Abstract
Purpose :
Blindness caused by corneal opacity can result from the corneal scarring that develops after infectious diseases or inflammation. The ‘gold standard’ of treatment is amniotic membrane (AM) transplant to the ocular surface that induces healing and reduces scarring, through the release of anti-fibrotic/anti-inflammatory factors. However, the reproducibility of the clinical effects of AM transplants is limited by biological variability. Consequently, a plethora of alternative anti-scarring treatment strategies have been investigated, with nothing yet adopted to replace AM transplants. We are developing a transparent gel eye drop that can be applied to the damaged ocular surface and is capable of protecting the injured eye, providing sufficient lubrication as well as delivering the anti-scarring agent, Decorin, in a sustained manner to the cornea to promote scarless wound healing.
Methods :
Gel dressings were produced with controlled temperature processing to form a fluid gel.In vitro Decorin release from the fluid gel was measured using a Decorin ELISA. For the ex vivo studies, the Decorin fluid gel was applied as a single dose to a rat corneal abrasion model to observe the effects on wound healing and re-epithelialisation. An in vivo mouse model of bacterial keratitis was used to assess the anti-scarring effects of the Decorin fluid gel when used in combination with the standard clinical treatments of gentamicin and steroid eye drops.
Results :
Gel thickening occurred immediately when placed on the rat cornea as an eye drop. The gel evenly covered the ocular surface and remained for up to 2h. Decorin gels released a sustained dose of Decorin over 4h. Corneal re-epithelialisation occurred within 48h in the presence of the Decorin gel in the ex vivo models when compared to a Decorin-PBS drop which showed limited wound closure. Additionally, Decorin gel reduced corneal opacity compared to controls in the bacterial keratitis model when administered together with the gold standard steroid and gentamicin treatment, compared with steroid and gentamicin treatment alone.
Conclusions :
We have successfully demonstrated the utility of a fluid gel ‘eye drop’ therapy for the attenuation of corneal scarring. The properties of the fluid gel allowed a sustained, effective dose of anti-fibrotic Decorin to be released onto the corneal surface and showed efficacy in reducing the corneal opacity associated with bacterial keratitis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.