Inflammatory Mediators of Glaucoma After Corneal Transplantation (AH-Tears)
- Conditions
- InflammationGlaucomaCorneal Transplantation
- Interventions
- Other: Sampling of tearsOther: Sampling of aqueous humor
- Registration Number
- NCT04339907
- Lead Sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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)
- Aged less than 18
- Inability to give informed consent
- Presence of ocular diseases other than those studied herein
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Corneal transplantation Sampling of aqueous humor 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. Cataract surgery only Sampling of aqueous humor Participants needing cataract surgery, without glaucoma or any other corneal diseases. Glaucoma surgery only Sampling of tears Participants needing glaucoma filtration surgery, without any prior corneal transplantation. Glaucoma surgery only Sampling of aqueous humor Participants needing glaucoma filtration surgery, without any prior corneal transplantation. Cataract surgery only Sampling of tears Participants needing cataract surgery, without glaucoma or any other corneal diseases. Corneal transplantation Sampling of tears 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. Intraocular surgery following corneal transplantation Sampling of tears 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. Glaucoma surgery following corneal transplantation Sampling of tears 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. Intraocular surgery following corneal transplantation Sampling of aqueous humor 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. Glaucoma surgery following corneal transplantation Sampling of aqueous humor 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.
- Primary Outcome Measures
Name Time Method Concentration of inflammatory mediators in tears Baseline Concentration (pg/mL) of inflammatory mediators in tears measured by ELISA multiplex.
Correlation between tears and aqueous humor Baseline Correlation between the concentration of inflammatory mediators in tears and aqueous humor, determined by Spearman correlation test.
Concentration of inflammatory mediators in aqueous humor Baseline Concentration (pg/mL) of inflammatory mediators in aqueous humor measured by ELISA multiplex.
- Secondary Outcome Measures
Name Time Method Incidence of anterior structural changes 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.
Change of visual acuity through time 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.
Proportion of participants with visual field loss of 30% or more 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.
Incidence of posterior structural changes 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.
Intraocular pressure Baseline, 3 months, 6 months, 12 months Evaluation of intraocular pressure (units of mmHg) at each time point using Goldman tonometry.
Trial Locations
- Locations (1)
Centre Hospitalier de l'Université de Montréal (CHUM)
🇨🇦Montréal, Quebec, Canada