Neovascularization Patterns in Corneal Graft Rejection

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

DESCRIPTION (provided by applicant): Corneal neovascularization (CN) is an established risk factor for corneal allograft rejection and failure. CN compromises the immune privileged status of the cornea and increases the risk of rejection and failure by introducing host immune cells and inflammatory mediators to the allograft. Studies of CN have been hampered by the limitations of conventional slit lamp biomicroscopy that does not permit comprehensive quantitation of CN features that predict which patients are at high risk for rejection and failure. Clinical experience has shown that many patients with corneal transplants have some degree of CN within the host bed, removed corneal button, or the allograft, yet most allografts survive without incident for many years. Thus, the precise patterns of CN that predict graft morbidity are unknown. The advent of confocal biomicroscopy (CBM) provides a new clinical examination method that has the ability to resolve previously undetectable CN and to permit precise assessment of CN circumferential extent, stromal depth, and axial penetration into the cornea. With CBM it is now possible to accurately determine the presence and patterns of CN in humans. This will assist in recognizing CN that poses high risk for allograft rejection or failure, identifying those patients who may benefit from therapeutic intervention. This study will determine specific CN patterns in human corneal allograft recipients to determine the characteristics that worsen the prognosis for graft survival. Comparing the results of CBM and conventional slit lamp biomicroscopy examinations to identify CN will show that CBM is a more sensitive method that images previously unseen new blood vessels at the single cell level. Correlative histopathologic studies will confirm the presence of CN imaged in vivo, and show CN and corneal tissue expression of cellular adhesion molecules that serve to promote trafficking and activation of leukocytes that mediate rejection. This will allow, for the first time, accurate clinical depiction of the presence and patterns of CN and act as a true basis for understanding the relationship between precise CN characteristics and undesirable allograft outcomes in humans. The identification of new blood vessel growth patterns in the cornea that confer high risk for transplant rejection and failure will allow development of new therapies aimed at reducing neovascularization and risk of rejection. Such therapies have already been shown to be safe and effective in human eyes, and are used on a routine basis for retinal neovascularization. This study will provide the basis for identifying those patients for whom such anti-angiogenic therapy is warranted.