Abstract

IntroductionDepletion of limbal stem cells leads to a debilitating condition known as limbal stem cell deficiency, characterised by impaired corneal wound healing and poor vision. The aim of this study was to determine whether delivering progenitor cells on a contact lens is a viable and effective alternative to current transplantation techniques, which are complicated by biological and xenogeneic materials.MethodsSixteen eyes of 16 patients who had total (n = 14) and partial (n = 2) limbal stem cell deficiency (chemical burns, five eyes; iatrogenic causes, four eyes; aniridia, three eyes; trachoma-induced, two eyes; contact lens over-wear, one eye; and cicatrising conjunctivitis, one eye) and who had failed prior therapy were recruited prospectively into the study. Autologous limbal (n = 7) or conjunctival epithelial (n = 9) biopsies were harvested from patients and placed on the concave surface of silicone hydrogel contact lenses. Cells were expanded in culture with autologous serum and transplanted onto the ocular surface.ResultsRestoration of a transparent avascular and clinically stable corneal epithelium was attained in 10 of 16 eyes (63%) at a median follow-up time of 2.5 years (range of 0.8 to 5.8 years). Although minor complications occurred in two eyes of two patients because of contact lens insertion or removal, these were not associated with long-term sequelae.ConclusionsThis is the first and largest study to evaluate the mid-term outcomes of autologous limbal/conjunctival stem cell transplantation via a US Food and Drug Administration-approved contact lens, demonstrating that delivery of ocular progenitor cells via this procedure offers a viable, effective, and xeno-free alternative to current transplantation methodologies.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN012607000211460. Registered 17 April 2007.

Highlights

  • Depletion of limbal stem cells leads to a debilitating condition known as limbal stem cell deficiency, characterised by impaired corneal wound healing and poor vision

  • Depletion of limbal epithelial stem cells (LESCs) through damage to their microenvironment or aberrant functional modification can result in limbal stem cell deficiency (LSCD), a disease characterised by impaired corneal wound healing, loss of vision, and chronic pain [2]

  • A halo of cells of similar morphology surrounded each limbal or conjunctival biopsy, and the migratory front of expanding cells reached the edge of the contact lens (CL) by 9 to 16 days post-explanting (Figure 1C-E)

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Summary

Introduction

Depletion of limbal stem cells leads to a debilitating condition known as limbal stem cell deficiency, characterised by impaired corneal wound healing and poor vision. The corneal epithelium is maintained by stem cells (SCs) presumed to reside in the transitional zone between the cornea and conjunctiva, known as the limbus [1]. Depletion of limbal epithelial stem cells (LESCs) through damage to their microenvironment (the niche) or aberrant functional modification can result in limbal stem cell deficiency (LSCD), a disease characterised by impaired corneal wound healing, loss of vision, and chronic pain [2]. The most commonly used substrate for LESC transplantation is human amniotic membrane (HAM), and reported success rates in patients with LSCD range from

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