanthin , 31 % ( 507 eyes [ 416 participants ] ) for DHA + EPA , and 30 % ( 472 eyes [ 387 participants ] ) for lutein + zeaxanthin and DHA + EPA  . Comparison with placebo in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD ( hazard ratio [ HR ] , 0.90 [ 98.7 % CI , 0.76 - 1.07 ] ; P = .12 for lutein + zeaxanthin ; 0.97 [ 98.7 % CI , 0.82 - 1.16 ] ; P = .70 for DHA + EPA ; 0.89 [ 98.7 % CI , 0.75 - 1.06 ] ; P = .10 for lutein + zeaxanthin and DHA + EPA ) . There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD . More lung cancers were noted in the beta carotene vs no beta carotene group ( 23 [ 2.0 % ] vs 11 [ 0.9 % ] , nominal P = .04 ) , mostly in former smokers . CONCLUSIONS AND RELEVANCE Addition of lutein + zeaxanthin , DHA + EPA , or both to the AREDS formulation in primary analyses did not further reduce risk of progression to advanced AMD . However , because of potential increased incidence of lung cancer in former smokers , lutein + zeaxanthin could be an appropriate carotenoid substitute in the AREDS formulation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00345176 Purpose : To assess the 2-year effectiveness of intravitreal ranibizumab combined with a dietary supplement rich in docosahexaenoic acid ( DHA ) plus antioxidants in 62 patients with diabetic macular edema . Methods : In a r and omized single-blind controlled study , 33 subjects ( 4 
    Output:
    
Conclusion : The findings of this systematic review will summarize current evidence of O3R for the treatment of patients with ARMD .