Trial Comparing Cataract Surgery with Triple-DMEK in Patients with Cataract and Fuchs Endothelial Corneal Dystrophy

The purpose of the study is to investigate whether there is a difference in BCVA in patients who receive one of the following two surgeries: intervention group (arm 1) cataract surgery alone and control group (arm 2) cataract surgery combined with removal of the diseased endothelial cells and the attached Descemet's membrane followed by transplantation of a healthy endothelial cell layer with attached Descemet's membrane ("triple-DMEK" group; comparator therapy).

The secondary objectives are to compare the two surgical methods with regard to other visual functions and optical as well as morphological differences, to safety, to quality of life, and to safety.

After signing the informed consent, patients are screened for eligibility for the trial regarding in- and exclusion criteria.

Different tests will be performed like ocular examination including slit lamp examination, fundus examination, IOP measurement, BCVA, Pentacam imaging, and Macular-OCT, vital signs. In addition, women below age of 60 have to perform a urine pregnancy test. Once all inclusion criteria and none of the exclusion criteria are met, the patient will be enrolled into the trial and will receive a subject-ID.

The Baseline Visit can take place up to 7 days after enrolment of the subject into the clinical trial. At the Baseline Visit a photograph of the cornea in retroillumination will be taken (can be taken either at Screening \& Enrolment Visit or at Baseline Visit) and uploaded into the eCRF for central grading by CORIC.

In addition, subjects have to complete vision related quality of life questionnaires and changes in relevant medical history/concomitant diseases as well as concomitant medications have to be documented.

Furthermore, a contrast sensitivity test and an optical quality test (if device available) will be peformed.

After all investigations are completed, the subject will be randomised via the central 24-7 Internetrandomisation service ALEA and distributed to the respective treatment groups.

Intervention (surgery):

On that day and before starting intervention all women below 60 years undergo a pregnancy test and changes in relevant medical history/concomitant diseases have to be documented. In arm 1 (intervention group) patients undergo exclusively cataract surgery, in arm 2 (control group) patients undergo triple-DMEK, i.e. cataract surgery and DMEK.

The immediate follow-up appointments for clinical examinations are, as per standard of care, at the discretion of the respective trial centres treating physician.

The Post-operative Visit will take place 22 weeks ± 14 days after the surgical intervention. During the Post-operative Visit an ocular examination including slit lamp examination, fundus examination, IOP measurement, BCVA, Pentacam imaging, contrast sensivity test, an optical quality test (if device available), and Macular-OCT will be performed. In addition, vital signs will be taken and subjects have to complete the vision related quality-of-life questionnaires again. Concomitant medications and AEs/SAEs have to be documented.

The duration of the clinical trial for every individual subject will be up to 29 weeks (time from Screening \& Enrolment Visit to Post-operative Visit).

Eligibility Criteria:
Inclusion Criteria:

1. Patients with FECD and nuclear cataract in study eye
2. Male and female patients ≥18 years of age
3. Subject must be able to understand and read the national language.
4. Written informed consent prior to any study-related procedures
5. Nuclear opalescence (NO) grades 2 and 3 according to the lens opacities classification system III (LOCS III)
6. Krachmer grade (3 \[2-5 mm diameter area with confluent guttae\]; 4 \[ \> 5 mm diameter area with confluent guttae\] without edema identified by slit lamp examination)
7. Central corneal thickness (CCT) measured with Pentacam below 620 µm between 8:00 am and 01:00 pm
8. BCVA logMAR \< 0,7 and \> 0,1
9. No previous cataract surgery or triple-DMEK on the opposite side
10. Pentacam quality specification: "OK"
11. For women below age of 60 negative urine pregnancy test

Exclusion Criteria:

1. Patients with ocular and/or systemic comorbidity affecting vision or clinically proven anterior and/or posterior segment disease other than FECD and cataract (exclusion of macular disease or edema by OCT)
2. Iris synechiae, pupil diameter \<6 mm after dilatation, pseudoexfoliation syndrome, subluxated lens, previous history of ocular trauma/surgery or inflammatory disease
3. Subjective diurnal changes in visual acuity with worse visual acuity in the morning
4. Corneal (epithelial) edema visible at slit lamp examination
5. Preoperative anterior chamber depth below 2 mm
6. Participation in other interventional trials parallel or within the last 4 weeks
7. Systemic use of Alpha-1-Adrenozeptor-Antagonists, immunosuppressive therapy or chemotherapy
8. Pregnant women and nursing mothers
9. Persons with any kind of dependency on the principal investigator or employed by the sponsor or principal investigator
10. Legally incapacitated persons
11. Persons held in an institution by legal or official order