Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06347107 |
| Other study ID # |
S67215 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 2024 |
| Est. completion date |
December 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Universitaire Ziekenhuizen KU Leuven |
| Contact |
Peter Stalmans, MD PhD |
| Phone |
016340768 |
| Email |
peter.stalmans[@]uzleuven.be |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In the RoTIS study, the investigators would like to test the robotic stabilizer for the
subretinal injection of tPA in patients with subretinal hemorrhage during standard-of-care
surgery. The surgical devices used during this procedure will be the following:
- The robotic stabilizer (prototype - FAMHP approval received)
- 41G subretinal needle (CE marked - used within label)
- Inicio micro-injection system (CE marked - used within label) The Inicio system mounted
with the 41G needle will be held by the robot, and guided by the surgeon towards the
required position. When the tip of the needle is in the desired subretinal position, the
robotic stabilizer will be locked and the tPA will be injected till sufficient
subretinal bleb formation is obtained, with a maximal duration of up to 3 minutes.
As performed routinely, the surgical view through the microscope will be video-recorded and
while the injection is being administered, the built-in iOCT of the Artevo surgical
microscope (Zeiss, Oberkochen, Germany) will be used to scan the retina area around the
injection site to record the subretinal bleb formation for later review.
Description:
Age-related macular degeneration is a common disease in the elderly population. In the
atrophic form, central retinal degeneration leads to the formation of central metamorphopsia
or scotoma. In 10% of all cases, the atrophic form becomes proliferative, whereby newly
formed vessels grow under the macular area. Although this proliferation can be controlled in
most patients with intravitreal injections of anti-VEGF, in some cases a subretinal
hemorrhage occurs which causes a drastic drop in visual acuity.
Before anti-VEGF treatment existed, removal of the subretinal vessels followed by a macular
translocation or transplantation of retinal pigment epithelium cells was sometimes considered
in such cases when the second eye became affected 1,2.
Later on, when anti-VEGF and other growth inhibiting products became available (Macugen,
Lucentis, Avastin, Eylea, BeoVue), ophthalmologistsdeveloped a far less invasive surgically
technique to inject tPA subretinally into the blood clot using a 41G (0.11mm) subretinal
needle, followed by an air fill of the vitreous cavity to displace the subretinal liquefied
blood away from the macular area 3,4.
Since the causal neovascular vessels are not removed during this procedure, repeat injections
with anti-VEGF or analogue products are mandatory afterwards to reduce the risk of recurring
hemorrhage.
This surgical technique typically consists of a standard three-port pars plana vitrectomy,
induction of posterior vitreous detachment (if not already present), core and peripheral
vitrectomy (EVA Nexus surgical system, DORC, Zuidland The Netherlands). Macular detachment is
induced by subretinal injection of a balanced salt solution (BSS). The injection device is a
41G polyimide straight subretinal cannula with 27G shaft (DORC) connected to the Inicio
micro-injection system (DORC). The EVA Nexus surgical system, the 41G subretinal needle and
the Inicio micro-injection system used in this study are all CE-labeled devices and used
on-label.
This surgical technique has been previously described in the literature3,4 albeit performed
using older generations surgical systems, the Associate and EVA, respectively (DORC,
Zuidland, The Netherlands). In our department, such surgical procedure with subretinal
injection of tPA is performed about 25 times yearly.
More recently, gene therapy is being developed to treat several different congenital eye
diseases. In 2021, the first of such products became commercially available (Luxturna,
Novartis). All the gene therapy vehicles which are either already available or are being
developed have in common that they need to be precisely subretinally injected in a very small
volume. For Luxturna application, the standard-of-care is to manually hold the subretinal
needle into the subretinal space and to ask the surgical assistant to manually inject the
product under the retina while the surgeon holds still the subretinal needle. It does not
need to be explained that such surgical conditions are far from ideal to inject a product
that costs Eur 375 000 per dose.
A tool that would help the surgeon to eliminate hand-tremor and to hold still the subretinal
needle in the subretinal space would be very much welcomed as adjunct in this type of
surgery. There is a robotic system available with the CE-mark for intra-ocular surgery
(Preceyes, Eindhoven, The Netherlands, recently acquired by Zeiss, Oberkochen, Germany), but
this was developed as an aiding tool for intra-ocular membrane peeling. Other systems are
being developed but not yet commercially available (eg. Accusurgical, Montpellier, France or
Foresight Robotics, Yokn'am Illit, Israel).
In 2017, after more than 10 years of development, the investigators performed robot-assisted
retinal vein cannulation with injection of Ocriplasmin during vitrectomy surgery in 4
patients to treat central retinal vein occlusion (study S58782)5. For that study, a robotic
stabilizer was used that has two main functions while holding a surgical instrument:
- It removes high-frequency movements from the surgeons' hand thereby offering a
tremor-dampening feature.
- It can be locked when the tip of the instrument (needle) is in the desired position
allowing a prolonged injection of liquid (medication) over several minutes while the tip
remains in the same position It must be emphasized here that our robotic stabilizer is
used as a co-manipulation system: the surgical instrument is held by both the surgeon
and the robot, therefore guaranteeing that the surgeon has always has control and
override possibility. This in contrast with almost all other robots for eye surgery that
are available or under development which are tele-manipulating devices. In such device,
the surgeon holds joysticks to remotely control the robot that holds the surgical
instrument, similar to the Da Vinci system, the well-known robot for more general
surgery.
During that cannulation study, three devices were under investigation (not CE-labeled):
- The robotic stabilizer
- The study drug (Ocriplasmin - Jetrea)
- The (glass) needle to penetrate the occluded retinal vein In all four patients of trial
S58782, the investigators were able to successfully introduce the needle into the
occluded vessel, and to inject ocriplasmin for up to 9 minutes long while the robotic
stabilizer held the needle in the vessel5.
In the RoTIS study, the investigators would like to test the robotic stabilizer for the
subretinal injection of tPA in patients with subretinal hemorrhage during standard-of-care
surgery. The surgical devices used during this procedure will be the following:
- The robotic stabilizer (prototype - FAMHP approval received)
- 41G subretinal needle (CE marked - used within label)
- Inicio micro-injection system (CE marked - used within label) The Inicio system mounted
with the 41G needle will be held by the robot, and guided by the surgeon towards the
required position. When the tip of the needle is in the desired subretinal position, the
robotic stabilizer will be locked and the tPA will be injected till sufficient
subretinal bleb formation is obtained, with a maximal duration of up to 3 minutes.
As performed routinely, the surgical view through the microscope will be video-recorded and
while the injection is being administered, the built-in iOCT of the Artevo surgical
microscope (Zeiss, Oberkochen, Germany) will be used to scan the retina area around the
injection site to record the subretinal bleb formation for later review.
