Fuchs' Endothelial DystrophyEarly Phase 1NCT03275896
Evaluation of the Efficacy of Descemet Membrane Transplantation for the Treatment of Fuchs' Endothelial Dystrophy
A Early Phase 1 study testing Descemet Membrane Transplantation in people with Fuchs' Endothelial Dystrophy, run by Singapore National Eye Centre at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Fuchs' Endothelial Dystrophy
- What is being tested?
- Descemet Membrane Transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSingapore
- Study dates
- Sep 2016to Dec 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Yu Qiang Soh, MBBS contact
Singapore1 site, 1 recruiting
- Recruiting
Singapore National Eye Centre
Singapore, 168751
Yu Qiang Soh, MBBS
Jodhbir Mehta, FRCS
About this study
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.
Read the 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
- Being tested
- Descemet Membrane Transplantation
- Medical subject headings
- Fuchs' Endothelial Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Descemet Membrane TransplantationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Descemet Membrane Transplantation | Experimental | Patients with severe, symptomatic Fuch's Endothelial Dystrophy (FED) will be offered Descemet Membrane Transplantation (DMT) for their condition. Receives: Other: Descemet Membrane Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central Endothelial Cell Density
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.
Measured: Measured monthly, for the first 6 post-operative months
Secondary outcomes (1)
Visual acuity
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.
Measured: Measured monthly, for the first 6 post-operative months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study startSep 2016
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Fuchs' Endothelial DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore National Eye Centre
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Jodhbir Mehta, FRCS, Principal investigator, Singapore National Eye Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03275896
- Sponsor's protocol ID
- R1366/52/2016
- Status last verified
- Sep 2017
- First submitted
- 4 Sep 2017
- Last updated
- 8 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No sharing of OPD with other researchers
Publications
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.
PubMed 26842752Arbelaez 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.
PubMed 25299425Bleyen 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.
PubMed 23283191Moloney 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.
PubMed 25677286Shah 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.
PubMed 21982414Kitagawa 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.
PubMed 12097795Soh 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.
PubMed 34633355
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy of Descemet Membrane Transplantation for the Treatment of Fuchs' Endothelial Dystrophy
- ClinicalTrials.gov ID
- NCT03275896
- Acronym / sponsor ID
- R1366/52/2016
- Conditions
- Fuchs' Endothelial Dystrophy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Singapore National Eye CentreOther government
- Study start
- Sep 2016 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 8 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Descemet Membrane Transplantation | Experimental | Other: Descemet Membrane TransplantationPatients with severe, symptomatic Fuch's Endothelial Dystrophy (FED) will be offered Descemet Membrane Transplantation (DMT) for their condition. |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Fuchs' Endothelial Dystrophy (FED) as defined by any of the following criteria:
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Descemet Membrane TransplantationThe 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. | Other | Descemet Membrane Transplantation |
Primary outcome
Central Endothelial Cell Density
Time frame: Measured monthly, for the first 6 post-operative months
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.
1 secondary outcome
Visual acuity
Time frame: Measured monthly, for the first 6 post-operative months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2017.
- Background: PubMed 26842752Soh 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.
- Background: PubMed 25299425Arbelaez 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.
- Background: PubMed 23283191Bleyen 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.
- Background: PubMed 25677286Moloney 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.
- Background: PubMed 21982414Shah 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.
- Background: PubMed 12097795Kitagawa 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.
- Derived from this study: PubMed 34633355Soh 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.
- Individual participant dataSharing planned: No. No sharing of OPD with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yu Qiang Soh, MBBS contact
Jodhbir Mehta, FRCS principal investigator
Singapore National Eye Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Descemet Membrane Transplantation in people with Fuchs' Endothelial Dystrophy, run by Singapore National Eye Centre at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yu Qiang Soh, MBBS (yuqiang.soh@mohh.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central Endothelial Cell Density (time frame: Measured monthly, for the first 6 post-operative months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03275896, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2017.