Existing data suggest that glucocorticoid use puts patients with rheumatoid arthritis (RA) at risk for developing cataracts, but data on the parameters of risk remain too sparse to form a definitive stance, according to the authors of a recently published systematic literature review.1 Underreporting of cataract and glaucoma incidence rates in RA seems apparent.

Cataract and glaucoma have long been regarded as potential adverse effects of systemic glucocorticoid therapy. Glucocorticoids remain widely prescribed as “bridge” therapy of RA and other inflammatory diseases nonetheless, and issues related to risk, such as dose and duration thresholds, are rarely explored in the literature. A multicenter team of British and Australian researchers sought to pin down the association between cataract and glaucoma and glucocorticoid use in RA by assessing findings from randomized clinical trials (RCTs) and observational studies.

In their literature search, the researchers gathered all RCTs on glucocorticoid use versus non-use in RA as well as observational studies that reported cataract or glaucoma among glucocorticoid users and non-users. Extracted data included incidence or prevalence of cataract or glaucoma in each arm of the studies reviewed, dose, and duration of therapy. 


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When it became apparent that cataract was not being adequately captured or reported in RCTs, the researchers introduced a secondary study goal, which was to compare RCT incidence with expected incidence of cataract based on general population rates derived from The Blue Mountains Eye Study (BMES), a population-based survey of vision and eye diseases in an urban Australian population aged 49 years or older.2

Of 95 RCTs identified for full-text review, 28 met eligibility criteria and were included, but only 3 reported cataract/glaucoma. Indeed, assessment of cataract or glaucoma was absent from the Methods of all but the 3 studies. For these 3 RCTs, the cumulative 2-year incidence of cataract was a mere 2%. The assessed incidence is in sharp contrast to the expected population cumulative incidence established by the BMES. Cataract incidence was 6% within 1 year and 12% within 2 years. Given that the median duration of 27 RCTs was 1 year, cataract cases should have been expected. Gross underreporting of cataract appears to be at play, according to the study authors.

As a result of the sparse data, an association between glucocorticoid use and cataract or glaucoma in RA could not be determined by RCT data; however, a statistically significant association was seen for cataract but not glaucoma in the observational studies that met eligibility criteria. Of these, 5 were cohort and 5 were cross-sectional studies. Of the 5 cohort studies, 4 reported a significantly increased risk of cataract in patients exposed to glucocorticoids. The combined risk difference was 0.07 events per person (95% CI 0.04-0.10) and the odds ratio was estimated at 2.1 (95% CI 1.5-2.9). Data were insufficient to determine the impact of dose and duration of therapy.

The researchers concluded that, although current literature suggests a possible association between glucocorticoids use and cataract, risk cannot be accurately quantified in relation to RA because RCTs have not adequately captured cataract-related outcomes. Further observational research is needed, they said.

Summary and Clinical Applicability

A review of the literature on incidence of cataract and glaucoma in RA and the possible association between cataract/glaucoma and glucocorticoid use shows that data are sparse and incidence of these ophthalmologic diseases in RA may be underreported. The existing data, though limited, suggest that glucocorticoid use in RA does puts patients at risk for cataract, but the parameters of that risk remain unknown. Further study of the issue will better help clinicians and patients understand the benefits and risks of glucocorticoid therapy in RA.

Limitations and Disclosures

  • Small number of studies met eligibility criteria
  • The heterogeneity of the studies may have compromised the ability for the authors to make meaningful conclusions

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References

  1. Black RJ, Hill CL, Lester S, Dixon WG. The association between systemic glucocorticoid use and the risk of cataract and glaucoma in patients with rheumatoid arthritis: a systematic review and meta-analysis. PLoS One. 2016;11(11): e0166468.
  2. Kanthan GL, Wang JJ, Rochtchina E, et al. Ten-year incidence of age-related cataract and cataract surgery in an older Australian population. The Blue Mountains Eye Study. Ophthalmology.2008; 115(5):808±14 e1.

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