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Peter Le, David Myung; A corneal tissue opacity model for the evaluation of corneal wound healing technologies. Invest. Ophthalmol. Vis. Sci. 2021;62(8):945.
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Corneal scarring is a major clinical problem worldwide that results in reduced vision and blindness. The development of new regenerative therapies to address corneal scarring and blindness requires a reliable, reproducible, and clinically relevant pre-clinical model of corneal scarring.
We have developed a method of creating a corneal scar of controlled diameter and depth on rabbit eyes through a transient microdose (TMD) of sodium hydroxide (NaOH). TMDs of varying time intervals and volumes were applied up to 30 seconds and 5 microliters, respectively. The eyes were then rinsed thoroughly with phosphate buffered saline for 10 seconds. The pH of the surface is checked to make sure no residual alkalinity remains. Optical coherence tomography (OCT) was used to evaluate the resulting depth and diameter of epithelial and stromal opacity formed, along with slit lamp images. A circular trephine is then used to perform an anterior lamellar keratectomy to remove the scar tissue and fill it with an in situ-forming hydrogel material to occupy the space where the scar was removed.
We found that 0.2 microliters of 1M sodium hydroxide (NaOH) added to the surface of an ex vivo rabbit cornea for 20 seconds results in an approximately 50% depth opacity that is 3 mm in diameter. This size scar presents a visually significant corneal scar covering the visual axis that typically requires corneal transplantation. With OCT to aid in visualization, we found that the entirety of the scar with minimal surrounding transparent stroma can be removed via controlled-depth, trephine-assisted manual keratectomy and substituted with a transparent, in situ-forming gel matrix.
The technique described serves as a corneal opacity tissue model that can be utilized to evaluate regenerative therapies such as engineered, in situ-forming, pre-formed, and/or cell-based biomaterial therapies designed to avoid the need for penetrating keratoplasty. Future directions include translation of this technique into the in vivo setting and the testing of candidate therapies.
This is a 2021 ARVO Annual Meeting abstract.
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