Cultivated Autologous Limbal Epithelial Cell Transplantation Is Promising for Managing Limbal Stem Cell Deficiency
Key findings
- Safety and feasibility of cultivated autologous limbal epithelial cell (CALEC) transplantation, a new surgical method for managing limbal stem cell deficiency developed at Mass Eye and Ear, was established in a phase 1/2 trial
- In 14 patients with limbal stem cell deficiency (LSCD) who received CALEC transplants, in vivo confocal microscopy (IVCM) showed that corneal epithelial cells improved from 20% to 75% in the central cornea, while the proportion of conjunctival epithelial cells decreased from 90% to 38%
- As measured on IVCM images, the proportion of corneal epithelial cells in the limbus improved to ≥60% in all quadrants of the limbus, and central epithelial basal cell density also increased
- Anterior segment optical coherence tomography scans evaluated central corneal epithelial thickness, but these results were more variable than those with IVCM
- CALEC transplantation is a promising modality for the management of LSCD, and in vivo confocal microscopy is the superior imaging modality for reliably gauging treatment response
Advanced-stage limbal stem cell deficiency (LSCD) may require a surgical procedure such as grafting of ex vivo proliferated autologous tissue, also known as cultivated limbal epithelial transplantation (CLET). Ula V. Jurkunas, MD, associate director of the Cornea Service at Mass Eye and Ear, and colleagues have developed a xenobiotic-free, serum-free, antibiotic-free standard manufacturing protocol for CLET that they call cultivated autologous limbal epithelial cell (CALEC) transplantation.
Subscribe to the latest updates from Ophthalmology Advances in Motion
Earlier this year the research group reported in Nature Communications on a phase 1/2 trial of CALEC. 93% of 14 participants had complete success (improvement in corneal epithelial surface integrity) or partial success (improvement in symptoms and/or extent of corneal neovascularization) within 1 year. Now, in Cornea, the group has published imaging results that corroborate the clinical improvement.
Methods
The trial cohort was 93% male, with a mean age at enrollment of 46 (range, 24–78). The primary underlying cause of LSCD was a chemical or thermal burn (78%). At baseline and 1 year after unilateral CALEC, a certified ophthalmic technician obtained anterior segment optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM) images. IVCM was deferred if contraindicated because of pain, presence of epithelial breakdown/defect, or use of a bandage contact lens.
IVCM Findings
The IVCM images indicated reconstitution of the cornea and clearing of the optical axis at 1 year:
- Mean epithelial basal cell density in the central cornea—3,316 cells/mm2 at baseline vs. 4,871 cells/mm2 at 1 year, a 59% increase (P=0.02)
- Proportion of corneal epithelial cells in the central cornea—20% (baseline) vs. 75% (1 year)
- Proportion of conjunctival epithelial cells in the central cornea—90% (baseline) vs. 38% (1 year)
In all quadrants of the limbus, the proportion of corneal epithelial cells improved to ≥60% within 1 year.
OCT Findings
OCT was used to evaluate different outcome measures:
- Mean (SD) corneal epithelial thickness was 51 (10) microns at baseline and 48 (17) microns at 1 year, not a statistically significant change, and patient-by-patient response was highly variable
- Deepest limbal epithelial thickness did not change significantly in any quadrant
IVCM Is an Essential Follow-up Tool
Besides supporting the efficacy of CALEC, this study indicates that IVCM is the superior modality for assessing the postoperative epithelial phenotype and thickness, which is critical in complex cases.
OCT measurements can be influenced by the presence of hyperreflective subepithelial fibrosis, a common complication in severe LSCD. Because the condition itself impedes accurate measurement of central and limbal epithelial thickness, IVCM is particularly warranted in affected patients.