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

Inflammation Clinical Trial

— AH-Tears  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04339907
• Other study ID #: 20.004
• Status: Recruiting
• Phase: N/A
• Start date: May 11, 2020
• Est. completion date: May 2025

Study information

• Verified date: July 2023
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: Marie-Catherine Tessier, M.Sc.
• Phone: 1-514-890-8000
• Email: marie-catherine.tessier.chum[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Corneal Transplantation
• Glaucoma
• Inflammation

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)

Country where clinical trial is conducted

Canada, 

References & Publications (16)

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of inflammatory mediators in aqueous humor	Concentration (pg/mL) of inflammatory mediators in aqueous humor measured by ELISA multiplex.	Baseline
Primary	Concentration of inflammatory mediators in tears	Concentration (pg/mL) of inflammatory mediators in tears measured by ELISA multiplex.	Baseline
Primary	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	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.	Baseline, 3 months, 6 months, 12 months
Secondary	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.	Baseline, 3 months, 6 months, 12 months
Secondary	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.	Baseline, 3 months, 6 months, 12 months
Secondary	Intraocular pressure	Evaluation of intraocular pressure (units of mmHg) at each time point using Goldman tonometry.	Baseline, 3 months, 6 months, 12 months
Secondary	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.	Baseline, 3 months, 6 months, 12 months