Development of a synthetic flowable dressing that prevents corneal scarring

Injuries caused by trauma, infections and inflammation to the surface of the eye can cause scarring that 'clouds' the transparent window of the eye called the cornea, interfering with vision and is sight-threatening. 'Corneal Blindness' affects millions of people and the World Health Organisation have made curing the problem a priority area programme to prevent world-wide blindness. The current treatment for damaged eyes caused by infection is to treat with antibiotic agents followed by strategies to promote healing. We are developing a synthetic, optically-transparent, anti-scarring dressing (biomembrane) suitable for the management of patients world-wide at risk of corneal scarring following injury, by promoting cells and molecules in tissues to heal without scarring improving patient visual outcomes. To date we have: (1), engaged closely with clinical colleagues to define and refine the characteristics and technical specifications of the fluid biomembrane dressing to ensure suitability for clinical use (2), investigated processes for its manufacture (3), performed limited testing of a dressing prototype (4), prepared a technical portfolio of the performance data generated thus far. We now seek further funding to allow progression of the project so that we can: (1), refine and improve the characteristics and performance of the dressing (2), scale-up its manufacture for use in humans (3), obtain regulatory approvals for testing in humans and finally (4), undertake a small clinical trial to check for safety and see how well the anti-scarring dressing works on patients with infected corneas. At this same time we will be (5), developing a commercialisation plan so that the new dressing becomes widely available for use in the clinic to reduce ocular scar formation that can cause blindness.

Corneal scarring occurs from a variety of aetiologies including infections, inflammatory conditions and ocular trauma leading to visual loss and is a WHO priority area programme for the prevention of worldwide blindness. Corneal infections are treated by a sterilisation phase with antimicrobial agents and a healing phase targeting inflammation control and promoting rapid wound closure to minimise scarring. There are few therapeutic options to modify, minimise or reverse scarring to maintain corneal transparency and visual function. We are developing a synthetic, optically-transparent, anti-scarring dressing suitable for the management of patients world-wide at risk of corneal scarring by promoting a microenvironment that enables anti-fibrotic and anti-inflammatory factors to promote scarless wound healing and improve clinician/patient-reported visual outcomes. To date we have: (1) engaged closely with clinicians to define the physico-chemical/phamacokinetic characteristics and technical specifications of the fluid biomembrane dressing according to a Target Product Profile to ensure suitability for clinical use, (2) investigated scaleable processes for manufacture, (3) performed pilot preclinical testing of a prototype using in vitro and in vivo models of corneal scarring, (4) prepared a GLP standard technical portfolio of data generated. We now seek further funding to allow progression of the project according to a defined translational and commercialisation strategy encompassed within a business plan that includes: (1) defining the pharmacokinetics/toxicology/efficacy of the released active compound, (2) reaching technical readiness for CE marking, (3) securing MHRA approval and a GMP manufacturing process for the ocular dressing and (4) executing a first-in-man clinical trial to assess safety and efficacy of our anti-scarring dressing to treat microbial keratitis. This will move the technology along the translational pathway towards commercial realisation.

NHS and wider healthcare and social services community: Corneal opacity is a leading cause of visual loss and forms a WHO priority area for new therapies to prevent worldwide blindness. With a global prevalence of 5.1%, visual loss results from corneal scarring and vascularisation after infection, inflammatory conditions and ocular trauma (incidence of ~8M people/year, costs ~£150 billion/year). A topical dressing that can be self-administered with minimal complications to prevent the devastating consequences of corneal damage would have significant socio-economic impact. Patients with ocular damage would carry a reduced direct and indirect cost of treatment burden since they would self-administer the eye drops negating the need for prolonged hospitalisation and clinic attendance. Hospitals and treatment centres will benefit because patient treatment costs will be reduced, both acutely and chronically as the patients will have a reduced requirement for hospitalisation and the demand for treatment by trained doctors and nurses. There would be an additional economic impact due to a reduction of time away from work, travel costs and avoiding redeployment for patients whose professions mandate bilateral good visual acuity such as public and heavy goods vehicle drivers etc. The impact on health of preserved sight, the most treasured of our senses, cannot be overstated. Reductions in the long-term welfare costs of patients who would normally develop significant visual impairment would also be significant, as will be the saving of taxable income of those who would remain fit to work.
Biomedical industry: Our aims are aligned with industry needs in terms of identification and exploitation of novel therapeutic targets. It also maps onto government's strategy for life sciences aiming to make the UK a world-leading place for life sciences investment: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/32457/11-1429-strategy-for-uklife-sciences.pdf
Other industries: Highlighting novel biomedical uses of hydrogels used in other industries will impact across many sectors as opportunities for new applications of this platform technology will become apparent through the lifetime of the project.
Economic impact: Enhanced UK competitiveness and prosperity would result through international commercialisation and exploitation alongside the planned programme to build the UK's capacity and research strength to tackle a range of fibroproliferative diseases that area heavy burden to the NHS.
The general public: Through public engagement, including the voluntary sector, we will continue to deliver information about the progress of our study.
Academia: The identification of a potent anti-fibrotic compound has already raised significant interest in the field of wound repair. We will continue to report our advances, not only in the context of our technology development but also in the new understanding of disease processes generated by our studies. Researchers working on other fibroproliferative diseases will benefit from discovery of a validated clinical compound and the associated shift in our capabilities to address a range of wound healing paradigms.