# Demonstration of Subretinal Injection Using Common-Path Swept Source OCT Guided Microinjector
## 1 Introduction  
Needle-based devices to inject therapeutic and diagnostic agents to patients are among the most commonly used medical devices. By delivering therapeutic materials directly to target areas, it is expected that maximal efficacy, while minimizing drug dose and side effects, will be achieved. In ocular surgery, the ability to consistently perform intraretinal microinjection with precision is not yet established, although the capability could revolutionize the treatment of degenerative retinal diseases that cause blindness. At present, there are many degenerative retinal diseases that cannot be treated completely and ocular gene therapy has emerged as a promising method to manage such untreatable inherited retinal diseases [1; 2]. Various gene vectors have been developed that are delivered to target areas by microinjection [3]. At present, subretinal injection is commonly performed to achieve gene therapy. During subretinal injection, the surgeon is totally dependent on manual manipulation of the tools and visual feedback through a stereomicroscope. However, these two requirements for success are limited by physiological hand tremor and the limited human ability to visually resolve on the micron scale in the axial axis. Moreover, there is potential obscuration of the injecting site by the tool shaft and needle tip [4].  
A variety of microinjection systems have been proposed. In bench cell biology, accurate injection of foreign materials such as DNA, RNAi, protein, and drug compounds is fundamentalto achieve successful expression of desired properties [5; 6; 7; 8; 9]. [PERSON] et al. developed a computer vision-based microinjection system and successfully performed zebrafish embryo injection with a 99% success rate [5]. However, this type of application was in a stable and predictable environment; a surgical environment requires a more dynamic system. The \"Steady-Hand Eye-Robot\" system has demonstrated its potential to remove physiological inaccuracy and guide a microneedle to small veins in the chorioallantoic membranes of chicken embryos [6]. In particular, [PERSON] et al. have developed a fully handheld micromanipulator, \"Micron\", and have demonstrated various handheld applications including retinal cannulation [8]. However, the solution does not address the limited visualization of the target through the microscope and additional supportive information is required. An example of relevant additional information may be provided by a force-sensing method [9] to assist retinal microinjection, but it is still not sufficient for precise depth control.  
Optical coherence tomography (OCT) has micron-levels of precision, subsurface imaging capability, as well as fast imaging speeds that can provide solutions to overcome existing limitations [10; 11; 12; 13; 14]. In particular, we have been developing an array of Sensorized Micromanipulation Aided Robotic-surgery Tool (SMART) that uses a common-path OCT (CP-OCT) distal sensor for axial motion sensing and guidance [15; 16]. We have also adopted a parallel programming technique using a graphics-processing unit (GPU) to reduce the processing time for real-time guidance [17]. This distal sensing approach is distinguished from typical OCT \"B-scan\" imaging in that the distal sensing system measures a distance value from the acquired A-scan data [18; 19; 20; 21; 22; 23; 24]. Motion sensitive interference patterns are sequentially measured at consistent time intervals and continuously converted to series of A-scans. The system counts the pixel distance in the image domain and then converts the number to a physical distance. Then, the measured distance is utilized for intraoperative motion guidance. Integrating CP-SSOCT feedback with a SMART injector via an intuitive control system that allows the tip of the injector to lock onto the desired depth, regardless of involuntary user and target motion, has been the goal of this development process. A SMART injector approach is therefore a logical extension for future development of handheld instruments.