Methodological quality of the review: High confidence

Author: Mathew MC, Ervin A, Tao J, Davis RM.

Region: Australia, Finland, India, Italy, United Kingdom and United States.

Sector: Cataract incidence and extraction

Sub-sector: Antioxidant vitamin supplementation.

Type of cataract: Age-related cataract

Equity focus: None specified

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis methods: Summary data tables

Background

Authors noted that ‘oxidative stress’ has been implicated in the formation and progression of age-related cataract. As a result, vitamin supplementation has been investigated as a potential treatment to prevent or slow the progression of cataract formation. To date results from observational studies had been inconclusive.

Research objectives

To assess the effectiveness of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract.

Main findings

Nine randomized controlled trials were included in this review and were conducted in Australia, Finland, India, Italy, United Kingdom and the United States. The review focused on trials in which antioxidant supplements namely: beta-carotene, vitamin C and vitamin E were compared to a placebo or no supplement and with a follow-up ranging from 2.1 to 12 years.

‘In the pooled analysis, there was no evidence of effect:

• Of beta-carotene supplementation in reducing the risk of cataract (two trials) relative risk (RR) 0.00, 95% confidence interval (CI) 0.91 to 1.08; n=57,703) or in reducing the risk of cataract extraction (three trials) (RR 1.00, 95% CI 0.91 to 1.10; n = 86,836).
• Of vitamin E supplementation in reducing the risk of cataract (three trials) (RR 0.97, 95% CI 0.91 to 1.04; n = 50,059) or of cataract extraction (five trials) (RR 0.98, 95% CI 0.91 to 1.05; n = 83,956)’.

Only one trial compared vitamin C with placebo to examine incidence of cataract and incidence of cataract extraction. There was no difference found between vitamin C and placebo in this trial over a mean period of eight years follow-up. The same trial found no difference between combination of vitamin C and vitamin E with placebo in the risk of incidence of cataract over mean period of eight years follow-up. No differences in effect were found between combined supplementation of either beta-carotene plus vitamin E versus placebo in the risk of incidence of cataract extraction.

The authors concluded that there was no evidence that vitamin supplements included in the trials prevents or slows the progression of age-related cataract or in slowing the loss of visual acuity; and do not recommend further investigation.

Methodology

The review included randomized controlled trials in which vitamin supplements vitamin C, vitamin E and beta-carotene for at least one year was compared to another vitamin antioxidant, to a placebo or no supplementation. Trial participants were 35 years of age and over with no restriction on demographic characteristics. It is noted that three of the trials were conducted on men only.

Primary outcomes included firstly the incidence of cataract as defined by the included studies and secondly the incidence of cataract extraction. Secondary outcomes included firstly the progression of cataract and secondly the loss of vision.

The authors conducted a systematic search of literature on various databases, including CENTRAL, MEDLINE (1950-2012), EMBASE (1980-2012) and LILACS (1982-2012). They also checked reference lists of included studies and ongoing trials to identify additional trials, contacted the investigators of included trails for additional information on unreported trials. At least two authors independently screened titles from searches and extracted data from included studies. Searches were conducted without any language restrictions.

The two authors independently conducted an assessment for bias, using the guidelines detailed in Chapter 8 of the Cochrane handbook for Systematic Reviews of Interventions (Higgins 2011) which included an assessment of the risk of blinding, selective reporting, random sequence generation and method of allocation concealment.

Authors examined included trials for heterogeneity by type of antioxidant and by participating age, gender and country of origin. Authors pooled data for primary outcomes but not for secondary outcomes due to issues of variability in the analysis and presentation of the data. Nine studies were included in qualitative synthesis and six studies in quantitative synthesis.

Applicability/external validity

Authors noted that all of the studies except for one were conducted in the developed world and, as a result, the nutritional status of the participants may be different than if more trials were conducted in the developing world. It was also noted that any conclusions made here can only apply to supplementation of beta-carotene, vitamin C and vitamin E. These trials also only dealt with participants aged 35 years or older and therefore, research into the impact of starting supplementation at a much earlier age has not been investigated.

Geographic focus

The review included a study from India. All other trials included are from developed, high-income countries. Authors noted that the nutritional status of the majority of participants would be different than if the trials were all taken from low- to middle- income countries.

Quality assessment

The systematic review was based on comprehensive searches and appropriate synthesis methods to reduce risk of bias. The authors explicitly stated inclusion and exclusion criteria and a meta-analysis seemed an appropriate method of synthesis. For secondary outcomes, given the differences between studies in terms of design, and data presentation, a narrative summary was appropriate. As such, overall there is a high confidence in the conclusions about the effects of this study.