Abstract
Purpose: :
To compare human donor tissue to a cell-free biomaterial in terms of biointegration after implantation into patient corneas to restore cell, nerve and extracellular architecture.
Methods: :
In the first cohort, 10 patients received conventionally transplanted human donor corneal tissue. In the second cohort, 10 patients received a biosynthetic lamellar implant. At 6, 12, 24, and 36 months, patients were examined by slit lamp biomicroscopy, anterior segment optical coherence tomography, Cochet-Bonnet esthesiometry, and in vivo confocal microscopy. Transparency, corneal thickness, epithelial cells, subbasal nerve density, ocular surface sensitivity, keratocytes, scar tissue, and the extracellular matrix were examined.
Results: :
Central corneal thickness remained constant over time in both groups of patients. Only minor transparency change occurred in human tissue while biosynthetic materials remained unchanged until two years, after which transparency was altered. At the cellular level, both discrete and diffuse alterations were observed within the biomaterial extracellular matrix. The biosynthetic material was incompletely populated by keratocytes, while human tissue contained keratocytes, inflammatory cells, and cell-free areas indicative of cell necrosis and/or apoptosis. Only partial ocular surface sensitivity was restored in both groups after three years, and corresponded to a delayed subbasal nerve recovery. Nerve regeneration into the central cornea appeared to be impeded by peripheral interface scar tissue. Epithelial-to-stromal transition was uneven in biosynthetic implants, while the epithelium overlying human donor tissue contained dendritic and other inflammatory cells. No such cells were observed with biosynthetic implants.
Conclusions: :
Three years after surgery, neither human donor tissue nor biosynthetic implants fully resemble a native cornea. A gradual regeneration of nerves, partial return of sensitivity, slow repopulation of keratocytes, and long-term stability of scar tissue and cell-free areas in both biosynthetic and human donor corneas was observed. Both tissue types integrated within patient corneas to a similar degree, however, only human donor corneas exhibited signs of an immune response at the microscopic level.
Clinical Trial: :
https://eudract.ema.europa.eu 2006-006585-42
Keywords: cornea: clinical science • transplantation • cornea: stroma and keratocytes