Corneal Allografts: Factors for and against Acceptance

Abstract

Cornea is one of the most commonly transplanted tissues worldwide. However, it is usually omitted in the field of transplantology. Transplantation of the cornea is performed to treat many ocular diseases. It restores eyesight significantly improving the quality of life. Advancements in banking of explanted corneas and progressive surgical techniques increased availability and outcomes of transplantation. Despite the vast growth in the field of transplantation laboratory testing, standards for corneal transplantation still do not include HLA typing or alloantibody detection. This standard practice is based on immune privilege dogma that accounts for high success rates of corneal transplantation. However, the increasing need for retransplantation in high-risk patients with markedly higher risk of rejection causes ophthalmology transplantation centers to reevaluate their standard algorithms. In this review we discuss immune privilege mechanisms influencing the allograft acceptance and factors disrupting the natural immunosuppressive environment of the eye. Current developments in testing and immunosuppressive treatments (including cell therapies), when applied in corneal transplantation, may give very good results, decrease the possibility of rejection, and reduce the need for retransplantation, which is fairly frequent nowadays.

Whole-eye transplantation: Current challenges and future perspectives

“…As a consequence of this knowledge, corneal transplantation has become one of the most successfully performed solid organ transplantation, with a more than 90% rate of success in low-risk condition, while in high-risk setting it lowers to less than 50%[ 49 , 50 ]. Interestingly, the impressive success rate often witnessed in low-risk corneal grafts, unlike with other solid organ transplants, can be attained without relying on HLA matching or extensive systemic immune suppression[ 51 , 52 ]. Following transplantation, inflammation in the eye triggers the upregulation of proinflammatory cytokines like IL-1, IL-6, and TNF-α, as well as chemokines such as MIP-1α, MIP-1β, MIP-2, and RANTES[ 53 ].…”

Novel technique of penetrating keratoplasty in high-risk grafts with significant corneal neovascularization

“…It has been shown that ACAID, which is a part of immune privilege contributes to corneal allograft survival. In corneal transplantation, the donor allografts are in direct contact with the AC and induce ACAID through provoking a series of immunological responses blocking normal delayed type hypersensitivity response [1,[4][5][6] . In our method, direct contact between the host endothelium and donor is absent.…”

Topical tacrolimus in high-risk corneal transplants

“…3 Several factors have been associated with increased graft rejection risk, such as pre-existing glaucoma, lens status, Human Leucocyte Antigen mismatches, among others. 2,4,5 The incidence of rejection appears to increase strongly with three risk factors: corneal neovascularization, namely the number of affected quadrants, density, and activity of neovessels; the number of previous ipsilateral corneal grafts; and an infectious or inflammatory disease that otherwise compromises corneal immune privilege. 5 In most corneal transplants, but more so in such highrisk cases, long-term topical or systemic immunosuppression is warranted.…”

“…2,4,5 The incidence of rejection appears to increase strongly with three risk factors: corneal neovascularization, namely the number of affected quadrants, density, and activity of neovessels; the number of previous ipsilateral corneal grafts; and an infectious or inflammatory disease that otherwise compromises corneal immune privilege. 5 In most corneal transplants, but more so in such highrisk cases, long-term topical or systemic immunosuppression is warranted. Current standard of care is based on topical corticosteroids, but its chronic use is associated with adverse effects such as increased intraocular pressure and cataract development.…”

“…2,4,5 The incidence of rejection appears to increase strongly with three risk factors: corneal neovascularization, namely the number of affected quadrants, density, and activity of neovessels; the number of previous ipsilateral corneal grafts; and an infectious or inflammatory disease that otherwise compromises corneal immune privilege. 5…”