GlaucomaAH-TearsNCT04339907
Inflammatory Mediators of Glaucoma After Corneal Transplantation (AH-Tears)
A study testing Sampling of tears and Sampling of aqueous humor in people with Glaucoma and Corneal Transplantation, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Glaucoma, Corneal Transplantation, Inflammation
- What is being tested?
- Sampling of tears and Sampling of aqueous humor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteCanada
- Study dates
- 11 May 2020to May 2029
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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)
Who cannot join
- Aged less than 18
- Inability to give informed consent
- Presence of ocular diseases other than those studied herein
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Marie-Catherine Tessier, M.Sc. contact
Canada1 site, 1 recruiting
- Recruiting
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X 3E4
Marie-Catherine Tessier, M.Sc., 1-514-890-8000 ext. 11550, marie-catherine.tessier.chum@ssss.gouv.qc.ca
Younes Agoumi, MD
About this study
Official title: 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.
Read the 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:
- To examine the (a) presence and (b) concentration of inflammatory mediators in glaucoma after corneal transplantation.
- To examine the correlation between the presence and concentration of inflammatory mediators and clinical ophthalmological data.
- To examine the correlation between the inflammatory mediators found in aqueous humor and tears.
- Conditions
- Glaucoma, Corneal Transplantation, Inflammation
- Being tested
- Sampling of tears, Sampling of aqueous humor
- Keywords
- Boston keratoprosthesis type 1, Glaucoma, Aqueous Humor, Tears, Inflammation, Penetrating keratoplasty
- Medical subject headings
- Glaucoma, Inflammation, Lacerations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Cataract surgery only | Sham comparator | Participants needing cataract surgery, without glaucoma or any other corneal diseases. Receives: Other: Sampling of tears; Other: Sampling of aqueous humor |
| Glaucoma surgery only | Sham comparator | Participants needing glaucoma filtration surgery, without any prior corneal transplantation. Receives: Other: Sampling of tears; Other: 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. Receives: Other: Sampling of tears; Other: 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. Receives: Other: Sampling of tears; Other: 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. Receives: Other: Sampling of tears; Other: Sampling of aqueous humor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of inflammatory mediators in aqueous humor
Concentration (pg/mL) of inflammatory mediators in aqueous humor measured by ELISA multiplex.
Measured: Baseline
Concentration of inflammatory mediators in tears
Concentration (pg/mL) of inflammatory mediators in tears measured by ELISA multiplex.
Measured: Baseline
Correlation between tears and aqueous humor
Correlation between the concentration of inflammatory mediators in tears and aqueous humor, determined by Spearman correlation test.
Measured: Baseline
Secondary outcomes (5)
Incidence of anterior structural changes
Incidence of anterior structural changes in the eye (iris, iridocorneal angle, trabecular meshwork, cornea), evaluated by anterior segment optical coherence tomography (AS-OCT) imaging.
Measured: Baseline, 3 months, 6 months, 12 months
Change of visual acuity through time
Change of visual acuity at each time point compared to baseline visual acuity. The visual acuity is measured using the Snellen chart.
Measured: Baseline, 3 months, 6 months, 12 months
Proportion of participants with visual field loss of 30% or more
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.
Measured: Baseline, 3 months, 6 months, 12 months
Intraocular pressure
Evaluation of intraocular pressure (units of mmHg) at each time point using Goldman tonometry.
Measured: Baseline, 3 months, 6 months, 12 months
Incidence of posterior structural changes
Incidence of posterior structural changes in the eye (optic nerve and retina), evaluated by spectral domain optical coherence tomography (SD-OCT) imaging.
Measured: Baseline, 3 months, 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2020
- Study start11 May 2020
- Primary completionOct 2028 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for GlaucomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Younes Agoumi, MD, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)Mona Harissi-Dagher, MD, Study director, Centre hospitalier de l'Université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04339907
- Sponsor's protocol ID
- 20.004
- Acronym
- AH-Tears
- Status last verified
- Mar 2026
- First submitted
- 6 Apr 2020
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32066560Wang 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.
PubMed 25174898Crnej 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.
PubMed 24531120Aldave 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.
PubMed 19243830Baltaziak 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.
PubMed 28923582Banitt M. Evaluation and management of glaucoma after keratoprosthesis. Curr Opin Ophthalmol. 2011 Mar;22(2):133-6. doi: 10.1097/ICU.0b013e328343723d.
PubMed 21191292Cueva 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.
PubMed 27163643Crnej 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.
PubMed 25515579Engel 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.
PubMed 24638257Freedman 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.
PubMed 23788371Burgos-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.
PubMed 32043817Robert 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.
PubMed 27191670Chen 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.
PubMed 10509659Hu 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.
PubMed 12362079Kuchtey 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.
PubMed 20592224