Inhaled corticosteroid exposure and risk of cataract in patients with asthma and COPD: A systematic review and meta-analysis

Authors: Savran O, Ulrik SP

Geographical coverage: Not reported

Sector: Cataracts

Sub-sector: Risk factors

Equity focus: None specified

Study population: Patients with asthma and/or chronic obstructive pulmonary disease (COPD) prescribed systemic and/or inhaled corticosteroids

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Long-term use of systemic corticosteroids has been linked to the development of cataracts, particularly posterior subcapsular cataract (PSC). There is growing interest in the potential association between cataract development and long-term use of inhaled corticosteroids (ICS) for asthma and chronic obstructive pulmonary disease (COPD). Although the risk of developing cataracts from ICS treatment is likely to be lower than that from systemic corticosteroids, this has been explored in only a few studies. Studies have also reported a high prevalence of comorbidities, including respiratory diseases such as asthma and COPD, among patients with cataracts.

Objective:

To evaluate the correlation between cataract development and corticosteroid exposure among individuals with asthma and COPD.

Main findings:

The authors found a doubled risk of cataracts in asthma and COPD patients exposed to corticosteroids. High doses of inhaled corticosteroids (≥ 1000 mcg daily) significantly increase cataract risk, potentially leading to cataract surgery. One study noted that systemic corticosteroids present an even higher risk than inhaled corticosteroids.

The review included a total of 19 studies comprising 1,274,878 individuals. Twelve of these studies, with sample sizes of 13,343 and 562,745 respectively, were included in the meta-analyses of cross-sectional and cohort studies. A further 25,693 individuals were included in the meta-analysis of case-control studies. In total, 62,292 (5%) cases of cataract and 996,328 (78%) patients with asthma and/or COPD who had been prescribed corticosteroids were reported. The authors attributed high risk of bias to half of the cross-sectional studies due to limited information on control group characteristics. The remaining studies were generally assessed as having low risk of bias.

In the pooled effect size analysis of cohort studies, the weighted odds ratio (OR) using a random-effects model was 1.60 (95% CI 1.11 to 2.31). For cross-sectional and case-control studies, the weighted ORs were 2.78 (95% CI 2.09–3.71) and 2.0 (95% CI 0.93–4.30), respectively. Sensitivity analyses showed no single study had a disproportionate impact on the OR estimates, with cohort studies ranging from 1.42 to 1.74 and cross-sectional studies from 2.63 to 3.00. Meta-regression demonstrated a significant dose-response relationship between corticosteroid exposure and cataract development (OR 1.99, 95% CI 1.39 to 2.88, p < 0.001). The Harbord test indicated no evidence of publication bias.

Methodology: 

The authors searched PubMed and Embase in March 2023 for original studies published in the last three decades that assessed the risk of cataract in patients with asthma and/or COPD who had been prescribed systemic and/or inhaled corticosteroids. Studies published in languages other than English and systematic reviews were excluded. Two reviewers independently screened studies based on the inclusion and exclusion criteria and extracted data from included studies. Quality assessment was conducted by one reviewer using the Newcastle-Ottawa Scale (NOS) for case-control and cohort studies, and the adapted NOS for cross-sectional studies.

Meta-analyses were performed using pre-calculated effect sizes based on binary outcome data (risk ratios and odds ratios). Outcomes of interest included treatment estimates, standard errors, confidence intervals, heterogeneity, and tau². Meta-regression was conducted by study type, and sensitivity analysis involved excluding individual studies in turn. Funnel plot asymmetry was used to assess publication bias.

Applicability/external validity:

The authors noted that the findings of their review are consistent with previous research. However, they highlighted the importance of considering heterogeneity among the included studies when interpreting the results.

Geographic focus:

The geographic locations of the included studies were not reported.

Summary of quality assessment:

There is low confidence in the review’s conclusions due to uncertainty about whether reviewers independently conducted screening, data extraction, and quality assessment. However, the authors did acknowledge these limitations.