Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease

doi:10.1016/S0161-6420(99)00176-1

Ophthalmology

Volume 107, Issue 4, April 2000, Pages 631-639

https://doi.org/10.1016/S0161-6420(99)00176-1 Get rights and content

Abstract

Objective

To compare the efficacy and safety of cyclosporin A ([CsA] 0.05% and 0.1% ophthalmic emulsions) to vehicle in patients with moderate to severe dry eye disease.

Design

Multicenter, randomized, double-masked, parallel-group, 6-month, vehicle-controlled.

Participants

A total of 877 patients with defined moderate to severe dry eye disease (292 to 293 in each treatment group).

Methods

Two identical clinical trials; patients were treated twice daily with either CsA, 0.05% or 0.1%, or vehicle. The results of these two trials were combined for analysis.

Main outcome measures

Efficacy: corneal and interpalpebral dye staining, Schirmer tear test (with and without anesthesia), tear break-up time, Ocular Surface Disease Index (OSDI), facial expression, patient subjective rating scale, symptoms of dry eye, investigator’s evaluation of global response to treatment, treatment success, and daily use of artificial tears. Safety: occurrence of adverse events, best-corrected visual acuity, intraocular pressure, biomicroscopy, and blood trough CsA concentrations.

Results

Treatment with CsA, 0.05% or 0.1%, gave significantly (P ≤ 0.05) greater improvements than vehicle in two objective signs of dry eye disease (corneal staining and categorized Schirmer values). CsA 0.05% treatment also gave significantly greater improvements (P < 0.05) in three subjective measures of dry eye disease (blurred vision, need for concomitant artificial tears, and the physician’s evaluation of global response to treatment). There was no dose-response effect. Both CsA treatments exhibited an excellent safety profile, and there were no significant topical or systemic adverse safety findings.

Conclusions

The novel ophthalmic formulations CsA 0.05% and 0.1% were safe and effective in the treatment of moderate to severe dry eye disease yielding improvements in both objective and subjective measures. Topical CsA represents a new pharmacologically based treatment for dry eye disease that may provide significant patient benefits.

Section snippets

Study design

Two identical multicenter, randomized, double-masked, parallel-group clinical trials were conducted to compare two concentrations of CsA ophthalmic emulsion to its vehicle. The 6-month treatment phase was preceded by a 2-week run-in phase to standardize all patients to a common regimen of artificial tear use. The results of these two trials were combined for analysis.

Both trials were conducted in compliance with Good Clinical Practices, investigational site Institutional Review Board

Participant flow and follow-up

A total of 877 patients was enrolled in approximately equal numbers in the three treatment groups and more than 76% (671/877) completed the study (Table 1). The first patient was enrolled in July 1997 and the last patient completed the 6-month treatment period and evaluation in September 1998. Most of the patients who exited the study prematurely did so as a result of protocol or enrollment violations, personal reasons, lost to follow-up, or other nontreatment-related reasons. Only 0.8% of

Discussion

Several recent publications have suggested that dry eye disease is the result of complex inflammatory processes and suggest that the immunomodulatory drug cyclosporine may have potential as a novel therapeutic treatment for moderate to severe dry eye disease (Foulks et al, Invest Ophthalmol Vis Sci 1996;37:3S646; Helms et al, Invest Ophthalmol Vis Sci 1996;37; 3S646; Kunert et al, Invest Ophthalmol Vis Sci 1999;40[4]:S771; Turner et al, Invest Ophthalmol Vis Sci 1999;40[4]:S558).2, 10, 11, 13,

Acknowledgements

The Cyclosporin Phase 3 Study Group: Penny A. Asbell, MD (Mt. Sinai Medical, New York, NY), Laurie G. Barber, MD (University of Arkansas for Medical Sciences, Little Rock, AR), Greg Berdy, MD (Creve Coeur, MO), Moira Burke, MD (Palm Harbor and Tampa, FL), H. Dwight Cavanagh, MD (University of Texas, Dallas, TX), Peter C. Donshik, MD (University of Connecticut Health Center, West Hartford, CT), Randy J. Epstein, MD (Rush Presbyterian–St. Luke’s Medical Center, Chicago, IL), Robert J. Foerster,

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^☆: Supported by a grant from Allergan Inc.

¹: Reprint requests to: Linda Lewis, 575 Anton Blvd, Suite 900, Costa Mesa, CA 92626.

²: Dr. Reis is an employee of Allergan, Inc. None of the other authors has a financial interest in any of the products mentioned in this paper.

View full text

Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease1☆,

Abstract

Objective

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Section snippets

Study design

Participant flow and follow-up

Discussion

Acknowledgements

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Keratoconjunctivitis sicca and primary Sjögren’s syndrome in a Danish population aged 30-60 years

Acta Ophthalmol Scand

Senile atrophy of the human lacrimal glandthe contribution of chronic inflammatory disease

Br J Ophthalmol

Prevalence of dry eye in Japanese eye centers

Graefes Arch Clin Exp Ophthalmol

Diagnosis and management of dry eye and ocular surface disorders

Ophthalmology Clinics of North America

Diagnostic implications of tear protein profiles

Br J Ophthalmol

The effect of ageing and disease on tear constituents

Trans Ophthalmol Soc UK

Traffic of major histocompatibility complex class II molecules in rabbit lacrimal gland acinar cells

Invest Ophthalmol Vis Sci

Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren’s syndrome keratoconjunctivitis sicca

Curr Eye Res

The pathology of dry eyethe interaction between the ocular surface and lacrimal glands

Cornea

Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease¹☆,