Inhaled Corticosteroids: Effect on Intraocular Pressure in Patients With Controlled Glaucoma

Ocular Hypertension Clinical Trial

Official title:

The Effect of Inhaled Corticosteroids on Intraocular Pressure in Patients With Ocular Hypertension or Controlled Glaucoma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02338362
• Other study ID #: 13-6069-A
• Status: Completed
• Phase: Phase 4
• Start date: September 2014
• Est. completion date: February 2015

Study information

• Verified date: April 2019
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Age 18 to 85 years, inclusive

• Mild-moderate open-angle glaucoma/ocular hypertension with cup:disc ratio <0.85 vertically and humphrey visual field mean deviation >-12.00 (BOTH EYES must meet this criteria for patient to be included)

• Glaucoma well-controlled, defined by IOP < 21 mmHg and at target with no visual field/disc progression for at least 6 months (BOTH EYES must meet this criteria for patient to be included)

Exclusion Criteria:

• Any form of steroid medication use within the prior 6 weeks

• Any previous intra-ocular surgery or refractive surgery in the study eye

• no light perception (i.e. blindness) in either eye

• unwilling/unable to give consent

• unwilling to accept randomization

• patient potentially unavailable for follow-up visits

Related Conditions & MeSH terms

• Glaucoma
• Glaucoma, Open-Angle
• Hypertension
• Ocular Hypertension

Intervention

Drug:
• Fluticasone propionate inhaler
fluticasone propionate 250 µg metered-dose inhaler
• Saline placebo inhaler
saline metered dose inhaler

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

References & Publications (25)

Aggarwal RK, Potamitis T, Chong NH, Guarro M, Shah P, Kheterpal S. Extensive visual loss with topical facial steroids. Eye (Lond). 1993;7 ( Pt 5):664-6. — View Citation

ALFANO JE. CHANGES IN THE INTRAOCULAR PRESSURE ASSOCIATED WITH SYSTEMIC STEROID THERAPY. Am J Ophthalmol. 1963 Aug;56:245-7. — View Citation

Allen DB, Bielory L, Derendorf H, Dluhy R, Colice GL, Szefler SJ. Inhaled corticosteroids: past lessons and future issues. J Allergy Clin Immunol. 2003 Sep;112(3 Suppl):S1-40. Review. — View Citation

ARMALY MF. EFFECT OF CORTICOSTEROIDS ON INTRAOCULAR PRESSURE AND FLUID DYNAMICS. I. THE EFFECT OF DEXAMETHASONE IN THE NORMAL EYE. Arch Ophthalmol. 1963 Oct;70:482-91. — View Citation

ARMALY MF. EFFECT OF CORTICOSTEROIDS ON INTRAOCULAR PRESSURE AND FLUID DYNAMICS. II. THE EFFECT OF DEXAMETHASONE IN THE GLAUCOMATOUS EYE. Arch Ophthalmol. 1963 Oct;70:492-9. — View Citation

BECKER B, MILLS DW. CORTICOSTEROIDS AND INTRAOCULAR PRESSURE. Arch Ophthalmol. 1963 Oct;70:500-7. — View Citation

BECKER B, MILLS DW. ELEVATED INTRAOCULAR PRESSURE FOLLOWING CORTICOSTEROID EYE DROPS. JAMA. 1963 Sep 14;185:884-6. — View Citation

BERNSTEIN HN, MILLS DW, BECKER B. Steroid-induced elevation of intraocular pressure. Arch Ophthalmol. 1963 Jul;70:15-8. — View Citation

BERNSTEIN HN, SCHWARTZ B. Effects of long-term systemic steroids on ocular pressure and tonographic values. Arch Ophthalmol. 1962 Dec;68:742-53. — View Citation

Buckley RJ. Allergic eye disease--a clinical challenge. Clin Exp Allergy. 1998 Dec;28 Suppl 6:39-43. — View Citation

Cave A, Arlett P, Lee E. Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects. Pharmacol Ther. 1999 Sep;83(3):153-79. Review. — View Citation

Desnoeck M, Casteels I, Casteels K. Intraocular pressure elevation in a child due to the use of inhalation steroids--a case report. Bull Soc Belge Ophtalmol. 2001;(280):97-100. — View Citation

Dreyer EB. Inhaled steroid use and glaucoma. N Engl J Med. 1993 Dec 9;329(24):1822. — View Citation

Duh MS, Walker AM, Lindmark B, Laties AM. Association between intraocular pressure and budesonide inhalation therapy in asthmatic patients. Ann Allergy Asthma Immunol. 2000 Nov;85(5):356-61. — View Citation

Garbe E, LeLorier J, Boivin JF, Suissa S. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA. 1997 Mar 5;277(9):722-7. — View Citation

Gonzalez AV, Li G, Suissa S, Ernst P. Risk of glaucoma in elderly patients treated with inhaled corticosteroids for chronic airflow obstruction. Pulm Pharmacol Ther. 2010 Apr;23(2):65-70. doi: 10.1016/j.pupt.2009.10.014. Epub 2009 Nov 1. — View Citation

Herschler J. Intractable intraocular hypertension induced by repository triamcinolone acetonide. Am J Ophthalmol. 1972 Sep;74(3):501-4. — View Citation

Kalina RE. Increased intraocular pressure following subconjunctival corticosteroid administration. Arch Ophthalmol. 1969 Jun;81(6):788-90. — View Citation

Kim H, Mazza J. Asthma. Allergy Asthma Clin Immunol. 2011 Nov 10;7 Suppl 1:S2. doi: 10.1186/1710-1492-7-S1-S2. — View Citation

Kwon YH, Fingert JH, Kuehn MH, Alward WL. Primary open-angle glaucoma. N Engl J Med. 2009 Mar 12;360(11):1113-24. doi: 10.1056/NEJMra0804630. Review. — View Citation

Marcus MW, Müskens RP, Ramdas WD, Wolfs RC, De Jong PT, Vingerling JR, Hofman A, Stricker BH, Jansonius NM. Corticosteroids and open-angle glaucoma in the elderly: a population-based cohort study. Drugs Aging. 2012 Dec;29(12):963-70. doi: 10.1007/s40266-012-0029-9. — View Citation

Opatowsky I, Feldman RM, Gross R, Feldman ST. Intraocular pressure elevation associated with inhalation and nasal corticosteroids. Ophthalmology. 1995 Feb;102(2):177-9. — View Citation

Samiy N, Walton DS, Dreyer EB. Inhaled steroids: effect on intraocular pressure in patients without glaucoma. Can J Ophthalmol. 1996 Apr;31(3):120-3. — View Citation

Tripathi RC, Parapuram SK, Tripathi BJ, Zhong Y, Chalam KV. Corticosteroids and glaucoma risk. Drugs Aging. 1999 Dec;15(6):439-50. Review. — View Citation

Yuen D, Buys YM, Jin YP, Alasbali T, Trope GE. Effect of beclomethasone nasal spray on intraocular pressure in ocular hypertension or controlled glaucoma. J Glaucoma. 2013 Feb;22(2):84-7. doi: 10.1097/IJG.0b013e3182254811. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Intraocular Pressure	Masked assessment of intraocular pressure using goldmann application tonometry. Mean of 2 measurements within 1 mmHg will be recorded.	week 6
Secondary	Mean Visual Acuity	best corrected logMAR visual acuity for each eye. 20/20 vision corresponds with a logMAR score of 0, while negative logMAR scores indicate better than 20/20 vision, values > 0.5 correspond with low vision, and values > 1.3 correspond with blindness.	week 6
Secondary	Side Effects	subjective (reported) and objective (slit lamp examination) side-effects attributable to study medications	from baseline to week 6
Secondary	Intraocular Pressure Elevation >20% From Baseline	Participants with 2 consecutive intraocular pressure measurements exceeding 20% increase from baseline were discontinued from study.	within 6-week observation period
Secondary	Adherence	Adherence was calculated from self-reported study diaries and correlated to a counter that measured number of inhaled puffs built into the placebo metered-dose inhalers	Completion of study, up to 6 weeks