- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03275896
Evaluation of the Efficacy of Descemet Membrane Transplantation for the Treatment of Fuchs' Endothelial Dystrophy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Fuchs Endothelial Dystrophy (FED) is a degenerative disease affecting the corneal endothelium, characterized clinically by guttate excrescences on the posterior corneal surface and dysfunctional corneal endothelial cells. While patients are commonly asymptomatic in their early stages, advanced FED can be associated with significant corneal edema, scarring and impairment of visual function.
Patients with mild FED are usually managed conservatively with the application of topical hypertonic saline eyedrops. For patients with advanced FED, endothelial keratoplasty may often be necessary. In 2014, FED represented the most common indication for endothelial keratoplasty in the United States, accounting for 47.7% (13,817 cases) of all endothelial keratoplasty procedures performed nationwide. In Singapore, FED was the second most common indication for corneal transplantation.
Endothelial keratoplasty is associated with endothelial cell attrition in the range of 29.7% - 47% by the 3rd post-operative year. Additionally, the global demand for corneal graft material currently still far outstrips supply, critically limiting the number of patients who can potentially benefit from these surgical interventions. As such, there is a need explore alternative, sustainable strategies for the management of FED.
In 2009, Shah et al. reported the treatment of a 34 years old patient, with the combined pathologies of FED and Posterior Polymorphous Corneal Dystrophy (PPMD), by primary stripping of the central 4-5mm of Descemet's membrane without corneal graft transplantation ('Primary Descemetorhexis'). Contrary to conventional expectations, there was complete repopulation of the posterior corneal surface by corneal endothelial cells following the surgery, with best-corrected-visual-acuity (BCVA) of 6/7.5 achieved by the 6th post-operative month. In 2014, Moloney et al. published a similar report of a 54 years old patient, diagnosed with FED, successfully treated by Primary Descemetorhexis. Rapid endothelial recovery, as evidenced by a central endothelial cell count of 620 cells/mm2 and BCVA of 6/6, was achieved by approximately 6 weeks after the surgery. The success of these cases raised the prospect of Primary Descemetorhexis as a feasible alternative for the treatment of FED.
To gain a better understanding of the factors which may affect endothelial recovery following Primary Descemetorhexis, investigators performed an ex vivo human corneal endothelial cell culture experiment in which Primary Descemetorhexis was performed on cadaveric human cornea buttons, followed by ex vivo culture for a duration of 2 weeks to allow for endothelial recovery. A less invasive approach of denuding endothelial cells from the Descemet's membrane (DM), while maintaining anatomical integrity of the DM, was also assessed. The investigators found that advanced patient age and the absence of DM were significantly associated with slower endothelial recovery.
As such, the investigators hypothesized that the outcomes of Primary Descemetorhexis for the treatment of FED may be improved by DM transplantation following Primary Descemetorhexis ('DM Transplantation'). The main difference between the proposed technique of DM transplantation and conventional endothelial keratoplasty is that the DM transplant does not require the presence of a functional corneal endothelial monolayer on the graft. If successful, the greatest advantage of this approach would be to greatly expand the pool of donors who are eligible to provide cadaveric corneal graft tissue for transplantation.
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Yu Qiang Soh, MBBS
- Email: yuqiang.soh@mohh.com.sg
Study Locations
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Singapore, Singapore, 168751
- Recruiting
- Singapore National Eye Centre
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Contact:
- Yu Qiang Soh, MBBS
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Principal Investigator:
- Jodhbir Mehta, FRCS
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Fuchs' Endothelial Dystrophy (FED) as defined by any of the following criteria:
- FED of at least Grade 4 on the Krachmer grading scale (i.e. greater than 5mm of confluent central corneal guttata)
- Best-corrected-visual-acuity of less than 6/12 in a patient clinically diagnosed with FED of any grade, in which poor visual acuity cannot be accounted by any other significant ophthalmic disease (e.g. cataracts, age-related macular degeneration, glaucoma, optic neuropathies)
- Patients in the range of <85 years old will be recruited for this study
- Only individuals with the mental capacity to provide informed consent will be included.
- Patients who are willing and able to sign a written Informed Consent Form prior to any study-specific procedures will be included
- Patients who are willing and able to return for scheduled follow-up examinations for up to 12 months after the surgery will be included
Exclusion Criteria:
Subjects that meet any of the following criteria will be excluded from participation:
- Eyes which have previously been subject to any form of keratoplasty
- An only-functioning eye in a patient who has lost visual potential in the contralateral eye
- Patients with chronic, advanced FED who meet the above mentioned inclusion criteria, but whose disease is associated with significant stromal scarring to such an extent that will predictably impair post-operative visual recovery after DSAEK or DM transplant
- Patients whose corneal endothelial disease may possibly be attributed to pathologies other than FED, including but not limited to pseudophakic bullous keratopathy, laser-peripheral-iridotomy induced bullous keratopathy, iridocorneal endothelial syndrome, Axenfeld Rieger syndrome, congenital hereditary endothelial dystrophy and any other anterior segment developmental anomalies
- Patients with visually significant cataracts
- Patients with diagnosed with visually significant retinal disease, including but not limited to age-related macular degeneration, myopic macular degeneration, diabetic retinopathy, diabetes related maculopathy, retinal vein occlusion related maculpathy, retinal dystrophies and previous retinal detachments.
- Patients with any form of glaucoma
- Patients diagnosed with visually significant, non-glaucomatous optic neuropathies, including but not limited to those related to ischemic (both arteritic and non-arteritic), toxic, nutritional, myopic, compression, infective and inflammatory causes
- Patients who are pregnant, lactating, of child-bearing potential and not practising a medically approved method of birth control, or planning to become pregnant during the course of the trial, and patients with other conditions associated with fluctuation of hormones that could lead to refractive changes.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Descemet Membrane Transplantation
Patients with severe, symptomatic Fuch's Endothelial Dystrophy (FED) will be offered Descemet Membrane Transplantation (DMT) for their condition.
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The diseased host Descemet membrane will first be stripped, as per a standard Descemet Stripping Automated Endothelial Keratoplasty surgery.
A cadaveric, acellular Descemet membrane graft will then be harvested and transplanted onto the host.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Central Endothelial Cell Density
Time Frame: Measured monthly, for the first 6 post-operative months
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Central endothelial cell density will be determined using a specular microscope (Konan Medical), measured as number of cells per square millimetre, using the automated cell counting algorithm.
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Measured monthly, for the first 6 post-operative months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Visual acuity
Time Frame: Measured monthly, for the first 6 post-operative months
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The visual acuity will be measured using the Snellen visual acuity scale, performed in a standardized room using a 6-metre visual acuity lane, by a fully qualified optometrist.
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Measured monthly, for the first 6 post-operative months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jodhbir Mehta, FRCS, Singapore National Eye Centre
Publications and helpful links
General Publications
- Arbelaez JG, Price MO, Price FW Jr. Long-term follow-up and complications of stripping descemet membrane without placement of graft in eyes with Fuchs endothelial dystrophy. Cornea. 2014 Dec;33(12):1295-9. doi: 10.1097/ICO.0000000000000270.
- Soh YQ, Peh G, George BL, Seah XY, Primalani NK, Adnan K, Mehta JS. Predicative Factors for Corneal Endothelial Cell Migration. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):338-48. doi: 10.1167/iovs.15-18300.
- Bleyen I, Saelens IE, van Dooren BT, van Rij G. Spontaneous corneal clearing after Descemet's stripping. Ophthalmology. 2013 Jan;120(1):215. doi: 10.1016/j.ophtha.2012.08.037. No abstract available.
- Moloney G, Chan UT, Hamilton A, Zahidin AM, Grigg JR, Devasahayam RN. Descemetorhexis for Fuchs' dystrophy. Can J Ophthalmol. 2015 Feb;50(1):68-72. doi: 10.1016/j.jcjo.2014.10.014. Epub 2014 Oct 31.
- Shah RD, Randleman JB, Grossniklaus HE. Spontaneous corneal clearing after Descemet's stripping without endothelial replacement. Ophthalmology. 2012 Feb;119(2):256-60. doi: 10.1016/j.ophtha.2011.07.032. Epub 2011 Oct 7.
- Kitagawa K, Kojima M, Sasaki H, Shui YB, Chew SJ, Cheng HM, Ono M, Morikawa Y, Sasaki K. Prevalence of primary cornea guttata and morphology of corneal endothelium in aging Japanese and Singaporean subjects. Ophthalmic Res. 2002 May-Jun;34(3):135-8. doi: 10.1159/000063656.
- Soh YQ, Poh SSJ, Peh GSL, Mehta JS. New Therapies for Corneal Endothelial Diseases: 2020 and Beyond. Cornea. 2021 Nov 1;40(11):1365-1373. doi: 10.1097/ICO.0000000000002687.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- R1366/52/2016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Centre Hospitalier Régional Metz-ThionvilleCompletedPseudophakic Bullous Keratopathy | Fuchs' Endothelial Corneal Dystrophy | Descemet Membrane Endothelial Keratoplasty | Graft DetachmentFrance
Clinical Trials on Descemet Membrane Transplantation
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University Hospital, RouenCompleted
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Cornea Research Foundation of AmericaCompletedBullous Keratopathy | Fuchs' Endothelial Corneal Dystrophy | Iridocorneal Endothelial Syndrome | Posterior Polymorphous DystrophyUnited States
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EDUARD PEDEMONTE-SARRIASCompletedFuchs' Endothelial Dystrophy | Corneal Endothelial Cell LossSpain
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Netherlands Institute for Innovative Ocular SurgeryAmnitrans Eyebank RotterdamCompletedCorneal Dystrophies, HereditaryNetherlands
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Beyoglu Eye Research and Education HospitalCompletedEndothelial Dysfunction | Fuchs' Endothelial Dystrophy | Pseudophakic Bullous Keratopathy | Herpetic Keratitis | Descemet's Membrane; Defect | Angle's ClassificationTurkey
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Charite University, Berlin, GermanyUnknownEndothelial Dysfunction | Bullous Keratopathy | Fuchs' Endothelial Corneal Dystrophy | Iridocorneal Endothelial Syndrome | Posterior Polymorphous DystrophyGermany
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Alexandria UniversityUnknownPseudophakic Bullous Keratopathy | Anterior Chamber Intraocular LensEgypt