Glaucoma After Corneal Trauma or Surgery—A Rapid, Inflammatory, IOP-Independent Pathway

Abstract

To review clinical aspects and cellular and molecular steps in the development of long-term glaucoma after corneal surgery or acute trauma-especially the pivotal role of tumor necrosis factor alpha (TNF-a), the rapidity of the secondary damage to the retinal ganglion cells, and the clinical promise of early antiinflammatory intervention.Methods: A series of laboratory studies on post-injury and postsurgery glaucoma have been compared to clinical outcome studies on the subject, focusing particularly on the vulnerability of the retinal ganglion cells. Alkali burn to the cornea of mice and rabbits served as the main experimental model. TNF-a titer, ganglion cell apoptosis, and depletion of optic nerve axons have been examined. Anti-TNF-a antibodies or corticosteroids have been used to protect the retinal ganglion cells. Intraocular pressure (IOP) postburn was recorded by manometric methods. Results:In animals with alkali burn to the cornea, damage to the retina can occur within 24 to 72 hours. This is not because of a direct pH change posteriorly-the alkali is effectively buffered at the iris-lens level. Rather, TNF-a (and other inflammatory cytokines), generated anteriorly, rapidly diffuses posteriorly to cause apoptosis of the ganglion cells. During this time, the IOP remains much lower than the reported values required to cause ganglion cell damage. The TNF-a antibody infliximab or corticosteroids, if administered promptly, are markedly protective of the ganglion cells.

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

“…In addition, the fact that TNF-α correlates with CDR but not IOP may support the IOP-independent pathway theory of glaucoma. 17 Because our results relate to tear fluid composition, we intend to investigate further the specific cytokines secreted in the aqueous humor of KPro eyes.…”

“…5,[11][12][13] Recent animal studies have suggested that inflammation might be one of the main IOP-independent causes, induced by the KPro device protruding in the anterior chamber, and diffusing to the retina, causing inevitable retinal ganglion cell (RGC) apoptosis. [14][15][16][17] Cytokines mediating immune and inflammatory responses play an important role in the process of glaucomatous optic neuropathy 18 and may play an important role in KPro-associated glaucoma, but this has not been thoroughly investigated. Increased expression of proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β have been shown in a miniature KPro murine model.…”

Intrinsic Optical Properties of Boston Keratoprosthesis

“…The clinical evaluation of patients with B-KPro, without prior or current history of extra-retinal pathology that spares the fovea, confirmed that the optical properties of the B-KPro devices permit 20/20 visual acuity. The limiting factors precluding normal visual acuity include compromised human retinal or optic nerve function, obstructions within the ocular media, [24][25][26] or surgical complications including tilt or decentration of the B-KPro implant. 27 Furthermore, the predicted postoperative refraction may be inaccurate due to postoperative changes in axial length due to lower or higher intraocular pressures than on preoperative testing.…”

“…In the grand scheme of long-term vision preservation in B-KPro patients, there are other important nonoptical challenges to overcome, such as glaucoma, retroprosthetic membrane formation, infection, and retinal detachment. Recent laboratory studies have revealed an inflammatory, intraocular pressureindependent pathway to glaucoma, 16,24,25,[35][36][37][38][39] and clinical studies have shown systemic elevation of tumor necrosis factor alpha and its receptor II in the blood of KPro patients. 16 Collectively, laboratory and clinical data suggest that targeted immunomodulation may be an important therapeutic adjunct to prevent glaucoma after corneal surgery.…”

“… 16 Collectively, laboratory and clinical data suggest that targeted immunomodulation may be an important therapeutic adjunct to prevent glaucoma after corneal surgery. 24 , 25 , 35 Because clinical studies may take years to conclude, engineering and optical innovations 17 , 21 , 27 , 41 – 47 can be implemented in the meanwhile to improve the overall performance and safety of B-KPro surgery. In this respect, the present study provides valuable information that can aid in improvement in the B-KPro optics.…”