Methodological quality of the review: High Confidence

Author: Liu F, Xiong J, Hu J, Ran Z, Wang J, Li Z, Chen M, Wang Y.

Region: United States of America (USA), Spain, Japan, Sweden, United Kingdom (UK), India, Canada, Italy, Greece, China.

Sector: Age-related cataract

Sub-sector: Risk

Type of cataract: Age-related cataract

Equity focus: None specified

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Some of the factors associated with age-related cataracts include smoking, stress and dietary antioxidant intake. However, there have been conflicting findings about the effects of vitamin C intake and serum ascorbate concentration on age-related cataract formation.

Research objectives:

To assess whether vitamin C prevents or slows progression of age-related cataracts.

Main findings:

Authors included a total of 26 studies in the review, of which one was a randomized controlled trial (RCT), 11 were cohort studies, six case-control studies and eight cross-sectional studies. The randomized controlled trial was classified as low risk of bias according to Cochrane’s Collaboration tool. Median bias risk score of cohort and case-control studies were 8 (range: 7-9), and cross-sectional studies was 6 (range: 5-7).

11 cohort studies, five case-control studies, and seven cross-sectional studies evaluated the relationship between vitamin C and risk of cataracts. Authors reported that among the cohort studies, the combined multivariate-adjusted relative risk (RR) of age-related cataracts comparing the highest and lowest vitamin C intake levels was 0.8 (95% CI: 0.66 to 0.97), with significant heterogeneity (I2 = 74.1%, P≤0.001). A similar result emerged from case-control studies (odds ratio (OR): 0.61, 95% confidence interval (CI): 0.47 to 0.79; I2 = 45.4%, P = 0.12). No such protective effect was found in cross-sectional studies (OR: 0.60, 95% CI: 0.31 to 1.13; I2 = 73.8%, P = 0.051).

Sub-group analysis according to types of cataracts showed that higher vitamin C intake has protective effects on nuclear cataracts (RR: 0.51, 95% CI: 0.32 to 0.81; I2 =58.5%, P = 0.065). Sub-group analysis based on whether cataract surgery was performed authors reported that higher vitamin C intake has protective effects on incidence of cataracts (RR: 0.74, 95% CI: 0.59 to 0.92; I2 = 70.8%, P≤0.001). In addition, findings from the analysis reported there was no evidence of the effect of higher vitamin C intake reducing risk of cataract extraction (RR: 0.95, 95% CI: 0.74 to 1.22; I2 =68.2%, P = 0.013).

Based on the sensitivity analysis conducted by the authors, it was noted that heterogeneity between studies had significantly decreased. Sub-group analysis based on types of cataracts showed that higher vitamin C intake has protective effects on any type cataracts (OR: 0.61, 95% CI: 0.47 to 0.79; I2 = 45.4%, P = 0.12) and nuclear cataracts (OR: 0.55, 95% CI: 0.44 to 0.68; I2 = 0%, P = 0.929). Sub-group analysis based on whether cataract surgery was performed showed that higher vitamin C intake has protective effects on incidence of cataracts (OR: 0.58, 95% CI: 0.44 to 0.78; I2 = 52.7%, P =0.096).

Pooled results of cross-sectional studies showed that higher serum ascorbate has a protective effect on age-related cataracts (OR: 0.72, 95% CI: 0.63 to 0.83, I2 = 8.1%, P= 0.367). Authors did not find this protective effect in cohort studies (RR: 0.86, 95% CI: 0.45 to 1.65, I2 = 65.5%, P = 0.055) or case-control studies (OR: 0.76, 95% CI: 0.13 to 4.54, I2 =96.8%, P≤0.001).

Methodology:

Authors included studies if they satisfied the following criteria: 1) Design: randomized controlled trial, case-control studies, cohort studies and cross-sectional studies; 2) Exposure: vitamin C or serum ascorbate; 3) Outcome: incidence of age-related cataracts or incidence of age-related cataract extraction; 4) Data: relative risk (RR) or odds ratio (OR), with corresponding 95% confidence interval (CI) (comparing the highest and lowest vitamin C or serum ascorbate levels).

Authors conducted a search on the following databases: Embase, PubMed, Web of Science and Cochrane library up through April 2017. Authors also screened references of included studies as part of the search strategy. No language or date restrictions were applied.

Three authors independently conducted a search of the literature, data extraction, risk of bias assessment and evidence grade assessment. Quality of the randomized controlled trial was evaluated using Cochrane’s Collaboration tool. The quality of cohort and case-control studies was evaluated using Newcastle-Ottawa Scale. Cross-sectional studies were assessed using an 11-item checklist recommended by Agency for Healthcare research and Quality. Quality of available evidence for outcomes was evaluated based on GRADE methodology for risk of bias, inconsistency, indirectness, imprecision, and publication bias.

Authors conducted a meta-analysis of included data. Relative risk ratio and odds ratio with corresponding 95% Cis were used to measured pooled data.

Applicability/external validity:

Authors state that the quality of evidence of prevention effects of vitamin C intake on age-related cataracts was at level B and moderate recommendation. Therefore, authors recommend that older people increase vitamin C intake to prevent cataract.

Geographic focus

Authors did not discuss applicability of findings to low- and middle-income countries.

Quality assessment

Overall, there is high confidence in the conclusions about the effects of this study. Authors conducted a thorough search of the literature avoiding publication bias. In addition, appropriate methods were used to screen studies, extract data and assess the methodological quality of included studies. Methods were rigorous and findings were clearly reported within the review.