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，这对英国国民健康保险制度和全球医疗体系构成了重大的健康挑战。在50-60岁到80岁及以上的成年人中，视网膜下方或视网膜内释放液体的新的渗漏血管的生长会导致严重的眼部疾病，如湿性老年性黄斑变性(AMD)和糖尿病的并发症：糖尿病视网膜病变(DR)和糖尿病黄斑水肿(DME)。例如，在英国，每天有近400人被诊断为AMD。近48%的英国成年AMD患者由于这种疾病而失明--这种疾病会影响老年人的中央视力，使阅读、看电视、开车或识别面孔等简单的日常任务变得困难。随着寿命的延长和肥胖发病率的增加，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剂来治疗湿性AMD患者。然而，由于需要每月/每两个月注射一次，患者的依从性较差，因为一些不良事件影响，如眼睛出血、不适、发红、刺激和眼压升高。一个主要的遵从性问题是往返医院的旅行，62%的患者需要护送到眼科诊所-导致遵从性较差。老年性黄斑变性患者数量的增加，再加上频繁注射的需要，给本已不堪重负的国民健康保险制度带来了压力，该制度仍在从新冠肺炎疫情的影响中恢复。黄斑学会、皇家眼科学会和皇家国家盲人研究所的调查显示，许多诊所未能达到AMD再次治疗的推荐等待时间。真实世界的数据显示，尽管由于粘连失败，临床试验前景看好，但视力仍会下降5-6年。Re-Vana开发了OcuLef-一种可注射、可生物降解的缓释制剂，与简单的紫外光脉冲装置进行原位交联。与目前每月的玻璃体内注射相比，这种小体积的植入物将提供显著的临床益处。在注射到眼睛后，植入物将在至少6个月和最多12个月甚至更长的时间内为有效的AMD治疗提供持续的释放。因此，这项研究的影响将为患者、科学家、临床医生、行业和医疗保健提供者等广泛的用户提供重大好处。

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.