Dose–response relationship of inhaled corticosteroids and cataracts: A systematic review and meta-analysis

Methodological quality of the review: Medium confidence

Author: Weatherall M, Clay J, James K, Perrin K, Shirtcliffe P, Beasley R.

Region: United Kingdom (UK) and Canada

Sector: Cataract

Sub-sector: Prevention/slowing progression

Type of cataract: Age-related cataract

Equity focus: None specified

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis methods: Not applicable

Background

The long term use of inhaled corticosteroids (ICS) is increasing and it is known that cataract is one of the risks of using them. However, this risk has not been quantified nor a dose-response relationship has been established. Given that, cataract is the leading cause of blindness worldwide, and an increase in the risk of cataract would potentially have major public health implications.

Research objectives

To determine the dose-response relationship of ICS use and risk of cataract in adults.

Main findings

Four case-control studies from the UK and Canada were included in this review. Authors found a dose-response relationship between ICS and risk of cataract, with random effects pooled odds ratio for risk of cataracts per 1000 microgram increase in daily beclomethasone diproprionate (BDP) dose as 1.25 (95% CI: 1.14 – 1.37). This reinforced the importance of prescribing the lowest effective dose for asthma and chronic obstructive pulmonary disease (COPD). It could also suggest that screening for the presence of cataracts in older subjects with these diseases could be useful.

Based on these findings, authors concluded that the risk of cataract increases by approximately 25% for each 1000 microgram increase in the daily dose of BDP or equivalent ICS. Authors noted that the dose-response relationship of ICS therapy for efficacy in COPD is an urgent priority so that the therapeutic benefit to side-effect profile can be established.

Methodology

Authors included case-control studies of cataracts and the use of ICS; included at least two doses of ICS reported as the equivalent dose of BDP per day. The studies had to report the number of cases and controls as well as odds ratios with confidence intervals after adjustment for confounders.

Searches of MEDLINE from Jan 1950 to Jan 2007 and EMBASE from Jan 1988 to Jan 2007 were conducted. Reference lists of relevant studies were also reviewed as part of the search strategy. No language restrictions were applied to searches. Two researchers examined the title and abstract of each paper and the full paper if necessary.

Applicability/external validity

Authors did not discuss the applicability/external validity of findings.

Geographic focus

The literature searches were not restricted to specific income countries, but yield results did not include any studies from low/middle-income countries. The main outcome of the review, the dose- response relationship, is likely to be the same in low/middle-income countries. However, due to the cost and accessibility to treatment, it may be possible that the treatment with inhaled corticosteroids in some of these countries is much lower than in high-income countries. Nevertheless, the policy recommendation to stay within a certain dose range to avoid risk of cataract could be generalized to low/middle-income countries.

Quality assessment

Authors conducted searches of MEDLINE (1950 to 2007) and EMBASE (1988 to 2007) avoiding language bias; and searches on reference lists of relevant studies. Two researchers examined the title and abstract of each paper. However, methods used to collect data as well as the criteria to quality assess the included studies was not reported. Overall, the method used to analyse findings is clearly reported and limitations are appropriately acknowledged by the reviewers.  Thus, a medium confidence was attributed to the conclusion about the effects of this review.