Inflammatory Mediators of Glaucoma After Corneal Transplantation (AH-Tears) (AH-Tears)

July 24, 2023 updated by: Centre hospitalier de l'Université de Montréal (CHUM)

Uncovering Inflammatory Mediators of Glaucoma Pathogenesis After Corneal Transplantation in Aqueous Humor and Tears

Glaucoma is the most common threat to vision rehabilitation in patients with Boston keratoprosthesis type 1 (KPro) implantation. High intraocular pressure (IOP) is the most important risk factor for glaucoma and may lead to irreversible retinal and optic nerve damage. Glaucoma drainage device (GDD) surgery is used to divert aqueous humor (AH) from the anterior chamber to an external reservoir to regulate flow and decrease the IOP. The AH is in direct communication with any corneal damage or surgery undertaken in the anterior chamber and can serve as a source of potential biomarkers to detect early inflammatory or glaucomatous changes. Tears are also one of the most accessible and non-invasive source of biomarkers, especially in Kpro eyes where the central optic allows communication between aqueous humor and the tears at the surface of the eye. The investigators propose to test the hypothesis that distinct inflammatory mediators in the AH and tears can serve as biomarkers for glaucoma development and progression after CT, making them specifically amenable to targeted treatment strategies to minimize vision loss.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The only curative treatment for corneal diseases that progress to vision loss is corneal transplantation (CT). Penetrating keratoplasty (PK) involves the surgical replacement of the host cornea with a donor cornea. In cases of graft failure with standard PK, the Boston keratoprosthesis (KPro), the most common artificial cornea, can alternatively restore vision rapidly. A current limitation in the use of KPro is that the vast majority of patients are at high risk of developing glaucoma. Glaucoma contributes to significant ocular morbidity after CT surgery and is the leading cause of irreversible vision loss after CT. High intraocular pressure (IOP) is the most important risk factor for glaucoma and may lead to irreversible retinal and optic nerve damage. Glaucoma is treated using drops or surgery to reduce IOP. When IOP-lowering drugs and laser surgery fail, glaucoma drainage device (GDD) surgery is used to divert aqueous humor (AH) from the anterior chamber to an external reservoir to regulate flow and decrease the IOP. The cause and mechanisms of glaucoma development and progression following CT are still unknown. Neuroinflammation has been suggested to play a key role in glaucomatous damage following CT. The role of inflammatory biomarkers in glaucoma pathogenesis after CT remains poorly understood and must be further studied. The AH is in direct communication with any corneal damage or surgery undertaken in the anterior chamber and can serve as a source of potential biomarkers to detect inflammatory changes in glaucoma. Tears are also one of the most accessible and non-invasive source of biomarkers, especially in Kpro eyes where the central optic allows communication between AH and the tears at the surface of the eye. Full thickness corneal transplantation (penetrating keratoplasty and Boston KPro) and intraocular surgeries for glaucoma, cataract and retina that are required by the participants of the study offer the opportunity to have access to the AH and tears in an accessible and safe way, without additional risks. These samples of AH and tears will be analyzed for multiple inflammatory mediators simultaneously.

HYPOTHESIS:

The investigators propose to test the hypothesis that distinct inflammatory mediators in the AH and tears can serve as biomarkers for glaucoma development and progression after CT, making them specifically amenable to targeted treatment strategies to minimize vision loss.

OBJECTIVES:

  1. To examine the (a) presence and (b) concentration of inflammatory mediators in glaucoma after corneal transplantation.
  2. To examine the correlation between the presence and concentration of inflammatory mediators and clinical ophthalmological data.
  3. To examine the correlation between the inflammatory mediators found in aqueous humor and tears.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H2X 3E4
        • Recruiting
        • Centre Hospitalier de L'Université de Montréal (CHUM)
        • Sub-Investigator:
          • Mona Harissi-Dagher, MD
        • Contact:
        • Principal Investigator:
          • Younes Agoumi, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Aged 18 years old or older
  • Informed consent
  • Ability to be followed for the duration of the study
  • Presence of ocular disease specified for each group

Specific criteria for each group:

  • Group 1 : have no glaucoma and no systemic diseases
  • Group 2 : need to have glaucoma filtration surgery without prior corneal transplantation
  • Group 3 : need to have corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis), with or without glaucoma
  • Group 4 : need to have intraocular surgery after prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis)
  • Group 5 : need to have glaucoma filtration surgery with prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis)

Exclusion Criteria:

  • Aged less than 18
  • Inability to give informed consent
  • Presence of ocular diseases other than those studied herein

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Cataract surgery only
Participants needing cataract surgery, without glaucoma or any other corneal diseases.
Other: Sampling of tears
Tears will be collected at the start of any of surgery for which the participant presents. It will be collected using a tear-wash method to allow for protein collection. 0.06 ml of saline solution 0.9% will be instilled on the ocular surface. The participants will turn their eyes with eyes closed. The tear-wash fluid will be collected from the inferior fornix of the eye using a micropipette. Tear-was fluid will be placed in codified tubes stored at -150 degrees.
Other: Sampling of aqueous humor
Aqueous humor will be collected at the start of any of surgery for which the participant presents. A paracentesis of the anterior chamber is a common first step in intraocular surgeries. Aqueous humor is then commonly diluted with viscoelastic material injected inside the anterior chamber to avoid collapse of the anterior chamber. This way, the aqueous humor is commonly diluted or replaced entirely by the viscoelastic material injected during intraocular surgeries. A volume of 0.1 ml of aqueous humor will be taken by paracentesis using a 30-gauge needle connected to a 1-ml syringe. It consists of less than half of the total volume of aqueous humor in the eye. Aqueous humor will be placed in codified tubes stored at -80 degrees.
Sham Comparator: Glaucoma surgery only
Participants needing glaucoma filtration surgery, without any prior corneal transplantation.
Other: Sampling of tears
Tears will be collected at the start of any of surgery for which the participant presents. It will be collected using a tear-wash method to allow for protein collection. 0.06 ml of saline solution 0.9% will be instilled on the ocular surface. The participants will turn their eyes with eyes closed. The tear-wash fluid will be collected from the inferior fornix of the eye using a micropipette. Tear-was fluid will be placed in codified tubes stored at -150 degrees.
Other: Sampling of aqueous humor
Aqueous humor will be collected at the start of any of surgery for which the participant presents. A paracentesis of the anterior chamber is a common first step in intraocular surgeries. Aqueous humor is then commonly diluted with viscoelastic material injected inside the anterior chamber to avoid collapse of the anterior chamber. This way, the aqueous humor is commonly diluted or replaced entirely by the viscoelastic material injected during intraocular surgeries. A volume of 0.1 ml of aqueous humor will be taken by paracentesis using a 30-gauge needle connected to a 1-ml syringe. It consists of less than half of the total volume of aqueous humor in the eye. Aqueous humor will be placed in codified tubes stored at -80 degrees.
Experimental: Corneal transplantation

Participants needing corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis), with or without glaucoma.

This allows analyzing samples at baseline (time 0), at the time of the corneal transplantation procedure.
Other: Sampling of tears
Tears will be collected at the start of any of surgery for which the participant presents. It will be collected using a tear-wash method to allow for protein collection. 0.06 ml of saline solution 0.9% will be instilled on the ocular surface. The participants will turn their eyes with eyes closed. The tear-wash fluid will be collected from the inferior fornix of the eye using a micropipette. Tear-was fluid will be placed in codified tubes stored at -150 degrees.
Other: Sampling of aqueous humor
Aqueous humor will be collected at the start of any of surgery for which the participant presents. A paracentesis of the anterior chamber is a common first step in intraocular surgeries. Aqueous humor is then commonly diluted with viscoelastic material injected inside the anterior chamber to avoid collapse of the anterior chamber. This way, the aqueous humor is commonly diluted or replaced entirely by the viscoelastic material injected during intraocular surgeries. A volume of 0.1 ml of aqueous humor will be taken by paracentesis using a 30-gauge needle connected to a 1-ml syringe. It consists of less than half of the total volume of aqueous humor in the eye. Aqueous humor will be placed in codified tubes stored at -80 degrees.
Experimental: Intraocular surgery following corneal transplantation

Participants needing intraocular surgery (cataract, retina or glaucoma), with prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis).

This allows analyzing samples during the potential development or progression of glaucoma in participants who have previously undergone corneal transplantation.
Other: Sampling of tears
Tears will be collected at the start of any of surgery for which the participant presents. It will be collected using a tear-wash method to allow for protein collection. 0.06 ml of saline solution 0.9% will be instilled on the ocular surface. The participants will turn their eyes with eyes closed. The tear-wash fluid will be collected from the inferior fornix of the eye using a micropipette. Tear-was fluid will be placed in codified tubes stored at -150 degrees.
Other: Sampling of aqueous humor
Aqueous humor will be collected at the start of any of surgery for which the participant presents. A paracentesis of the anterior chamber is a common first step in intraocular surgeries. Aqueous humor is then commonly diluted with viscoelastic material injected inside the anterior chamber to avoid collapse of the anterior chamber. This way, the aqueous humor is commonly diluted or replaced entirely by the viscoelastic material injected during intraocular surgeries. A volume of 0.1 ml of aqueous humor will be taken by paracentesis using a 30-gauge needle connected to a 1-ml syringe. It consists of less than half of the total volume of aqueous humor in the eye. Aqueous humor will be placed in codified tubes stored at -80 degrees.
Experimental: Glaucoma surgery following corneal transplantation

Participants needing glaucoma filtration surgery, with prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis).

This allows analyzing samples once glaucoma is confirmed in participants who have previously undergone corneal transplantation.
Other: Sampling of tears
Tears will be collected at the start of any of surgery for which the participant presents. It will be collected using a tear-wash method to allow for protein collection. 0.06 ml of saline solution 0.9% will be instilled on the ocular surface. The participants will turn their eyes with eyes closed. The tear-wash fluid will be collected from the inferior fornix of the eye using a micropipette. Tear-was fluid will be placed in codified tubes stored at -150 degrees.
Other: Sampling of aqueous humor
Aqueous humor will be collected at the start of any of surgery for which the participant presents. A paracentesis of the anterior chamber is a common first step in intraocular surgeries. Aqueous humor is then commonly diluted with viscoelastic material injected inside the anterior chamber to avoid collapse of the anterior chamber. This way, the aqueous humor is commonly diluted or replaced entirely by the viscoelastic material injected during intraocular surgeries. A volume of 0.1 ml of aqueous humor will be taken by paracentesis using a 30-gauge needle connected to a 1-ml syringe. It consists of less than half of the total volume of aqueous humor in the eye. Aqueous humor will be placed in codified tubes stored at -80 degrees.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concentration of inflammatory mediators in aqueous humor
Time Frame: Baseline
Concentration (pg/mL) of inflammatory mediators in aqueous humor measured by ELISA multiplex.
Baseline
Concentration of inflammatory mediators in tears
Time Frame: Baseline
Concentration (pg/mL) of inflammatory mediators in tears measured by ELISA multiplex.
Baseline
Correlation between tears and aqueous humor
Time Frame: Baseline
Correlation between the concentration of inflammatory mediators in tears and aqueous humor, determined by Spearman correlation test.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of anterior structural changes
Time Frame: Baseline, 3 months, 6 months, 12 months
Incidence of anterior structural changes in the eye (iris, iridocorneal angle, trabecular meshwork, cornea), evaluated by anterior segment optical coherence tomography (AS-OCT) imaging.
Baseline, 3 months, 6 months, 12 months
Change of visual acuity through time
Time Frame: Baseline, 3 months, 6 months, 12 months
Change of visual acuity at each time point compared to baseline visual acuity. The visual acuity is measured using the Snellen chart.
Baseline, 3 months, 6 months, 12 months
Proportion of participants with visual field loss of 30% or more
Time Frame: Baseline, 3 months, 6 months, 12 months
Proportion of participants with visual field loss of 30% or more at each time point, measured using the automated Humphrey 24-2 visual field. The loss of 30% or more of visual field is calculated using the baseline test as reference.
Baseline, 3 months, 6 months, 12 months
Intraocular pressure
Time Frame: Baseline, 3 months, 6 months, 12 months
Evaluation of intraocular pressure (units of mmHg) at each time point using Goldman tonometry.
Baseline, 3 months, 6 months, 12 months
Incidence of posterior structural changes
Time Frame: Baseline, 3 months, 6 months, 12 months
Incidence of posterior structural changes in the eye (optic nerve and retina), evaluated by spectral domain optical coherence tomography (SD-OCT) imaging.
Baseline, 3 months, 6 months, 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Investigators

  • Principal Investigator: Younes Agoumi, MD, Centre Hospitalier de L'Université de Montréal (CHUM)
  • Study Director: Mona Harissi-Dagher, MD, Centre Hospitalier de L'Université de Montréal (CHUM)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 11, 2020

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

May 1, 2025

Study Registration Dates

First Submitted

April 6, 2020

First Submitted That Met QC Criteria

April 8, 2020

First Posted (Actual)

April 9, 2020

Study Record Updates

Last Update Posted (Actual)

July 27, 2023

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20.004

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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