Co-development of a novel injection and crosslinking device for delivering long-acting biologic formulations for ocular drug delivery

在英国，每天有超过250人开始失明，这对英国国家医疗服务体系和全球医疗体系构成了重大的健康挑战。在50-60岁至80岁及以上的成年人中，新的渗漏血管的生长会释放视网膜下或视网膜内的液体，从而导致严重的眼部疾病，如“湿性”年龄相关性黄斑变性（AMD）和糖尿病并发症：糖尿病视网膜病变（DR）和糖尿病性黄斑水肿（DME）。例如，在英国，每天有近400人被诊断患有AMD。近48%的英国成年黄斑变性患者因这种疾病而失明，这种疾病影响了老年人的中央视力，使他们难以完成阅读、看电视、开车或识别面孔等简单的日常任务。随着寿命的延长和肥胖的发病率，这些疾病的患病率将继续上升。目前，眼科医生通过直接眼部注射昂贵的生物制剂水制剂来治疗“湿性”AMD患者。然而，由于一些不良事件的影响，如眼出血、不适、发红、刺激和眼压升高，需要每月或每两个月注射一次，导致患者依从性差。一个主要的依从性问题是往返医院，62%的患者需要陪同前往眼科诊所，导致依从性差。AMD患者数量的增加，加上频繁注射的需求，给已经不堪重负的NHS带来了压力，该NHS仍在从Covid-19大流行的影响中恢复过来。黄斑学会、皇家眼科学院和皇家国家盲人研究所的调查显示，许多诊所未能满足黄斑变性再治疗的建议等待时间。现实世界的数据显示，尽管临床试验很有希望，但由于未能坚持服用，视力会恶化5-6年。Re-Vana开发了OcuLief，这是一种破坏性的可注射可生物降解的缓释制剂，与简单的紫外线脉冲装置交联在一起。与目前每月一次的玻璃体内注射相比，小体积植入物将提供显著的临床益处。注射入眼后，植入物将提供持续释放，有效治疗AMD至少6个月，最多12个月，甚至更长时间。因此，这项研究的影响将为各种各样的用户（如患者、科学家、临床医生、行业和医疗保健提供者）带来重大好处。

In the UK, every day more than 250 people start to lose their sight - creating a major health challenge to the NHS and global healthcare systems. The growth of new leaky blood vessels releasing fluid below or within the retina contributes to severe ocular diseases such as 'wet' age-related macular degeneration (AMD) and the complications of diabetes: diabetic retinopathy (DR) and diabetic macular edema (DME), in adults over 50-60 yrs old to 80 and beyond. For example, in the UK, nearly 400 individuals are diagnosed with AMD every day. Nearly 48% of UK adult AMD sufferers go blind due to the disease - which affects the central vision in the elderly making simple daily tasks such as reading, watching TV, car driving or recognising faces difficult. With increasing lifespan and the incidence of obesity, the prevalence of these diseases will continue to rise.Currently, ophthalmologists treat 'wet' AMD patients by direct ocular injection of expensive aqueous formulations of biologics. However, the need for monthly/bimonthly injections leads to poor patient compliance due to some adverse events effects such as bleeding in the eye, discomfort, redness, irritation and increase in intraocular pressure. A major compliance issue is the travel to and from the hospital, with 62% of patients requiring an escort to the ophthalmology clinic - leading to poor adherence. The rise in the number of AMD patients combined with the need for frequent injections puts pressure on an already over-stretched NHS still recovering from the impact of the Covid-19 pandemic. Surveys by the Macular Society, the Royal College of Ophthalmologists, and the Royal National Institute of Blind People, have shown that many clinics fail to meet recommended waiting times for AMD retreatment. Real-world data shows visual acuity deteriorates by 5-6 years despite promising clinical trials due to failed adherence.Re-Vana has developed OcuLief - a disruptive injectable biodegradable sustained-release formulation, crosslinked _in situ_ with a simple uv light pulsed device. The small volume implant will provide significant clinical benefits over current monthly intravitreal injections. Following injection into the eye, the implant would provide a continuous release for effective AMD treatment over a minimum of a 6 months and up to 12 months and potentially beyond. Therefore, the impact of this research will offer major benefits to a wide variety of users such as patients, scientists, clinicians, industry, and healthcare providers.