Novel Chemical Crosslinking of the Cornea for Treatment of Keratoconus

The Aravind Eye Care System in Southern India was established as a health care model that could supplement the efforts of the government and also be self-supporting to overcome the problem of avoidable blindness in a developing country. The company Aurolab is an integral part of the Aravind Eye Care System. It manufactures a wide range of high quality ophthalmic consumables. Developing a translational alliance with the Aravind Eye Care System and Aurolab will provide us with the opportunities to gain access to a commercial infra-structure which includes support for polymer technologies and manufacture, product commercialisation in terms of regulatory approvals, IP protection and advertising, as well as distribution and labelling. Aurolab's products are exported to 130 and more countries worldwide and their products meet the regulatory requirements of the USA, EU and WHO. All Aurolab products are manufactured on efficient production lines with strict quality assurance measures.
We intend to develop this translational alliance with Aurolab and the Aravind Eye Care System to exploit our novel chemical cross-linking therapy for the treatment of keratoconus. Keratoconus is a progressive condition, often affecting young and working age people, in which the cornea becomes misshapen significantly disrupting the refraction of light into the eye. One of the key features of keratoconus is a loss of corneal mechanical stability. Increasing the stiffness of the cornea can reduce the progression of this debilitating eye disease. Corneal collagen cross-linking focuses on stiffening the cornea in order to preserve corneal integrity due to strong bonds formed within the collagen. Using our understanding of the engineering principles that define the relationship between the structure and mechanical properties of materials we will develop a novel collagen cross-linking therapy using di-carboxylic acids thus this proposal lies clearly at the interface between Engineering and Healthcare Technologies and aligns closely with the Synthetic Biology for Health area.
To establish the partnership we will make multiple visits to India regularly over the 2 years of the project. We will also host visits from senior scientists and clinicians from India. In particular we will host a 3 month research exchange for a Product Development Scientist from Aurolab to learn about our research and facilitate a research exchange for our PDRA to spend 3 months at Aurolab to learn about product manufacture and scale up. We will jointly supervise a clinical research fellow at the Aravind Eye Care System and we will establish an in vivo animal model facility in Liverpool which will support this project and future development projects as part of the long term partnership. These other project areas that would benefit greatly from the alliance could lead to translational opportunities and impact to the health and wealth of societies in the UK and globally. By working together to design these projects we will ensure that they address the clinical and commercial requirements for India, the UK and globally. Specific examples could include the extrapolation of the cross-linking therapy to the development of a strategy to increase the mechanical properties of ulcerated cornea to protect against perforation and aid healing and the potential to increase the stiffness of the sclera as a treatment for myopia and/or glaucoma. A further area of particular interest to our project partners is the development of bandage contact lenses with the potential to deliver anti-fungal agents such as voriconazole for the treatment of fungal keratitis which is a major clinical problem in India. In the more longer term there are several projects within the Department of Eye and Vision Science at the University of Liverpool that would benefit from this alliance such as the development of drug delivery devices for the front and back of the eye.

The development of a long term translational alliance between the Department of Eye and Vision Science at the University of Liverpool and Aurolab in the Aravind Eye Care System in Southern India has the potential to lead to the exploitation of a number of innovative research projects that could lead to new strategies and therapies to treat vision loss worldwide. Specifically, working with Aurolab will allow the development of cost effective solutions appropriate for developing countries as well as other world markets. UK Vision Strategy is an RNIB initiative. Research is a key part of this strategy and in 2011 key stakeholders came together and through the James Lind Alliance produced The Sight Loss and Vision Priority Setting Partnership (http://fightforsight.org.uk/sightlosspsp). Corneal and external eye disease was established as one of the 12 priority areas for research and within this area one of the main questions was 'What causes keratoconus to progress and can progression be prevented?'. This proposal could have a significant impact on addressing this issue. Keratoconus affects around 1 in 2000 people worldwide and is a lifelong, degenerative corneal disease and is a significant health burden in young adults. The condition is associated with low vision and as a consequence a poor quality of life, and ultimately loss of vision. As well as the devastating loss to the patient, the loss of sight has a significant cost to the UK economy both in terms of healthcare costs and indirect costs such as loss of employment and carer costs. Keratoconus is the leading cause of corneal transplantation in the Western world and accounts for 25 % of the corneal transplants performed annually in the UK. Each transplant is estimated to cost the NHS £5000 and is not always a successful procedure due to rejection or complications due to infection. The development of an effective strategy to stiffen the cornea could reduce the number of patients requiring corneal transplants. Furthermore the simplicity of the proposed treatment could lead to it being available to more patients in more healthcare settings.
The potential to develop other ophthalmic devices and therapies in the longer term could lead to major healthcare impact, for example, the development of bandage contact lenses with the capability to deliver antimicrobials, both anti-fungal and anti-bacterial, could significantly improve the treatment of corneal infections both in terms of reducing the microbial load and the comfort for the patient during treatment, possibly removing the need for hospital admission in many cases.
All Aurolab products are manufactured on efficient production lines with strict quality assurance measures that comply with US FDA, EU GMP, WHO GMP norms. Thus products developed and testing in Aurolab will be translatable to the UK markets for use in the NHS. With the expertise of the Clinical Research Department in Aurolab and the Clinical Eye Research Centre with St. Paul's Eye Unit, Liverpool we will be able to run Phase I, Phase II and Phase III clinical trials to produce clinical data to support the translation of the new products into the clinic. Liverpool was the first centre in the UK to offer corneal cross-linking using riboflavin and UVA and has been awarded an NIHR EME grant (KERALINK): Efficacy and safety of cross-linking in children with keratoconus with London (Moorfields) and Sheffield.