Award Title: Sensorised Micro-Surgical Robot for Safe Regenerative Retinal Therapy Delivery
Funder: Department of Health and Social Care

Abstract: Research question  Gene and cellular therapies are emerging transformative treatments for blinding retinal diseases. Treatment delivery into delicate retinal tissue layers, some as thin as 10-20um, requires precision and force sensing beyond human capabilities, and calls for robotic assistance. Therefore, we must create systems that augment surgical delivery by offering dexterous assistance and information about tool/tissue interaction.  Background   Research on robot-assisted vitreoretinal surgery originally focused on vessel cannulation and epiretinal membrane peeling. Research has now pivoted to regenerative therapy delivery, where robotic assistance is critical due to the precision required. However, retrofitting existing systems to adhere to the stricter requirements of therapy delivery cannot lead to optimal performance.  The majority of robotic systems under research and development are straight-tool holders that follow conventional surgical protocols. Further, they do not offer simultaneous force and depth-of-implantation sensing due to the challenge of incorporating multi-modal sensors within a sub-millimetre tool. On the contrary, our research focuses from the onset on cellular and gene therapy delivery. Our prototyped telemanipulated system can improve clinical performance near the retina due to its snake-like flexibility, offering both precision and dexterity.  Aims and Objectives   We will produce a sensorised flexible micro-surgical robot to deliver retinal therapies by:   1. Sensorising a flexible robot with fibre-based force sensing and high-resolution imaging at its tip.   2. Developing algorithms for retina tracking and semi-automated therapy delivery.   3. Compiling documentation in support of first-in-human evaluation of a Minimum Viable Product (MVP).  Methods and Timelines   The project lasts 12 Quarters (Q). The objectives will be met via 5 development work-packages:   WP1 (Q1-Q4) will deliver a flexible submillimetre core that will house five sensing fibres, a therapy delivery channel and a forceps. The core will be embedded within the robot body to maintain the separation of the fibres. It will be created through fibre-pulling technology.  WP2 (Q2-Q10) will deliver two optical imagers based on single-fibre OCT. The “S” profiler provides an A-scan that will enable the robot to maintain a safe distance from the retina. The “I” imager will produce a detailed B-scan (series of A-scans) to guide injection thanks to the innovative use of a rotating cleaved fibre.  WP3 (Q1-Q10) will develop the first ever Fibre-Bragg grating based force/shape sensor for submillimetre robots. System calibration will be achieved through a bespoke cable-driven force applicator and tailored deep-learning models.  WP4 (Q5-Q12) builds on our software to develop “operating room ready” retina and tool tracking algorithms. By detecting the tools and motion of the retina, our robot will be stabilised in lateral dimensions to perform minute-long therapy injection.  WP5 (Q1-Q12) will identify desired features of an MVP through interviews with surgeons, redevelop our robot prototype under a Quality Management System, and submit to regulators application for first-in-human consideration.  Impact and Dissemination   The project de-risks our innovation while generating publications, new knowledge, and IP in support of a multi-stage commercialisation strategy. Robust mechanisms to engage and be informed by public and patients will advise the presentation and orientation of the research, while also broadly disseminating our results.

Lay Abstract: Age-related macular degeneration (AMD) is one of the commonest irreversible eye diseases, affecting almost a million people in the UK alone. The economic effect of AMD is tremendous, rising to more than £1 Billion of associated costs. The development of novel therapies to reverse AMD is therefore crucial from both a societal and an economic perspective.  AMD can be  wet , when abnormal blood vessels grow into the seeing nerve layer of the eye and bleed, while  dry  degeneration occurs when the seeing nerves are spontaneously lost. Both forms eventually lead to vision loss. Laser and injection of drugs into the eye, which destroy or suppress the abnormal vessels, are the only treatment for wet AMD; dry AMD has no treatment. Overall, however, the progress of the disease is slowed but never reversed.  Pioneering studies conducted worldwide and in the UK, including a pivotal preliminary clinical trial by the lead clinical investigator within the research team, demonstrated that sight restoration in AMD may be possible with regenerative therapies. The research team evaluated a novel cell-based therapy that replaces the damaged cells in the eye. Promising results showcasing sight restoration were captured within a year of follow-up studies.  Delivery of these upcoming treatments, under the retina, is currently performed using a hand-held needle. This manipulation is very demanding for surgeons as it lies at the limit of what humans can achieve. Furthermore, the forces that are applied during these subretinal injections are very low and generally not perceivable. Finally, similar to inserting a hypodermic needle, there is no direct indication of where exactly the needle is within the retina. These factors make the efficacy of novel therapeutics limited by manual skills and adversely affect their success.  As one of the major limitations of regenerative therapy is delivery, we have been working on a flexible robotic system to boost the capabilities of surgeons and clinical outcomes. Our new research will endow our system with micro-scale force sensing to enable the surgeon to feel the generally imperceivable forces exercised in retinal microsurgery. Further, we will develop sensors to see through the retina directly from the robot s tip with Optical Coherence Tomography, which is a technology drawing parallels to ultrasound imaging. We will develop a semi-automated stabilisation system to aid when steady prolonged therapy delivery is required. Similar to a lane-following vehicle, the developed algorithms will allow our robot to maintain its targeting at predetermined locations in the retina and account for physiological patient motion. The plurality of sensors will allow for targeted safe delivery of regenerative therapies anywhere within the retina.  With our proposed system the success of novel therapies will not be held back by conventional and limited conventional retinal surgery protocols.

Research Activity Codes: 5.4 SURGERY
Health Categories: EYE