From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy

Overview

There is a lack of evidence on the impact of switching from a combined preserved anti-glaucoma regimen to a preservative-free (PF) one, while employing sufficiently robust OSD metrics. The investigators have therefore carried out a single center, prospective, crossover investigation to compare the 6-month effect of switching well controlled open-angle glaucoma patients with at least moderate glaucoma therapy-related ocular surface disease from preserved to triple preservative-free therapy with and without cyclosporine 0.1% dosed in the evening.

Full Title of Study: “Changing From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy: Impact on the Rate and Severity of Ocular Surface Disease”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: December 31, 2019

Detailed Description

Halting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide. Chronic medical therapy for glaucoma may be immensely benefitted by limiting disabling GTR-OSD, which would aid in the prevention of blindness. In 2015 a novel cationic formulation of cyclosporine A 0.1% was approved with once in the evening dosing in Europe. It is an effective, targeted immunomodulatory compound reducing inflammatory mediators and providing healing of the ocular epithelium. There remains however a paucity of published controlled evidence for GTR-OSD patients treated with this formulation. In addition, there is a lack of evidence on the impact of switching from a combined preserved anti-glaucoma regimen, to a preservative-free one, while employing sufficiently robust OSD metrics. The investigators have therefore carried out a single center prospective, crossover investigation to compare the 6-month effect of switching well controlled open-angle glaucoma patients with at least moderate GTR-OSD, from preserved to triple PF therapy with and without PF cyclosporine 0.1% dosed in the evening.

Interventions

  • Diagnostic Test: Assessment of ocular surface staining (Oxford score 0-15 scale)
    • Corneal and conjunctiva staining will be recorded according to the Oxford grading scheme for ocular staining (0-15 score).
  • Drug: mean diurnal intraocular pressure-lowering
    • At the end of each 6-month period patients will undergo diurnal intraocular pressure assessment with both therapies.

Arms, Groups and Cohorts

  • Placebo Comparator: Triple preservative-free therapy with placebo in the evening
    • In this arm subjects will be randomized to topical therapy comprising preservative-free tafluprost drops dosed in the evening (20:30) and dorzolamide/timolol fixed combination drops administered twice daily (8:00 and 20:00). Patients will use placebo (artificial tears) in the evening (21:00) for 6 months. At the end of this period patients will be crossed over to the other therapy (cyclosporine 0.1% in the evening)
  • Active Comparator: Triple preservative-free therapy with cyclosporine 0.1% in the evening
    • In this arm subjects will be randomized to topical therapy comprising preservative-free tafluprost drops dosed in the evening (20:30) and dorzolamide/timolol fixed combination drops administered twice daily (8:00 and 20:00). Patients will use cyclosporine 0.1% drops in the evening (21:00) for 6 months. At the end of this period all patients will be crossed over to the other therapy (placebo in the evening)

Clinical Trial Outcome Measures

Primary Measures

  • Mean change from baseline in ocular staining (Oxford score)
    • Time Frame: 6 months
    • The primary efficacy endpoint for this crossover study will be the mean change from baseline in the total ocular staining score as determined by the 15-point Oxford scale of staining on the study eye.

Secondary Measures

  • Mean diurnal IOP
    • Time Frame: 6 months
    • Mean diurnal intraocular pressure with the two preservative-free therapies versus preserved baseline will be evaluated as secondary endpoint.
  • Osmolarity
    • Time Frame: 6-months
    • Mean tear osmolarity with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.
  • Matrix-metalloproteinase-9 (MMP-9) over-expression
    • Time Frame: 6 months
    • Mean MMP-9 over-expression with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.

Participating in This Clinical Trial

Inclusion criteria

  • Adult patients with well controlled open-angle glaucoma – Patients chronically treated for more than 6 months with preserved, branded, or generic, triple antiglaucoma therapy comprising latanoprost and dorzolamide/timolol fixed combination – Subjects should have experienced at least 1 symptom of dry eye (soreness, scratchiness, dryness, grittiness, and burning) – Additionally, patients should demonstrate at least one of the objective signs for OSD at baseline: positive conjunctival staining with lissamine green and/or evidence of positive corneal staining with fluorescein (assessed with the 15-point Oxford scale), – Patients must show a BUT<8 seconds – On screening patients should show a Schirmer test without anesthesia (Schirmer-I test) ≥3 and ≤10 mm in 5 minutes. – When both eyes qualify the worse eye will be included in the study. Exclusion criteria – Best corrected visual acuity <1/10 – Patients with severe dry eye disease or Sjogren's disease – Presence of eyelid abnormality, corneal disorder or abnormality, ocular surface metaplasia, filamentous keratitis, or corneal neovascularization – Patients who have undergone ocular surgery (of any type, including laser surgery), or ocular trauma within 4 months prior to screening – Subjects who had punctal occlusion, or diathermy within 3 months prior to screening or abnormality of the nasolacrimal drainage apparatus. – Known allergy, or sensitivity to any of the study medications – Uncontrolled systemic disease, or history or active signs of ocular trauma, infection, inflammation, allergic disease, or herpes; corneal ulcers; recurrent erosions; or uveitis – Female patients will be excluded if they are pregnant, breastfeeding, planning a pregnancy, or are unwilling to use a reliable form of contraception.

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Aristotle University Of Thessaloniki
  • Provider of Information About this Clinical Study
    • Principal Investigator: AGP Konstas, Professor in Ophthalmology – Aristotle University Of Thessaloniki
  • Overall Official(s)
    • Andreas Katsanos, MD, PhD, Study Director, University of Ioannina

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