Advantages of robotic assistance over a manual approach in simulated subretinal injections and its relevance for gene therapy

Abstract

Subretinal injection is a method for gene delivery to treat genetic diseases of the photoreceptors and retinal pigment epithelium. A reflux-free subretinal injection is important to allow effective, safe, and cost-effective gene therapy to the retina. We report on a comparison between manual and robotic assistance in simulated subretinal injections using an artificial retina model. Nine surgeons carried out the procedure with and without the Preceyes Surgical System, using an OPMI Lumera 700 Zeiss surgical microscope equipped with intra-operative optical coherence tomography. Success in creating a bleb without reflux, injection duration, drift, tremor, and increase in the diameter of the puncture hole were analyzed. Robotic assistance improved drift (median 16 vs 212 µm), tremor (median 1 vs 18 µm), enlargement of the retinal hole, and allowed for prolonged injection times (median 52 vs 29 sec). Robotic assistance allowed higher rate of bleb formation (8/9 vs 4/9 attempts) with a moderate reduction in reflux (7/9 vs 8/9 attempts) in this artificial model. Robotic assistance can significantly contribute to subretinal injections and provide quantifiable parameters in assessing surgical and clinical success of novel retinal gene therapies.

Subretinal Therapy: Technological Solutions to Surgical and Immunological Challenges

“…Recent advances in imaging and robotics can overcome the limitations listed above ( 7 , 22 ). Robotic systems have been in routine use for more than 20 years in other surgical specialties.…”

“…This ability to reduce variability was clearly shown in an experiment carried out with retinal surgeons of various skill levels at a European retinal meeting (Euretina). Vitreoretinal surgeons, who had never used the PSS were asked to perform a simulated subretinal injection with and without the robotic device ( 7 ). A bleb was created more frequently with the use of the PSS (88 vs. 44%) with a reduction in the rate and severity of reflux (77 vs. 88%) was observed in this model that lacked any elastic tissue.…”

“…It has been assumed that current available surgical techniques are sufficient and reliable in the hands of surgeons, many of whom, have limited training in performing this type of surgery ( 5 , 6 ). Several lines of evidence indicate that this may not be the case ( 7 – 9 ).…”

Controlled Subretinal Injection Pressure Prevents Damage in Pigs

“…Controlled injection systems for the administration of subretinal injections are already in use in clinical settings. The technique could be further advanced with robotic assistance to compensate for patient-/surgeon-related movements and intraoperative OCT guidance to optimize precision of the injection site [23, 24].…”

Robot-assisted subretinal injection system: development and preliminary verification

“…While the iRAM!S and Preceyes ophthalmic surgical robots are capable of performing surgical operations with subretinal injections [ 16 , 17 ], and there are few such studies in China [ 18 ]. So, in this study, we designed and constructed an ophthalmic surgical robotic system with high stability, which aims to be capable of performing subretinal injection operations, and the performance of the system was initially verified in isolated porcine eye model.…”