Title: Image-Guided Micro-Precise Flexible Robotic Tools for Retinal Therapeutics Delivery
Funder: Department of Health and Social Care

Abstract: This project will deliver a retinal therapeutics delivery robot that innovates in three ways: Novelty-1: The robot will have end effectors based on concentric tube technology (Bergeles, A. H. Gosline, et al. 2015). Concentric tube robots are compliant robots comprising pre-curved telescoping tubes that elastically interact to control the robot’s pose. A six degree-of-freedom (DoF) robot acting as a wrist at the retinal level will be designed. The tubes’ lumen will deliver tools to the tip location. Our research will pioneer computationally optimised robot stiffness based on micropatterning to ensure safe robot/tissue interaction. This improves upon existing systems that require force sensors and complex force/position control. [Implemented via WP1, WP2 towards Obj-1, Obj2]. Novelty-2: Master/slave robot architecture will be followed. The surgeon will operate the robot-slave from a console-master via handles that capture his/her wrist motions. Master/slave architecture can abstract the complexity of flexible kinematics and allow intuitive motion replication at the robot tip. Stereo images from the ophthalmic microscope will be relayed to the console and used to register OCT/angiography images. The console will be a da Vinci Console, programmable through the Research Kit available at UCL. [Implemented via WP3 towards Obj.-1]. Novelty-3: 3D-to-3D deformable image registration algorithms will use vasculature landmarks to align preoperative OCT/angiography volumes to stereo fundus images and provide subretinal layer information as the robot tip advances. Vessels are visible in both the fundus images and the angiography volumes, and angiography is already aligned with OCT since they are acquired simultaneously. The subretina will be visualised via inverse realism (Lerotic et al. 2007), a rendering technique wherein pre-operative information is fused to real-time images while retaining salient features from both modalities for perception augmentation. [Implemented via WP4, WP5, WP6 towards Obj.1,3] The robot will be mounted from the optical microscope to minimise its footprint in the operating theatre. The research is organised in work packages (WP) (see Fig. 3) with associated deliverables (De) and duration in months (M): • WP1: Computational design of 6-DoF flexible robot (M1-18): De1.1: Software for optimal robot design. De1.2: Design (tube length, curvature, stiffness) of the therapeutics-delivery robot end-effector. • WP2: Slave robot engineering and control algorithm development (M6-30): De2.1: Hardware: a flexible forceps, knife, and a pressure-controlled piston. De2.2: Hardware: designed tubes micromachined to desired stiffness, shapes, and lengths. De2.3: Hardware: final prototype of high-resolution actuation system. De2.4: Software: robot controller and fine-tuned system for high-precision micromanipulation. • WP3: Kinematics abstraction and linking with master console (M12-32): De3.1: Hardware/software: ophthalmic microscope images relayed to master console. De3.2: Software: linked simulated robot and master console for designed tube set. De3.3: Hardware/software: linked robot prototype and master console. • WP4: Preoperative data acquisition and vessel segmentation (M1-12): De4.1: Report: OCT and 3D Angiography volume acquisition protocol on the Zeiss Angio 3D. De4.2: Software for segmentation of OCTA and microscopy (retinal) images. • WP5: Deformable multi-modal image registration (M12–26): De5.1: Software for real-time registration of OCT/angiography to fundus images. • WP6: Augmented reality for effective image-guided ophthalmic surgery (M18–30): De6.1: Software for inverse realism fusion of OCT/angiography to fundus images. De6.2: Software: OCT/angiography visualisation updated to reflect robot-tip position. • WP7: System integration and evaluation: horizontal activity ensuring component interoperability (M1–36): De7.1: Software: own NifTK framework expanded to include interfacing with mechatronics. De7.2: Software: training simulator linking master console and virtual robot. De7.3: Report: benchtop evaluation results (10um precision) for robot. De7.4: Report: clinical ease-of-use evaluation through NASA’s task load metrics.

Lay abstract: Age-related macular degeneration (AMD) is one of the commonest irreversible eye diseases, affecting almost a million people in the UK alone. 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 slowly lost spontaneously. Both eventually lead to vision loss as the seeing cells of the eye are lost. 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. Sight restoration in AMD may be possible with novel cell-based therapies that replace the damaged cells in the eye. Delivery of these treatments, under the retina, is currently performed using a hand-held needle. This manipulation is very demanding for humans and lies at the limit of conventional surgery. Furthermore, there is currently only a limited visual indication of where the needle is, as it is guided based on the surgeon's direct view through the pupil. These factors make the efficacy of novel therapeutics limited by manual skills and adversely affect their success. As one of the major limitations of cell and novel therapies is delivery, we propose the development of a tailored flexible robotic system for therapeutics delivery to the eye. The robot will comprise soft components and enable safe, dexterous interventions at the retinal and subretinal layers. Coupled with Optical Coherence Tomography and Angiography, which allow visualisation of all subretinal layers and vessels, the robot will provide the surgeon with microscopic-tissue information, enabling him/her to safely target the desired retinal layers for treatment. As such, the success of novel therapies will not be held back by conventional and limited retinal surgery protocols.

Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: EYE