Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial Supplements and Age-Related Macular Degeneration

Wed, 15 May 2013 00:00:00 GMT

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, randomized, 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 randomized 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 randomization 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

clinicaltrials.gov Identifier: NCT00345176

Do Findings on Routine Examination Identify Patients at Risk for Primary Open-Angle Glaucoma? The Rational Clinical Examination Systematic Review Patients at Risk for Primary Open-Angle Glaucoma

Hollands H, Johnson D, Hollands S, et al. — Wed, 15 May 2013 00:00:00 GMT

Importance

Glaucoma is the second leading cause of blindness worldwide, and its insidious onset is often associated with diagnostic delay. Since glaucoma progression can often be effectively diminished when treated, identifying individuals at risk for glaucoma could potentially lead to earlier detection and prevent associated vision loss.

Objective

To quantify the diagnostic accuracy of examination findings and relevant risk factors in identifying individuals with primary open-angle glaucoma (POAG), the most common form of glaucoma in North America.

Data Sources

Structured Medline (January 1950-January 2013) search and a hand search of references and citations of retrieved articles yielding 57 articles from 41 studies.

Study Selection

Population-based studies of high-level methods relating relevant examination findings of cup-to-disc ratio (CDR), CDR asymmetry, intraocular pressure (IOP), and demographic risk factors to the presence of POAG.

Results

The summary prevalence of glaucoma in the highest-quality studies was 2.6% (95% CI, 2.1%-3.1%). Among risk factors evaluated, high myopia (≥6 diopters; odds ratio [OR], 5.7; 95% CI, 3.1-11) and family history (OR, 3.3; 95% CI, 2.0-5.6) had the strongest association with glaucoma. Black race (OR, 2.9; 95% CI, 1.4-5.9) and increasing age (especially age >80 years; OR, 2.9; 95% CI, 1.9-4.3) were also associated with an increased risk. As CDR increased, the likelihood for POAG increased with a likelihood ratio (LR) of 14 (95% CI, 5.3-39) for CDR of 0.7 or greater. Increasing CDR asymmetry was also associated with an increased likelihood for POAG (CDR asymmetry ≥0.3; LR, 7.3; 95% CI, 3.3-16). No single threshold for CDR or asymmetry ruled out glaucoma. The presence of a disc hemorrhage (LR, 12; 95% CI, 2.9-48) was highly suggestive of glaucoma, but the absence of a hemorrhage was nondiagnostic (LR, 0.94; 95% CI, 0.83-0.98). At the commonly used cutoff for high IOP (≥22), the LR was 13 (95% CI, 8.2-17), while lower IOP made glaucoma less likely (LR, 0.65; 95% CI, 0.55-0.76). We found no studies of screening examinations performed by generalist physicians in a routine setting.

Conclusions and Relevance

Individual findings of increased CDR, CDR asymmetry, disc hemorrhage, and elevated IOP, as well as demographic risk factors of family history, black race, and advanced age are associated with increased risk for POAG, but their absence does not effectively rule out POAG. The best available data support examination by an ophthalmologist as the most accurate way to detect glaucoma.

JAMA: Ophthalmology Topic Collection

Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial Supplements and Age-Related Macular Degeneration

Do Findings on Routine Examination Identify Patients at Risk for Primary Open-Angle Glaucoma? The Rational Clinical Examination Systematic Review Patients at Risk for Primary Open-Angle Glaucoma