About Limbal Stem Cell Deficiency


Treatment & management of LSCD

Discover more about your treatment options

LSCD is a rare condition, and LSCD due to ocular burns occurs in around 30 people per million of the population in Europe.1
There is a range of treatment options, depending on the cause and severity of the condition.2
Medical treatment takes a stepwise approach, aimed at limiting traumatic or chemical damage to the limbus, controlling inflammation, and helping to achieve a healthy corneal epithelium.34

The Stepwise approach
to treating damage to the limbus

Initial treatment after trauma/injury includes:

  1. preservative-free artificial tears, which help to lubricate your eye5
  2. the use of steroids in a cream or liquid form, to reduce inflammation in your eye67
  3. ‘bandage’ contact lenses to protect your eye and relieve pain89
  4. eye drops made from your own blood serum to help reduce your symptoms.10

Initial treatment usually gives temporary relief, but the condition tends to deteriorate over time. Surgery is also an option, but isn’t possible until inflammation has settled – usually after several months.11

Once the surface of your eye has become sufficiently stable, your doctor might consider a number of surgical options to help restore your sight.12

Surgery is the main approach to treating patients who have LSCD. Corneal transplant surgery (known as keratoplasty) alone is not considered an option for LSCD, as it invariably fails when undertaken in the absence of a healthy limbus.13

If the condition involves a partial LSCD, an operation known as a sequential sector conjunctival epitheliectomy (SSCE) can be performed to remove any tissue (known as pannus) that has grown over the cornea.14 This procedure is sometimes used as a temporary measure until further surgical interventions are possible.

Once the inflammation has disappeared and the surface stabilizes (a process that may take several months), limbal transplantation can be considered.15

  1. The transplantation of amniotic membrane from a placenta may also help. Although amniotic membrane does not have stem cells of its own, it supports regeneration of LSCs.16
  2. However, further surgical intervention may be needed if these approaches are unsuccessful, or when disease is more severe.

The main traditional surgical options include:

  • Conjunctival limbal autograft (CLAU)

    Conjunctival limbal autograft (CLAU) involves transplantation of limbal tissue from a patient’s healthy eye.1718 As the procedure is achieved by transplanting autologous limbal epithelial stem cells from your healthy eye, there is no risk of immune rejection19 and hence no need for systemic immunosuppression.20 To perform this procedure, the fellow eye must be normal with no limbal stem cell problems. Consequently, the procedure can only be performed if just one eye is affected (i.e. unilateral LSCD),

    and removal of tissue from the healthy eye risks the potential for LSCD in the donor eye.2122 As donor tissue is so valuable, the recipient eye must be in the best condition possible to avoid tissue wastage.23 Limbal stem cells are obtained by removing 2 to 4 strips of conjunctival-free limbal grafts from the superior and inferior limbus of the donor eye.24. Complications have been reported with this procedure,25and given its nature, it cannot be repeated if unsuccessful or only partially successful.

    Potential limitations to CLAU

    • This procedure represents a risk for the donor’s eye as the patient already has one damaged eye:26 patients often prefer to abstain from the procedure, and the surgeons must be conservative in selecting their patients and harvesting tissue;
    • Using a live donor, only a part of the donor limbus can be transplanted;27
    • Given the nature of the procedure, it cannot be repeated in case of failure.
  • Living Related Conjunctival limbal allograft (LR-CLAL)

    If both eyes are affected (known as bilateral LSCD), it may be possible to transplant limbal tissue from a living donor (usually a relative). This is known as a living related conjunctival limbal allograft (LR-CLAL).2829 LR-CLAL can be performed with both partial or total LSCD. The donor tissue is usually from a sibling or parent (and is therefore an allogenic transplant).

    Donor and recipient immunologic matching is based on blood type and antigens.30The procedure is otherwise the same as for CLAU. LR-CLAL involves taking a transplant from another person, systemic (whole body) immunosuppression is required, using drugs to damp down the immune response, in order to prevent rejection.3132

    Potential limitations to LR-CLAL

    • These procedures represent a risk for the donor’s eye33
    • Using a live donor, only a part of the donor limbus can be transplanted;34
    • It requires immunosuppression as there is the risk of rejection;3536
    • Given the nature of the procedure, it cannot be repeated in case of failure (another donor must be found).
  • Kerato-limbal allograft (KLAL)

    Another alternative involves transplantation from someone who has died and donated their organs (cadaver donor). This is known as a kerato-limbal allograft (KLAL).4041 KLAL can be used for cases of bilateral LSCD when a living related donor is not available,42 or for patients with unilateral LSCD, who don’t want to jeopardise their healthy eye.4344 However, most of these types of transplant fail within five years.45 In this type of surgery the corneoscleral rims from both eyes of one donor are used for one recipient eye.46 Instead of 2 small limbal grafts, a 360-degree ring that consists of the entire donor eye’s limbus, most of the peripheral cornea, and a minimal portion of the scleral tissue is used.

    The recipient eye preparation and grafting procedures are otherwise the same as those described for the CLAU and LR-CLAL transplantation. As KLAL involve taking a transplant from another person, systemic (whole body) immunosuppression is required, using drugs to damp down the immune response, in order to prevent rejection.4748 While KLAL offers the advantage of providing the entire donor limbus for transplantation, as compared with LR-CLAL,49 the tissue used in LR-CLAL (being from a living donor) will be fresher (and likely to be healthier) than that used in KLAL,50and LR-CLAL is associated with better outcomes.51

    Potential limitations to KLAL

    • The graft is usually up to 24 hours old before retrieval and a further period of time is often required to screen the cadaver’s blood before the tissue can be used52
    • Often the limbus is found to be damaged53
    • The tissue is not immunocompatible and risk of rejection is high between the recipient and the donor cadaver54
    • Studies report only a temporary success in terms of transplant effectiveness, with most failing after 5 years.55
  • Simple limbal epithelial transplantation (SLET)

    Another recent procedure, less invasive than CLAU, although which so far has been tested only in unilateral cases, is known as simple limbal epithelial transplantation (SLET). In this procedure, healthy limbal tissue from the patient’s good eye is cut into a number of pieces and transferred directly to human amniotic membrane covering the cornea in the damaged eye.565758 Slightly modified procedures have been reported in some of the published studies.59

    Potential limitations to SLET

    • Studies published so far have only investigated the procedure in unilaterally affected patients.606162
    • The long-term effectiveness of the technique is yet to be proven.6364
    • No clear efficacy data available for patients undergoing subsequent keratoplasty65 (concomitant keratoplasty identified as a factor associated with clinical failure).66
  • Cultivated Limbal Epithelial Transplant (CLET)

    A recent innovation is cultivated limbal epithelial transplant (CLET),67 either autologous (where donor and recipient are the same patient) or allogenic (where donor and recipient are different patients).68 This approach can be used when either one or both eyes are affected, providing there is sufficient limbal tissue available (1-2 mm2).69

    A small sample of limbal cells is taken from a healthy part of the eye, and these cells are grown in a sterile laboratory to produce a sheet of cells sufficient for transplantation. Once transplanted, they multiply and regrow the corneal epithelium.7071 The manufacturing process is designed to ensure implantation of the right number, size and quality of cells.72


    CLET avoids the issues related to the other limbal transplantation procedures, and does not pose a threat to the integrity of the donor eye.73 It also offers the possibility of re-grafting in case of failure of the first graft or clinical need for a further graft.7475 In Europe, autologous CLET is approved by EMA for the treatment of LSCD due to ocular burns.76 Often CLET represents a preparatory surgery for further treatments (eg keratoplasty), as it restores a normal and functional corneal epithelium and replenishes the pool of limbal stem cells, both of which are necessary for successful keratoplasty.77

    Potential limitations to CLET

    • Requires the presence of a small area of preserved limbus (1-2 mm2),78 which needs to be biopsied, expanded in culture, and transplanted onto the LSCD-affected eye.79
    • Comprises 2 separate procedures, and the patient has to wait while the cell sheet is grown before having the implantation.80
    • In some instances (eg poor biopsy quality, patient characteristics, or manufacturing failure), the original biopsy may contain insufficient numbers of holoclones to be expandable.81
    • Ex-vivo stem-cell expansion is a complex, time-consuming and expensive procedure.82

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