The corneal epithelium is a stratified squamous epithelium from which superficial terminal cells are naturally shed. Limbal stem cell deficiency (LSCD) is characterized by a loss or deficiency of the stem cells in the limbus that are vital for re-population of the corneal epithelium and to the barrier function of the limbus [1 2]. When these stem cells are lost, the corneal epithelium is unable to repair and renew itself. This results in epithelial breakdown and persistent epithelial defects, corneal conjunctivalization and neovascularization, corneal scarring, and chronic inflammation. All of these contribute to loss of corneal clarity, potential vision loss, chronic pain, photophobia, and keratoplasty failure[2 3].
The etiologies can be genetic, acquired, or idiopathic. 

LSCD Causes.png


Limbal stem cell deficiency has been associated with PAX6 gene mutations, which are also implicated in aniridia[4] and Peter’s Anomaly[5]. Other genetic disorders that have been reported with LSCD include ectrodactylyl-ectodermal-dysplasia-clefting syndrome[6], keratitis-ichthyosis-deafness (KID) Syndrome[7], Xeroderma Pigmentosum[8], Dominantly Inherited Keratitis[9], Turner Syndrome[3] and Dyskeratosis Congenita[10].



Other causes include inflammatory insults such as those seen in Steven-Johnsons Syndrome (SJS) [11], ocular cicatricial pemphigoid[12], and graft versus host disease[13]. Chronic ocular allergy such as Vernal Keratoconjunctivitis is another reported cause[14]. Neurotrophic keratopathy, whether neuronal or ischemic, can lead to this disease as well[2], as can bullous keratopathy [15].


Any infections of the corneal surface such as herpes keratitis[16] and trachoma [17] can predispose to this condition.


Acquired causes also include trauma from chemical or thermal burns, and patients who have undergone prior ocular surgeries or cryotherapies at the limbus may be more susceptible[16 18]. Radiation and chemotherapy are other potential causes, and systemic[19] as well as topical chemotherapeutic medications may be sufficient to cause deficiency[20].  LSCD has also been seen with benzalkonium chloride toxicity with glaucoma medications [21]. Inappropriate contact lens use with consequent hypoxia and ocular irritation with destruction of the limbus may also contribute to both focal and total limbal stem cell deficiency[22 23].

Tumors/Overgrowth of Other Tissue:

Ocular surface tumors are a known cause of LSCD[2]. Pterygium may also cause a focal acquired absence of limbal stem cells[24].

Management is typically symptomatic in nature early in the disease. When limbal stem cell injury is transient, sometimes termed limbal stem cell disease or limbal stem cell distress, conservative medical measures as above may be sufficient[21 31 38]  However, total limbal stem cell deficiency must be surgically managed.

Untreated limbal stem cell deficiency causes pain, decreased vision, and recurrent epithelial erosions that predispose to infection and loss of vision. Infectious keratitis is common with this disease, and patients who wear contact lenses for extended periods of time, have persistent epithelial defects, and use topical immunosuppressive medications are at increased risk[32]. After surgical treatment, there is a risk of rejection from allogeneic transplants[49]. It is possible that the cornea will not remain clear and further surgery such as repeat stem cell transplant or penetrating keratoplasty may be necessary[49]

Cultivated Oral Mucosal Epithelial Transplantation (COMET):

Patients with live related stem cell transplantation or cultivated oral mucosal epithelial transplantation (COMET) along with lamellar or penetrating keratoplasty have poor outcomes even with long-term immunosuppression[54-56]. The use of fibrin glue rather than amniotic membrane for COMET and optimizing the ocular surface prior to transplant improved outcomes in a recent study, and it is possible that future modifications to technique may improve these outcomes further[57]. 

Cultivated Limbal Epithelial Transplantation (CLET):

Studies have shown that CLET is as effective as direct limbal transplantation for LSCD while requiring less donor tissue and thus being safer for donor eyes[45 58-61]. Studies of CLET have shown a 68-80% success rate.[62 63]  In a review of outcomes of cultured limbal epithelial cell therapy published from 1997 to 2011 with data from 583 patients, the overall success rate was 76%[60]. However, this varies by The success rate of a transplant is significantly higher with an increased number of transplanted stem cells and failures tend to happen within the first year[63]. 

The largest study of xeno-free explant culture transplants showed a 71% success rate in 200 recipient eyes with a mean follow-up of approximately 5 years and up to 10 years.[46 49] Supplemental corneal transplant (PK) has a survival rate of 1 year, with a median survival of 3.3 years.[49]

In a recent meta-analysis of the outcomes of keratolimbal allografting for LSCD, postoperative corrected distance visual acuity (CDVA) was 2 or more lines better than the preoperative visual acuity in 31%to 67% of eyes [55]. 

Simple Limbal Epithelial Transplant:

 In a study of 6 patients with total unilateral LSCD, visual acuity improved from worse than 20/200 in all recipient eyes before SLET surgery to 20/60 or better in four (66.6%) eyes, while none of the donor eyes developed any complications. Mean follow-up was 9.2 months.[48]

Boston Keratoprosthesis:

The Boston K-pro has been found to have good short-term visual and anatomical outcome in patients with bilateral LSCD[64] with vision of 20/40 or better at 6 months. One large study found a final postoperative CDVA 2 or more lines better than the preoperative visual acuity in 86% (18 of 21) of eyes and a CDVA of 20/50 or better in more than two thirds of eyes up to 3 years after surgery, though these prostheses should be used with caution in eyes with SJS and other immune causes as there is an increased retention failure rate [51]. 

If the all treatment fails an ocular prosthesis is desired, many times it is is very hard to have very symmetrical eye prosthesis, at International prosthetic Eye Center we try to make as life like possible,


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