The ADVISE Study: Advanced Visualization In Corneal Surgery Evaluation

NCT03763721 | Completed DMC

• 1 other identifier: NL64392.041.17
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 3

Brief 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 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.

Conditions

Fuchs Dystrophy; Endothelial Corneal Dystrophy; Bullous Keratopathy; Vision Disorders

Outcome Measures

Primary Outcomes (1)

• 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

  within 6 weeks post-operatively

Secondary Outcomes (4)

• Surgical time

  during surgery

• Best-corrected visual acuity

  3 and 6 months follow-up

• Graft endothelial cell densities

  3 and 6 months follow-up

• Surgical manipulations

  during surgery

Study Arms (2)

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)

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

Device: intraoperative optical coherence tomography (iOCT)

Interventions

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.

current practice protocol (CP-p); iOCT optimized protocol (iOCT-p)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• UMC Utrecht: lead
• Maastricht University Medical Center: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator
• Carl Zeiss Surgical GmbH: collaborator

Study Sites (3)

Universiteitsziekenhuis Leuven

Leuven, Belgium

Location

Maastricht University Hospital

Maastricht, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 38983542 DERIVED

• Muijzer 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.

  PMID: 36730371 DERIVED

• Muijzer 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.

  PMID: 35184123 DERIVED

MeSH Terms

Conditions

Fuchs' Endothelial Dystrophy; Corneal endothelial dystrophy type 2; Vision Disorders

Condition Hierarchy (Ancestors)

Corneal Dystrophies, Hereditary; Corneal Diseases; Eye Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The patient will be blinded in the study, to prevent detection bias in filling out the questionnaires
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: academic staff member

Model Details: 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.

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: December 4, 2018
• Study Start: November 13, 2018
• Primary Completion: August 1, 2021
• Study Completion: September 1, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NL (2)