Q:

3/23/2012
Has the risk for developing cataracts/glaucoma for patients receiving inhaled steroid therapy for asthma been determined? In your opinion, should we be referring all patients on inhaled steroids to the ophthalmologist for annual evaluation? I usually have recommended annual check ups for patients on high dose inhaled therapy who often receive oral steroid bursts as well. But what about patients on low to medium dose therapy? Thanks for your thoughts.

A:

Thank you for your inquiry.

The literature examining the risk of development of glaucoma and/or cataracts from the use of inhaled corticosteroids is complex and somewhat contradictory as you can see from the two fairly recent abstracts (Wang, et al. and Miller, et al) copied for you below.

Thus a definitive answer to your questions is difficult to come by. In my viewpoint, all studies such as the ones cited below are based on mean data. Thus, it is hard to draw conclusions from them in regards to a particular patient because, as you well know, there are always outliers. For example, an older individual with a strong family history of glaucoma with modest elevation of intraocular pressure at the time of the initiation of therapy could clearly be at greater risk for this condition than a young person with a negative family history and a low intraocular pressure when therapy is initiated. Thus it is hard to draw conclusions from epidemiologic studies because the data are almost always dependent upon statistical calculations and very rarely reflect individual variation in risks in "outliers."

The person most qualified to interpret this literature is Dr. Leonard Bielory who is, as you know, a nationally known expert in ocular disease and the effects of corticosteroids on the eye. Dr. Bielory has done two reviews in this area; one is a white paper for the College and Academy on the effects of intranasal corticosteroids on the eye, and the other on the effect of inhaled corticosteroids on the eye. I have copied, for your convenience, abstracts of both reviews for you below.

In addition, I am asking Dr. Bielory to assist us in answering your inquiry. As soon as I hear from him, I will forward his response to you.

Thank you again for your inquiry.

Ophthalmology. 2009 Apr;116(4):652-7. Epub 2009 Feb 25.
Use of inhaled and oral corticosteroids and the long-term risk of cataract.
Wang JJ, Rochtchina E, Tan AG, Cumming RG, Leeder SR, Mitchell P.
Source
Centre for Vision Research, Department of Ophthalmology, University of Sydney, Sydney, Australia.
Abstract
Objective: Longitudinal associations between inhaled and oral corticosteroid use and 10-year incident cataract were examined.
Design: Population-based cohort study.
Participants: The Blue Mountains Eye Study examined 3654 Australians aged 49 years or older (1992-1994); 2335 were re-examined after 5 years and 1952 were re-examined after 10 years (75.1%, 75.6% of survivors, respectively).
Methods: Questionnaires were used to assess inhaled and oral corticosteroid use at baseline. Past users were participants who had used these medications for at least 1 month in the past but were not using them at baseline. Current users were those who were using these medications at baseline and had been doing so for at least 1 month. Ever users combined past and current users.
Main Outcome Measures: Lens photographs were obtained at each examination and graded for nuclear, cortical, and posterior subcapsular (PSC) cataracts following the Wisconsin Cataract Grading System. Participants without a specific subtype of cataract in either eye at baseline were considered to be at risk of that type of cataract developing over the 10-year follow-up. Incidence of each cataract subtype in this report refers to person-specific, first-eye incidence.
Results: At baseline, 103 participants were current and 120 past users of inhaled corticosteroids, and 31 were current and 147 were past users of oral corticosteroids. Current users had a greater risk of developing PSC cataract after adjustment for age and gender (inhaled: odds ratio [OR] 2.50, 95% confidence interval [CI] 1.33-4.69; oral: OR 4.11; 95% CI 1.67-10.08) and nuclear cataract (inhaled: OR 2.04, 95% CI 1.21-3.43; oral: OR 3.45, 95% CI 1.26-9.43) but not cortical cataract. Interaction between inhaled and oral corticosteroid use was significant for PSC (P = 0.01) and nuclear (P = 0.02) cataract incidence. In subgroup analyses, only individuals who used both inhaled and oral steroids were at increased risk of PSC cataract (after adjusting for age, sex, smoking, hypertension, diabetes, and education levels; OR 4.76, 95% CI 2.59-8.74), comparing ever users of both with users of neither.
Conclusions: High long-term risks of PSC and nuclear cataract development were found for users of combined inhaled and oral corticosteroids.

Int J Chron Obstruct Pulmon Dis. 2011;6:467-76. Epub 2011 Sep 16.
Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database.
Miller DP, Watkins SE, Sampson T, Davis KJ.
Source
WorldWide Epidemiology, GlaxoSmithKline, Research Triangle Park, Durham, NC 27709-3398, USA.
Abstract
Objectives: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom.
Methods: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents.
Results: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8).
Conclusions: FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom.

Compr Ophthalmol Update. 2006 Jan-Feb;7(1):31-9.
Risk of cataracts and glaucoma with inhaled steroid use in children.
Nootheti S, Bielory L.
Source
University of Medicine and Dentistry of New Jersey, 90 Bergen Street, Newark, NJ 07103, USA.
Abstract
With the increasing use of inhaled corticosteroids as first-line therapy in the treatment of asthma, the adverse effects of these preparations have become the topic of much research in recent years. While it is known that orally administered steroids can have metabolic, musculoskeletal, dermatologic, hematologic, and ophthalmologic effects (inhaled corticosteroids have minimal reported hematologic or musculoskeletal effects, but have some effects on metabolic processes such as calcium metabolism), it is less understood whether or not, and at what doses, inhaled corticosteroids will effect the eye. A computerized literature search was performed to search for literature pertaining to the specific use of oral or inhaled (nasal or bronchial) steroids, adverse effects, side effects, long-term use, chronic use, glaucoma, ocular effects, and increased ocular pressure. The search focused on the effects of inhaled corticosteroids in both adults and children, but contained an emphasis on children; studies pertaining to the effects in children, however, are limited.

Ann Allergy Asthma Immunol. 2006 Apr;96(4):514-25.
Concerns about intranasal corticosteroids for over-the-counter use: position statement of the Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology.
Bielory L, Blaiss M, Fineman SM, Ledford DK, Lieberman P, Simons FE, Skoner DP, Storms WW; Joint Task Force of the American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology.
Source
Department of Medicine, UMDNJ-New Jersey Medical School, Newark, USA.
Abstract
The Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology was charged with formulating a position paper regarding the potential release of intranasal corticosteroids for over-the-counter use. We took the position that safety issues regarding this proposal would be our sole concern. We reviewed the literature to evaluate the frequency and severity of potential adverse events related to the administration of intranasal corticosteroids. We limited this review to 5 areas: (1) effects on growth, (2) ocular effects, (3) effects on bone, (4) effects on the hypothalamic-pituitary-adrenal axis, and (5) local adverse effects. After review of the available data, we concluded that intranasal corticosteroids should remain prescription-only drugs. Patients receiving an intranasal corticosteroid should be instructed in its use and that use should be monitored by a physician or an appropriately trained medical provider (eg, nurse practitioner or physician assistant) under the direct supervision of a physician. This conclusion was reached based on the evidence that corticosteroids administered by any route, including the intranasal route, have the potential to cause adverse effects in all the areas noted herein. Our conclusion was strengthened by the fact that these adverse effects can be insidious and therefore not evident for many years; there is the potential for overuse; patients could also have access to other forms of topically administered corticosteroids, thus increasing their total dose; and individuals vary in their susceptibility to corticosteroid-induced adverse effects. We were also influenced to take this position knowing that generally reassuring data regarding the use of respiratory tract-administered corticosteroids are based on mean data and that all such studies have shown outliers in whom adverse effects were evident. Thus, as stated, we recommend that intranasal corticosteroids remain prescription-only drugs.

Sincerely,
Phil Lieberman, M.D.

We have received a response from Dr. Bielory. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Leonard Bielory:
The question as to whether there is a risk from steroids for cataract and glaucoma. For oral steroids definitely yes (ref Toogood), but unknown for inhaled although they are commonly combined with oral.

The other issue is whether one would consider increased opacifications with inhaled steroids as significant.

The timeline of their use i.e. 1-3 is minimal when one expects see the consequences when one approached >40 years of age.

Leonard Bielory

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