Inhaled Corticosteroids: Effect on Intraocular Pressure in Patients With Controlled Glaucoma
Condition: Ocular Hypertension; Glaucoma, Open-Angle
MeSH terms: Glaucoma; Ocular Hypertension; Glaucoma, Open-Angle; Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether a commonly prescribed orally inhaled
      corticosteroid treatment will induce a clinically meaningful elevation in intraocular
      pressure, when administered to patients with ocular hypertension (OHT) or open-angle glaucoma
      (OAG). Based on the response to high-dose corticosteroids, this patient group is more likely
      than the normal population to demonstrate this adverse effect.
    

Detailed description: 
      Systemic and topical ophthalmic steroids have long been associated with ocular effects, such
      as glaucoma or cataracts.[Alfano JE; Bernstein HN et al. 1962; Bernstein HN et al. 1963;
      Becker B and Mills DW in Arch Ophthalm 1963; Becker B and Mills DW in JAMA 1963; Armaly MF
      1963 (1); Armaly MF 1963 (2); and Buckley RJ] Periocular steroid injections [Herschler J;
      Kalina RE] and steroids applied to periocular skin [Aggarwal RK et al.] have also been
      reported to increase intraocular pressure (IOP) and raised IOP is the major risk factor for
      glaucoma.

      Ocular hypertension (OHT) is defined as an IOP above 21mmHg in one or both eyes without
      detectable glaucomatous damage. Primary open-angle glaucoma (POAG) is a chronic and
      progressive optic neuropathy of unknown etiology characterized by disc cupping, and often
      associated with visual field defects and elevated IOP. This disease is one of the leading
      causes of blindness worldwide.[Kwon YH et al.] Approximately 18% to 36% of the general
      population are corticosteroid responders. This response is increased to 46% to 92% in
      patients with POAG.[Tripathi RC et al.] Asthma is the most common chronic respiratory illness
      in Canada, affecting approximately 10% of the population. For the majority of these patients,
      long-term inhaled corticosteroids (ICS) are standard of care to prevent acute asthma
      exacerbations.[Kim H and Mazza J] Although the systemic absorption of inhaled and nasal
      steroids has been established, the clinically relevant ocular side effects are poorly
      defined. [Cave A et al.; Allen DB et al.] A large prospective study in 1995 by Samiy et al
      reported no statistically significant increase of IOP in 187 patients without glaucoma taking
      inhaled steroids for various pulmonary conditions.[Samiy N et al.] However, six cases of
      increased IOP associated with combined nasal and inhaled steroid use in non-glaucomatous
      patients have been reported. [Dreyer EB; Desnoeck M et al.; Opatowsky I et al.] A large
      case-control study in 1997 suggested that current users of high doses of ICS prescribed
      regularly for 3 or more months were at increased risk of OHT or OAG (OR 1.44; 95% CI
      1.01-2.06).[Garbe E et al.] In contrast, Gozalez et al. conducted a nested case-control study
      in 2010 with Quebec data which showed current and continuous use of ICS did not result in
      increased risk of glaucoma or raised IOP requiring treatment.[Gonzalez AV et al.] Similarly,
      Duh et al. reported no association between inhaled budesonide daily therapy and increased IOP
      in 1255 asthmatic patients.[Duh MS et al.] Further, a prospective population-based cohort
      study published in 2012 suggested no association between the development of OAG and ICS in
      the elderly.[Marcus MW et al.] In 2013, our group published a randomized double-masked
      controlled trial that showed no evidence of IOP elevation after 6 weeks use of beclomethasone
      nasal spray in 19 patients with OHT and POAG.[Yuen D et al.] The purpose of the current study
      protocol would be to extend the study to investigate ICS in the same patient population.

      To date, the effect of inhaled corticosteroids in those with pre-existing OHT or POAG remains
      uncertain. Considering the large number of patients on inhaled steroids, investigating the
      use of inhaled steroid in glaucoma patients could have significant clinical impact. This
      study was designed to evaluate the effect of inhaled fluticasone propionate on intraocular
      pressure (IOP) in patients with OHT or controlled open-angle glaucoma (OAG).

      Patient randomization was performed by an independent Research Coordinator in a separate
      physical space and kept sealed from the principal study investigators, who assessed and
      recorded outcome measures, until the completion of study data collection. IOP was measured in
      a masked fashion, using a second observer to record values. Two measurements within 1 mmHg
      were averaged for each data point. With a sample size of 8 patients per interventional arm,
      the study is powered at 0.80 to detect an elevation of 3.2 mmHg (≥20%) from mean, assuming a
      standard deviation of 2.5 mmHg. Baseline data will be compared between groups using the
      student's t test and Fisher exact test. A 2-sided p value of <0.05 will be considered
      statistically significant. The primary outcome measure (mean IOP) will be assessed using a
      1-sided Student t test.
    

Intervention name(s): Fluticasone propionate inhaler; Saline placebo inhaler
Intervention type(s): Drug; Drug
Intervention description(s): fluticasone propionate 250 µg metered-dose inhaler; saline metered dose inhaler
Intervention MeSH terms: Fluticasone; Xhance
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Corticosteroids; Bronchodilator Agents; Intraocular Pressure