LONDON—It is well established that systemic corticosteroids increase one’s risk for cataracts. Now, a new study has shown that inhaled corticosteroids (ICs), when used at high doses and for a long duration, also raise the likelihood of cataract development.[1]

Liam Smeeth, MD, from the London School of Hygiene and Tropical Medicine and the study’s primary investigator, said that the immediate practical implication of this research is the need to use the lowest doses of ICs “compatible with good control of airways disease.” However, “a small risk of cataract is much less important than out-of-control asthma,” he cautioned.

To quantify the risk of cataracts with IC use, Dr. Smeeth and his colleagues performed a population-based study of 15,479 cases and an equal number of controls. Both groups were identified using the General Practice Research Database, the largest source of continuous information on illness and prescribing habits in the United Kingdom.

Cases were persons 40 or older who had been given a first diagnosis of cataract; the date of the diagnosis was considered the index date. Patients in whom the cataract was deemed congenital in origin or due to trauma were excluded. Controls were persons without a cataract diagnosis; they were randomly selected and matched with cases for age (within one year), sex, practice, and observation period. The final case-control cohort had a mean age of 75 and consisted primarily of women (65%). Only drug exposure before the index date was included in the analyses.

RISK DATA

A total of 11.4% of the cases and 7.6% of the controls were found to have had exposure to ICs. The crude odds ratio (OR) for the association between cataracts and ever-use of ICs was 1.58. Adjustments for systemic corticosteroid exposure and mean annual consultation rates (which were higher in cases than in controls) reduced the association to 1.10; this increase in risk, although small, remained statistically significant. However, the increase in risk was confined to current IC users (defined as those who had used the medications within 180 days of their index date); the risk in previous IC users was similar to that in controls.

A higher cataract risk was initially identified in persons with asthma (OR, 1.52) or COPD (OR, 1.49). Both of these associations, however, disappeared after adjustments for consultation rates and use of inhaled and/or systemic corticosteroids.

“MORE” IS PROBLEMATIC

A dose-response relationship was evident. The adjusted OR for a cataract diagnosis rose from 0.99 among those taking a low dose of an IC (up to 400 µg/d) to 1.69 in those taking a very high dose (greater than 1,600 µg/d). Similarly, as the number of IC prescriptions rose, so too did cataract risk. For patients who had received between one and nine prescriptions, the adjusted OR was 1.03, compared with an adjusted OR of 1.28 for patients who had received 40 or more prescriptions.

BROAD-LEVEL RISK

Exposure to any type of corticosteroid was associated with a diagnosis of cataract. Oral or parenteral systemic corticosteroids had associated risks that were comparable to those of high-dose ICs (crude ORs, 1.59 and 1.56, respectively). The highest risk was associated with ocular corticosteroid use (crude OR, 2.12). Lower associations were found for topical corticosteroids applied to the skin, ear, or nose (the respective ORs were 1.43, 1.31, and 1.33).

For these data, however, interpretation should be cautious. “Levels of exposure were low, and there is a lot of uncertainty in the estimates,” Dr. Smeeth said. “But the eye itself gets a high dose with ocular steroids, so here I would expect to see an effect [on cataract risk].”

Of those exposed to ICs, 77% of the cases (1,359) and 79.5% of the controls (938) had used beclomethasone only. Rates of exposure to budesonide only, fluticasone only, or for mixed use were substantially lower among both cases and controls, and because of this, there was insufficient power to reliably assess differences in cataract risk between the individual ICs.

What will be the effect of early exposure on cataract risk? “We just don’t know,” Dr. Smeeth said. “But I would suggest some long-term follow-up studies are needed, because it is clear some people will need ICs for decades.” The mechanism of how ICs promote cataract development also remains largely unknown.

—Verna L. Schwartz, MS