Cataract and Fuchs Endothelial Corneal Dystrophy, Cataract Surgery
Conditions
Keywords
Fuchs´ Endothelial Corneal Dystrophy Krachmer grade 3 and 4, nuclear cataract, Nuclear opalescence (NO) grades 2, Nuclear opalescence (NO) grades 3, Central corneal thickness
Brief summary
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.
Detailed description
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).
Interventions
PROCEDUREIntervention group /arm 1 (Cataract surgery alone)
Cataract surgery (arm 1) is performed using a small incision technique. The tunnel is used both for cataract surgery and for implantation of the DMEK graft (arm 2). The centres confirmed that the main incision will be localized between 11 and 12 o'clock and will have a width of 2.4 to 2.8 mm. A tunnel suture will only be placed if there is leakage from the incisions. If cataract surgery alone (arm 1) is performed, a thin dispersive viscoelastic is applied to the endothelium for protection before phacoemulsification. A hydrophobic acrylic monofocal IOL will be implanted into the bag. The centers confirmed that Barret Universal II formula is the standard IOL calculation formula for both groups and for all axial lengths.
PROCEDUREControl group /arm 2: Corneal transplantation as Descemet Membrane Endothelial Keratoplasty (DMEK) in combination with cataract surgery (triple-DMEK)
After cataract surgery DMEK is continued using the surgeon's standard technique for graft implantation and unfolding in triple-DMEK. In all cases the graft will be implanted using the same main incision as for IOL implantation. Once the DMEK graft is unrolled and attached to the posterior corneal stroma the complete anterior chamber will be filled with SF6 20%.
Sponsors
The Clinical Trials Centre Cologne
ESCRS (European Society of Cataract and Refractive Surgeons)
University of Cologne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
After screening and enrollement subjects will be randomly allocated to the trial groups (cataract surgery versus triple-DMEK, allocation rate 1:1)
Intervention model description
The trial will be a prospective, randomised, controlled, European, multicentre, open clinical trial in which patients with FECD and cataract will receive either cataract surgery without DMEK (intervention goup/arm 1) or triple-DMEK (DMEK in combination with cataract surgery; control group/arm 2). (Protocol V02\_0\_TC page 37)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BCVA 22 | 22 weeks +/- 14 days after surgery | Best corrected visual acuity (BCVA) is messured with EDTRS-charts (transformed to logMAR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Contrast sensitivity | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Total score of Freiburg Vision Test FrACT; Analysis metric (participant level): Value Method of aggregation (summary measure for each study group): Mean |
| Change in contrast sensitivity | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Total score of Freiburg Vision Test FrACT; Analysis metric (participant level): Difference Value at follow-up-baseline value; Method of aggregation (summary measure for each study group): Mean difference |
| Optical quality measured by HD-analyzer | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Total score of objective scattering index (OSI); Analysis metric (participant level): Value Method of aggregation (summary measure for each study group): Mean |
| Change in optical quality measured by HD-analyzer | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Total score of objective scattering index (OSI); Analysis metric (participant level): Difference value at follow-up- baseline value Method of aggregation (summary measure for each study group): Mean difference |
| Change in Optical quality measured by HD-analyzer | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Total score of Strehl ratio; Analysis metric (participant level): Difference value at follow-up- baseline value Method of aggregation (summary measure for each study group): Mean difference |
| Refractive accuracy:spherical equivalent | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Deviation from target refraction from IOL calculation \[D\], Analysis metric (participant level): Value Method of aggregation (summary measure for each study group): Mean numerical prediction error (ME) and Mean absolute prediction error (MAE) |
| Corneal topography/ tomography parameters | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Corneal densitometry (grayscale unit GSU) (anterior, central, posterior and total layer) Analysis metric (participant level): Value; Method of aggregation (summary measure for each study group): Mean |
| Change in corneal topography/tomography parameters | At baseline and 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Corneal densitometry (grayscale unit GSU) (anterior, central, posterior and total layer); Analysis metric (participant level): Difference value at follow-up - baseline value; Method of aggregation (summary measure for each study group): Mean difference |
| Change in visual acuity (BCVA) | Baseline (pre-op) and 22 weeks +/- 14 days after initial surgery | Specific measurement variable: ETDRS-charts (transformed to logMAR); Analysis metric (participant level): Difference value at follow-up- baseline value Method of aggregation (summary measure for each study group): Mean difference |
| Change in central corneal thickness (CCT) | At baseline and 22 weeks +/- 14 days after initial surgery | Specific measurement variable: CCT measured by Pentacam \[μm\]; Analysis metric (participant level): Difference value at follow-up - baseline value Method of aggregation (summary measure for each study group): Mean difference |
| Quality of life | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Catquest-9SF (all centers) and V-Fuchs (Germany only); Analysis metric (participant level): Total score \[no dimension\]; Method of aggregation (summary measure for each study group): Mean |
| Change in quality of life | At baseline and at 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Catquest-9SF (all centers) and V-Fuchs (Germany only); Analysis metric (participant level): Difference total score at follow-up- baseline total score; Method of aggregation (summary measure for each study group): Mean difference |
| Change in central retinal thickness | At baseline and at 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Measured by OCT Analysis metric (participant level): Difference value at follow-up- baseline value; Method of aggregation (summary measure for each study group): Mean difference |
| Change in intraocular pressure (IOP) | At baseline and at 22 weeks +/- 14 days after initial surgery | Specific measurement variable: IOP \[mmHg\] Analysis metric (participant level): Difference value at follow-up - baseline value Method of aggregation (summary measure for each study group): Mean difference |
| Additional ocular surgeries | At baseline and at 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Per patient anamnesis Analysis metric (participant level): Value (yes/no) Method of aggregation (summary measure for each study group): Proportion |
| Endothelial decompensation with indication for endothelial keratoplasty (either planned or already performed) | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: Per patient anamnesis (decision made by treating ophthalmologist; incl. ophthalmologist outside the study team) Analysis metric (participant level): Value \[yes/no\] Method of aggregation (summary measure for each study group): Proportion |
| Cystoid macular edema | 22 weeks +/- 14 days after initial surgery | Specific measurement variable: CME visualized by OCT Analysis metric (participant level): Value \[yes/no\] Method of aggregation (summary measure for each study group): Proportion |
| Central corneal thickness (CCT) | At baseline and 22 weeks +/- 14 days after initial surgery | Specific measurement variable: CCT measured by Pentacam \[μm\]; Analysis metric (participant level): Value; Method of aggregation (summary measure for each study group): Mean |
Countries
Denmark, Germany, Netherlands, Spain
Contacts
Primary ContactBjörn Bachmann, Prof.
Outcome results
None listed