Suprachoroidal Injection of Triamcinolone Acetonide, CLS-Ta, for Macular Edema Due to Noninfectious Uveitis

Yeh, Steven; Kurup, Shree K.; Wang, Robert C.; Foster, C. Stephen; Noronha, Glenn; Nguyen, Quan Dong; Diana, V.; Team, Dogwood Study

doi:10.1097/iae.0000000000002279

Cited by 63 publications

(38 citation statements)

References 22 publications

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“…Number 11 November 2019 ocular section from posterior retina in the quadrant the injection was done showed colocalization of fluorescence and anti-GFP staining in RPE and photoreceptor inner and outer segments and cell bodies ( Figure 5G). There was also a small region of GFP expression in the inner retina.…”

Section: Volume 129 Number 11mentioning

confidence: 99%

“…Most small molecules have a half-life of a few hours in the suprachoroidal space, but lipophilic molecules such as triamcinolone acetonide form precipitates that dissolve slowly, providing sustained delivery to the retina (9,10). Clinical trials have demonstrated prolonged improvement in macular edema in multiple disease processes after suprachoroidal injection of triamcinolone acetonide (11,12). In this study, we investigated the potential value of suprachoroidal injection of AAV8 vectors for ocular gene transfer.…”

Section: Introductionmentioning

confidence: 99%

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AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

Ding¹,

Shen²,

Hafiz³

et al. 2019

Journal of Clinical Investigation

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There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, the preferred route of delivery for most applications, requires a surgical procedure that has risks. Herein we report a novel gene therapy delivery approach, suprachoroidal injection of AAV8 vectors, which is less invasive and could be done in an outpatient setting. Two weeks after suprachoroidal injection of AAV8.GFP in rats, GFP fluorescence covered 18.9% of RPE flat mounts and extended entirely around sagittal and transverse sections in RPE and photoreceptors. After 2 suprachoroidal injections of AAV8.GFP, GFP fluorescence covered 30.5% of RPE flat mounts. Similarly, widespread expression of GFP occurred in nonhuman primate and pig eyes after suprachoroidal injection of AAV8. GFP. Compared with subretinal injection in rats of RGX-314, an AAV8 vector expressing an anti-VEGF Fab, suprachoroidal injection of the same dose of RGX-314 resulted in similar expression of anti-VEGF Fab and similar suppression of VEGFinduced vascular leakage. Suprachoroidal AAV8 vector injection provides a noninvasive outpatient procedure to obtain widespread transgene expression in retina and RPE.

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Section: Volume 129 Number 11mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

Ding¹,

Shen²,

Hafiz³

et al. 2019

Journal of Clinical Investigation

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“…Fluorescently labeled particles injected near the limbus flow circumferentially around the eye, resulting in a broad area of exposure ( 22 ). Suprachoroidal injection of triamcinolone acetonide results in sustained anti-inflammatory effects in the retina ( 22 , 23 ) and prolonged improvements in macular edema in patients with uveitis or retinal vein occlusion ( 24 , 25 ). We have recently demonstrated that suprachoroidal injection of AAV8.GFP, an AAV8-expressing green fluorescent protein (GFP), results in widespread expression of GFP in RPE cells and photoreceptors ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Suprachoroidal gene transfer with nonviral nanoparticles

et al. 2020

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Subretinal injections of viral vectors provide great benefits but have limited cargo capacity; they induce innate and adaptive immune responses, which may cause damage and preclude repeated injections; and they pose administration risks. As a new biotechnology, suprachoroidal injections of biodegradable nanoparticles (NPs) containing a reporter plasmid induce reporter expression in rat photoreceptors and RPE throughout the entire eye and maintain expression for at least 8 months. Multiple injections markedly increase expression. Suprachoroidal injection of NPs containing a VEGF expression plasmid caused severe subretinal neovascularization progressing to subretinal fibrosis, similar to what occurs in untreated patients with neovascular age-related macular degeneration, providing a new model and proof of concept for level and duration of expression. Suprachoroidal injection of NPs containing a VEGF-binding protein expression plasmid significantly suppressed VEGF-induced vascular leakage and neovascularization demonstrating therapeutic potential. These data suggest that nonviral NP suprachoroidal gene transfer may provide a noninvasive, repeatable alternative to subretinal injection of viral vectors.

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“…Complications were mild, with one eye experiencing a transient intraocular pressure elevation at 3 months postprocedure and two eyes had an apparent increase in pre-existing nuclear sclerotic cataract. 60 The results of a phase II study to evaluate suprachoroidal injection of triamcinolone acetonide suspension in patients with macular oedema due to non-infectious uveitis (NCT02255032) were recently published with good tolerability and significantly improved VA. 61 gene TherAPIes for nAMd Gene therapy holds the potential to continuously express therapeutic levels of angiostatic proteins. The completed and ongoing gene therapy trials for nAMD are summarised in table 1 and discussed in detail in the following sections.…”

Section: Routes Of Vector Deliverymentioning

confidence: 99%

Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions

et al. 2020

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Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the developed world. Antivascular endothelial growth factor therapy has transformed the management and outcome of neovascular AMD (nAMD), although the need for repeated intravitreal injections—even lifelong—and the related complications, high drug costs, frequent clinic visits and repeated imaging have resulted in an enormous burden both to healthcare systems and patients. The application of gene therapy approaches for sustained delivery of a range of antiangiogenic proteins has the promise of helping to address these aforementioned challenges. A number of early phase clinical trials of gene therapy in nAMD have provided encouraging results, with many more ongoing or anticipated. There remain significant areas of controversy, including regarding the optimal treatment targets, routes of administration and potential safety concerns. In this review we aim to provide an update of the current status of gene therapy for nAMD and briefly discuss future prospects.

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Suprachoroidal Injection of Triamcinolone Acetonide, CLS-Ta, for Macular Edema Due to Noninfectious Uveitis

Abstract: A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

Cited by 63 publications

References 22 publications

AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

Suprachoroidal gene transfer with nonviral nanoparticles

Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions

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