Limbal Stem Cell Deficiency

Limbal stem cell deficiency (LSCD) is loss or dysfunction of the corneal epithelial stem cells at the limbal palisades of Vogt, with failure of epithelial renewal, conjunctival invasion of the cornea (conjunctivalisation), neovascularisation, chronic inflammation, and persistent epithelial defects.

• Acquired: chemical (alkali and acid) and thermal burns, Stevens-Johnson syndrome and toxic epidermal necrosis, ocular cicatricial pemphigoid, contact lens overwear, severe microbial keratitis, multiple ocular surgeries and cryotherapy, topical toxicity (preservatives, mitomycin C, 5-fluorouracil), radiation, and chronic limbitis (atopic and vernal disease).
• Inherited: aniridia (PAX6), ectodermal dysplasia, keratitis-ichthyosis-deafness syndrome, and xeroderma pigmentosum.
• Partial (sectoral) or total; unilateral or bilateral. The cause determines the surgical options.

• Photophobia, pain, tearing, reduced vision, recurrent erosions, and redness.
• Loss of limbal palisades, irregular epithelial surface with a dull, hazy appearance, whorl or vortex pattern, late fluorescein staining (an irregular pattern of uptake with stippled or fluorescein pooled areas), conjunctivalisation (vascularised, thickened tissue with a stippled pattern), and neovascularisation, stromal scarring.
• Persistent or recurrent epithelial defects, corneal melt and perforation, symblepharon.
• Total LSCD with severe visual loss.

• Clinical diagnosis at the slit lamp, supported by:
  • Impression cytology: goblet cells and conjunctival keratins (CK7, CK13, CK19) on the corneal surface, absence of the corneal keratin CK12.
  • Anterior segment OCT: thinned, irregular epithelium and absent limbal palisades.
  • In vivo confocal microscopy: conjunctival type epithelium with goblet cells.
• Assess the fellow eye and the cause (autoimmune screen, genetic testing in aniridia).
• Quantify extent in clock hours: partial (under 12 hours) or total.

• Treat ocular surface disease: preservative free lubricants, autologous serum 20 to 50 percent four to eight times daily, control of inflammation, lid correction, treat dry eye, stop toxic drops, scleral lenses.
• Partial LSCD: sequential sectoral conjunctival epitheliectomy (removal of conjunctivalised epithelium, with amniotic membrane) to let remaining limbal stem cells repopulate the surface.
• Unilateral total LSCD (healthy fellow eye): autologous limbal stem cell transplantation:
  • Simple limbal epithelial transplantation (SLET): a 2 x 2 mm limbal biopsy is divided into small pieces and placed on amniotic membrane over a fibrin glue base; success about 75 to 85 percent.
  • Cultivated limbal epithelial transplantation (CLET) from small biopsy, and conjunctival limbal autograft (CLAU) using 2 clock hour grafts from the fellow eye.
• Bilateral total LSCD:
  • Allogeneic limbal transplantation (keratolimbal allograft, living related conjunctival limbal allograft), with systemic immunosuppression: oral tacrolimus 0.05 to 0.1 mg/kg twice daily (target trough 5 to 10 ng/mL), mycophenolate mofetil 1 g twice daily, and prednisolone 0.5 to 1 mg/kg daily tapered, for at least 1 to 2 years.
  • Cultivated oral mucosal epithelial transplantation (COMET), using autologous oral mucosa, for patients where allograft is contraindicated.
• Visual rehabilitation after the surface is stable (6 to 12 months): penetrating keratoplasty or deep lamellar keratoplasty, or keratoprosthesis (Boston type 1) for refractory bilateral disease.
• Do not carry out keratoplasty before restoration of the surface (high failure).
• Lifelong follow up with regular review of pressure and surface.