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Limbal Stem Cell Deficiency Advanced Treatment

Cultured cellular and tissue-based therapies for ocular surface reconstruction

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Göz Hastalıkları department. Book Appointment →

What is Limbal Stem Cell Deficiency Advanced Treatment?

Limbal stem cells reside at the corneoscleral limbus and continuously regenerate corneal epithelium. Limbal stem cell deficiency (LSCD) results from chemical burns, thermal injuries, severe Stevens-Johnson syndrome, ocular cicatricial pemphigoid, aniridia, contact lens overuse, prior multiple surgeries, and radiation therapy. Without functional limbal stem cells, the cornea is overrun by conjunctival epithelium with goblet cells (conjunctivalization), neovascularization, and chronic surface inflammation, leading to vision loss and pain.

Modern therapies have transformed LSCD management beyond simple penetrating keratoplasty. Autologous options include conjunctival limbal autograft (CLAU) from the contralateral eye for unilateral disease, simple limbal epithelial transplantation (SLET) using a small autologous biopsy, and cultivated limbal epithelial transplantation (CLET) using ex vivo expanded cells on amniotic membrane or fibrin scaffold. Holoclar, the first regulatory-approved cell-based therapy in Europe, uses autologous cultured limbal stem cells.

For bilateral disease lacking autologous donor tissue, allogeneic options include living-related conjunctival limbal allograft (LR-CLAL), cadaveric keratolimbal allograft (KLAL), and cultivated oral mucosal epithelial transplantation (COMET) using buccal mucosal cells expanded ex vivo. All allogeneic transplants require systemic immunosuppression (cyclosporine, tacrolimus, mycophenolate). Boston keratoprosthesis Type 1 or osteo-odonto-keratoprosthesis (OOKP) serves as ultimate option for end-stage disease.

Symptoms

Persistent epithelial defects
Recurrent corneal erosions
Conjunctivalization of the cornea (loss of palisades of Vogt)
Corneal neovascularization
Stromal opacification, scarring
Photophobia, foreign body sensation
Pain, blepharospasm
Reduced visual acuity
Tear film instability, dry eye
Late stromal melting and perforation in severe cases
Symblepharon (conjunctiva-cornea adhesions)
Lid abnormalities (entropion, ectropion, lagophthalmos) compounding surface disease
Aqueous tear deficiency
Mucous discharge
Chronic conjunctival hyperemia
Failed prior penetrating keratoplasty
Bilateral involvement (severe form)

Risk Factors

Chemical burns (alkali more severe than acid)
Thermal burns
Severe Stevens-Johnson syndrome and toxic epidermal necrolysis
Ocular cicatricial pemphigoid
Atopic keratoconjunctivitis
Vernal keratoconjunctivitis
Aniridia (PAX6-associated)
Contact lens overuse
Prior multiple ocular surgeries
Radiation therapy to ocular region
Mitomycin-C exposure
Iatrogenic injury
Congenital corneal disorders
Persistent epithelial defects
Diabetes mellitus (delayed healing)
Severe dry eye
Lid abnormalities
Nutritional deficiency (vitamin A)
Acid burns from explosions or assaults
Industrial accidents

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Severe ocular surface burn (chemical or thermal) requiring urgent care
  • Persistent epithelial defect not healing
  • Recurrent corneal erosions
  • Worsening photophobia, pain, vision
  • Conjunctivalization on slit-lamp examination
  • Neovascularization of cornea
  • Failure of conventional therapy (lubrication, bandage contact lens, autologous serum)
  • Severe Stevens-Johnson syndrome with ocular involvement
  • Ocular cicatricial pemphigoid diagnosis
  • Aniridia with progressive surface disease
  • Failed prior penetrating keratoplasty
  • Considering cell-based or alloplastic therapy
  • Bilateral disease with severe vision loss

Treatment Methods

01
Comprehensive evaluation by cornea specialist with experience in ocular surface reconstruction
02
Slit-lamp examination with fluorescein staining and impression cytology to confirm conjunctivalization
03
Anterior segment OCT and in vivo confocal microscopy for objective LSCD assessment
04
Optimization of ocular surface (lid hygiene, lubrication, autologous serum drops, scleral lenses, punctal occlusion)
05
Treatment of underlying disease (immunosuppression for cicatricial pemphigoid, hydroxychloroquine, cyclophosphamide)
06
Symblepharon release and amniotic membrane transplantation as adjunct
07
Conjunctival limbal autograft (CLAU) from healthy contralateral eye for unilateral LSCD
08
Simple limbal epithelial transplantation (SLET) with small autologous biopsy on amniotic membrane
09
Cultivated limbal epithelial transplantation (CLET) with ex vivo expansion on amniotic membrane
10
Holoclar (regulatory-approved cultivated autologous limbal stem cell therapy in Europe)
11
Living-related conjunctival limbal allograft (LR-CLAL) for bilateral disease
12
Cadaveric keratolimbal allograft (KLAL)
13
Cultivated oral mucosal epithelial transplantation (COMET) using buccal cells
14
Penetrating keratoplasty after limbal reconstruction (delayed 6-12 months)
15
Deep anterior lamellar keratoplasty (DALK) when stroma intact
16
Boston keratoprosthesis Type 1 for end-stage LSCD
17
Osteo-odonto-keratoprosthesis (OOKP) for severe Stevens-Johnson syndrome with severe dry eye
18
Systemic immunosuppression (cyclosporine, tacrolimus, mycophenolate) for allograft survival
19
Topical steroids and cyclosporine 0.05%
20
Lubrication with preservative-free artificial tears, autologous serum, plasma rich in growth factors
21
Scleral contact lenses (PROSE, EyePrint Pro)
22
Glaucoma management often required postoperatively
23
Long-term follow-up with frequent slit-lamp examinations
24
Multidisciplinary care including ocular surface specialists, transplant immunology, dermatology for systemic disease

Which Department to Visit?

You can visit our Göz Hastalıkları department for these complaints. Our specialist physicians will create the most suitable treatment plan for you.

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Health Disclaimer: The information on this page is prepared for general informational purposes only. It does not replace medical diagnosis and treatment. Please consult your physician for your complaints. Saygı Hospital does not accept responsibility for actions taken based on the information on this page.