Effect of Penetrating Keratoplasty and Keratoprosthesis Implantation on the Posterior Segment of the Eye

Abstract

PurposeTo compare the effects of post-penetrating keratoplasty (PK) and post-keratoprosthesis (KPro) surgery-related inflammation on the posterior segment of the eye and to assess inhibition of tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) on these effects.MethodsBALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or miniature KPro (m-KPro) implantation. Intraocular pressure (IOP) was measured via an intracameral pressure sensor; tissues were harvested and analyzed 8 weeks after surgery. Expression of TNFα and IL-1β in the retina was analyzed using real-time quantitative (q)PCR. Optic nerve degeneration (axon count, circularity, and area) was assessed quantitatively using ImageJ software. After m-KPro implantation, mice were treated with saline, anti-TNFα, or anti-IL-1β antibody, and axonal loss was assessed after 10 weeks.ResultsMean IOP was within normal limits in the operated and fellow eyes in all groups. The mRNA expression of TNFα and IL-1β was highest in m-KPro groups with either syngeneic or an allogeneic carrier. We observed optic nerve degeneration in both allogeneic PK and m-KPro implanted eyes with an allogeneic carrier. However, TNFα blockade significantly reduced axonal loss by 35%.ConclusionsAllogeneic PK and m-KPro implants with an allogeneic carrier lead to chronic inflammation in the posterior segment of the eye, resulting in optic nerve degeneration. In addition, blockade of TNFα prevents axonal degeneration in this preclinical model of allogeneic m-KPro (alloKPro) implantation.

Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye

“…12 Prompt inhibition with an anti-TNF-α antibody (infliximab) after alkali burn has been shown to protect the cornea and promote healing. 12,13 This effect has also been demonstrated in animals with experimental keratoprosthesis 14 and in other settings. 15,16 Clinically, infliximab has been found to very effectively suppress inflammation after keratoprosthesis surgery in autoimmune diseases, 17,18 as well as in corneal ulceration.…”

“…14 Sections from burned and contralateral nonburned eyes were used for comparison. A portion of the nerve between the orbit and chiasm was surgically dissected, and fixed with half strength Karnovsky's fixative (2% formaldehyde + 2.5% glutaraldehyde, in 0.1 M sodium cacodylate buffer, pH 7.4 [Electron Microscopy Sciences, Hatfield, PA, USA]) for a minimum of 24 hours at 40°C.…”

Müller Muscle-conjunctival Resection with or without Tarsectomy and Combined with Bandage Contact Lens Use in Ptosis Patients with Corneal Graft

“…1 One form of this transplantation, penetrating keratoplasty (PK), is a sight-saving surgery in many patients with corneal blindness. 2 Overall, approximately 90% of all corneal transplantation procedures performed in 95 reporting countries are PK, regardless of the surgical indication. 3,4 Patients who undergo PK may experience eyelid ptosis [5][6][7] and blepharoptosis that may restrict the visual acuity and the visual field that was improved with the PK.…”

“…Corneal transplantation is the most common type of tissue transplantation performed worldwide [ 1 ]. One form of this transplantation, penetrating keratoplasty (PK), is a sight-saving surgery in many patients with corneal blindness [ 2 ]. Overall, approximately 90% of all corneal transplantation procedures performed in 95 reporting countries are PK, regardless of the surgical indication [ 3 , 4 ].…”

Tear Film Cytokine Profile of Patients With the Boston Keratoprosthesis Type 1: Comparing Patients With and Without Glaucoma

“…Increased expression of proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β have been shown in a miniature KPro murine model. 15,19 Our team also showed that soluble TNF-α is a major culprit in RGC death in glaucoma and that TNF-α inhibition is beneficial. 20 However, neither the exact mechanism of KPro glaucoma nor the role of cytokines has been elucidated yet in humans.…”