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Limbal Stem Cell Deficiency & Eye Prosthesis

April 7, 2016


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].
Etiologies: 
The etiologies can be genetic, acquired, or idiopathic. 

LSCD Causes.png

Genetic:

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].

Acquired:

Inflammatory:

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].

Infectious:

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

Traumatic/Iatrogenic:

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: 
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.

Complication:
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,


Reference: 

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2. Sangwan VS. Limbal stem cells in health and disease. Bioscience reports 2001;21(4):385-405 

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4. Skeens HM, Brooks BP, Holland EJ. Congenital aniridia variant: minimally abnormal irides with severe limbal stem cell deficiency. Ophthalmology 2011;118(7):1260-4 doi: 10.1016/j.ophtha.2010.11.021[published Online First].

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19. Ding X, Bishop RJ, Herzlich AA, Patel M, Chan CC. Limbal stem cell deficiency arising from systemic chemotherapy with hydroxycarbamide. Cornea 2009;28(2):221-3 doi: 10.1097/ICO.0b013e318183a3bd[published Online First].

20. Lichtinger A, Pe'er J, Frucht-Pery J, Solomon A. Limbal stem cell deficiency after topical mitomycin C therapy for primary acquired melanosis with atypia. Ophthalmology 2010;117(3):431-7 doi: 10.1016/j.ophtha.2009.07.032[published Online First].

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23. Chan CC, Holland EJ. Severe limbal stem cell deficiency from contact lens wear: patient clinical features. American journal of ophthalmology 2013;155(3):544-49 e2 doi: 10.1016/j.ajo.2012.09.013[published Online First].

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26. Shapiro MS, Friend J, Thoft RA. Corneal re-epithelialization from the conjunctiva. Investigative ophthalmology & visual science 1981;21(1 Pt 1):135-42 

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30. Osei-Bempong C, Figueiredo FC, Lako M. The limbal epithelium of the eye--a review of limbal stem cell biology, disease and treatment. BioEssays : news and reviews in molecular, cellular and developmental biology 2013;35(3):211-9 doi: 10.1002/bies.201200086[published Online First].

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32. Sandali O, Gaujoux T, Goldschmidt P, Ghoubay-Benallaoua D, Laroche L, Borderie VM. Infectious keratitis in severe limbal stem cell deficiency: characteristics and risk factors. Ocular immunology and inflammation 2012;20(3):182-9 doi: 10.3109/09273948.2012.672617[published Online First].

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40. Rathi VM, Sudharman Mandathara P, Vaddavalli PK, Dumpati S, Chakrabarti T, Sangwan VS. Fluid-filled scleral contact lenses in vernal keratoconjunctivitis. Eye & contact lens 2012;38(3):203-6 doi: 10.1097/ICL.0b013e3182482eb5[published Online First].

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42. Sangwan VS, Matalia HP, Vemuganti GK, Rao GN. Amniotic membrane transplantation for reconstruction of corneal epithelial surface in cases of partial limbal stem cell deficiency. Indian journal of ophthalmology 2004;52(4):281-5 

43. Fernandes M, Sangwan VS, Rao SK, et al. Limbal stem cell transplantation. Indian journal of ophthalmology 2004;52(1):5-22 

44. Shimazaki J, Higa K, Morito F, et al. Factors influencing outcomes in cultivated limbal epithelial transplantation for chronic cicatricial ocular surface disorders. American journal of ophthalmology 2007;143(6):945-53 doi: 10.1016/j.ajo.2007.03.005[published Online First].

45. Pellegrini G, Traverso CE, Franzi AT, Zingirian M, Cancedda R, De Luca M. Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet 1997;349(9057):990-3 doi: 10.1016/S0140-6736(96)11188-0[published Online First].

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47. Johnen S, Wickert L, Meier M, Salz AK, Walter P, Thumann G. Presence of xenogenic mouse RNA in RPE and IPE cells cultured on mitotically inhibited 3T3 fibroblasts. Investigative ophthalmology & visual science 2011;52(5):2817-24 doi: 10.1167/iovs.10-6429[published Online First].

48. Sangwan VS, Basu S, MacNeil S, Balasubramanian D. Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. The British journal of ophthalmology 2012;96(7):931-4 doi: 10.1136/bjophthalmol-2011-301164[published Online First].

49. Basu S, Fernandez MM, Das S, Gaddipati S, Vemuganti GK, Sangwan VS. Clinical outcomes of xeno-free allogeneic cultivated limbal epithelial transplantation for bilateral limbal stem cell deficiency. The British journal of ophthalmology 2012;96(12):1504-9 doi: 10.1136/bjophthalmol-2012-301869[published Online First].

50. Brown KD, Low S, Mariappan I, et al. Plasma polymer-coated contact lenses for the culture and transfer of corneal epithelial cells in the treatment of limbal stem cell deficiency. Tissue engineering. Part A 2014;20(3-4):646-55 doi: 10.1089/ten.TEA.2013.0089[published Online First].

51. Sejpal K, Yu F, Aldave AJ. The Boston keratoprosthesis in the management of corneal limbal stem cell deficiency. Cornea 2011;30(11):1187-94 doi: 10.1097/ICO.0b013e3182114467[published Online First].

52. Espana EM, Di Pascuale M, Grueterich M, Solomon A, Tseng SC. Keratolimbal allograft in corneal reconstruction. Eye 2004;18(4):406-17 doi: 10.1038/sj.eye.6700670[published Online First].

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54. Liang L, Sheha H, Tseng SC. Long-term outcomes of keratolimbal allograft for total limbal stem cell deficiency using combined immunosuppressive agents and correction of ocular surface deficits. Archives of ophthalmology 2009;127(11):1428-34 doi: 10.1001/archophthalmol.2009.263[published Online First].

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61. Shortt AJ, Secker GA, Notara MD, et al. Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Survey of ophthalmology 2007;52(5):483-502 doi: 10.1016/j.survophthal.2007.06.013[published Online First].

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Treatment for Facial Paralysis & Lagophthalmos

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"We suggest to use the temporary eye lid weight using the double sided tape so that it stay over the eye lid, newer implant made of 24K gold, they donot give any allergy and reaction to skin and very comfortable, front or anterior surface of eye lid weight is coated with silicone in skin shades to mimics normal" 


Kit of temporary eye lids implants with adhesive

The great advantage with these implant you can use the night time, and no surgery involved, which is very easy to use.
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In a well-made prosthetic eye, tears should flow evenly across the prosthesis just as they do over the natural eye — in a sheet-like fashion, rather than collecting in droplets. We call this type of behavior hydrophilic — “water loving.” Hydrophobic (“water fearing”) artificial eyes repel water, much like the surface of a waxed car.

The difference between a hydrophilic and a hydrophobic piece can have dramatic differences in the satisfaction for the patient. Hydr...


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Kuldeep Raizada, Ph D, B.C.O., B.A.D.O, LICENSED OCULARIST

Kuldeep Raizada is a Licensed Ocularist in Hyderabad, a Board Certified Ocularist (BCO)  from National examination Board of ocularist’s, USA and a Board Approved Diplomate Ocularist (BADO) from American Society of ocularist’s, specializing in ocular prosthetics since 2001, Kuldeep places his emphasis on the satisfaction and well-being of every patient. His clinical  skill and expertise are equally matched by his pe...


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A phthisis bulbi is a small, shrunken, non-functional eye. The affected eye may have partial vision retained in some cases; though blindness with this disorder is very common. The condition may result from an eye disease, trauma or inflammation.

In phthisis bulbi, the eye has a scary and shrunken appearance. An eye ball may appear soft.

Alternative names

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Causes & Risk factors 

Phthisis bulbi occurs as a result of trauma, accident, exposure to the radiation, tumour, eye infection ...

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Auto-enucleation (oedipism) and other forms of serious self inflicted eye injury are an extremely rare form of severe self-harm which usually results from serious mental illnesses such as schizophrenia.[2] The ...


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About Me


Dr Kuldeep Raizada, Ph D, BCO BADO Kuldeep Raizada completed his basic optometry education at Gandhi Eye Hospital, Aligarh, and has his training at L V Prasad Eye Institute, Hyderabad. where he was also Founder and Head of the Department of Ocular Prosthesis services till 2009. He completed a second fellowship, in Anaplastolgy, at MD Anderson Cancer Centre, Houston. He has also been trained by the top most ocularist and anaplastologist in United States of America. His clinical interests include ocular and facial prosthesis, particularly in pediatric patients. His research interests lie in newer advancement in development of new types of prosthesis, newer solution for ptosis corrective glasses. Kuldeep Raizada, is Founder & Director of the International Prosthetic Eye Center since 2010, where he is practicing since 2010. Kuldeep Raizada has been recognized by the American Society of Ocularist, USA and American Anaplastology Association,USA and by several other professional organizations, for his excellence in research and clinical practice. Kuldeep Raizada, have completed all requirements by American Society of Ocularist, which is hard work of 14000 working hours as well extensive study for prosthetics, Hence awarded the Diplomate Ocularist from American Society of Ocularist, USA, 2012, Chicago, USA, which is the First ever received all over Asia Pacific & throughout Middle East so ever. At present he is reviewer of several journals like Contact Lens & Anterior Eye, International Journal of Anaplastology, Oculoplasty & Reconstructive Surgery (OPRS) and Many others. He has published and presented world widely