Clinical outcomes of xeno-free expansion and transplantation of autologous ocular surface epithelial stem cells via contact lens delivery: a prospective case series

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.

Nature and incidence of severe limbal stem cell deficiency in Australia and New Zealand

“…Both questionnaires (Appendix I, Appendix II) received input from senior leading ophthalmologists and senior ocular scientists across five states in Australia and New Zealand. Severe LSCD was defined and characterized by; at least 6 clock hours of whorl‐like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium, and superficial neovascularization or conjunctivalization . The initial questionnaire (No.…”

“…Severe LSCD was defined and characterized by; at least 6 clock hours of whorl-like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium, and superficial neovascularization or conjunctivalization. 7,8,[11][12][13] The initial questionnaire (No. 1) requested patient demographics including; age, sex and postcode, as well as date of diagnosis, how the diagnosis was made, investigations performed, other ocular disease, the underlying diagnosis, CL wear, previous limbal grafts, medical, drug and surgical history, and any treatment initiated after diagnosis.…”

Synthesis and Characterization of Poly(2-hydroxyethylmethacrylate) Contact Lenses Containing Chitosan Nanoparticles as an Ocular Delivery System for Dexamethasone Sodium Phosphate

“…A number of research groups, however, have worked on improving in vitro experiments [11,20] in an effort to ensure that only the most suitable materials progress to human trials. A recent publication by Bobba et al did, however, use contact lens delivery for stem cells to human eyes [21] with generally positive results, citing only two (of sixteen) patients suffering minor complications from contact lens insertion and removal. It is necessary to note that the type of procedures documented for stem cell transplant would be inherently more prone to complications than the type of contact lens use proposed in the majority of works cited in this article.…”

Progress in corneal wound healing

“…Recent efforts were focused on developing xenobiotic-free LESC cultures with no feeder cells or with human cells. Human autologous serum has been used to expand LESC on HAM (Shahdadfar et al, 2012) or on soft contact lenses (Bobba et al, 2015). The latter technique has been used in a clinical trial in 16 LSCD patients with reported success in 10 of 16 eyes (63%) at a median follow-up time of 2.5 years with the advantage of autologous transplantation (Bobba et al, 2015).…”