Age-Related Eye Disease Study 2 (AREDS2) (AREDS2)

• ClinicalTrials.gov Identifier: NCT00345176
• Recruitment Status: Completed
• First Posted: June 27, 2006
• Results First Posted: December 24, 2013
• Last Update Posted: May 5, 2015
• Sponsor: National Eye Institute (NEI)
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Office of Dietary Supplements (ODS); National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): National Eye Institute (NEI)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Age-related Macular Degeneration; Cataract
• Interventions: Dietary Supplement: Lutein/zeaxanthin; Dietary Supplement: DHA/EPA; Drug: Lutein/zeaxanthin and DHA/EPA
• Enrollment: 4203

Participant Flow

Recruitment Details	Between October 2006 and September 2008 a total of 4,203 participants aged 50 - 85 years were randomized at 82 clinical sites.
Pre-assignment Details	Prior to randomization, participants had to complete the Qualification phase. They could only be randomized if they took at least 75% of the run-in medication.

Arm/Group Title	Placebo/Control	Lutein/Zeaxanthin	DHA/EPA	Lutein/Zeaxanthin + DHA/EPA
Arm/Group Description	Considered control because all participants received the AREDS formulation	lutein (10mg)/zeaxanthin (2 mg)	DHA (350 mg)/EPA (650 mg)	lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
Period Title: Overall Study
Started	1012	1044	1068	1079
Completed	1007	1038	1062	1069
Not Completed	5	6	6	10

Baseline Characteristics

Arm/Group Title		Placebo/Control	Lutein/Zeaxanthin	DHA/EPA	Lutein/Zeaxanthin + DHA/EPA	Total
Arm/Group Description		Considered control because all participants received the AREDS formulation	lutein (10mg)/zeaxanthin (2 mg)	DHA (350 mg)/EPA (650 mg)	lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)	Total of all reporting groups
Overall Number of Baseline Participants		1012	1044	1068	1079	4203
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Participants
	Number Analyzed	1012 participants	1044 participants	1068 participants	1079 participants	4203 participants
		74; (68 to 79)	74; (68 to 79)	74; (68 to 79)	75; (68 to 79)	74; (68 to 79)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1012 participants	1044 participants	1068 participants	1079 participants	4203 participants
	Female	548 54.2%	596 57.1%	603 56.5%	641 59.4%	2388 56.8%
	Male	464 45.8%	448 42.9%	465 43.5%	438 40.6%	1815 43.2%

Outcome Measures

1. Primary Outcome

Title	Development of Advanced AMD in People at Moderate to High Risk for Progression.
Description	Defined as central geographic atrophy or retinal features of choroidal neovascularization detected on central grading of the stereoscopic fundus photographs or a history of treatment for advanced AMD after study enrollment.
Time Frame	5 years of follow-up

Outcome Measure Data

Analysis Population Description

Intention to Treat. Participants lost to follow-up during the course of the study were censored at the time of last contact.

Arm/Group Title	Placebo/Control	Lutein/Zeaxanthin	DHA/EPA	Lutein/Zeaxanthin + DHA/EPA
Arm/Group Description:	Considered control because all participants received the AREDS formulation	lutein (10mg)/zeaxanthin (2 mg)	DHA (350 mg)/EPA (650 mg)	lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
Overall Number of Participants Analyzed	1007	1038	1062	1069
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	1691	1709	1749	1742
Measure Type: Number; Unit of Measure: Eyes
	493	468	507	472

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, Lutein/Zeaxanthin
	Comments	Each of the 3 active arms was compared to the placebo/control arm.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.013
	Comments	Adjusted for 3 treatment versus placebo comparisons and interim analyses
	Method	Regression, Cox
	Comments	Adjusted for baseline AMD status
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 98.7%; 0.76 to 1.07
	Estimation Comments	The reference group is placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, DHA/EPA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.013
	Comments	Adjusted for multiple comparisons
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 98.7%; 0.82 to 1.16
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, Lutein/Zeaxanthin + DHA/EPA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.013
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Adjusted for multiple comparisons
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 98.7%; 0.75 to 1.06
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Progression to Moderate Vision Loss
Description	Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization
Time Frame	5 years of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo/Control	Lutein/Zeaxanthin	DHA/EPA	Lutein/Zeaxanthin + DHA/EPA
Arm/Group Description:	Considered control because all participants received the AREDS formulation	lutein (10mg)/zeaxanthin (2 mg)	DHA (350 mg)/EPA (650 mg)	lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
Overall Number of Participants Analyzed	1007	1038	1062	1069
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	1630	1660	1694	1672
Measure Type: Number; Unit of Measure: Eyes
	515	509	519	506

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, Lutein/Zeaxanthin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.08
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, DHA/EPA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.09
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, Lutein/Zeaxanthin + DHA/EPA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.07
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Adverse Events
Description	Safety outcomes included serious adverse events and mortality.
Time Frame	5 years of follow-up

Outcome Measure Data

Analysis Population Description

Number of deaths in 5 years

Arm/Group Title	Placebo/Control	Lutein/Zeaxanthin	DHA/EPA	Lutein/Zeaxanthin + DHA/EPA
Arm/Group Description:	Considered control because all participants received the AREDS formulation	lutein (10mg)/zeaxanthin (2 mg)	DHA (350 mg)/EPA (650 mg)	lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
Overall Number of Participants Analyzed	1012	1044	1068	1079
Measure Type: Number; Unit of Measure: Participants
Mortality	81	87	96	104
Serious Adverse Events	479	484	505	519

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, Lutein/Zeaxanthin
	Comments	Comparison of Lutein/Zeaxantin versus Control for mortality
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.40
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, DHA/EPA
	Comments	Comparison of DHA/EPA versus Placebo for mortality
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.52
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Control, Lutein/Zeaxanthin + DHA/EPA
	Comments	Comparison of Lutein/Zeaxanthin + DHA/EPA versus Placebo for Mortality
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.65
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Progression to Cataract Surgery
Description	The study examined the effects of lutein/zeaxanthin on progression to cataract surgery with data collected during regular telephone contacts and the annual study visits.
Time Frame	5 years of follow-up

Outcome Measure Data

Analysis Population Description

Includes participants who were phakic in at least 1 eye at baseline

Arm/Group Title	No Lutein/Zeaxanthin	Lutein/Zeaxanthin
Arm/Group Description:	Lutein main effect - includes participants who did not receive Lutein/Zeaxanthin	Lutein main effect - includes all participants who received Lutein/Zeaxanthin
Overall Number of Participants Analyzed	1577	1578
Overall Number of Units Analyzed; Type of Units Analyzed: Eyes	3022	3005
Measure Type: Number; Unit of Measure: Eyes
	708	681

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	No Lutein/Zeaxanthin, Lutein/Zeaxanthin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.10
	Estimation Comments	[Not Specified]

5. Other Pre-specified Outcome

Title	Incident Cardiovascular Disease
Description	Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease
Time Frame	5 years of follow-up

Outcome Measure Data Not Reported

6. Other Pre-specified Outcome

Title	Cognition as Measured by a Telephone Battery
Description	Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function
Time Frame	5 years of follow-up

Outcome Measure Data Not Reported

7. Other Pre-specified Outcome

Title	Prevalence of Peripheral Changes as Measured Using OPTOS Imaging
Description	Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
Time Frame	5 years of follow-up

Outcome Measure Data Not Reported

8. Other Pre-specified Outcome

Title	Genetics for the Association of AMD and Cataract
Description	[Not Specified]
Time Frame	5 years of follow-up

Outcome Measure Data Not Reported

9. Other Pre-specified Outcome

Title	Genetics for the Progression of AMD and Cataract
Description	[Not Specified]
Time Frame	5 years of follow-up

Outcome Measure Data Not Reported

Adverse Events

Time Frame	5 years
Adverse Event Reporting Description	Adverse events reported by System Organ Class
Arm/Group Title	Placebo/Control		Lutein/Zeaxanthin		DHA/EPA		Lutein/Zeaxanthin + DHA/EPA
Arm/Group Description	Considered control because all participants received the AREDS formulation		lutein (10mg)/zeaxanthin (2 mg)		DHA (350 mg)/EPA (650 mg)		lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
All-Cause Mortality
	Placebo/Control		Lutein/Zeaxanthin		DHA/EPA		Lutein/Zeaxanthin + DHA/EPA
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	Placebo/Control		Lutein/Zeaxanthin		DHA/EPA		Lutein/Zeaxanthin + DHA/EPA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	479/1012 (47.33%)		484/1044 (46.36%)		505/1068 (47.28%)		519/1079 (48.10%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders * 1	12/1012 (1.19%)	14	11/1044 (1.05%)	11	9/1068 (0.84%)	10	7/1079 (0.65%)	7
Cardiac disorders
Cardiac Disorders * 1	96/1012 (9.49%)	122	110/1044 (10.54%)	138	119/1068 (11.14%)	144	103/1079 (9.55%)	133
Congenital, familial and genetic disorders
Congenital, familian and genetic disorders * 1	3/1012 (0.30%)	3	1/1044 (0.10%)	1	0/1068 (0.00%)	0	0/1079 (0.00%)	0
Ear and labyrinth disorders
Ear and labyrinth disorders * 1	7/1012 (0.69%)	7	3/1044 (0.29%)	3	4/1068 (0.37%)	4	1/1079 (0.09%)	1
Endocrine disorders
Endocrine disorders * 1	2/1012 (0.20%)	2	3/1044 (0.29%)	3	3/1068 (0.28%)	3	0/1079 (0.00%)	0
Eye disorders
Eye disorders * 1	3/1012 (0.30%)	3	11/1044 (1.05%)	13	4/1068 (0.37%)	6	0/1079 (0.00%)	0
Gastrointestinal disorders
Gastrointestinal disorders * 1	76/1012 (7.51%)	101	69/1044 (6.61%)	81	58/1068 (5.43%)	72	61/1079 (5.65%)	71
General disorders
General disorders and administration site conditions * 1	54/1012 (5.34%)	60	50/1044 (4.79%)	54	51/1068 (4.78%)	58	46/1079 (4.26%)	50
Hepatobiliary disorders
Hepatobiliary disorders * 1	8/1012 (0.79%)	8	16/1044 (1.53%)	16	16/1068 (1.50%)	16	17/1079 (1.58%)	18
Immune system disorders
Immune system disorders * 1	2/1012 (0.20%)	2	1/1044 (0.10%)	1	2/1068 (0.19%)	2	2/1079 (0.19%)	2
Infections and infestations
Infections and infestations * 1	90/1012 (8.89%)	109	102/1044 (9.77%)	139	103/1068 (9.64%)	144	99/1079 (9.18%)	127
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications * 1	76/1012 (7.51%)	90	62/1044 (5.94%)	72	74/1068 (6.93%)	90	66/1079 (6.12%)	84
Investigations
Investigations * 1	14/1012 (1.38%)	14	19/1044 (1.82%)	20	13/1068 (1.22%)	15	12/1079 (1.11%)	12
Metabolism and nutrition disorders
Metabolism and nutrition disorders * 1	21/1012 (2.08%)	22	16/1044 (1.53%)	18	13/1068 (1.22%)	13	23/1079 (2.13%)	25
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders * 1	66/1012 (6.52%)	77	74/1044 (7.09%)	91	71/1068 (6.65%)	85	85/1079 (7.88%)	101
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) * 1	80/1012 (7.91%)	103	88/1044 (8.43%)	111	83/1068 (7.77%)	100	92/1079 (8.53%)	112
Nervous system disorders
Nervous system disorders * 1	66/1012 (6.52%)	73	74/1044 (7.09%)	93	72/1068 (6.74%)	87	73/1079 (6.77%)	86
Psychiatric disorders
Psychiatric disorders * 1	4/1012 (0.40%)	4	5/1044 (0.48%)	5	5/1068 (0.47%)	5	9/1079 (0.83%)	11
Renal and urinary disorders
Renal and urinary disorders * 1	19/1012 (1.88%)	20	25/1044 (2.39%)	26	24/1068 (2.25%)	25	25/1079 (2.32%)	29
Reproductive system and breast disorders
Reproductive system and breast disorders * 1	9/1012 (0.89%)	11	8/1044 (0.77%)	8	12/1068 (1.12%)	13	11/1079 (1.02%)	11
Respiratory, thoracic and mediastinal disorders
Respioratory, thoracic and mediastinal disorders * 1	44/1012 (4.35%)	59	43/1044 (4.12%)	52	37/1068 (3.46%)	50	46/1079 (4.26%)	51
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders * 1	1/1012 (0.10%)	1	6/1044 (0.57%)	7	3/1068 (0.28%)	3	5/1079 (0.46%)	5
Surgical and medical procedures
Surgical and medical procedures * 1	32/1012 (3.16%)	32	29/1044 (2.78%)	31	27/1068 (2.53%)	30	32/1079 (2.97%)	32
Vascular disorders
Vascular disorders * 1	41/1012 (4.05%)	45	40/1044 (3.83%)	42	42/1068 (3.93%)	45	42/1079 (3.89%)	46
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (10.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo/Control		Lutein/Zeaxanthin		DHA/EPA		Lutein/Zeaxanthin + DHA/EPA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	717/1012 (70.85%)		791/1044 (75.77%)		759/1068 (71.07%)		791/1079 (73.31%)
Eye disorders
Dry eye † 1	55/1012 (5.43%)	62	39/1044 (3.74%)	40	64/1068 (5.99%)	70	62/1079 (5.75%)	70
Eye disorder † 1	67/1012 (6.62%)	100	67/1044 (6.42%)	96	62/1068 (5.81%)	98	82/1079 (7.60%)	152
Visual disturbance † 1	88/1012 (8.70%)	118	110/1044 (10.54%)	139	84/1068 (7.87%)	116	88/1079 (8.16%)	119
Vitreous disorder † 1	133/1012 (13.14%)	208	154/1044 (14.75%)	213	165/1068 (15.45%)	228	162/1079 (15.01%)	208
Gastrointestinal disorders
Change in bowel habit † 1	57/1012 (5.63%)	69	67/1044 (6.42%)	77	48/1068 (4.49%)	58	57/1079 (5.28%)	60
Infections and infestations
Bronchitis † 1	62/1012 (6.13%)	72	69/1044 (6.61%)	83	57/1068 (5.34%)	80	56/1079 (5.19%)	66
Upper respiratory tract infection † 1	139/1012 (13.74%)	175	150/1044 (14.37%)	190	139/1068 (13.01%)	179	138/1079 (12.79%)	173
Urinary tract infection † 1	57/1012 (5.63%)	82	75/1044 (7.18%)	103	71/1068 (6.65%)	108	73/1079 (6.77%)	96
Vascular disorders
Hypertension † 1	59/1012 (5.83%)	66	60/1044 (5.75%)	62	69/1068 (6.46%)	72	73/1079 (6.77%)	73
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Traci Clemons, PhD
• Organization: The EMMES Corporation
• Phone: 301-251-1161 ext 212
• EMail: tclemons@emmes.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bhandari S, Vitale S, Agrón E, Clemons TE, Chew EY; Age-Related Eye Disease Study 2 Research Group. Cataract Surgery and the Risk of Developing Late Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 Report Number 27. Ophthalmology. 2022 Apr;129(4):414-420. doi: 10.1016/j.ophtha.2021.11.014. Epub 2021 Nov 16.

Keenan TD, Agrón E, Mares JA, Clemons TE, van Asten F, Swaroop A, Chew EY; AREDS and AREDS2 Research Groups. Adherence to a Mediterranean diet and cognitive function in the Age-Related Eye Disease Studies 1 & 2. Alzheimers Dement. 2020 Jun;16(6):831-842. doi: 10.1002/alz.12077. Epub 2020 Apr 13.

Chew EY, Clemons TE, Agrón E, Launer LJ, Grodstein F, Bernstein PS; Age-Related Eye Disease Study 2 (AREDS2) Research Group. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. JAMA. 2015 Aug 25;314(8):791-801. doi: 10.1001/jama.2015.9677.

Writing Group for the AREDS2 Research Group, Bonds DE, Harrington M, Worrall BB, Bertoni AG, Eaton CB, Hsia J, Robinson J, Clemons TE, Fine LJ, Chew EY. Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med. 2014 May;174(5):763-71. doi: 10.1001/jamainternmed.2014.328.

Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, Clemons TE, Sangiovanni JP, Danis RP, Ferris FL 3rd, Elman MJ, Antoszyk AN, Ruby AJ, Orth D, Bressler SB, Fish GE, Hubbard GB, Klein ML, Chandra SR, Blodi BA, Domalpally A, Friberg T, Wong WT, Rosenfeld PJ, Agrón E, Toth CA, Bernstein PS, Sperduto RD. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014 Feb;132(2):142-9. doi: 10.1001/jamaophthalmol.2013.7376.

Domalpally A, Danis RP, Chew EY, Clemons TE, Reed S, Sangiovanni JP, Ferris FL 3rd; Age-Related Eye Disease Study 2 Research Group. Evaluation of optimized digital fundus reflex photographs for lens opacities in the age-related eye disease study 2: AREDS2 report 7. Invest Ophthalmol Vis Sci. 2013 Sep 5;54(9):5989-94. doi: 10.1167/iovs.13-12301.

Toy BC, Krishnadev N, Indaram M, Cunningham D, Cukras CA, Chew EY, Wong WT. Drusen regression is associated with local changes in fundus autofluorescence in intermediate age-related macular degeneration. Am J Ophthalmol. 2013 Sep;156(3):532-542.e1. doi: 10.1016/j.ajo.2013.04.031. Epub 2013 Jul 3.

Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, SanGiovanni JP, Ferris FL, Wong WT, Agron E, Clemons TE, Sperduto R, Danis R, Chandra SR, Blodi BA, Domalpally A, Elman MJ, Antoszyk AN, Ruby AJ, Orth D, Bressler SB, Fish GE, Hubbard GB, Klein ML, Friberg TR, Rosenfeld PJ, Toth CA, Bernstein P. Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. JAMA Ophthalmol. 2013 Jul;131(7):843-50. doi: 10.1001/jamaophthalmol.2013.4412.

Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013 May 15;309(19):2005-15. doi: 10.1001/jama.2013.4997. Erratum in: JAMA. 2013 Jul 10;310(2):208.

Danis RP, Domalpally A, Chew EY, Clemons TE, Armstrong J, SanGiovanni JP, Ferris FL 3rd; AREDS2 Study Group. Methods and reproducibility of grading optimized digital color fundus photographs in the Age-Related Eye Disease Study 2 (AREDS2 Report Number 2). Invest Ophthalmol Vis Sci. 2013 Jul 8;54(7):4548-54. doi: 10.1167/iovs.13-11804.

Bernstein PS, Ahmed F, Liu A, Allman S, Sheng X, Sharifzadeh M, Ermakov I, Gellermann W. Macular pigment imaging in AREDS2 participants: an ancillary study of AREDS2 subjects enrolled at the Moran Eye Center. Invest Ophthalmol Vis Sci. 2012 Sep 14;53(10):6178-86. doi: 10.1167/iovs.12-10275.

Hubbard LD, Danis RP, Neider MW, Thayer DW, Wabers HD, White JK, Pugliese AJ, Pugliese MF; Age-Related Eye Disease 2 Research Group. Brightness, contrast, and color balance of digital versus film retinal images in the age-related eye disease study 2. Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3269-82. doi: 10.1167/iovs.07-1267. Epub 2008 Apr 17.

• Responsible Party: National Eye Institute (NEI)
• ClinicalTrials.gov Identifier: NCT00345176
• Obsolete Identifiers: NCT00409513
• Other Study ID Numbers: NEI-120; N01-EY-5-0007 ( Other Grant/Funding Number: NIH ); HHS-N-260-2005-00007-C ( Other Grant/Funding Number: HHS ); CC-070025 ( Other Identifier: NIH Clinical Center ); 07-EI-0025 ( Other Identifier: National Eye Institute )
• First Submitted: June 14, 2006
• First Posted: June 27, 2006
• Results First Submitted: November 1, 2013
• Results First Posted: December 24, 2013
• Last Update Posted: May 5, 2015