Three-Year Outcomes of Cultured Limbal Epithelial Allografts in Aniridia and Stevens-Johnson Syndrome Evaluated Using the Clinical Outcome Assessment in Surgical Trials Assessment Tool

Abstract

Limbal stem cell deficiency (LSCD) is an eye disorder in which the stem cells responsible for forming the surface skin of the cornea are destroyed by disease. This results in pain, loss of vision, and a cosmetically unpleasant appearance. Many new treatments, including stem cell therapies, are emerging for the treatment of this condition, but assessment of these new technologies is severely hampered by the lack of biomarkers for this disease or validated tools for assessing its severity. The aims of this study were to design and test the reliability of a tool for grading LSCD, to define a set of core outcome measures for use in evaluating treatments for this condition, and to demonstrate their utility. This was achieved by using our defined outcome set (which included the Clinical Outcome Assessment in Surgical Trials of Limbal stem cell deficiency [COASTL] tool) to evaluate the 3-year outcomes for allogeneic ex vivo cultivated limbal epithelial transplantation (allo-CLET) in patients who had bilateral total LSCD secondary to aniridia or Stevens-Johnson syndrome. The results demonstrate that our new grading tool for LSCD, the COASTL tool, is reliable and repeatable, and that improvements in the biomarkers used in this tool correlate positively with improvements in visual acuity. The COASTL tool showed that following allo-CLET there was a decrease in LSCD severity and an increase in visual acuity up to 12 months post-treatment, but thereafter LSCD severity and visual acuity progressively deteriorated.

In Vivo Confocal Microscopy 1 Year after Autologous Cultured Limbal Stem Cell Grafts

“…5 Actually, we agree that the identification of cell types is subjective, is dependent on the operator's experience, and is affected by light scattering when severe corneal stromal scarring is present. Moreover, the continuing migration of epithelial cells over the corneal surface during regeneration can limit the applicability of IVCM in the early postoperative phases.…”

“…3,4 Likewise, outcomes of limbal stem cell transplantation (LSCT) surgery usually are assessed based on subjective grading, and this raises the issue of how efficacy of treatment should be defined. 5 Recently, a more reliable diagnostic procedure in patients with a suspected clinical diagnosis of LSCD was obtained using laser scanning in vivo confocal microscopy (IVCM). 6,7 Compared with clinical slit-lamp examination, IVCM resulted in less ambiguous microscopic morphologicbased differentiation of conjunctival and corneal-type epithelium 8,9 ; in identification and quantification of goblet cells, dendritic cells and leucocytes; and in better recognition of alterations in the limbal anatomic features in eyes with LSCD.…”

Stem Cell Therapies in Clinical Trials: Progress and Challenges

“…This result suggests allogeneic limbal stem cell therapies are steadily progressing. However, a recent study on allografts in Aniridia and Stevens-Johnson Syndrome that used a defined outcomes set procedure for cultured limbal cell epithelium transplants for bilateral limbal cell deficiency showed improvements in epithelial integrity and visual acuity up to 12 months but then a gradual decline over 3 years (Shortt et al, 2014). Typically restoration of the corneal epithelium can now be achieved in the majority (67%) of auto-and allogeneic transplants for partial and total limbal stem cell deficiency without easily detectable alteration to visual acuity (Zakaria et al, 2014).…”

Congenital Aniridia and the Ocular Surface

“…Future studies should focus on longitudinal monitoring of the POV and associated morphology in patients, to clarify the processes of degradation of the limbal stem cell niche and offer potential insights for future treatment. 37 …”