Personalized Medicine in Ophthalmology: Treatment of Total Limbal Stem Cell Deficiency with Autologous Ex Vivo Cultivated Limbal Epithelial Stem Cell Graft

Abstract

Most of the blinding corneal diseases are treatable by corneal transplantation in which a corneal allograft is used. However, in severe corneal burns that often result in total limbal epithelial stem cell (LECS) deficiency, corneal transplantation alone is not feasible, as corneal graft in eyes without stem cells cannot survive. Total LESC deficiency is clinically characterized by growth of conjunctival tissue over the cornea, corneal neovascularization and opacification. It unfortunately affects mostly younger population. Two decades ago, it has been shown that a successful corneal graft in patients with corneal burns can only be performed as a second surgical act; namely only after transplantation of limbal stem cells cultivated ex vivo have restored a healthy anterior ocular surface. Cultivation of LESC ex vivo has been adopted as treatment of choice for such cases. Various carriers of LESC in vitro has been tested and clinically applied, such as fibrin, amniotic membrane and contact lens. LESC samples for cultivation in vitro can be autologous grafts harvested from the contralateral healthy eye (if only one eye has corneal burn), or allografts retrieved from a healthy relative or donor corneo-scleral rim. The most effective way of treatment is collection of healthy LESC from patient’s healthy eye, their multiplication ex vivo on certain carrier and final grafting of cultivated epithelial sheet on the diseased eye of the same patient. Transplantation of such LESC becomes a personalized ocular treatment as epithelial sheet of cells must be cultivated for each particular patient. Other sources of LESC for ex vivo cultures, such as allografts, are significantly less successful and has disadvantage that the patient must receive systemic immunosuppressive treatment with unwanted side-effects.