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

NCT ID: NCT04339907

Last Updated: 2023-07-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-11

Study Completion Date

2025-05-31

Brief Summary

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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

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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.

Conditions

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Glaucoma Corneal Transplantation Inflammation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

5 groups will be compared:

* participant needing cataract surgery without glaucoma
* participant needing glaucoma filtration surgery without prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis)
* participant needing corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis), with or without glaucoma
* participant needing intraocular surgery (cataract, retina or glaucoma) with prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis)
* participant needing glaucoma filtration surgery with prior corneal transplantation (penetrating keratoplasty or Boston keratoprosthesis)
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Cataract surgery only

Participants needing cataract surgery, without glaucoma or any other corneal diseases.

Group Type SHAM_COMPARATOR

Sampling of tears

Intervention Type OTHER

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.

Sampling of aqueous humor

Intervention Type OTHER

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.

Glaucoma surgery only

Participants needing glaucoma filtration surgery, without any prior corneal transplantation.

Group Type SHAM_COMPARATOR

Sampling of tears

Intervention Type OTHER

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.

Sampling of aqueous humor

Intervention Type OTHER

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.

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.

Group Type EXPERIMENTAL

Sampling of tears

Intervention Type OTHER

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.

Sampling of aqueous humor

Intervention Type OTHER

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.

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.

Group Type EXPERIMENTAL

Sampling of tears

Intervention Type OTHER

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.

Sampling of aqueous humor

Intervention Type OTHER

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.

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.

Group Type EXPERIMENTAL

Sampling of tears

Intervention Type OTHER

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.

Sampling of aqueous humor

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type 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.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Younes Agoumi, MD

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier de l'Université de Montréal (CHUM)

Mona Harissi-Dagher, MD

Role: STUDY_DIRECTOR

Centre hospitalier de l'Université de Montréal (CHUM)

Locations

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Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Marie-Catherine Tessier, M.Sc.

Role: CONTACT

1-514-890-8000 ext. 11550

Dominique Geoffrion, B.Sc.

Role: CONTACT

1-514-890-8000 ext. 11550

Facility Contacts

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Marie-Catherine Tessier, M.Sc.

Role: primary

1-514-890-8000 ext. 11550

References

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Szigiato AA, Bostan C, Nayman T, Harissi-Dagher M. Long-term visual outcomes of the Boston type I keratoprosthesis in Canada. Br J Ophthalmol. 2020 Nov;104(11):1601-1607. doi: 10.1136/bjophthalmol-2019-315345. Epub 2020 Feb 17.

Reference Type BACKGROUND
PMID: 32066560 (View on PubMed)

Wang Q, Harissi-Dagher M. Characteristics and management of patients with Boston type 1 keratoprosthesis explantation--the University of Montreal Hospital Center experience. Am J Ophthalmol. 2014 Dec;158(6):1297-1304.e1. doi: 10.1016/j.ajo.2014.08.037. Epub 2014 Aug 28.

Reference Type BACKGROUND
PMID: 25174898 (View on PubMed)

Crnej A, Paschalis EI, Salvador-Culla B, Tauber A, Drnovsek-Olup B, Shen LQ, Dohlman CH. Glaucoma progression and role of glaucoma surgery in patients with Boston keratoprosthesis. Cornea. 2014 Apr;33(4):349-54. doi: 10.1097/ICO.0000000000000067.

Reference Type BACKGROUND
PMID: 24531120 (View on PubMed)

Aldave AJ, Kamal KM, Vo RC, Yu F. The Boston type I keratoprosthesis: improving outcomes and expanding indications. Ophthalmology. 2009 Apr;116(4):640-51. doi: 10.1016/j.ophtha.2008.12.058. Epub 2009 Feb 25.

Reference Type BACKGROUND
PMID: 19243830 (View on PubMed)

Baltaziak M, Chew HF, Podbielski DW, Ahmed IIK. Glaucoma after corneal replacement. Surv Ophthalmol. 2018 Mar-Apr;63(2):135-148. doi: 10.1016/j.survophthal.2017.09.003. Epub 2017 Sep 18.

Reference Type BACKGROUND
PMID: 28923582 (View on PubMed)

Banitt M. Evaluation and management of glaucoma after keratoprosthesis. Curr Opin Ophthalmol. 2011 Mar;22(2):133-6. doi: 10.1097/ICU.0b013e328343723d.

Reference Type BACKGROUND
PMID: 21191292 (View on PubMed)

Cueva Vargas JL, Belforte N, Di Polo A. The glial cell modulator ibudilast attenuates neuroinflammation and enhances retinal ganglion cell viability in glaucoma through protein kinase A signaling. Neurobiol Dis. 2016 Sep;93:156-71. doi: 10.1016/j.nbd.2016.05.002. Epub 2016 May 6.

Reference Type BACKGROUND
PMID: 27163643 (View on PubMed)

Crnej A, Omoto M, Dohlman TH, Dohlman CH, Dana R. Corneal inflammation after miniature keratoprosthesis implantation. Invest Ophthalmol Vis Sci. 2014 Dec 16;56(1):185-9. doi: 10.1167/iovs.14-15884.

Reference Type BACKGROUND
PMID: 25515579 (View on PubMed)

Engel LA, Muether PS, Fauser S, Hueber A. The effect of previous surgery and topical eye drops for primary open-angle glaucoma on cytokine expression in aqueous humor. Graefes Arch Clin Exp Ophthalmol. 2014 May;252(5):791-9. doi: 10.1007/s00417-014-2607-5. Epub 2014 Mar 18.

Reference Type BACKGROUND
PMID: 24638257 (View on PubMed)

Freedman J, Iserovich P. Pro-inflammatory cytokines in glaucomatous aqueous and encysted Molteno implant blebs and their relationship to pressure. Invest Ophthalmol Vis Sci. 2013 Jul 18;54(7):4851-5. doi: 10.1167/iovs.13-12274.

Reference Type BACKGROUND
PMID: 23788371 (View on PubMed)

Burgos-Blasco B, Vidal-Villegas B, Saenz-Frances F, Morales-Fernandez L, Perucho-Gonzalez L, Garcia-Feijoo J, Martinez-de-la-Casa JM. Tear and aqueous humour cytokine profile in primary open-angle glaucoma. Acta Ophthalmol. 2020 Sep;98(6):e768-e772. doi: 10.1111/aos.14374. Epub 2020 Feb 11.

Reference Type BACKGROUND
PMID: 32043817 (View on PubMed)

Robert MC, Arafat SN, Spurr-Michaud S, Chodosh J, Dohlman CH, Gipson IK. Tear Matrix Metalloproteinases and Myeloperoxidase Levels in Patients With Boston Keratoprosthesis Type I. Cornea. 2016 Jul;35(7):1008-14. doi: 10.1097/ICO.0000000000000893.

Reference Type BACKGROUND
PMID: 27191670 (View on PubMed)

Chen KH, Wu CC, Roy S, Lee SM, Liu JH. Increased interleukin-6 in aqueous humor of neovascular glaucoma. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2627-32.

Reference Type BACKGROUND
PMID: 10509659 (View on PubMed)

Hu DN, Ritch R, Liebmann J, Liu Y, Cheng B, Hu MS. Vascular endothelial growth factor is increased in aqueous humor of glaucomatous eyes. J Glaucoma. 2002 Oct;11(5):406-10. doi: 10.1097/00061198-200210000-00006.

Reference Type BACKGROUND
PMID: 12362079 (View on PubMed)

Kuchtey J, Rezaei KA, Jaru-Ampornpan P, Sternberg P Jr, Kuchtey RW. Multiplex cytokine analysis reveals elevated concentration of interleukin-8 in glaucomatous aqueous humor. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6441-7. doi: 10.1167/iovs.10-5216. Epub 2010 Jun 30.

Reference Type BACKGROUND
PMID: 20592224 (View on PubMed)

Dohlman CH, Zhou C, Lei F, Cade F, Regatieri CV, Crnej A, Dohlman JG, Shen LQ, Paschalis EI. Glaucoma After Corneal Trauma or Surgery-A Rapid, Inflammatory, IOP-Independent Pathway. Cornea. 2019 Dec;38(12):1589-1594. doi: 10.1097/ICO.0000000000002106.

Reference Type BACKGROUND
PMID: 31453878 (View on PubMed)

Other Identifiers

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20.004

Identifier Type: -

Identifier Source: org_study_id

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