Intranasal corticosteroids and the eye: from negative ocular effects to clinical efficacy as a class effect.

Glucocorticosteroids, in their various formulations, ranging from oral to topical ophthalmic, have been associated with negative “ocular effects” that include infections, increased intraocular pressure leading to a risk for glaucoma, scleral thinning, and cataracts.1 In addition, there have been concerns about the systemic effects of inhaled and intranasal steroids on growth, bones, and the hypothalamic-pituitary-adrenal axis and about local adverse events. These concerns led to the development of a position statement from a Joint Task Force of the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology, recommending that intranasal corticosteroids (INSs) should remain prescription-only drugs and not be indicated for over-the-counter use.2 A particular concern of many ophthalmologists has been the possible development of increased intraocular pressure during treatment with corticosteroids. In a study3 of patients being treated for glaucoma who were also receiving an INS, the discontinuation of challenge and rechallenge studies with various INS formulations led to a significant reduction in intraocular pressure. However, increasing recent interest is focusing on whether the INSs, as a class effect, may have beneficial effects on the eye, especially in reducing the symptoms of allergic conjunctivitis frequently found in patients with allergic rhinitis (AR). The eye is especially susceptible to the symptoms of AR— itching (pruritus), tearing (epiphora), and redness (erythema)—because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen, on the conjunctival surface.4 These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction.5 A number of recently published clinical studies apparently support the positive effect of INS agents on ocular allergy symptoms. One possible reason that the INSs were not regarded as effective for ocular symptoms earlier is that studies published before the late 1990s did not consistently focus on the ocular domain of allergy symptoms. Instead, they included ocular and other nonnasal symptoms (eg, otic and palatal pruritus) into a single component of the total nonnasal symptom score in AR studies. However, studies published during the past 5 years have collected and reported ocular allergy signs and symptoms separately as part of a total ocular symptom score (TOSS). One of the earliest reports demonstrating the positive effects of INSs as a class on ocular allergy domains is a meta-analysis published almost a decade ago of studies (conducted between 1966 and 1997) that compared oral antihistamines with INSs. The meta-analysis6 concluded that the INSs and oral antihistamines had a similar effect on ocular symptoms in AR studies and recommended the use of INSs over oral antihistamines as first-line treatment for AR. These results have been verified in many of the more recent studies7–16 with INS agents. Studies with fluticasone propionate,7,8 mometasone furoate nasal spray,9–11 fluticasone furoate,12 budesonide,13 and, to some degree, triamcinolone acetonide aqueous nasal spray14 and beclomethasone dipropionate aqueous nasal spray15,16 provide further support for the favorable effect of INSs for ocular symptoms. For example, Bernstein et al7 concluded from a 28-day study with fluticasone propionate, oral loratadine, and vehicle placebo that patients treated with fluticasone propionate had statistically significant decreases compared with placebo in TOSS, which was the sum of scores for the symptoms of itching, tearing, and redness. The data also suggested that fluticasone propionate had reduced ocular symptoms more than or comparable to oral loratadine.7 Furthermore, an analysis of pooled data from the fluticasone propionate and placebo arms of 7 studies found that, after 7 and 14 days of treatment, patients receiving fluticasone propionate experienced significantly greater reductions in TOSS (sum of itching, tearing, redness, and puffiness symptom scores) than did patients in the placebo group.8 The positive effect of mometasone furoate nasal spray on ocular allergy symptoms was seen in an analysis of pooled data from 4 randomized, placebo-controlled, double-blind, Affiliations: Division of Allergy, Immunology, and Rheumatology, Departments of Medicine, Pediatrics, Ophthalmology and Visual Sciences, UMDNJ–New Jersey Medical School, Newark, New Jersey. Disclosures: Pfizer, Forest, Schering-Plough, Glaxo Smith Kline, Merck, Novartis, Sanofi-Aventis, Genentech, Sepracor, UCB-Pharma, Astra-Zeneca, Alcon, MedPointe, Ciba-Vision (Novartis), Inspire, Santen, Eye-Tech, Advanced Plant Pharmaceuticals, Lev Pharmaceuticals, Abbott, Vistakon, and Dyax. Received for publication September 19, 2007; Accepted for publication January 2, 2008.