A Prospective, Multicenter, Randomized Controlled Study of Loteprednol Initiation Therapy Followed b

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A Prospective, Multi-center, Randomized
Controlled Study of Loteprednol Initiation
Therapy Followed by Cyclosporine Maintenance for
Dry EyeJohn D. Sheppard, MD,1 Eric D.
Donnenfeld, MD,2 Edward J. Holland, MD, Charles
B. Slonim, MD, Renée Solomon, MD, Kerry D.
Solomon, MD, Marguerite B. McDonald, MD, Henry D.
Perry, MD, Stephen S. Lane, MD, and Stephen C.
Pflugfelder, MD.1Virginia Eye Consultants,
Norfolk, VA, 23502, and 2Ophthalmic Consultants
of Long island, Rockville Center, NY, 11570
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Financial Disclosures

• This study was supported by an unrestricted
  research grant from Bausch Lomb, Inc.

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Abstract

• Purpose To evaluate the impact of loteprednol
  0.5 as initiation therapy, followed by topical
  cyclosporine (tCSA) maintenance therapy in
  patients with dry eye disease (DED).
• Methods 121 patients with DED were enrolled in
  a multicenter, randomized, controlled, masked,
  prospective clinical trial. Patients received
  either initial loteprednol 0.5 or artificial
  tears for 2 weeks prior to starting maintenance
  tCSA therapy.
• Results The loteprednol initiation group showed
  improved OSDI scores (plt0.01) at Day 14,
  decreased cyclosporine stinging at Day 30
  (plt0.04), and improved corneal staining at Day 30
  (plt0.05) compared to the placebo initiation
  group.
• Conclusion Loteprednol initiation followed by
  tCSA maintenance improves patient compliance,
  reduces stinging and provides more rapid relief
  of dry eye disease than tCSA therapy alone.

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Introduction

• Dry eye disease (DED) is an ocular surface
  disease that produces discomfort and irritation.
• Cyclosporine ophthalmic emulsion 0.05
  (Restasis) is indicated to increase tear
  production in patients whose tear production is
  presumed to be suppressed due to ocular
  inflammation associated with keratoconjunctivitis
  sicca. However, the relief of dry eye signs and
  symptoms with cyclosporine therapy is often
  delayed by 1 to 6 months from the initiation of
  therapy, and 17 of patients experience burning
  and stinging leading to poor patient compliance.1
• Marsh Pflugfelder2 showed that corticosteroid
  therapy in patients with DED improved signs and
  symptoms, improved tear clearance, and normalized
  mucus production, often having a sustained
  benefit after a 2 week pulse. In addition,
  corticosteroid treatment improved tear production
  by controlling inflammation and decreased the
  irritation associated with the use of
  cyclosporine by 75.2,3
• Loteprednol etabonate ophthalmic suspension 0.5
  (Lotemax) is indicated for the treatment of
  steroid responsive inflammatory conditions
  associated with the palpebral and bulbar
  conjunctiva, cornea, and anterior segment of the
  globe.

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Purpose

• The purpose of this study was to evaluate the
  impact of loteprednol 0.5 as initiation therapy
  in patients with DED.
• Methods
• A total of 121 patients with DED were enrolled in
  this multicenter, randomized, controlled, masked,
  prospective clinical trial.
• Patients received either initial loteprednol 0.5
  or artificial tears for two weeks (Day 1 to14)
  prior to starting maintenance tCSA therapy (Day
  15 to 60). Additional use of artificial tears
  was allowed as needed.
• Patients were evaluated by the Ocular Surface
  Disease Index (OSDI) for symptoms and underwent
  full ophthalmic examination including BCVA,
  biomicroscopy with fluorescein and lissamine
  green staining, applanation IOP and Schirmers
  test without anesthesia on days 14, 30 and 60.

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Results

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate/tCSA was more effective
  than artificial tears/tCSA in reducing central
  corneal staining (P0.003).

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).

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Results (cont.)

• Although both treatments decreased lissamine
  green staining grade, loteprednol etabonate with
  tCSA was more effective in all cases (Plt0.05).

Data compared with ANOVA

• Although both treatments decreased lissamine
  green staining, loteprednol etabonate with tCSA
  was more effective in all cases (Plt0.05).

• Although both treatments decreased lissamine
  green staining, loteprednol etabonate with tCSA
  was more effective in all cases (Plt0.05).

• Although both treatments decreased lissamine
  green staining, loteprednol etabonate with tCSA
  was more effective in all cases (Plt0.05).

• Although both treatments decreased lissamine
  green staining, loteprednol etabonate with tCSA
  was more effective in all cases (Plt0.05).

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Results (cont.)

• At baseline, tear production in both groups was
  similar (P0.48).
• Both treatments increased tear production from
  baseline (P0.01 for loteprednol etabonate with
  tCSA, P0.05 for artificial tears with tCSA ).
• When normalized to baseline, loteprednol
  etabonate with tCSA increased tear production by
  27 vs. 17 with artificial tears with tCSA over
  a 60 day period (Plt0.005).

Data compared with ANOVA after outliers were
removed. Data is pooled (OD and OS)
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Results (cont.)

• Both treatments decreased the frequency of
  adjunct tear use in patients.
• After long term treatment (60 days), loteprednol
  etabonate/tCSA treatment reduced the overall tear
  use in patients.

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Results (cont.)

• Baseline OSDI scores were not different between
  treatment groups.
• Both treatments reduced OSDI scores over a period
  of 60 days (Plt0.05).
• Loteprednol etabonate with tCSA reduced OSDI
  scores significantly more than artificial tears
  with tCSA (Plt0.001).

Data compared with ANOVA after outliers were
removed.
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Results (cont.)

• With long term treatment (60 days), loteprednol
  etabonate/tCSA did not affect IOP (P0.22).

Data compared with ANOVA after outliers were
removed. Data is pooled (OD and OS) Data
presented is the mean SEM
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• Conclusion
• Loteprednol initiation followed by tCSA
  maintenance improves patient compliance, reduces
  stinging and provides more rapid relief of dry
  eye disease than tCSA therapy alone.

• References
• Sall K, Stevenson OD, Mundorf TK, Reis BL. Two
  multicenter, randomized studies of the efficacy
  and safety of cyclosporine ophthalmic emulsion in
  moderate to severe dry eye disease. CsA Phase 3
  Study Group. Ophthalmology 2000107631-639.
• Marsh P, Pflugfelder SC. Topical non-preserved
  methylprednisolone therapy for keratoconjunctiviti
  s sicca in Sjögren syndrome. Ophthalmology
  1999106939-943.
• Sheppard JD. Topical loteprednol pre-treatment
  reduces cyclosporine stinging. ASCRS Presentation
  39384, Washington DC, 2005.

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).

• Both treatments decreased central corneal
  staining over 60 days (Plt0.005).
• Loteprednol etabonate was more effective than
  artificial tears in reducing central corneal
  staining (P0.003).