Injection pressure levels for creating blebs during subretinal gene therapy

Scruggs, Brittni A.; Vasconcelos, Huber; Palma, Mariana Matioli da; Kogachi, Katie; Pennesi, Mark E.; Yang, Paul; Bailey, Steven T.; Lauer, Andreas K.

doi:10.1038/s41434-021-00294-2

Cited by 10 publications

(13 citation statements)

References 13 publications

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“…This is the first report in humans to thoroughly analyze the behavior of subretinal bleb formation from a TSI approach for gene augmentation therapy intending to treat the macula. 12,13 Although multiple factors were analyzed, the proximity of the retinotomy to the fovea was the most important modifiable predictor of whether the bleb would reach the fovea. Surprisingly, the direction of the subretinal cannula and its associated fluid wave did not predict bleb propagation, except when cannula entry was nearly tangential.…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Bleb Behavior in Subretinal Gene Augmentation Therapy for Inherited Retinal Diseases

Sisk¹,

Berger

Williams

et al. 2023

Retina

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Purpose: In subretinal gene therapy for inherited retinal diseases (IRDs), blebs may not propagate predictably in the direction of the injection cannula. We evaluated factors that influenced bleb propagation among various IRDs. Methods: Retrospective review of all subretinal gene therapy procedures performed by a single surgeon between September 2018 and March 2020 for various IRDs. Main outcome measures were directional bias of bleb propagation and intraoperative foveal detachment. Results: Desired injection volumes and/or foveal treatment were successfully achieved in all 70 eyes of 46 patients with IRD regardless of IRD indication. Bullous foveal detachment was associated with retinotomy closer to the fovea, posterior bleb bias, and greater bleb volumes (P < 0.01). Blebs biased anteriorly or posteriorly based on disease indication (P = 0.04) and age (P < 0.001). Retinotomy location ≤ 3.7 mm (approximately two disk diameters) from the fovea favored foveal detachment (P < 0.001). Multiple retinotomies and blebs allowed greater surface area coverage in some eyes, but intersecting blebs did not propagate further. Conclusion: Bleb formation and propagation are predictable based on patient age, retinotomy location, disease indication, and how tangentially fluid is directed into the subretinal space.

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Section: Discussionmentioning

confidence: 99%

Intraoperative Bleb Behavior in Subretinal Gene Augmentation Therapy for Inherited Retinal Diseases

Sisk¹,

Berger

Williams

et al. 2023

Retina

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“…The injection pressure is then set on the machine, more commonly between 12–18 psi [ 15 , 16 ]. Younger patients may require higher infusion pressures during creation of the pre-bleb [ 21 ]. The identification of the optimal injection pressure is crucial for the safety of this technique as both low and high injection pressure may be associated with mechanical RPE/retinal damage due to a prolonged permanence of the needle in the subretinal space and the high flow generated, respectively [ 22 ].…”

Section: Subretinal Injection For Gene Therapymentioning

confidence: 99%

“…In this regard, a recent study on porcine eyes in vivo reported that injection pressure up to 24 psi might be safe, resulting in minimal retinal damage and no functional changes on the multifocal electroretinogram [ 22 ]. To note, the injection pressure to initiate the bleb formation is higher than that required for the bleb propagation [ 21 ]. The infusion pressure of the vitrectomy machine is lowered to 10 mmHg to allow for a smooth subretinal injection.…”

Section: Subretinal Injection For Gene Therapymentioning

confidence: 99%

The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications

Tripepi

Jalil

Ally

et al. 2023

IJMS

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Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.

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“…Statistical hypothesis testing and linear regression models are widely utilised in analysing the correlation between surgical parameters, conditions, and outcomes 15,16 . For SRI, the relationship between age and injection pressure has been found and modelled to assist surgeons in determining a better surgical setup 17 . However, establishing a comprehensive predictive model for bleb formation in SRI requires precise control of experimental variables and a large collection of experimental results.…”

Section: Introductionmentioning

confidence: 99%

“…15,16 For SRI, the relationship between age and injection pressure has been found and modelled to assist surgeons in determining a better surgical setup. 17 However, establishing a comprehensive predictive model for bleb formation in SRI requires precise control of experimental variables and a large collection of experimental results. To achieve this, we utilised the intraOcular RoBotic Interventional System (iORBIS), a state-of-theart robotic system recently developed by Chen et al 18 The iORBIS provides exceptional motion resolution of 0.49 μm for instrument insertion and retraction and an attitude error of less than 0.1°.…”

mentioning

confidence: 99%

Analysis on key parameters in subretinal injection facilitating a predictable and automated robot‐assisted treatment in gene therapy

Huang

Yang

Chen

et al. 2023

Robotics Computer Surgery

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BackgroundSubretinal injection (SRI) has become an important surgical method for treating vitreoretinal diseases. Nevertheless, the optimisation of bleb formation in SRI, for the attainment of desired therapeutic outcomes, still requires further investigation.MethodsThis study analysed the influence of surgical parameters on SRI using a robotic setup. The surgical procedure was automated using visual guidance. A predictive model for bleb formation was established through regression analysis. To validate the model, we compared the clinical data's target area with the simulated SRI's actual area using parameters determined by the predictive model.ResultsThe insertion angle dominated the eccentricity and area of the bleb. The injection speed dominated the axial angle. Automated SRI increased success rate and produced predictable outcomes.ConclusionsWe could provide accurate SRI on phantom models by adjusting surgical parameters based on the patient's clinical information. Automatic robot‐assisted SRI is a promising surgical technique with highly predictable results.

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Injection pressure levels for creating blebs during subretinal gene therapy

Cited by 10 publications

References 13 publications

Intraoperative Bleb Behavior in Subretinal Gene Augmentation Therapy for Inherited Retinal Diseases

Intraoperative Bleb Behavior in Subretinal Gene Augmentation Therapy for Inherited Retinal Diseases

The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications

Analysis on key parameters in subretinal injection facilitating a predictable and automated robot‐assisted treatment in gene therapy

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