Microsurgery of the retina would be dramatically improved by instruments that offer supra-human precision. Here, we report the results of a first-in-human study of remotely controlled robot-assisted retinal surgery performed through a telemanipulation device. Specifically, 12 patients that required dissection of the epiretinal or inner limiting membrane over the macula were randomly assigned to either undergo robot-assisted surgery or manual surgery, under general anaesthesia. We evaluated surgical success, the duration of surgery and the amount of retinal microtrauma as a proxy for safety. Surgical outcomes were equally successful in the robotic surgery and manual surgery groups. Differences in the amount of retinal microtrauma between the two groups were statistically insignificant, yet dissection took longer with robotic surgery (median time: 4 min 55 s) than with manual surgery (1 min 20 s). We also show the feasibility of using the robot to inject recombinant tissue plasminogen activator under the retina to displace sight-threatening haemorrhage in three patients under local anaesthesia. A safe and viable robotic system for intraocular surgery would enable precise and minimally traumatic delivery of gene therapy or cell therapy to the retina.
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Eshner, A. A. A graphic study of tremor. J. Exp. Med. 2, 301–312 (1897).
Harwell, R. C. & Ferguson, R. L. Physiologic tremor and microsurgery. Microsurgery 4, 187–192 (1983).
Riviere, C. N., Rader, R. S. & Khosla, P. K. Characteristics of hand motion of eye surgeons. In Engineering in Medicine and Biology Society, 1997. Proc. 19th Annual International Conference of the IEEE 1690–1693 (IEEE, 1997).
Spitznas, M. Motorized teleguided stereotactic micromanipulator for vitreous microsurgery. Arch. Ophthalmol. 101, 623–630 (1983).
Guerrouad, A. & Vidal, P. SMOS: stereotaxical microtelemanipulator for ocular surgery. In Images of the Twenty-First Century. Proc. Annual International Engineering in Medicine and Biology Society 879–880 (IEEE, 1989).
Silver, D. M. & Csutak, A. Human eye dimensions for pressure-volume relations. Invest. Ophthalmol. Vis. Sci. 51, 5019 (2010).
Wei Tech Ang, Riviere, C. N. & Khosla, P. K. Design and implementation of active error canceling in hand-held microsurgical instrument. In Proc. 2001 IEEE/RSJ International Conference on Intelligent Robots and Systems. Expanding the Societal Role of Robotics in the Next Millennium 1106–1111 (IEEE, 2001).
Stetten, G. et al. Hand-held force magnifier for surgical instruments. In I nformation Processing in Computer-Assisted Interventions. Lecture Notes in Computer Science (eds Taylor, R. H. & Yang, G.-Z.) Vol 6689, 90–100 (Springer, Berlin, Heidelberg, 2011).
Taylor, R. et al. A steady-hand robotic system for microsurgical augmentation. Int. J. Robot. Res. 18, 1201–1210 (1999).
Uneri, A. et al. New steady-hand eye robot with micro-force sensing for vitreoretinal surgery. Proc. IEEE RAS EMBS Int. Conf. Biomed. Robot. Biomechatron. 2010, 814–819 (2010).
Nakano, T., Sugita, N., Ueta, T., Tamaki, Y. & Mitsuishi, M. A parallel robot to assist vitreoretinal surgery. Int. J. Comput. Assist. Radiol. Surg. 4, 517–526 (2009).
Rahimy, E., Wilson, J., Tsao, T.-C., Schwartz, S. & Hubschman, J.-P. Robot-assisted intraocular surgery: development of the IRISS and feasibility studies in an animal model. Eye 27, 972–978 (2013).
Meenink, H. C. M. et al. A master-slave robot for vitreo-retinal eye surgery. In Proceedings of the 10th International Conference of European Society for Precision Engineering and Nanotechnology (eds Spaan, H. et al.) 408–411 (Delft Netherlands, EUSPEN, Bedford, UK, 2010).
Kummer, M. P. et al. OctoMag: an electromagnetic system for 5-DOF wireless micromanipulation. IEEE Trans. Robot. 26, 1006–1017 (2010).
de Smet, M. D. et al. Robotic assisted cannulation of occluded retinal veins. PLoS ONE 11, e0162037 (2016).
de Smet, M. D. et al. Release of experimental retinal vein occlusions by direct intraluminal injection of ocriplasmin. Br. J. Ophthalmol. 100, 1742–1746 (2016).
Meenink, T., Naus, G., de Smet, M., Beelen, M. & Steinbuch, M. Robot assistance for micrometer precision in vitreoretinal surgery. Invest. Ophthalmol. Vis. Sci. 54, 5808 (2013).
Wilkins, J. R. et al. Characterization of epiretinal membranes using optical coherence tomography. Ophthalmology 103, 2142–2151 (1996).
Kelly, N. E. & Wendel, R. T. Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch. Ophthalmol. 109, 654–659 (1991).
Olivier, S. Subretinal recombinant tissue plasminogen activator injection and pneumatic displacement of thick submacular hemorrhage in age-related macular degeneration. Ophthalmology 111, 1201–1208 (2004).
Peyman, G. A. et al. Tissue plasminogen activating factor assisted removal of subretinal hemorrhage. Ophthalmic Surg. 22, 575–582 (1991).
Wedmid, A., Llukani, E. & Lee, D. I. Future perspectives in robotic surgery. BJU Int. 108, 1028–1036 (2011).
Sim, H. G., Yip, S. K. H. & Cheng, C. W. S. Equipment and technology in surgical robotics. World J. Urol. 24, 128–135 (2006).
Morel, P. et al. Robotic versus open liver resections: a case-matched comparison. Int. J. Med. Robot. 13, e1800 (2017).
Chen, Y. J. et al. Outcomes of robot-assisted versus laparoscopic repair of small-sized ventral hernias. Surg. Endosc. 31, 1275–1279 (2017).
Ahmad, A., Ahmad, Z. F., Carleton, J. D. & Agarwala, A. Robotic surgery: current perceptions and the clinical evidence. Surg. Endosc. 31, 255–263 (2017).
Hiatt, L. M., Narber, C., Bekele, E., Khemlani, S. S. & Trafton, J. G. Human modeling for human–robot collaboration. Int. J. Robot. Res. 36, 580–596 (2017).
Milne, V., Tierney, M. & Doig, C. Is robotic surgery worth the cost? Healthy Debate (20 October 2016); http://healthydebate.ca/2016/10/topic/robotic-surgery
Veluvolu, K. C., Tatinati, S., Hong, S.-M. & Ang, W. T. Multistep prediction of physiological tremor for surgical robotics applications. IEEE Trans. Biomed. Eng. 60, 3074–3082 (2013).
Gonenc, B. et al. Towards robot-assisted vitreoretinal surgery: force-sensing micro-forceps integrated witha handheld micromanipulator. In 2014 IEEE International Conference on Robotics and Automation (ICRA) 1399–1404 (IEEE, 2014)
Gijbels, A. et al. Experimental validation of a robotic comanipulation and telemanipulation system for retinalsurgery. In 5th IEEE RAS/EMBS International Conference on Biomedical Robotics and Biomechatronics 144–150 (IEEE, 2014)
Meenink, H. C. M. et al. in Medical Robotics: Minimally Invasive Surgery (ed. Gomes, P.) 185–209 (Woodhead Publishing Series in Biomaterials, no. 51, Cornwall, Woodhead, 2012).
Xue, K., Groppe, M., Salvetti, A. P. & MacLaren, R. E. Technique of retinal gene therapy: delivery of viral vector into the subretinal space. Eye 31, 1308–1316 (2017).
Fischer, M. D., Hickey, D. G., Singh, M. S. & MacLaren, R. E. Evaluation of an optimized injection system for retinal gene therapy in human patients. Hum. Gene Ther. Methods 27, 150–158 (2016).
We acknowledge funding from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Zien Zonder Zorgen (ZIZOZ)—a Dutch charity—and the Nuffield Medical Fellowship.
T.L.E., K.X., M.L., R.E.M., M.P.S. and A.D.F. declare no competing interests. H.C.M.M., M.J.B., G.J.L.N. are employed in the robot engineering and development department at Preceyes BV, Eindhoven, the Netherlands, and M.D.d.S. is a shareholder in Preceyes BV.
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Supplementary Notes, Supplementary Figures 1–38, Supplementary Tables 1–7, Supplementary References 1–16.
Tremor comparison between robot-assisted and manual membrane peel under light pipe.
Tremor comparison between robot-assisted and manual membrane peel under chandelier illumination.
Subretinal injection of tissue plasminogen activator using a 41G needle and chandelier illumination.
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Edwards, T.L., Xue, K., Meenink, H.C.M. et al. First-in-human study of the safety and viability of intraocular robotic surgery. Nat Biomed Eng 2, 649–656 (2018). https://doi.org/10.1038/s41551-018-0248-4
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