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| Procedure | Mechanism of action and remarks | References |
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| Conservative nonsurgical options |
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| Autologous serum drops | Serum drops promote migration and proliferation of healthy epithelium while lubricating the ocular surface, preventing epithelial adhesion to the tarsal conjunctiva, and reducing shear stress. | [86–88] |
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| Therapeutic soft contact lens | Therapeutic lenses promote healing of persistent epithelial defects (PED) and prevent the formation of new defects. | [89] |
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| Therapeutic scleral lens | Scleral lenses promote healing of PED while improving vision (optical effect) and reducing pain and photophobia (therapeutic effect). They also prevent formation of new epithelial defects. | [90] |
|
| Eye lubrication | Ocular surface lubrication prevents epithelial adhesion to the tarsal conjunctiva and reduces shear stress. Unlike autologous serum drops, residual stem cell migration and proliferation is not enhanced. | [89] |
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| Conservative surgical options |
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| Corneal scraping | During scraping the overgrown conjunctiva is removed, enabling reepithelialisation by islands of functioning corneal epithelial stem cells. However, because the conjunctival epithelium migrates more rapidly than the corneal epithelium, it may be necessary to repeat the procedure two to three times. | [91] |
|
| Amniotic membrane transplantation (AMT) | AMT promotes proliferation and migration of residual LESCs, contributing to the recovery of the corneal surface, improved visual acuity, and alleviation of pain and photophobia. Low immunogenicity, and anti-inflammatory, antiangiogenic, antifibrotic, antimicrobial, and antiapoptotic properties of the amniotic membrane assist in its therapeutic effect. An AMT is performed immediately after corneal scraping as the overgrown conjunctiva is removed and the amnion membrane is patched over the epithelial defect. Variable clinical outcome may be attributed to inter- and intradonor variation of the biologically sourced membrane. | [88, 92] |
|
| Limbal epithelial stem cell transplantation |
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| Conjunctival limbal autograft (CLAU) | Autologous graft derived from the patient’s healthy eye, using the conjunctiva as carrier tissue. As this procedure involves dissecting 2 clock hours each of limbal tissue superiorly and inferiorly, CLAU holds the risk of inducing LSCD in the healthy donor eye. | [6, 21, 50, 89] |
|
| Conjunctival limbal allograft (CLAL) | Allogenic graft derived from a living related (lr-CLAL) or deceased donor (c-CLAL), using the conjunctiva as carrier tissue. CLAL comes with an increased risk of transmitting infectious disease and promoting neoplasia due to the long-term use of immunosuppressants. The surgical procedure and number of clock hours to be dissected are similar to that for CLAU. Lr-CLAL may induce LSCD in the healthy donor eye. | [6, 21, 50, 89] |
|
| Keratolimbal allograft (KLAL) | Allogenic graft derived from a deceased donor, using the cornea as carrier tissue. As in CLAL, there is an increased risk of disease transmission and formation of neoplasia. KLAL requires approximately 6 clock hours of tissue to be removed from the donor limbus and transplanted onto the stem cell deficient eye. | [6, 21, 50, 89] |
|
| Ex vivo cultivated limbal epithelial stem cells (CLET) | Autologous or allogenic transplantation of cultivated stem cells, most commonly using the human amniotic membrane or fibrin as a carrier for the composite graft. The major advantage of this technique is the reduced risk of inducing LSCD in the healthy donor eye, and the decreased incidence of immunological rejection as Langerhans cells are not cultured in the composite graft. However, the use of HAM or the transplantation of allogenic LESCs bears the risk of disease transmission. Furthermore, the use of immunosuppressants may be necessary in allogenic transplantation with limited HLA-compatibility. Finally, some culture protocols use animal-derived products, which pose the theoretical risk of zoonosis and/or elicit an immune response in the acceptor. | [21, 22, 59, 93] |
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| Simple limbal epithelial transplantation (SLET) | Autologous transplantation of tiny limbal grafts that are distributed and glued evenly over a HAM. Circumventing difficulties of ex vivo culture techniques, epithelialisation is achieved in vivo. As seen in CLET, there is limited risk of immunological rejection or induction of LSCD in the healthy donor eye. Furthermore difficulties of ex vivo culturing are avoided, promoting cost-effectiveness. However, the rate of LESC expansion in vivo must be greater than that of the rapidly proliferative conjunctiva to attain successful engraftment. | [94] |
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