The ADVISE Study: Advanced Visualization In Corneal Surgery Evaluation (ADVISE)

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.

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 Overview

• Status: Completed
• Conditions: Vision Disorders; Fuchs Dystrophy; Bullous Keratopathy; Endothelial Corneal Dystrophy
• Intervention / Treatment: Device: intraoperative optical coherence tomography (iOCT)

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • Universiteitsziekenhuis Leuven
• Netherlands
  • Maastricht, Netherlands
    • Maastricht University Hospital
  • Utrecht, Netherlands
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iOCT optimized protocol (iOCT-p); 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); 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.
Active Comparator: current practice protocol (CP-p); 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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.	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	during surgery

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Maastricht University Medical Center; Carl Zeiss Surgical GmbH

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 4, 2018

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Corneal Diseases; Sensation Disorders; Corneal Dystrophies, Hereditary; Vision Disorders; Fuchs' Endothelial Dystrophy
• Other Study ID Numbers: NL64392.041.17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No