Robotic-Assisted Vitreoretinal Surgery (RAVS) is an advanced surgical technique that performs intraocular operations via a surgical robot. It reduces the physiological tremor (average amplitude 156 μm) inevitable in human hands and enables micron-level precision 1).
The history of vitreoretinal surgery dates back to Machemer’s vitrectomy in the 1970s. Attempts at robotic assistance continued until the application of the da Vinci system in 2007, and the ophthalmic-specific surgical robot “Preceyes” obtained CE marking (Europe) in 2019. Currently, only two systems have clinical use experience: Preceyes and the KU Leuven co-manipulation robot 1).
Ophthalmic surgical robots are broadly classified into three types based on the operation method.
Handheld Type
Representative example: Micron (smart handheld instrument)
Features: Built-in active cancellation function that reduces tremor by up to 90%. Appearance is similar to conventional surgical instruments.
Use: Easy to integrate into existing surgical environments, requiring minimal additional equipment.
Co-manipulation Type
Representative examples: KU Leuven co-manipulator, Steady-Hand Robot
Features: The surgeon and robot hold the instrument together, precisely guiding the surgeon’s movements.
Use: Applied in procedures requiring high precision, such as retinal vein cannulation.
Teleoperated Type
Representative examples: Preceyes (CE marked), IRISS
Features: The surgeon controls remotely via joystick. Equipped with tremor filtering, motion scaling, and virtual safety boundaries.
Use: Subretinal injection, internal limiting membrane peeling, etc. Most widely used in clinical research.
RCTs have confirmed that the safety of robotic and manual groups is equivalent, with the robotic group suggesting a reduction in tremor-related microtrauma. However, there is a different risk profile including longer setup time (≥20 minutes more than manual) and lack of haptic feedback.
Procedures for which RAVS is considered particularly useful are as follows.
The internal limiting membrane (ILM) and epiretinal membrane (ERM) are extremely thin, semi-transparent membranes, and peeling requires delicate force control. Robot-assisted tremor reduction and force control may reduce the risk of retinal damage during this maneuver. It has also been reported that ILM removal reduces injection pressure during subretinal injection by approximately 6 PSI1).
Applied for precise delivery of gene therapy drugs (e.g., voretigene neparvovec) into the subretinal space 1). Manual direct injection has a steep learning curve and carries risks of Bruch’s membrane perforation and subretinal hemorrhage 1). Robot-assisted stable injection may reduce these risks.
The first human retinal vein cannulation (RVC) using the KU Leuven system enabled drug delivery into small vessels with diameters of 80–120 μm. Manual performance of this procedure is extremely difficult, making it one of the clearest indications for the advantage of RAVS.
In subretinal administration of t-PA (tissue plasminogen activator) for subretinal hematoma, robot assistance has been reported to reduce the number of required retinotomies.
Internal Limiting Membrane / ERM Peeling
Indication: Epiretinal membrane, macular hole
Effect: Reduced infusion pressure, decreased risk of microtrauma 1)
Subretinal Injection
Indication: Gene therapy (e.g., RPE65 mutation)
Effect: Reduced risk of Bruch’s membrane perforation 1)
Retinal Vein Cannulation
Indication: Retinal vein occlusion
Effect: Enables direct drug delivery into vessels of 80–120 μm
Submacular Hemorrhage Management
Indication: Hemorrhage associated with age-related macular degeneration
Effect: Reduction in the number of retinotomies
Retinal vein cannulation (RVC) is an extremely difficult procedure to perform manually, and the usefulness of RAVS is most evident. Subretinal injection is also becoming increasingly important with the spread of gene therapy, and stable delivery via robotic assistance is expected.
Preceyes enables 4-axis manipulation with a tip accuracy of approximately 10 μm. The main control functions are as follows.
Intraoperative optical coherence tomography (iOCT) is used to estimate the volume of the bleb (subretinal fluid accumulation) in real time (applying the spherical cap formula)1). This prevents over- or under-injection and enables appropriate bleb formation.
This technique uses the “puddle” formed after internal limiting membrane peeling as a delivery route for subretinal injection 1). Performing peeling and injection consecutively improves procedural efficiency.
This method involves forming a pre-bleb with BSS (balanced salt solution) and then injecting the drug additionally. It has the effect of suppressing pressure increase during injection but carries the risk of retinotomy enlargement 1).
The first human robot-assisted subretinal drug delivery using Preceyes was performed under local anesthesia in 2022 2).
The characteristics of Preceyes and the KU Leuven cooperative manipulation robot are compared below.
| Item | Preceyes | KU Leuven |
|---|---|---|
| Operation method | Remote control | Cooperative manipulation |
| Tip precision | Approximately 10 μm | Micron order |
| Main indications | Subretinal injection, internal limiting membrane peeling | Retinal vein cannulation |
The tip accuracy of Preceyes is reported to be approximately 10 μm. Compared to human physiological tremor (average amplitude 156 μm), it can suppress motion blur to about 1/15 or less1).
In a randomized controlled trial (RCT) on RAVS, there was no significant difference in safety between the robot group and the manual group, and the robot group showed a tendency toward fewer microtraumas.
Surgical time was longer in the robot group (internal limiting membrane peeling time in a 12-case RCT: robot group 4 minutes 5 seconds vs. manual group 1 minute 20 seconds). This difference is expected to be reduced with familiarity of setup procedures and system improvements.
The main comparison indicators are shown below.
| Indicator | Robot group | Manual group |
|---|---|---|
| Physiological tremor | Approximately 10 μm after correction | 156 μm (average) |
| Internal limiting membrane peeling time | 4 minutes 5 seconds | 1 minute 20 seconds |
| Safety | Equivalent to manual | (Reference) |
In the first robot-assisted subretinal drug delivery reported in 2022, delivery using Preceyes under local anesthesia was successfully performed 2).
Cehajic-Kapetanovi et al. (2022) published the first human report of robot-assisted subretinal drug delivery performed under local anesthesia 2). Delivery to the target site was confirmed without surgical complications.
Although RAVS has promising potential, there are currently several challenges to overcome.
As a new device for subretinal injection, the NANO SubRet Gateway Device is under development. It is designed to access the subretinal space without requiring posterior vitreous detachment (PVD), which is expected to simplify the surgical procedure 1). In addition, the Orbit SDS, which enables access to the suprachoroidal space, is also being developed 1).
Research is underway to further enhance the safety and precision of robotic operations by combining real-time tissue recognition via intraoperative OCT with AI-assisted decision support. Integration of force feedback systems is also a major development goal.
Teleoperated robotic systems are being considered for telesurgery applications, enabling surgery in areas with limited physical access to specialists. Communication latency and safety assurance are challenges to be addressed.
At present, RAVS is not yet in clinical use and is at the research and clinical trial stage. Preceyes has obtained CE marking in Europe, but it is not implemented as standard practice in many countries, including Japan. Future widespread adoption requires approval, reimbursement system development, and training programs.
