The OPTIMISE Study

NCT05716945 | Recruiting Phase 4 DMC

• 1 other identifier: 2022-500109-41-00
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 8

Brief Summary

Rationale: The cornea is the most transplanted tissue in the Netherlands, with more than 1,500 procedures performed each year. A minimally invasive technique called Descemet Membrane Endothelial Keratoplasty (DMEK) has become the preferred method in the past decade. The main advantage of DMEK over previous techniques is a low graft rejection rate (1-2% per year). Despite this, rejection prophylaxis after DMEK follows the same high potency regimen as previous techniques in the first year, and patients are burdened with indefinite immunosuppression. The current project, OPTIMISE, aims to establish an evidence-based, cost-effective regimen that effectively prevents rejection and minimizes side effects. Corticosteroid eye drops are the mainstay of ocular immunomodulatory therapy. Their main side effect is a steroid-induced increase in intraocular pressure (IOP). It manifests in about one-fourth of patients within the first year after surgery and can lead to irreversible optic nerve damage and vision loss. Patients with IOP elevation require additional medications and hospital visits resulting in reduced quality of life and increased costs. The optimal dosing regimen in the first year after DMEK and whether patients may safely stop steroids after one year remains unknown. As a result, protocols in the Netherlands vary considerably from surgeon to surgeon. Patients are potentially over-treated in the short and long-term, resulting in undue burden for the patient and increased costs. Consequently, the Dutch Ophthalmology Society (NOG) identified the optimal short- and long-term immunosuppressive protocol for corneal transplantation as one of its Top 10 knowledge gaps, underscoring relevance for clinical practice. With this work, the investigators expect to address this knowledge gap to the benefit of our patients and society. Objective: The OPTIMISE study aims to establish an evidence-based, cost-effective regimen that effectively prevents rejection and minimizes side effects. The hypothesis of this study is that Fluorometholone 0.1% in the first year and discontinuing medication in the second year is a cost-effective treatment strategy after DMEK. Study design: The design of this study is a randomized, controlled multicentre trial with a duration of 24 months. Study population: The study population will consist of 342 patients aged 21 years or older undergoing DMEK surgery in one eye. Intervention: All patients will receive Descemet's Membrane Endothelial Keratoplasty. Following this procedure, patients will be randomized into the following post-operative regime in two stages: STEP-I (Year 1): Control group: DMS 0.1% 6 times a day for 1 month tapered off to once daily within 6 months and then once a day for 6 months. Intervention group: DMS 0.1% 6 times a day for 1 month followed by FML 0.1% 4 times a day for two months tapered off to once daily within four months and then once a day for 6 months. STEP-II (Year 2): Control Group: Half the patients in each study arm will use FML 0.1% daily. Intervention Group: Half the patients in each study arm will discontinue steroids. Main study parameters/endpoints: Primary outcomes: Step-I: IOP elevation compared to baseline Step-II: Endothelial cell loss (ECL) in the second year Secondary outcomes are:

• Rejection free graft survival.
• Patient reported outcome measures.
• Incremental cost-effectiveness ratios, including a short term trial-based economic evaluation (TBEE) and a life-long model-based economic evaluation (MBEE)
• Structural outcomes including corneal, central macular and retinal nerve fibre layer thicknesses, and optic nerve head imaging.

Conditions

Pseudophakic Bullous Keratopathy; Fuchs' Endothelial Dystrophy; Intraocular Pressure

Keywords

Descemet Stripping Endothelial Keratoplasty; Cornea

Outcome Measures

Primary Outcomes (2)

• Difference of intraocular pressure elevation between the two arms

  Year 1

• Difference of endothelial cell loss (ECL) in the second year

  Year 2

Secondary Outcomes (3)

• Difference of rejection free graft survival between arms

  1-2 years

• Differences of patient reported outcome measures between groups

  1-2 years

• Differences of incremental cost-effectiveness ratios, including a short term trial-based economic evaluation (TBEE) and a life-long model-based economic evaluation (MBEE)

  1-2 years

Study Arms (4)

Intervention STEP I (Year 1 after DMEK)

EXPERIMENTAL

Drug: Fluorometholone 0.1% Oph Susp; Drug: Dexamethasone 0.1% ophthalmic suspension

Control STEP I (Year 1 after DMEK)

ACTIVE COMPARATOR

Drug: Dexamethasone 0.1% ophthalmic suspension

Intervention STEP II (Year 2 after DMEK)

EXPERIMENTAL

Other: Stop steroids

Control STEP II (Year 2 after DMEK)

ACTIVE COMPARATOR

Drug: Fluorometholone 0.1% Oph Susp

Interventions

Fluorometholone 0.1% Oph Susp DRUG

Year 1: DMS 0.1% 6 times a day for 1 month followed by FML 0.1% 4 times a day for two months tapered off to once daily within four months and then once a day for 6 months. Year 2: Half the patients in each study arm will use FML 0.1% daily.

Control STEP II (Year 2 after DMEK); Intervention STEP I (Year 1 after DMEK)

Dexamethasone 0.1% ophthalmic suspension DRUG

Year 1: DMS 0.1% 6 times a day for 1 month tapered off to once daily within 6 months and then once a day for 6 months.

Control STEP I (Year 1 after DMEK); Intervention STEP I (Year 1 after DMEK)

Stop steroids OTHER

Half the patients in each study arm will discontinue steroids.

Intervention STEP II (Year 2 after DMEK)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients aged 21 years or older registered on the NOTR as candidates for DMEK corneal transplantation

You may not qualify if:

• Inability to complete follow up or comply with study procedures
• The participant is vulnerable
• Previous corneal graft in the study eye
• Known sensitivity or contraindication to the ingredients in the study medications
• History of uveitis
• History of any herpes simplex infection
• Human Leukocyte Antigen (HLA) typed allograft
• Pregnancy (current and planned) or lactation
• Use of other local or systemic immunosuppressive drugs

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (8)

Gelre Ziekenhuizen

Apeldoorn, Gelderland, 7300 DS, Netherlands

RECRUITING

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, 6500 HB, Netherlands

RECRUITING

Maastricht Universitair Medisch Centrum+

Maastricht, Limburg, 6202 AZ, Netherlands

RECRUITING

Amsterdam Universitair Medisch Centrum

Amsterdam, North Holland, 1105 AZ, Netherlands

RECRUITING

Deventer Ziekenhuis

Deventer, Overijssel, 7400 GC, Netherlands

RECRUITING

Universitair Medisch Centrum Groningen

Groningen, Provincie Groningen, 9700 RB, Netherlands

NOT YET RECRUITING

Leiden Universitair Medisch Centrum

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Universitair Medisch Centrum Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

NOT YET RECRUITING

MeSH Terms

Conditions

Fuchs' Endothelial Dystrophy; Corneal Diseases

Interventions

Fluorometholone; Dexamethasone

Condition Hierarchy (Ancestors)

Corneal Dystrophies, Hereditary; Eye Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienetriols

Central Study Contacts

Yexin Ye, MD

CONTACT

+31 43 387 5406; yexin.ye@mumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 8, 2023
• Study Start: July 29, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (8)