Fuchs DystrophyADVISENCT03763721
The ADVISE Study: Advanced Visualization In Corneal Surgery Evaluation
A study testing intraoperative optical coherence tomography (iOCT) in people with Fuchs Dystrophy and Endothelial Corneal Dystrophy, run by UMC Utrecht at 3 sites in 2 countries.
Trial summary
Rationale: Intra-operative optical coherence tomography (iOCT) is a new technology that incorporates advanced imaging techniques in the ophthalmic operating theatre. This allows surgeons to visualize tissues in a way previously impossible We conceptualized an iOCT-guided surgical protocol for the treatment of… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Fuchs Dystrophy, Endothelial Corneal Dystrophy, Bullous Keratopathy
- What is being tested?
- intraoperative optical coherence tomography (iOCT)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 13 Nov 2018to 1 Sep 2022
- Phase
- Interventional
- 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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Irreversible corneal decompensation caused by Fuchs corneal endothelial dystrophy or pseudophakic bullous keratopathy
- Eligible for posterior lamellar keratoplasty, specifically Descemet Membrane Endothelial Keratoplasty (DMEK)
Who cannot join
- Any ocular co-morbidity other than cataract, mild dry eye disease, ocular hypertension, simple primary open angle glaucoma, and mild age-related macular degeneration
- Prior corneal transplant surgery
- Human leukocyte antigen (HLA) matched keratoplasty
- Any disability that will interfere with performing or understanding the procedures and questionnaire fulfilment except if it is temporary of nature.
- Combined phaco-emulsification-DMEK surgery (triple procedure)
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Maastricht University Hospital
Maastricht
University Medical Center Utrecht
Utrecht
About this study
Official title: The ADVISE Study: Advanced Visualization In Corneal Surgery Evaluation Intra-operative Optical Coherence Tomography in Posterior Lamellar Keratoplasty
Rationale: Intra-operative optical coherence tomography (iOCT) is a new technology that incorporates advanced imaging techniques in the ophthalmic operating theatre. This allows surgeons to visualize tissues in a way previously impossible We conceptualized an iOCT-guided surgical protocol for the treatment of endothelial cell dysfunction, that refrains from the current practice of over-pressurizing the eye at the end of surgery.
Objective: The aim of this study is to assess the clinical value of intraoperative OCT (iOCT) for Descemet Membrane Endothelial Keratoplasty (DMEK) by comparing an iOCT-optimized surgical protocol with current practice, where the eye is over-pressurized for a set period of time, in terms of surgical efficiency, clinical outcomes, and adverse events.
Read more
Study design: International multicentre non-inferiority randomized clinical trial Study population: Patients scheduled for posterior lamellar corneal surgery for endothelial cell dysfunction above the age of 18 years.
Intervention: Both groups will undergo Descemet Membrane Endothelial Keratoplasty. Patients will be randomized for either the iOCT optimized surgical protocol or current standard surgical protocol using 8 minutes of overpressure to facilitate graft adherence. Both groups will be evaluated with iOCT at the end of surgery.
Main study parameters/endpoints:
The main study parameter is the rate of adverse events (particularly graft dislocations). Secondary parameters/endpoints are surgical time, the recovery of visual acuity and endothelial graft quality at 3 and 6 months follow-up, and a detailed evaluation of the extent/duration of surgical tissue manipulations.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The use of iOCT during surgery does not entail additional risk to the patient. Participants to this study will adhere to the standard of care after corneal transplant surgery. In addition, they will receive study specific measurements and questionnaires. The additional measurements and questionnaires will be combined with regular follow up moments.
- Being tested
- intraoperative optical coherence tomography (iOCT)
- Medical subject headings
- Fuchs' Endothelial Dystrophy, Corneal endothelial dystrophy type 2, Vision Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intraoperative optical coherence tomography (iOCT)Device
The OCT technology is fully integrated in a conventional ophthalmic surgical microscope (Zeiss LUMERA 700 platform). The OCT consists of A-scans (length/thickness) and B-scans (X-Y plane) to create the three dimensional image. Alternatively C-scans (3D cube scans) are available. All scans are non-invasive. The surgeon can continue surgery whilst using the iOCT and view a live image projected in the binocular or on the external screen and the video stream can be recorded as well.
The iOCT features are controlled using the foot paddle and the images are recorded on device. Investigations will be performed in a standardized matter: iOCT imagery and cube-scans after graft insertion, air injection, and the end of surgery.
| Study group | Role | What they receive |
|---|---|---|
| iOCT optimized protocol (iOCT-p) | Experimental | In the iOCT optimized protocol (iOCT-p) group, graft apposition will be assessed with special detail for graft orientation, interface fluid, and any peripheral folds as described by Xu et al. Potential tissue manipulations will be therefore based on the iOCT image. Apposition of the graft will be obtained using a complete filling of the anterior chamber with 20% sulphur hexafluoride (SF6) endotamponade for 1-2 minutes, whilst the OCT image is assessed and any graft manipulation can be performed if deemed necessary. After this period, the gas is partly exchanged for BSS (Balanced Salt Solution, Alcon) to achieve a bubble with a diameter of approximately the same size of the graft (i.e. 8.5mm) Receives: Device: intraoperative optical coherence tomography (iOCT) |
| current practice protocol (CP-p) | Active comparator | In the current practice protocol (CP-p), graft apposition will be obtained using a complete and pressurized (approx. 65mmHg) filling of the anterior chamber with 20% SF6, for 8 minutes. Tissue manipulations, such as corneal swiping, will be performed as deemed necessary by the surgeon, based on the en face view from the conventional microscope image. The intraocular pressure is normalized by exchanging the SF6 gas for BSS, to achieve a gas bubble approximately the size of the graft (i.e 8.5mm). Now, the graft apposition is assessed using iOCT, to ensure all trial patients eventually undergo advanced iOCT imaging. Should this iOCT image reveal improper graft adherence or any other irregularity, the surgeon will perform additional manipulations or interventions as deemed necessary Receives: Device: intraoperative optical coherence tomography (iOCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
rate of the most relevant post-operative surgical complications
the number of patients that develop adverse events relating to lamellar corneal surgery, specifically graft detachments that necessitate a surgical intervention, early graft failures that lead to intractable corneal edema, or induced iatrogenic acute glaucoma
Measured: within 6 weeks post-operatively
Secondary outcomes (4)
Surgical time
times are recorded at entry of the OR, start time of the surgery, actual first incision, timepoint for injection of gas, duration of gas, closing time and departure time of the OR. Out of these both skin-to-skin and overall time in surgery can be calculated (i.e. gross/net)
Measured: during surgery
Best-corrected visual acuity
Visual acuity is assessed using an ETDRS (Early Treatment Diabetic Retinopathy Study Chart) visual acuity chart with a spectacle correction. Visual acuity measurement ranges from light perception, hand movements, finger counting, 0.05 till 1.0. (US equivalent 20/20)
Measured: 3 and 6 months follow-up
Graft endothelial cell densities
The quality of the graft is based on the amount and viability of endothelial cells. These will be measured (number of cells/mm2, variation in size (variation coefficient), hexagonality-coefficient) with in vivo specular microscopy.
Measured: 3 and 6 months follow-up
Surgical manipulations
the recorded videos will be reviewed and scored considering the amount of surgical manipulations, the duration of all steps of the procedure, and the use of iOCT. All according to a study specific standard operating procedure
Measured: during surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2018
- Study start13 Nov 2018
- Primary completion1 Aug 2021
- Study completion1 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Fuchs 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
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The design of the study is a prospective, international, multicenter, non-inferiority, randomized controlled interventional clinical trial to compare the outcomes after posterior lamellar surgery with an iOCT optimized surgical protocol, and current practice, where the eye is over-pressurized for a set period of time. These groups will be labelled iOCT optimized protocol (iOCT-p) and current practice protocol (CP-p). Eligible patients will be assigned to either one of the groups. The study will be conducted simultaneously at the University Medical Center Utrecht (UMCU), Maastricht University Medical Center (MUMC) and the University Hospitals Leuven (UZL, Belgium). The inclusion, preoperative and postoperative measurements and questionnaires will take place at the Ophthalmology department of the site were the surgery was conducted. The research activities will be coordinated by the UMCU.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center, Universitaire Ziekenhuizen KU Leuven, Carl Zeiss Surgical GmbH
- Responsible party
- Principal investigator, Robert P.L. Wisse, MD PhD, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03763721
- Sponsor's protocol ID
- NL64392.041.17
- Acronym
- ADVISE
- Status last verified
- Nov 2022
- First submitted
- 15 Nov 2018
- Last updated
- 15 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Muijzer MB, Delbeke H, Dickman MM, Nuijts RMMA, Noordmans HJ, Imhof SM, Wisse RPL. Outcomes of the advanced visualization in corneal surgery evaluation trial; a non-inferiority randomized control trial to evaluate the use of intraoperative OCT during Descemet membrane endothelial keratoplasty. Front Ophthalmol (Lausanne). 2023 Jan 11;2:1041778. doi: 10.3389/fopht.2022.1041778. eCollection 2022.
PubMed 38983542Muijzer MB, Delbeke H, Dickman MM, Nuijts RMMA, Jimale H, van Luijk CM, Imhof SM, Wisse RPL. Video Grading of Descemet Membrane Endothelial Keratoplasty Surgery to Identify Surgeon Risk Factors for Graft Detachment and Rebubbling: A Post Hoc Observational Analysis of the Advanced Visualization In Corneal Surgery Evaluation Trial. Cornea. 2023 Sep 1;42(9):1074-1082. doi: 10.1097/ICO.0000000000003181. Epub 2022 Nov 21.
PubMed 36730371Muijzer MB, Noordmans HJ, Delbeke H, Dickman MM, Nuijts RMMA, Dunker S, Imhof SM, Wisse RPL. Establishing a Biomarker for the Prediction of Short-Term Graft Detachment After Descemet Membrane Endothelial Keratoplasty. Cornea. 2023 Feb 1;42(2):204-210. doi: 10.1097/ICO.0000000000003006. Epub 2022 Feb 18.
PubMed 35184123
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The ADVISE Study: Advanced Visualization In Corneal Surgery Evaluation Intra-operative Optical Coherence Tomography in Posterior Lamellar Keratoplasty
- ClinicalTrials.gov ID
- NCT03763721
- Acronym / sponsor ID
- ADVISE / NL64392.041.17
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center, Universitaire Ziekenhuizen KU Leuven, Carl Zeiss Surgical GmbH
- Study start
- 13 Nov 2018 (actual)
- Primary completion
- 1 Aug 2021 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 4 Dec 2018 (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.
Rationale: Intra-operative optical coherence tomography (iOCT) is a new technology that incorporates advanced imaging techniques in the ophthalmic operating theatre. This allows surgeons to visualize tissues in a way previously impossible We conceptualized an iOCT-guided surgical protocol for the treatment of endothelial cell dysfunction, that refrains from the current practice of over-pressurizing the eye at the end of surgery.
Objective: The aim of this study is to assess the clinical value of intraoperative OCT (iOCT) for Descemet Membrane Endothelial Keratoplasty (DMEK) by comparing an iOCT-optimized surgical protocol with current practice, where the eye is over-pressurized for a set period of time, in terms of surgical efficiency, clinical outcomes, and adverse events.
Study design: International multicentre non-inferiority randomized clinical trial Study population: Patients scheduled for posterior lamellar corneal surgery for endothelial cell dysfunction above the age of 18 years.
Intervention: Both groups will undergo Descemet Membrane Endothelial Keratoplasty. Patients will be randomized for either the iOCT optimized surgical protocol or current standard surgical protocol using 8 minutes of overpressure to facilitate graft adherence. Both groups will be evaluated with iOCT at the end of surgery.
Main study parameters/endpoints:
The main study parameter is the rate of adverse events (particularly graft dislocations). Secondary parameters/endpoints are surgical time, the recovery of visual acuity and endothelial graft quality at 3 and 6 months follow-up, and a detailed evaluation of the extent/duration of surgical tissue manipulations.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The use of iOCT during surgery does not entail additional risk to the patient. Participants to this study will adhere to the standard of care after corneal transplant surgery. In addition, they will receive study specific measurements and questionnaires. The additional measurements and questionnaires will be combined with regular follow up moments.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- The design of the study is a prospective, international, multicenter, non-inferiority, randomized controlled interventional clinical trial to compare the outcomes after posterior lamellar surgery with an iOCT optimized surgical protocol, and current practice, where the eye is over-pressurized for a set period of time. These groups will be labelled iOCT optimized protocol (iOCT-p) and current practice protocol (CP-p). Eligible patients will be assigned to either one of the groups. The study will be conducted simultaneously at the University Medical Center Utrecht (UMCU), Maastricht University Medical Center (MUMC) and the University Hospitals Leuven (UZL, Belgium). The inclusion, preoperative and postoperative measurements and questionnaires will take place at the Ophthalmology department of the site were the surgery was conducted. The research activities will be coordinated by the UMCU.
| Arm | Type | Receives |
|---|---|---|
| iOCT optimized protocol (iOCT-p) | Experimental | Device: intraoperative optical coherence tomography (iOCT)In the iOCT optimized protocol (iOCT-p) group, graft apposition will be assessed with special detail for graft orientation, interface fluid, and any peripheral folds as described by Xu et al. Potential tissue manipulations will be therefore based on the iOCT image. Apposition of the graft will be obtained using a complete filling of the anterior chamber with 20% sulphur hexafluoride (SF6) endotamponade for 1-2 minutes, whilst the OCT image is assessed and any graft manipulation can be performed if deemed necessary. After this period, the gas is partly exchanged for BSS (Balanced Salt Solution, Alcon) to achieve a bubble with a diameter of approximately the same size of the graft (i.e. 8.5mm) |
| current practice protocol (CP-p) | Active comparator | Device: intraoperative optical coherence tomography (iOCT)In the current practice protocol (CP-p), graft apposition will be obtained using a complete and pressurized (approx. 65mmHg) filling of the anterior chamber with 20% SF6, for 8 minutes. Tissue manipulations, such as corneal swiping, will be performed as deemed necessary by the surgeon, based on the en face view from the conventional microscope image. The intraocular pressure is normalized by exchanging the SF6 gas for BSS, to achieve a gas bubble approximately the size of the graft (i.e 8.5mm). Now, the graft apposition is assessed using iOCT, to ensure all trial patients eventually undergo advanced iOCT imaging. Should this iOCT image reveal improper graft adherence or any other irregularity, the surgeon will perform additional manipulations or interventions as deemed necessary |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 18 years
- Irreversible corneal decompensation caused by Fuchs corneal endothelial dystrophy or pseudophakic bullous keratopathy
- Eligible for posterior lamellar keratoplasty, specifically Descemet Membrane Endothelial Keratoplasty (DMEK)
Key exclusion criteria (5 listed)
- Any ocular co-morbidity other than cataract, mild dry eye disease, ocular hypertension, simple primary open angle glaucoma, and mild age-related macular degeneration
- Prior corneal transplant surgery
- Human leukocyte antigen (HLA) matched keratoplasty
- Any disability that will interfere with performing or understanding the procedures and questionnaire fulfilment except if it is temporary of nature.
- Combined phaco-emulsification-DMEK surgery (triple procedure)
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 |
|---|---|---|
| intraoperative optical coherence tomography (iOCT)The OCT technology is fully integrated in a conventional ophthalmic surgical microscope (Zeiss LUMERA 700 platform). The OCT consists of A-scans (length/thickness) and B-scans (X-Y plane) to create the three dimensional image. Alternatively C-scans (3D cube scans) are available. All scans are non-invasive. The surgeon can continue surgery whilst using the iOCT and view a live image projected in the binocular or on the external screen and the video stream can be recorded as well. The iOCT features are controlled using the foot paddle and the images are recorded on device. Investigations will be performed in a standardized matter: iOCT imagery and cube-scans after graft insertion, air injection, and the end of surgery. | Device | current practice protocol (CP-p), iOCT optimized protocol (iOCT-p) |
Primary outcome
rate of the most relevant post-operative surgical complications
Time frame: within 6 weeks post-operatively
the number of patients that develop adverse events relating to lamellar corneal surgery, specifically graft detachments that necessitate a surgical intervention, early graft failures that lead to intractable corneal edema, or induced iatrogenic acute glaucoma
4 secondary outcomes
Surgical time
Time frame: during surgery
Best-corrected visual acuity
Time frame: 3 and 6 months follow-up
Graft endothelial cell densities
Time frame: 3 and 6 months follow-up
Surgical manipulations
Time frame: during surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2022.
- Derived from this study: PubMed 38983542Muijzer MB, Delbeke H, Dickman MM, Nuijts RMMA, Noordmans HJ, Imhof SM, Wisse RPL. Outcomes of the advanced visualization in corneal surgery evaluation trial; a non-inferiority randomized control trial to evaluate the use of intraoperative OCT during Descemet membrane endothelial keratoplasty. Front Ophthalmol (Lausanne). 2023 Jan 11;2:1041778. doi: 10.3389/fopht.2022.1041778. eCollection 2022.
- Derived from this study: PubMed 36730371Muijzer MB, Delbeke H, Dickman MM, Nuijts RMMA, Jimale H, van Luijk CM, Imhof SM, Wisse RPL. Video Grading of Descemet Membrane Endothelial Keratoplasty Surgery to Identify Surgeon Risk Factors for Graft Detachment and Rebubbling: A Post Hoc Observational Analysis of the Advanced Visualization In Corneal Surgery Evaluation Trial. Cornea. 2023 Sep 1;42(9):1074-1082. doi: 10.1097/ICO.0000000000003181. Epub 2022 Nov 21.
- Derived from this study: PubMed 35184123Muijzer MB, Noordmans HJ, Delbeke H, Dickman MM, Nuijts RMMA, Dunker S, Imhof SM, Wisse RPL. Establishing a Biomarker for the Prediction of Short-Term Graft Detachment After Descemet Membrane Endothelial Keratoplasty. Cornea. 2023 Feb 1;42(2):204-210. doi: 10.1097/ICO.0000000000003006. Epub 2022 Feb 18.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intraoperative optical coherence tomography (iOCT) in people with Fuchs Dystrophy and Endothelial Corneal Dystrophy, run by UMC Utrecht at 3 sites in 2 countries.
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 3 inclusion and 5 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: finished, as of the sponsor's last update on 15 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands, Belgium. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rate of the most relevant post-operative surgical complications (time frame: within 6 weeks post-operatively). 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 NCT03763721, which also lists 3 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 15 Nov 2022.