Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration

Background: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of age-related macular degeneration (AMD). Objectives: The objective of this review was to assess the effects of antioxidant vitamin or mineral supplementation on the progression of AMD in people with AMD. Search methods: We searched CENTRAL (2017, Issue 2), MEDLINE Ovid (1946 to March 2017), Embase Ovid (1947 to March 2017), AMED (1985 to March 2017), OpenGrey (System for Information on Grey Literature in Europe, the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 March 2017. Selection criteria: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation (alone or in combination) to placebo or no intervention, in people with AMD. Data collection and analysis: Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We graded the certainty of the evidence using GRADE. Main results: We included 19 studies conducted in USA, Europe, China, and Australia. We judged the trials that contributed data to the review to be at low or unclear risk of bias. Nine studies compared multivitamins with placebo (7 studies) or no treatment (2 studies) in people with early and moderate AMD. The duration of supplementation and follow-up ranged from nine months to six years; one trial followed up beyond two years. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 2445 participants; 3 RCTs; moderate-certainty evidence). In people with very early signs of AMD, who are at low risk of progression, this would mean that there would be approximately 4 fewer cases of progression to late AMD for every 1000 people taking vitamins (1 fewer to 6 fewer cases). In people at high risk of progression (i.e. people with moderate AMD) this would correspond to approximately 8 fewer cases of progression for every 100 people taking vitamins (3 fewer to 13 fewer). In one study of 1206 people, there was a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence) and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; 1791 participants; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (National Eye Institute Visual Function Questionnaire) in treated compared with the non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). Six studies compared lutein (with or without zeaxanthin) with placebo. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA. People taking lutein or zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01; 6891 eyes; low-certainty evidence), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02; 6891 eyes; low-certainty evidence), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05; 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (measured with Visual Function Questionnaire) was similar between groups in one study of 108 participants (MD 1.48, 95% -5.53 to 8.49, moderate-certainty evidence). One study, conducted in Australia, compared vitamin E with placebo. This study randomised 1204 people to vitamin E or placebo, and followed up for four years. Participants were enrolled from the general population; 19% had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05, very low-certainty evidence). There were no data on neovascular AMD or geographic atrophy.There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47, low-certainty evidence). There were no data on quality of life. Five studies compared zinc with placebo. The duration of supplementation and follow-up ranged from six months to seven years. People taking zinc supplements may be less likely to progress to late AMD (OR 0.83, 95% CI 0.70 to 0.98; 3790 participants; 3 RCTs; low-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; 2442 participants; 1 RCT; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; 2442 participants; 1 RCT; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 3791 participants; 2 RCTs; moderate-certainty evidence). There were no data reported on quality of life. Very low-certainty evidence was available on adverse effects because the included studies were underpowered and adverse effects inconsistently reported. Authors' conclusions: People with AMD may experience some delay in progression of the disease with multivitamin antioxidant vitamin and mineral supplementation. This finding was largely drawn from one large trial, conducted in a relatively well-nourished American population. We do not know the generalisability of these findings to other populations. Although generally regarded as safe, vitamin supplements may have harmful effects. A systematic review of the evidence on harms of vitamin supplements is needed. Supplements containing lutein and zeaxanthin are heavily marketed for people with age-related macular degeneration but our review shows they may have little or no effect on the progression of AMD

Omega 3 fatty acids for preventing or slowing the progression of age-related macular degeneration.

BACKGROUND: Evidence from animal models and observational studies in humans has suggested that there is an inverse relationship between dietary intake of omega 3 long-chain polyunsaturated fatty acids (LCPUFA) and risk of developing age-related macular degeneration (AMD) or progression to advanced AMD. OBJECTIVES: To review the evidence that increasing the levels of omega 3 LCPUFA in the diet (either by eating more foods rich in omega 3 or by taking nutritional supplements) prevents AMD or slows the progression of AMD. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2015), EMBASE (January 1980 to February 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 February 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where increased dietary intake of omega 3 LCPUFA was compared to placebo or no intervention with the aim of preventing the development of AMD, or slowing its progression. DATA COLLECTION AND ANALYSIS: Both authors independently selected studies, assessed them for risk of bias and extracted data. One author entered data into RevMan 5 and the other author checked the data entry. We conducted a meta-analysis for one primary outcome, progression of AMD, using a fixed-effect inverse variance model. MAIN RESULTS: We included two RCTs in this review, in which 2343 participants with AMD were randomised to receive either omega 3 fatty acid supplements or a placebo. The trials, which had a low risk of bias, were conducted in the USA and France. Overall, there was no evidence that people who took omega 3 fatty acid supplements were at decreased (or increased risk) of progression to advanced AMD (pooled hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.84 to 1.10, high quality evidence). Similarly, people taking these supplements were no more (or less) likely to lose 15 or more letters of visual acuity (USA study HR 0.96, 95% CI 0.84 to 1.09; French study at 36 months risk ratio (RR) 1.25, 95% CI 0.69 to 2.26, participants = 230). The number of adverse events was similar in the intervention and placebo groups (USA study participants with one or more serious adverse event RR 1.00, 95% CI 0.91 to 1.09, participants = 2080; French study total adverse events RR 1.05, 95% CI 0.97 to 1.13, participants = 263). AUTHORS' CONCLUSIONS: This review found that omega 3 LCPUFA supplementation in people with AMD for periods up to five years does not reduce the risk of progression to advanced AMD or the development of moderate to severe visual loss. No published randomised trials were identified on dietary omega 3 fatty acids for primary prevention of AMD. Currently available evidence does not support increasing dietary intake of omega 3 LCPUFA for the explicit purpose of preventing or slowing the progression of AMD

Age-related macular degeneration in a randomized controlled trial of low-dose aspirin: Rationale and study design of the ASPREE-AMD study

Purpose: Although aspirin therapy is used widely in older adults for prevention of cardiovascular disease, its impact on the incidence, progression and severity of age-related macular degeneration (AMD) is uncertain. The effect of low-dose aspirin on the course of AMD will be evaluated in this clinical trial. Design: A sub-study of the ‘ASPirin in Reducing Events in the Elderly’ (ASPREE) trial, ASPREE-AMD is a 5-year follow-up double-blind, placebo-controlled, randomized trial of the effect of 100 mg daily aspirin on the course of AMD in 5000 subjects aged 70 years or older, with normal cognitive function and without cardiovascular disease at baseline. Non-mydriatic fundus photography will be performed at baseline, 3-year and 5-year follow-up to determine AMD status. Primary outcome measures: The incidence and progression of AMD. Exploratory analyses will determine whether aspirin affects the risk of retinal hemorrhage in late AMD, and whether other factors, such as genotype, systemic disease, inflammatory biomarkers, influence the effect of aspirin on AMD. Conclusion: The study findings will be of significant clinical and public interest due to a potential to identify a possible low cost therapy for preventing AMD worldwide and to determine risk/benefit balance of the aspirin usage by the AMD-affected elderly. The ASPREE-AMD study provides a unique opportunity to determine the effect of aspirin on AMD incidence and progression, by adding retinal imaging to an ongoing, large-scale primary prevention randomized clinical trial

Visual Acuity after Cataract Surgery in Patients with Age-Related Macular Degeneration

OBJECTIVE: To evaluate visual acuity outcomes after cataract surgery in persons with varying severity of age-related macular degeneration (AMD). DESIGN: Cohort study. PARTICIPANTS: A total of 1232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2 (AREDS2), a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD. METHODS: Preoperative and postoperative characteristics of participants who underwent cataract extraction during the 5 year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the 6 month telephone calls. Analyses were conducted using multivariate repeated-measures regression. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. RESULTS: Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n=30) gained 11.2 letters (95% confidence interval (CI), 6.9-15.5), eyes with moderate AMD (n=346) gained 11.1 letters (95% CI, 9.1-13.2), eyes with severe AMD (n=462) gained 8.7 letters (95% CI, 6.7-10.7), eyes with non-central geographic atrophy (n=70) gained 8.9 letters (95% CI, 5.8-12.1), and eyes with advanced AMD (central geographic atrophy and/or neovascular) AMD (n=324) gained 6.8 letters (95% CI, 4.9-8.8). The visual acuity gain across all AMD severity groups was statistically significant from pre-operative state (P<0.0001). CONCLUSIONS: Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity