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

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.

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.

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