NCT04339907

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started May 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 6, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 9, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

May 11, 2020

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2024

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2025

Completed
Last Updated

July 27, 2023

Status Verified

July 1, 2023

Enrollment Period

4.4 years

First QC Date

April 6, 2020

Last Update Submit

July 24, 2023

Conditions

GlaucomaCorneal TransplantationInflammation

Keywords

Boston keratoprosthesis type 1GlaucomaAqueous HumorTearsInflammationPenetrating keratoplasty

Outcome Measures

Primary Outcomes (3)

  • Concentration of inflammatory mediators in aqueous humor

    Concentration (pg/mL) of inflammatory mediators in aqueous humor measured by ELISA multiplex.

    Baseline

  • Concentration of inflammatory mediators in tears

    Concentration (pg/mL) of inflammatory mediators in tears measured by ELISA multiplex.

    Baseline

  • Correlation between tears and aqueous humor

    Correlation between the concentration of inflammatory mediators in tears and aqueous humor, determined by Spearman correlation test.

    Baseline

Secondary Outcomes (5)

  • Incidence of anterior structural changes

    Baseline, 3 months, 6 months, 12 months

  • Change of visual acuity through time

    Baseline, 3 months, 6 months, 12 months

  • Proportion of participants with visual field loss of 30% or more

    Baseline, 3 months, 6 months, 12 months

  • Intraocular pressure

    Baseline, 3 months, 6 months, 12 months

  • Incidence of posterior structural changes

    Baseline, 3 months, 6 months, 12 months

Study Arms (5)

Cataract surgery only

SHAM COMPARATOR

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

Other: Sampling of tearsOther: Sampling of aqueous humor

Glaucoma surgery only

SHAM COMPARATOR

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

Other: Sampling of tearsOther: Sampling of aqueous humor

Corneal transplantation

EXPERIMENTAL

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 tearsOther: Sampling of aqueous humor

Intraocular surgery following corneal transplantation

EXPERIMENTAL

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 tearsOther: Sampling of aqueous humor

Glaucoma surgery following corneal transplantation

EXPERIMENTAL

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 tearsOther: Sampling of aqueous humor

Interventions

Sampling of tearsOTHER

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.

Cataract surgery onlyCorneal transplantationGlaucoma surgery following corneal transplantationGlaucoma surgery onlyIntraocular surgery following corneal transplantation
Sampling of aqueous humorOTHER

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.

Cataract surgery onlyCorneal transplantationGlaucoma surgery following corneal transplantationGlaucoma surgery onlyIntraocular surgery following corneal transplantation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

Related Publications (16)

  • 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.

    PMID: 32066560BACKGROUND

  • 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.

    PMID: 25174898BACKGROUND

  • 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.

    PMID: 24531120BACKGROUND

  • 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.

    PMID: 19243830BACKGROUND

  • 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.

    PMID: 28923582BACKGROUND

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

    PMID: 21191292BACKGROUND

  • 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.

    PMID: 27163643BACKGROUND

  • 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.

    PMID: 25515579BACKGROUND

  • 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.

    PMID: 24638257BACKGROUND

  • 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.

    PMID: 23788371BACKGROUND

  • 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.

    PMID: 32043817BACKGROUND

  • 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.

    PMID: 27191670BACKGROUND

  • 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.

    PMID: 10509659BACKGROUND

  • 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.

    PMID: 12362079BACKGROUND

  • 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.

    PMID: 20592224BACKGROUND

  • 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.

    PMID: 31453878BACKGROUND

MeSH Terms

Conditions

GlaucomaInflammationLacerations

Condition Hierarchy (Ancestors)

Ocular HypertensionEye DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsWounds and Injuries

Study Officials

  • Younes Agoumi, MD

    Centre hospitalier de l'Université de Montréal (CHUM)

    PRINCIPAL INVESTIGATOR

  • Mona Harissi-Dagher, MD

    Centre hospitalier de l'Université de Montréal (CHUM)

    STUDY DIRECTOR

Central Study Contacts

Marie-Catherine Tessier, M.Sc.

CONTACT

1-514-890-8000marie-catherine.tessier.chum@ssss.gouv.qc.ca

Dominique Geoffrion, B.Sc.

CONTACT

1-514-890-8000dominique.geoffrion@mail.mcgill.ca

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
FACTORIAL
Model Details: 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)
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 6, 2020

First Posted

April 9, 2020

Study Start

May 11, 2020

Primary Completion

October 1, 2024

Study Completion

May 1, 2025

Last Updated

July 27, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)