Evaluation of the Efficacy of Descemet Membrane Transplantation for the Treatment of Fuchs' Endothelial Dystrophy

NCT ID: NCT03275896

Last Updated: 2017-09-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2020-12-31

Brief Summary

Fuchs Endothelial Dystrophy (FED) is a degenerative disease affecting the corneal endothelium. The current gold-standard for treatment of severe FED is endothelial keratoplasty, wherein a cadaveric Descemet's membrane / endothelium graft is transplanted. In this study, the investigators hypothesized that the transplantation of an acellular Descemet's membrane (i.e. Descemet Membrane Transplantation, 'DMT') may be equally efficacious in promoting recovery of endothelial function in this group of patients.

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.

Conditions

Fuchs' Endothelial Dystrophy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Descemet Membrane Transplantation

Patients with severe, symptomatic Fuch's Endothelial Dystrophy (FED) will be offered Descemet Membrane Transplantation (DMT) for their condition.

Group Type: EXPERIMENTAL

Descemet Membrane Transplantation

Intervention Type: OTHER

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.

Interventions

Descemet Membrane Transplantation

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Fuchs' Endothelial Dystrophy (FED) as defined by any of the following criteria:

1. FED of at least Grade 4 on the Krachmer grading scale (i.e. greater than 5mm of confluent central corneal guttata)

2. 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)

2. Patients in the range of <85 years old will be recruited for this study

3. Only individuals with the mental capacity to provide informed consent will be included.

4. Patients who are willing and able to sign a written Informed Consent Form prior to any study-specific procedures will be included

5. Patients who are willing and able to return for scheduled follow-up examinations for up to 12 months after the surgery will be included

4. 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

5. Patients with visually significant cataracts

6. 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.

7. Patients with any form of glaucoma

8. 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

9. 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.

Exclusion Criteria

Subjects that meet any of the following criteria will be excluded from participation:

1. Eyes which have previously been subject to any form of keratoplasty

2. An only-functioning eye in a patient who has lost visual potential in the contralateral eye

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Singapore National Eye Centre

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jodhbir Mehta, FRCS

Role: PRINCIPAL_INVESTIGATOR

Singapore National Eye Centre

Locations

Singapore National Eye Centre

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Yu Qiang Soh, MBBS

Role: CONTACT

yuqiang.soh@mohh.com.sg

Facility Contacts

Yu Qiang Soh, MBBS

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 26842752 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25299425 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23283191 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25677286 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21982414 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12097795 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34633355 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R1366/52/2016

Identifier Type: -

Identifier Source: org_study_id