Title: Fluid-Gels as Resorbable Protective Dressings for Ocular Surface Disease
Funder: Department of Health and Social Care

Abstract: Background: Ocular surface disease (OSD) leading to dry eye is a global public-health problem. Symptoms significantly impact upon visual function and quality-of-life similar to that of severe angina. Therapeutic options range from patient education, optimising the local environmental, applying lubricants (regulated as MHRA Class II invasive devices), anti-inflammatory eye drops and tablets, together with physical protection of the ocular surface from blink-related biomechanical trauma with therapeutic bandage and scleral contact lenses. Our patented fluid-gel technology overcomes limitations of existing strategies by providing a resorbable long-lived dressing (FLG-1001) that has the ability to protect and repair the ocular surface. Methods and Timelines: The project comprises three work packages (WPs) with clearly defined milestones. WP1 Product Development for Commercialisation (0-9 months): In a related MRC DPFS funded proof-of-concept study, absence of local toxicity and reduction of inflammatory and fibrosis markers have been demonstrated following application of FLG-1001 in a murine corneal injury model. WP1 aims to develop a formulation to meet the clinical and practical patient needs in the treatment of OSD with the Target Product Profile identified by a patient advisory group. Technical tasks will include formulation development; sterilisation and physicochemical characterisation; and optimising manufacture to deliver nutritive substances such as allogeneic donor-serum (FLG-SED1). All data will be compiled into a technical file to support the finished product entering the clinical trial. WP2 Scale-up Manufacture (6-18 months): Will construct a GMP-compliant manufacturing process for FLG-1001 and FLG-SED1 within NHSBT for clinical trial supply. Manufacturing and quality control processes will be validated to ensure manufacture to the technical specification. Pre-clinical GLP toxicity studies are currently being conducted followed by a first-in-man safety and toxicity study of FLG-1001 during the healing phase of corneal infection (planned Q4 2018). WP3 Clinical Utility Design Dossier (0-36 months). Three parts. Clinical (C)WP1 Development of a Clinical Utility Questionnaire (0-12 months): A short-answer, PPI-coordinated daily-diary questionnaire (ocular patient device tolerability and utility questionnaire, OPTiQ)) will be developed for assessment of daily discomfort and ocular tolerability of FLG-1001 using existing symptom questionnaires, and additional psychometric items. The final utility will be made available in a variety of formats (hardcopy, web-based diary). CWP2 Clinical Safety and Tolerability Studies (6-24 months). Following HRA approval and compilation of site set-up dossiers (6-18 months), quantification of FLG-1001 and FLG-SED1 tolerability measured by OPTiQ after a single dose (Stage 1, 18-20 months) and required instillation dosing/frequency (Stage 2, 20-24 months) will be determined. CWP3 Pilot study (24-36 months) will randomise patients evaluating the tolerability of the FLG-1001, FLG-SED1 versus Allogeneic-Serum eye drops (Allo-SED) in patients with moderate to severe OSD. Impact and dissemination: Durable and protective therapy for OSD will enable patients to undertake daily activities over extended time, offering some, the ability to return to work and/or an independent life. Developing a scalable manufacturing process within NHSBT &ndash; the sole UK suppliers of serum drops at cost price &ndash; will accelerate patient access and impact. Data will be disseminated at patient group meetings, newsletters, international conferences and open-access publications.

Lay abstract: Constant eye discomfort can affect many patients whether they are awake or asleep impacting upon their working and social life, driving and wellbeing. The most common cause is a group of conditions known as ocular surface disease (OSD) caused by inflammation. Many patients suffer from disabling grittiness, dryness and eye pain that can further lead to anxiety or depression and an inability to function. Severe inflammation may cause sight-threatening scarring, where the cornea (the transparent dome-shaped window in front of the eye) becomes cloudy. There is no long-lasting treatment that can alleviate the discomfort and there is seldom a complete cure. Treatment remains the greatest challenge with 19 million people worldwide visually-impaired from OSD. Standard care includes self-help such as using humidifiers, avoiding irritant smoky atmospheres, and wearing tinted-glasses or moisture-chamber spectacles/goggles. Pain-relief is obtained by use of devices such as lubricant-drops or contact-lenses. Patient dissatisfaction with these devices is high. This is because symptom-relief with lubricant-drops may be as short as a few minutes. Some patients wear special protective bandage contact-lenses to gain longer-lasting comfort, but these are difficult to put into the eyes and to take-out. Listening to our patients, we have developed a new fluid-gel technology that is part-lubricant and part-contact-lens. Engineered to become a liquid as it is squeezed out of the bottle, it restructures to a soft protective shield similar to a contact-lens when the eye is open and becomes a liquid again when blinking. This means it is as simple as putting in an eyedrop but has the longer-lasting effect of a bandage contact lens. In this project, a patient advisory group will handle the fluid-gel prototype and will provide feedback on ideal characteristics such as storage temperature, duration of effect, impact on symptoms, texture, preferred type of delivery packaging including multidose-dropper-bottles, unit-dose vials or squeezy-tube. This information will be summarised in a Technical Specification document and we will alter the chemistry to develop the patient-ideal fluid-gel. Patients with OSD-related dryness lack nutrition normally obtained from a healthy tear-film and in severe cases, require blood-serum drops. We will manufacture the fluid-gel that is capable of delivering essential nutrients to the surface of the eye. Finally, the fluid-gel will be tested in a safety clinical trial where tolerability and effect on eye-comfort will be examined. We will communicate our project at patient group meetings and in newsletters. Professional colleagues will be informed at national and international conferences and through open-access publications. Ultimately, patients will be able to use the fluid-gel dressing either as a dissolvable , protective, transparent bandage for providing eye comfort, or, in a form that delivers essential nutrients to help recondition and restore eye surface health; thus, improving the quality of patient lives.

Research activity codes: 6.3 MEDICAL DEVICES;5.3 MEDICAL DEVICES
Health categories: EYE