Original article
Factors Influencing Outcomes in Cultivated Limbal Epithelial Transplantation for Chronic Cicatricial Ocular Surface Disorders

https://doi.org/10.1016/j.ajo.2007.03.005Get rights and content

Purpose

To analyze factors influencing clinical outcomes in cultivated limbal epithelial transplantation (CLET).

Design

Retrospective, observational case series.

Methods

Twenty-seven eyes of 27 patients that had CLET for severe chronic cicatricial ocular surface disorders were studied. Two different cultivation methods were used to prepare epithelial sheets. Method 1 used the explant technique and neither feeder cells nor air-lifting were used. In Method 2, cell suspension technique and 3T3 feeder cells were used, and air-lifting was applied after cultivated cells became confluent. Clinical outcomes including corneal surface epithelialization and incidence of postoperative complications were studied. The relationship between the clinical outcome and type of cultivation method, original diseases, tear function, or preoperative ocular surface status was also studied.

Results

Both cultivation methods produced transplantable epithelial sheets with corneal phenotype. With a mean follow-up period of 127 weeks, corneal epithelialization was achieved in 16 eyes (59.3%). Eyes that had CLET with Method 1 suffered more severe postoperative complications such as infection, ulceration, and perforation (P = .053). Eyes with Stevens-Johnson syndrome (SJS) had poor final corneal epithelialization compared with other diseases (P = .034). CLET was more successful when performed to conjunctivalized corneas compared with eyes with persistent epithelial defects or with dermalized corneas.

Conclusions

CLET offers new treatment modalities to chronic cicatricial ocular surface disorders with moderate success rates. The treatment is feasible for eyes with non–immune-mediated disorders with stable ocular surface conditions. Epithelial sheets with better structural integrity seem to be superior to obtain early postoperative epithelialization and to avoid serious postoperative complications.

Section snippets

Patients

Twenty-seven eyes of 27 patients that had CLET between June 1999 and November 2003 were retrospectively analyzed in this study. Patients consisted of 16 males and 11 females, with a mean age of 50.2 ± 20.7 years (15 to 82 years). All eyes had total limbal dysfunction. Conjunctivalization was confirmed preoperatively by impression cytology in 10 of 27 eyes. Mean corrected visual acuity was counting fingers, and two-thirds of the eyes were lower than 20/2000. The Schirmer test was performed in 21

Histologic Examinations

Multilayered epithelial cells were reconstructed on AM in the epithelial sheets produced by both Methods 1 and 2. The cells in Method 2 gave rise to four to five layers of epithelial cells with cuboidal basal cells and flat superficial cells. The cells in Method 1 showed relatively poor polarity and rough surface (Figure 1). Immunohistochemistry for cornea-specific keratins (keratin 3 and 12) demonstrated that cultivated epithelial cells in both methods were corneal phenotype.

Influence of Cultivation Methods on Surgical Outcomes

Demographic

Discussion

There have been increasing numbers of studies of CLET in both clinical outcome and research aspects.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 Although short-term outcomes appeared promising, only a few mid-term or long-term results have been reported. Validity of CLET for acute phase of chemical burns and SJS was reported6; however, the efficacy of the method for chronic cicatricial keratoconjunctivitis seems to be less dramatic.7 In the present study, we

References (39)

  • A. Solomon et al.

    Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency

    Ophthalmology

    (2002)
  • Y. Ban et al.

    Comparison of ultra-structure, tight junction-related protein expression and barrier function of human corneal epithelial cells cultivated on amniotic membrane with and without air-lifting

    Exp Eye Res

    (2003)
  • R.J. Tsai et al.

    Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells

    N Engl J Med

    (2000)
  • I.R. Schwab et al.

    Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease

    Cornea

    (2000)
  • P. Rama et al.

    Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of patients with total limbal stem cell deficiency

    Transplantation

    (2001)
  • N. Koizumi et al.

    Cultivated corneal epithelial transplantation for ocular surface reconstruction in acute phase of Stevens-Johnson syndrome

    Arch Ophthalmol

    (2001)
  • D. Meller et al.

    Ex vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane cultures

    Br J Ophthalmol

    (2002)
  • V.S. Sangwan et al.

    Use of autologous cultured limbal and conjunctival epithelium in a patient with severe bilateral ocular surface disease induced by acid injury: a case report of unique application

    Cornea

    (2003)
  • K. Nishida et al.

    Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface

    Transplantation

    (2004)
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      We currently intensively treat epithelial defects prior to surgical intervention with various medical or surgical approaches, including artificial tears, mucin secretagogues, medical-use contact lenses, punctal plugs/surgical occlusions, semi- or full-scleral contact lenses, mucous membrane grafting to the lid margin, and AM transplantation, which potentially improve the clinical outcome of CCST. A characteristic of the present study was that many kinds of surgical methods were included, such as CLET [7,8,10,21,23,31–60] and COMET [13,19,45,61–75]. Because this was a single center study, various factors that may influence surgical outcomes such as the preparation methods of the epithelial sheets, surgical methods, and postoperative management were relatively standardized.

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