First in human clinical trial of robot-assisted subretinal drug delivery under local anaesthesia

Abstract

Purpose : To investigate the feasibility and safety of robot-assisted subretinal drug delivery in patients undergoing vitreo-retinal surgery for acute sub-macular haemorrhage as a model for future robot-assisted retinal gene or cell therapy.

Methods : We conducted a double-armed interventional randomized clinical trial comparing robot-assisted (Preceyes BV, Eindhoven, the Netherlands) versus manual retinal surgery under local anaesthesia in patients with submacular haemorrhage (ClinicalTrials.gov NCT03052881). After standard vitrectomy, intraoperative OCT-guided (Zeiss Resight 7000) subretinal injection of recombinant tissue plasminogen activator (rt-PA, Alteplase, Boehringer-Ingelheim, Germany) was performed either by robot-assisted or conventional manual technique. The robotic part of the procedure involved advancement of a 41 gauge Teflon cannula slowly through the retina and stabilizing it during foot controlled subretinal injection of up to 100µl of rt-PA in balanced salt solution (1mg/ml). We assessed surgical success, duration of surgery, adverse intraoperative events and tolerability of surgery under local anaesthesia.

Results : To date, 11 out of 12 patients have completed the trial, 5 in the robot-assisted (mean age 74.8±3.32 years) and 6 in the control arm (mean age 87.5±2.01 years). All patients presented with acute central visual loss (mean LogMar visual acuity 1.45±0.36 in robot-assisted and 2.08±0.21 in manual surgery arm; p=0.12) and had OCT-confirmed large sub-foveal haemorrhage secondary to age-related macular degeneration. The procedure, performed under local anaesthesia, was well tolerated by all participants and there were no adverse intraoperative events in either arm. Time taken to complete the subretinal injection was similar in both groups (mean 7.04±1.59 min in robot-assisted and 6.73±2.74 min in the manual surgery arm; p=0.935). Subretinal haemorrhage was successfully displaced at 1-month post surgery in all subjects except for one in the manual surgery arm who needed a repeat intravitreal tPA injection. Gain in visual acuity at 1 month was similar between the two arms (mean gain 0.79±0.34 in robot-assisted and 1.373±0.31 in manual; p=0.24).

Conclusions : This first in human study demonstrates the feasibility and safety of high precision robot-assisted subretinal drug delivery under local anaesthesia, simulating its potential future application in subretinal gene or cell therapy.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.