Clinical trial NCT04673604: From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glaucoma
Ocular Surface Disease
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
First posted: 2020-12-17
Enrollment: 42
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Masked, prospective, placebo-controlled, crossover trial of glaucoma patients with moderate to severe GTR-OSD on preserved latanoprost and dorzolamide/timolol fixed combination therapy for well-controlled open-angle glaucoma was conducted. Patients were randomized to receive preservative-free tafluprost and dorzolamide/timolol fixed combination with either topical placebo or cyclosporine 0.1% for 6 months and will then be crossed over to the opposite therapy. Oxford score of staining will be the primary outcome; osmolarity, matrix-metalloproteinase-9 testing (MMP-9), meibomian gland dysfunction (MGD), adverse events and diurnal intraocular pressure (IOP) comprise the secondary outcomes.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean change from baseline in ocular staining (Oxford score)
timeFrame: 6 months
Secondary outcomes:
measure: Mean diurnal IOP
timeFrame: 6 months
measure: Osmolarity
timeFrame: 6-months
measure: Matrix-metalloproteinase-9 (MMP-9) over-expression
timeFrame: 6 months
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: University Department of Ophthalmology
Study officials:
affiliation: University of Ioannina
name: Andreas Katsanos, MD, PhD
role: STUDY_DIRECTOR
References: