Limbal stem cell deficiency (LSCD) results from a loss of corneal epithelial stem cells and a breakdown of the limbal barrier, due to acquired or congenital diseases. This condition causes varying ocular surface morbidity, dependent on the degree of limbal stem cell damage. Severe LSCD is characterised by vascularisation and conjunctivalisation of the cornea, leading to pain, photophobia and blindness, and is considered to be one of the most challenging ocular surface conditions to manage. Limbal stem cell grafts aim to restore the limbal barrier and reconstruct the ocular surface, improving rates of subsequent corneal graft survival. While the earliest techniques of stem cell transplantation required large sections of limbal donor tissue, the introduction of ex vivo cultivated limbal epithelial stem cell transplantations (CLET) offered an alternative to overcome the limited access to limbal tissue available for transplantation and the potential risks for the donor eye. The core of this dissertation was the conduction of a multicentre, single-arm phase II clinical trial, to assess the safety and efficacy of transplanting standardized, non-xenogeneic limbal epithelial cell grafts for patients with LSCD. Since the start of the trial in April 2014, a total of 32 transplants have been performed on 26 severe limbal stem cell deficient eyes. Furthermore, in this thesis, we additionally considered aspects ‘beyond the limbal stem cell technique’. Doing so, we have made efforts to optimize the CLET procedure: from image-based clinical examination, grading of LSCD and the ethics of consenting, to targeted biopsy harvesting, performing a safer surgery, critically examining adverse events and implementing resolutions, reporting the results over the long-term and, finally, developing better tools for follow-up and grading results.
|Date of Award||4 Oct 2019|
- Vrije Universiteit Brussel
- University of Antwerp
|Supervisor||Marcel Ten Tusscher (Promotor), Carina Koppen (Promotor), Sorcha Ní Dhubhghaill, (Promotor), Stefano Ferrari (Jury), Bernard Duschesne (Jury), Emeline Van Craenenbroeck (Jury), Brigitte Velkeniers-Hoebanckx (Jury), Robert Kuijpers (Jury) & Vigor Van Tendeloo (Jury)|
- Limbal stem cell
- vascularisation ; conjunctivalisation