Rationale:
The cornea is the most transplanted tissue in the Netherlands, with more than 1,500
procedures performed each year.1 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).2
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 surgery3 and can lead to irreversible
optic nerve damage and vision loss.4 Patients with IOP elevation require additional
medications and hospital visits resulting in reduced quality of life and increased costs.5
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.6 With this work, we 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 randomised 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) compared to
pre-surgical baseline
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.