Stanford Advisors


All Publications


  • Development of a novel SupraChoroidal-to-Optic-NervE (SCONE) drug delivery system. Drug delivery Chiang, B., Heng, K., Jang, K., Dalal, R., Liao, Y. J., Myung, D., Goldberg, J. L. 2024; 31 (1): 2379369

    Abstract

    Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique.Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo.Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye.SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies.Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies.

    View details for DOI 10.1080/10717544.2024.2379369

    View details for PubMedID 39010743

  • Photoactivated growth factor release from bio-orthogonally crosslinked hydrogels for the regeneration of corneal defects. Bioactive materials Kang, N., Seo, Y. A., Jackson, K. J., Jang, K., Song, E., Han, U., Chen, F., Heilshorn, S. C., Myung, D. 2024; 40: 417-429

    Abstract

    In situ-forming hydrogels are an attractive option for corneal regeneration, and the delivery of growth factors from such constructs have the potential to improve re-epithelialization and stromal remodeling. However, challenges persist in controlling the release of therapeutic molecules from hydrogels. Here, an in situ-forming bio-orthogonally crosslinked hydrogel containing growth factors tethered via photocleavable linkages (PC-HACol hydrogel) was developed to accelerate corneal regeneration. Epidermal growth factor (EGF) was conjugated to the hydrogel backbone through photo-cleavable (PC) spacer arms and was released when exposed to mild intensity ultraviolet (UV) light (2-5mW/cm2, 365nm). The PC-HACol hydrogel rapidly gelled within a few minutes when applied to corneal defects, with excellent transparency and biocompatibility. After subsequent exposure to UV irradiation, the hydrogel promoted the proliferation and migration of corneal epithelial cells in vitro. The rate of re-epithelialization was positively correlated to the frequency of irradiation, verified through ex vivo rabbit cornea organ culture studies. In an in vivo rat corneal wound healing study, the PC-HACol hydrogel exposed to UV light significantly promoted re-epithelialization, the remodeling of stromal layers, and exhibited significant anti-scarring effects, with minimal alpha-SMA and robust ALDH3A1 expression. Normal differentiation of the regenerated epithelia after healing was evaluated by expression of the corneal epithelial biomarker, CK12. The remodeled cornea exhibited full recovery of corneal thickness and layer number without hyperplasia of the epithelium.

    View details for DOI 10.1016/j.bioactmat.2024.05.045

    View details for PubMedID 39022184

  • Design and ex vivo development of a suprachoroidal spacer implant to treat glaucoma. Research square Chiang, B., Jang, K., Goldberg, J., Myung, D. 2024

    Abstract

    Glaucoma is a leading cause of visual impairment and blindness in the United States and worldwide. Elevated intraocular pressure (IOP) has been identified as the only modifiable risk factor in glaucoma, and there exists a need for a glaucoma procedure that is safe, efficacious, and can be performed in the outpatient clinic setting. Suprachoroidal expansion has been explored as a method to lower IOP previously. The purpose of this work was to design a monolithic hydrogel implant that would not clear or degrade to potentially achieve long term (possibly permanent) IOP reduction. Here, we developed and showed ex vivo testing of a novel photo-crosslinked polyethylene glycol (PEG) suprachoroidal spacer implant delivered via a custom-designed injector system. We optimized the composition, shape, and mechanics of the implant to be suitable for implantation with the suprachoroidal space. We developed a microneedle injector system to deliver this implant. We showed precise control over implant location and volume occupied within the suprachoroidal space. Further preclinical testing is needed to demonstrate efficacy.

    View details for DOI 10.21203/rs.3.rs-3895533/v1

    View details for PubMedID 38352508