Final Report Summary - MICROCORNEA (In-vivo microstructure of the cornea: implications for vision, health, and disease)
Optical imaging provides a means for non-invasive and in-vivo examination and diagnosis with sub-cellular resolution and without the use of extrinsic contrast agents. In the Marie Curie International Incoming Fellowships program ‘MICROCORNEA’ optical coherence tomography, in vivo confocal microscopy, and fluorescence microscopy have been used to examine corneas in clinical and experimental studies, to elucidate the mechanisms of tissue regeneration, wound healing, and pathologic changes in the injured, diseased or surgically-treated cornea. The work involved live-cell imaging and the interpretation of observed phenomena for scientific and diagnostic purposes.
The objectives of this research program were divided along clinical and experimental lines. In the clinical part of the research, the main objectives were to: i) present a detailed microscopic picture of how a biomaterial interacts with a patient’s cornea after implantation; ii) to examine the impact of laser-tissue interaction in the cornea in terms of microscopic-level clinical outcomes in a cross-sectional group of patients; and iii) to examine microscopic-level corneal pathology in inherited corneal diseases in Swedish families. Objectives of the experimental part of the research were to: i) develop a means for non-invasive imaging to track cell behavior during wound healing in biomaterials in vitro; and ii) to attempt the first in-vivo detection of invisible corneal lymph vessels in a murine model of corneal inflammation.
Since the start of the MICROCORNEA program, the specific program objectives have been addressed by performing clinical corneal patient examinations across transplant and hereditary disease patient groups, and analyzing corneal microstructure by image analysis and statistical methods, reporting novel findings and their implications. In experimental work, new models have been developed to enable corneal vessels and cells to be studied in vitro and in-vivo by non-invasive means.
In the biosynthetic cornea study, the first group of trial patients to receive biosynthetic tissue to replace human donor corneas was followed for two years. In MICROCORNEA, the regeneration of host nerves and cells to cover and invade the implanted material was envisaged directly, and the slow but gradual conversion of the biomaterial into a human corneal architecture over time was found. The results were reported in translational medicine journals in 2009 and 2010. A third study was submitted in 2011, describing biointegration of implants within hosts, comparing microscopic corneal architecture with a parallel group of transplant patients with human donor corneas over the same three-year period. Numerous data was collected, detailing the structural and functional similarity of biosynthetic and human donor material in vivo, giving further evidence that laboratorymade biosynthetic materials could one day be used in place of scarce human donor tissue for the treatment of corneal blindness.
In the laser phototherapeutic keratectomy cross-sectional study, 39 patients treated for a corneal epithelial dystrophy over an 8-year period were examined for microscopic and clinical signs of recurrence of the disorder. After the laser treatment, the cornea is thought to regenerate to resemble a normal, healthy cornea. Microscopically, however, signs of the dystrophy were found in 40% of patients, with a greater number of treated patients developing these signs over time. The micro-structure of the dystrophy was found to be milder than in untreated eyes in the same patients. A complex relationship between the micro-morphology and the clinical symptomatology of the dystrophy was uncovered. The study lays the groundwork for a deeper investigation into mechanisms of recurrence of the dystrophy after treatment, which is painful for patients and costly to re-treat.
The objectives of this research program were divided along clinical and experimental lines. In the clinical part of the research, the main objectives were to: i) present a detailed microscopic picture of how a biomaterial interacts with a patient’s cornea after implantation; ii) to examine the impact of laser-tissue interaction in the cornea in terms of microscopic-level clinical outcomes in a cross-sectional group of patients; and iii) to examine microscopic-level corneal pathology in inherited corneal diseases in Swedish families. Objectives of the experimental part of the research were to: i) develop a means for non-invasive imaging to track cell behavior during wound healing in biomaterials in vitro; and ii) to attempt the first in-vivo detection of invisible corneal lymph vessels in a murine model of corneal inflammation.
Since the start of the MICROCORNEA program, the specific program objectives have been addressed by performing clinical corneal patient examinations across transplant and hereditary disease patient groups, and analyzing corneal microstructure by image analysis and statistical methods, reporting novel findings and their implications. In experimental work, new models have been developed to enable corneal vessels and cells to be studied in vitro and in-vivo by non-invasive means.
In the biosynthetic cornea study, the first group of trial patients to receive biosynthetic tissue to replace human donor corneas was followed for two years. In MICROCORNEA, the regeneration of host nerves and cells to cover and invade the implanted material was envisaged directly, and the slow but gradual conversion of the biomaterial into a human corneal architecture over time was found. The results were reported in translational medicine journals in 2009 and 2010. A third study was submitted in 2011, describing biointegration of implants within hosts, comparing microscopic corneal architecture with a parallel group of transplant patients with human donor corneas over the same three-year period. Numerous data was collected, detailing the structural and functional similarity of biosynthetic and human donor material in vivo, giving further evidence that laboratorymade biosynthetic materials could one day be used in place of scarce human donor tissue for the treatment of corneal blindness.
In the laser phototherapeutic keratectomy cross-sectional study, 39 patients treated for a corneal epithelial dystrophy over an 8-year period were examined for microscopic and clinical signs of recurrence of the disorder. After the laser treatment, the cornea is thought to regenerate to resemble a normal, healthy cornea. Microscopically, however, signs of the dystrophy were found in 40% of patients, with a greater number of treated patients developing these signs over time. The micro-structure of the dystrophy was found to be milder than in untreated eyes in the same patients. A complex relationship between the micro-morphology and the clinical symptomatology of the dystrophy was uncovered. The study lays the groundwork for a deeper investigation into mechanisms of recurrence of the dystrophy after treatment, which is painful for patients and costly to re-treat.
