Advantages of robotic assistance over a manual approach in simulated subretinal injections and its relevance for gene therapy
Open accessAbstract
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.
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Several lines of evidence indicate that current available surgical techniques may not be sufficient and reliable.
“Several lines of evidence indicate that this may not be the case (7–9).”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
Recent advances in imaging and robotics can overcome the limitations listed above.
“Recent advances in imaging and robotics can overcome the limitations listed above (7, 22).”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
In simulated subretinal injections, the ability to hold the instrument steadily at the point of insertion deviated 40-266 μm manually depending on the individual surgeon, versus 1-2 μm with robotic assistance.
“The ability to hold the instrument steadily at the point of insertion ranged from 40 to 266 μm, depending on the individual surgeon, when surgeries were performed manually as compared to, 1–2 μm with robotic assistance”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
In simulated subretinal injections performed by vitreoretinal surgeons who had never used the Preceyes surgical system, a bleb was created more frequently with robotic assistance than manually (88% vs 44%).
“A bleb was created more frequently with the use of the PSS (88 vs. 44%)”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
In the same simulated subretinal injection model lacking elastic tissue, the rate and severity of reflux were reduced with robotic assistance compared with manual injection (77% vs 88%).
“with a reduction in the rate and severity of reflux (77 vs. 88%) was observed in this model that lacked any elastic tissue.”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
Use of the robotic arm led to a longer infusion time (13-108 s) than manual injections (18-85 s) in simulated subretinal injections.
“The use of the robotic arm also led to a longer “infusion time” ranging from 13 to 108 s, while the injections performed manually ranged from 18 to 85 s.”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
Tremor was reduced when using the robot in simulated subretinal injections.
“Tremor was clearly reduced (Supplementary Video 1) when using the robot.”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
Robotic assistance reduces variability in simulated subretinal injections, as shown in an experiment with retinal surgeons of various skill levels.
“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).”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [7]
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- Authors
- Ladha, R., Meenink, T., Smit, J., & de Smet, M. D.
- Affiliations
- Université Libre de Bruxelles (BE)
- Corresponding author
- Ladha, Reza
- Venue
- Gene Therapy
- Published
- 2021-05-17
- Volume
- 30
- Issue
- 3-4
- Pages
- 264-270
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC10113148
- OpenAlex
- W3163477925
- Cited by
- 42
- References
- 25
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 1
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Gene Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, cc-by)
- Funders
- Carl Zeiss Meditec AG
- Allergan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- subretinal injection, robotic surgical assistance, bleb formation, intraoperative optical coherence tomography, retinal gene delivery
- MeSH terms
- Humans, Retina, Tremor, Genetic Therapy, Retinal Pigment Epithelium, Robotic Surgical Procedures
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