Fuchs Endothelial Dystrophy

Descemet Endothelial Thickness Comparison Trial (DETECT) II is a multi-center, outcome assessor-masked, placebo-controlled clinical trial randomizing 60 patients with Fuchs endothelial dystrophy to DMEK versus Descemet Stripping Only (DSO) with adjunctive Ripasudil.

The purpose of the study is to determine the safety and efficacy of brief intraoperative corneal endothelial graft incubation in plasma rich in growth factors (PRGF) for reducing postoperative endothelial cell loss.

This study is designed as a randomised multicentric parallel group pragmatic trial of Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) versus Descemet Membrane Endothelial Keratoplasty (DMEK) in corneal endothelial decompensation. the purpose is to compare the clinical and patient reported outcomes of both therapies across a broad range of indications.

The goal of this clinical trial is to learn if PVEK, a corneal implant , is safe and well tolerated for people with corneal swelling caused by Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy who need endothelial keratoplasty. The main questions it aims to answer are: What side effects may happen after the PVEK implant? How many participants can complete the first 6 months after surgery without needing another treatment because the implant did not help enough or was not tolerable? This is a Phase 1 (first-in-human) study with one study group, meaning all participants receive the PVEK implant (there is no placebo or comparison group). About 15 participants will take part and will be followed for up to 12 months after surgery. Participants will: Complete screening tests (including eye exams and routine health checks) Have the PVEK implantation surgery Use prescribed eye drops after surgery Return for follow-up visits over the next 12 months for eye exams and tests (such as vision testing, eye pressure checks, and eye scans)

The goal of this clinical study is to assess the safety of multiple intracameral injections of EO2002 with and without topical Ripasudil.

We have developed novel Brillouin microscopy and we are testing its potential for keratoconus and ectasia diagnostics. We plan to perform axial scans of the cornea in human volunteers in order to compare biomechanical properties of Keratoconus vs. Normal corneas and compare biomechanical properties of post-LASIK ectasia vs. normal corneas.

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.

Assessment of safety and efficacy of tissue-engineered corneal endothelial graft material generated using cultured human corneal endothelial cells for tissue-engineered endothelial keratoplasty (TE-EK).

Optical coherence tomography (OCT )provides high resolution information regarding the anatomic structure of the tissues of the eye in a cross-sectional and 3 dimensional view. Much of this information is not able to be visualized by a clinician. Utilizing this information during surgery will allow for the ophthalmic surgeons to better understand how surgical procedures impact the anatomic structure of the eye. In this study an OCT device that has been built into the microscope (rather than mounted on the side or held in the surgeon's hand) and will be utilized to take images at various milestones during surgery to assess feasibility and potential utility of this technology. Since it is built into the microscope, there are potential significant advantages over a separate system including increased efficiency, improved working distance, and the ability to visualize tissue-instrument interactions.

This study aims to explore the mechanical properties of the cornea using a non-invasive imaging technique called Brillouin microscopy. This innovative method measures corneal elasticity by detecting small shifts in light frequency, which occur due to interactions with acoustic waves in the tissue. These measurements can provide insights into how corneal stiffness is altered in various eye diseases or after surgery. The study includes 100 participants, divided into different groups: patients with Fuchs' Endothelial Dystrophy (FED), Map Dot Fingerprint Dystrophy (MDFD), and those who have undergone corneal surgeries such as Penetrating Keratoplasty (PKP), Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK), and Descemet Membrane Endothelial Keratoplasty (DMEK). Healthy individuals will also be studied as a control group. Participants will first receive a standard eye exam, including a slit-lamp examination. Then, Brillouin microscopy will be used to measure the cornea's mechanical stiffness. Additional tests include optical coherence tomography (OCT), corneal topography and tomography, pachymetry (measuring corneal thickness), endothelial cell count, and intraocular pressure (IOP) measurement. The purpose of this study is to better understand how diseases and surgeries affect corneal biomechanics. The researchers will also examine how well the Brillouin measurements match with findings from other clinical imaging tests. The results may help improve diagnosis and treatment options for corneal disorders.

FECD-TRACE is an integral component of a large research program dedicated to Fuchs Endothelial Corneal Dystrophy (FECD) in the United Kingdom. This longitudinal, observational study aims to comprehensively characterize a cohort of younger research participants who have a genetic predisposition to developing FECD. By utilizing advanced anterior segment imaging techniques, the study will monitor these individuals over a span of several years, capturing phenotypic changes that reflect the progression of the disease. Concurrently, genetic biomarkers will be examined to establish correlations with the observed phenotypic changes. The primary objective of FECD-TRACE is to enhance our understanding of the intricate genetic mechanisms underlying FECD and establish connections between these genetic findings and clinical outcomes. Ultimately, this research strives to facilitate the development of personalized care approaches for individuals affected by FECD.

The purpose of this research is to investigate the effects of ripasudil administered as an ophthalmic solution in patients with FED after femtosecond laser assisted cataract surgery. The secondary aim is to identity the characteristics of patients who will benefit the most with the use of ripasudil based on the test results obtained from this study.

To evaluate the clinical outcomes (pos toperative best corrected visual acuity, endothelial count) and anatomical results (interface smoothness) of DSAEK with Femto LDV-prepared grafts from the endothelial side.

In brief, the objective of this study is to investigate whether the drug Glanatec ® which is approved in Japan for glaucoma and ocular hypertension, can be used in patients with Fuchs endothelial dystrophy who have had a descemet stripping procedure without endothelial keratoplasty. While some limited data exists as a proof of concept in in vitro or animal studies, and Glanatec® has been successfully used in a recently published case series for this indication, there is insufficient data to show that this drug can be effectively used for corneal cell clearing while maintaining patient safety. The goal of the study is to provide sufficient proof of concept for the use of this drug in patients with FED whose only treatment alternative is to undergo corneal transplant.