Perspectives for preclinical mouse models of glaucoma after Boston keratoprosthesis type 1

Geoffrion, Dominique; Robert, Marie-Claude; Chodosh, James; Polo, Adriana Di; Harissi‐Dagher, Mona

doi:10.1016/j.exer.2021.108615

Cited by 3 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While inflammation may also have an important role in KPro‐associated glaucoma, no study has yet investigated ocular fluids from KPro patients with glaucoma. The objective of this study was to compare cytokine levels in the tear film of KPro patients with and without glaucoma, relative to controls and correlate levels with clinical parameters (Geoffrion, Robert, Chodosh, et al, 2021; Geoffrion, Robert, Di Polo, et al, 2021). The long‐term goal was to establish how clinical care can be best tailored to the KPro patient population to improve outcomes despite high prevalence of glaucoma.…”

Section: Introductionmentioning

confidence: 99%

“…We wanted to determine whether this mouse model was a proper model to examine inflammatory mechanisms and retinal ganglion cell apoptosis involved in glaucomatous optic neuropathy after KPro surgery. We investigated whether it was feasible to establish a reproducible animal model of glaucoma post‐KPro with the hope to use it to validate human outcomes in the future (Geoffrion, Robert, Chodosh, et al, 2021; Geoffrion, Robert, Di Polo, et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery

Geoffrion

Koenekoop

Harissi‐Dagher

2022

Acta Ophthalmologica

Self Cite

View full text Add to dashboard Cite

ENGLISH SUMMARY Corneal blindness is a leading cause of visual impairment worldwide. The most common treatment is to replace the diseased cornea by standard corneal transplantation. In eyes at high risk of graft failure, the Boston keratoprosthesis type 1 (KPro) can be used to restore vision and is currently the most frequently used artificial cornea in the world. However, glaucoma is a well‐known complication of KPro surgery and is the most important threat to vision in KPro‐implanted eyes (paper I). This chronic disease is influenced by elevated intraocular pressure (IOP) and damages the optic nerve, leading to progressive vision loss. In KPro patients, glaucoma is highly prevalent and extremely challenging to manage, yet its exact cause remains unknown. The overall purpose of this PhD Thesis (Geoffrion, 2021) was to better understand the mechanisms and how to improve management of glaucoma after KPro implantation. The approaches used in this thesis included investigating one of the largest KPro patient cohorts in North America, with a total of 157 operated patients at that time, as well as studying KPro surgery and outcomes in mice. The first objective was to identify risk factors for glaucoma development and progression after KPro implantation (paper II). Multivariate logistic regression revealed that high preoperative IOP signals a higher risk for both glaucoma development and progression. Stromal and endothelial corneal disorders were less associated with glaucoma progression, while autoimmune and ocular surface diseases precipitated glaucoma development. Second, there is no objective evidence that indicates the best order for glaucoma surgeries and KPro implantation. By comparing medical and surgical management in KPro eyes with either preexisting or de novo glaucoma (paper III), we showed that glaucoma surgery may be performed before or at the time of KPro in eyes with preexisting glaucoma to limit progression without increasing complications. In eyes with de novo glaucoma, glaucoma surgery did not increase complications compared with medications. Third, among glaucoma surgery interventions, the two most frequently implanted glaucoma drainage devices were compared in KPro patients (paper IV). Compared with the Ahmed glaucoma valve, the Baerveldt glaucoma implant was associated with lower failure rates, without increased postoperative complications. Fourth, even with aggressive management, many KPro patients suffer from progressive optic nerve damage, sometimes despite normal IOP. Inflammatory cytokines play an important role in glaucomatous optic neuropathy, but their role in KPro‐associated glaucoma is still unknown. By analysing tear fluid of KPro patients by multiplex bead immunoassay (paper V), we identified that cytokines TNF‐a, IL‐1b, FGF‐basic and IFN‐g were elevated in KPro patients with glaucoma compared to those without. These cytokines correlated with optic nerve excavation and IOP. For the first time in humans, these results concorded with the elevations of TNF‐a and IL‐1b documented ...

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery

Geoffrion

Koenekoop

Harissi‐Dagher

2022

Acta Ophthalmologica

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fifth, we determined that miniaturized mouse KPro implantation requires extensive practice to be used as a reproducible model of glaucoma post‐KPro. KPro animal models with larger eyes and a full‐thickness, 360‐degree corneal excision should be prioritized to best validate human outcomes (Geoffrion et al, 2021b).…”

mentioning

confidence: 99%

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery

Geoffrion

Koenekoop

Harissi‐Dagher

2023

Acta Ophthalmologica

Self Cite

View full text Add to dashboard Cite

Corneal blindness is a leading cause of visual impairment worldwide. The most common treatment is to replace the diseased cornea with standard corneal transplantation. In eyes at high risk of graft failure, the Boston keratoprosthesis type 1 (KPro) can be used to restore vision and is currently the most frequently used artificial cornea in the world. However, glaucoma is a well‐known complication of KPro surgery and is the most important threat to vision in KPro‐implanted eyes. This chronic disease is influenced by elevated intraocular pressure (IOP) and damages the optic nerve, leading to progressive vision loss. In KPro patients, glaucoma is highly prevalent and extremely challenging to manage, yet its exact cause remains unknown.

show abstract

The treatment of end-stage corneal disease: penetrating keratoplasty compared with Boston type 1 keratoprosthesis

Bonneau

Tong

Yang

et al. 2022

Graefes Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

Perspectives for preclinical mouse models of glaucoma after Boston keratoprosthesis type 1

Cited by 3 publications

References 23 publications

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery

Probing mechanisms and improving management of glaucoma following Boston keratoprosthesis surgery

The treatment of end-stage corneal disease: penetrating keratoplasty compared with Boston type 1 keratoprosthesis

Contact Info

Product

Resources

About