Correspondence

Inhaled Corticosteroids and the Risk of Cataracts

N Engl J Med 1997; 337:1554-1555November 20, 1997

Article

To the Editor:

Cumming et al. (July 3 issue)1 concluded that “the use of inhaled corticosteroids is associated with the development of posterior subcapsular and nuclear cataracts” without considering possible confounders, including a history of atopic dermatitis2-4 and the use of topical corticosteroids on the face and eyelids.5 Both factors were probably present in at least some of the study subjects. It is likely that both were more common in the subjects who were using inhaled corticosteroids than in those who were not, since a major indication for the use of inhaled corticosteroids is allergic asthma, an atopic condition often found in persons with atopic dermatitis.

S. Elizabeth Whitmore, M.D.
Johns Hopkins University, Baltimore, MD 21205

5 References

1
Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997;337:8-14
Full Text | Web of Science | Medline

2
Philps AS. Clinical meeting held at the Royal Westminster Ophthalmic Hospital, London: four cases. Proc R Soc Med 1947;40:817-817
Medline

3
Cordes FC, Cordero-Moreno R. Atopic cataracts: report of four cases. Am J Ophthalmol 1946;29:402-407
Web of Science | Medline

4
Hurlbut WR, Domonkos AN. Cataract and retinal detachment associated with atopic dermatitis. Arch Ophthalmol 1954;52:852-857
Web of Science

5
Phillips CI, Donnelly CA, Clayton RM, Cuthbert J. Skin disease and age-related cataract. Acta Derm Venereol 1996;76:314-318
Web of Science | Medline

To the Editor:

Did Cumming et al. collect information about which of their subjects regularly used spacers (portable holding chambers that are attached to inhalers to maximize the amount of drug delivered to the lungs)? When a multidose inhaler is discharged a short distance from the mouth without the use of a spacer, some small portion of the aerosol might well be deposited directly in the person's eyes. Topical application of ophthalmic corticosteroids is believed to increase the risk of cataracts.1-3

Steven Leiner, C.F.N.P., P.A.-C.
University of California, San Francisco, San Francisco, CA 94143

3 References

1
Urban RC Jr, Cotlier E. Corticosteroid-induced cataracts. Surv Ophthalmol 1986;31:102-110
CrossRef | Web of Science | Medline

2
Butcher JM, Austin M, McGalliard J, Bourke RD. Bilateral cataracts and glaucoma induced by long term use of steroid eye drops. BMJ 1994;309:43-43
CrossRef | Web of Science | Medline

3
Donshik PC, Cavanaugh HD, Boruchoff SA, Dohlman CH. Posterior subcapsular cataracts induced by topical corticosteroids following keratoplasty for keratoconus. Ann Ophthalmol 1981;13:29-32
Web of Science | Medline

To the Editor:

Spacer devices decrease the amount of corticosteroid delivered to the mouth and pharynx. If the increased frequency of cataracts is due to systemic effects of orally deposited and absorbed corticosteroid, then patients who inhale corticosteroids through a spacer device might not have an increased incidence of cataracts.

Teresa R. Corcoran, M.D.
Cambridge Hospital, Cambridge, MA 02139

To the Editor:

Cumming et al. state that they “have no reason to suspect . . . that the effect of budesonide would differ from that of beclomethasone.” Beclomethasone has greater systemic bioactivity per inhaled dose than budesonide.1,2 . . . Since no evidence was presented that budesonide is associated with the same relative risk of cataracts as beclomethasone, it should be assumed that the risk of cataracts is lower at therapeutically equivalent doses.

Tony R. Bai, M.D.
St. Paul's Hospital, Vancouver, BC V6Y 1Y6, Canada

2 References

1
Lipworth BJ. Airway and systemic effects of inhaled corticosteroids in asthma: dose response relationship. Pulm Pharmacol 1996;9:19-27
CrossRef | Medline

2
Brown PH, Matusiewicz SP, Shearing C, Tibi L, Greening AP, Crompton GK. Systemic effects of high dose inhaled steroids: comparison of beclomethasone dipropionate and budesonide in healthy subjects. Thorax 1993;48:967-973
CrossRef | Web of Science | Medline

To the Editor:

The measure of exposure to inhaled corticosteroids used by Cumming et al. is based on the lifetime dose, which they describe as “perhaps the best measure of exposure to inhaled corticosteroids.” The lifetime dose, calculated as the product of weekly dose and the duration of use, is an informative measure when the outcome is a function of the total cumulative dose, when the effects are irreversible, and when there is no threshold value with respect to the outcome. With respect to inhaled corticosteroids, several studies have suggested that they must be given in high doses to increase the risk of systemic effects.1

In our study of inhaled and nasally administered glucocorticoids and the risk of ocular hypertension or open-angle glaucoma, we observed an increased risk only with prolonged exposure to high doses of inhaled corticosteroids.2 Although the results of Cumming et al. similarly point to an increased risk of cataracts with increasing doses of beclomethasone, their risk estimates for different weekly doses of beclomethasone do not take into account the duration of exposure. It is therefore not possible to judge the risk of cataracts with prolonged exposure to low doses of inhaled corticosteroids.

Further studies investigating this association should, in addition to calculating risk estimates for lifetime doses of inhaled corticosteroids, perform stratified analyses according to the dose and the duration of use. The daily dose of inhaled corticosteroids may vary considerably in patients with asthma.

Edeltraut Garbe, M.D.
Potsdam Institute of Pharmacoepidemiology and Technology Assessment, 14482 Potsdam, Germany

Samy Suissa, Ph.D.
Royal Victoria Hospital, Montreal, QC H3A 1A1, Canada

2 References

1
Barnes PJ. Inhaled glucocorticoids for asthma. N Engl J Med 1995;332:868-875
Full Text | Web of Science | Medline

2
Garbe E, LeLorier J, Boivin JF, Suissa S. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA 1997;277:722-727
CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Whitmore raises the possibility that our findings may be due to confounding. Because of a susceptibility to allergic disorders, some people who use inhaled corticosteroids may also use topical corticosteroids on the face. Unfortunately, we did not collect data on the use of dermatologic preparations, and so we cannot rule this out as a possible explanation.

We agree with Leiner and Corcoran that at least some of the effect of inhaled corticosteroids on the eye may result from direct entry into the eye or absorption from the oropharynx. This could explain why we found that the magnitude of the effect of inhaled corticosteroids on the lens was similar to or even greater than that of oral corticosteroids. The use of spacer devices, and generally improved inhaler technique, would certainly reduce the amount of corticosteroid that goes directly into the eye.

If the effect of inhaled corticosteroids on the eye is mediated systemically, then Bai is correct in suggesting that the effect of budesonide on the lens would probably be less than that of beclomethasone. On the other hand, if the effect is due to direct entry of corticosteroid into the eye, there might be little difference between the effects of these two medications.

We had data on both the dose and the duration of use in only 70 current users of beclomethasone, too few to conduct the stratified analyses suggested by Garbe and Suissa. We agree that more research is needed to answer the central clinical questions: What is a safe daily dose of inhaled corticosteroid, and how long can this dose be maintained?

Robert G. Cumming, M.B., B.S., Ph.D.
Paul Mitchell, M.D.
Stephen R. Leeder, M.B., B.S., Ph.D.
University of Sydney, Sydney, NSW 2006, Australia

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