Safety and Efficacy of Supersaturated Oxygen Emulsion (SSOE) as a Novel Topical Treatment in Open Globe Injury
Abstract
Rationale: As a most severe form of ocular trauma, open globe injury is a full thickness wound to the wall of the eye, leading to a ruptured globe. It is a common cause leading to profound and intractable visual impairment, both in military actions and civilian society worldwide. On the battlefield, about 80% of eye injuries are related to explosive blast, which often causes the devastating globe penetration along with the devastating injury to the retina (the film layer of the eye in the back that is critical to visual function). Open globe injury has been demonstrated as an independent, significant risk factor for severe visual acuity loss in active American Service Members. The current standard of care for open globe injury is prompt surgical intervention to preserve ocular tissues, which on the battlefield is often delayed or impossible until evacuation. Such delay from injury to repair can negatively impact final visual outcome and result in permanent vision loss. Even with early surgical intervention, the management of OGI remains a challenge, as surgery itself does not prevent the serious complication of intraocular scarring, termed proliferative vitreoretinopathy (PVR), and instead surgical intervention can promote the development of PVR. Currently, there is no approved therapy to effectively prevent PVR. Military studies on U.S. Service Members showed significantly worse final visual acuity in ocular injuries with development of PVR as compared to those without PVR. Therefore, a safe and effective therapeutic deliverable at the time of injury without any delay to promote wound-healing and prevent PVR formation has the potential to change the current standard of care for open globe injury. It is well-recognized that injury frequently causes localized insufficient oxygen supply relative to body demand (hypoxia) within the wound, which can propagate secondary tissue damage and impair wound healing process. Thus, restoration of local normal oxygen levels at the injury site to meet the energy-generating demand can help to preserve tissues and promote wound repair. In addition, hypoxia can promote excessive inflammation and drive retinal cells to abnormally transform into scar-forming cells (a process known as epithelial-mesenchymal transformation, EMT), both are the most critical mechanisms underlying trauma-induced PVR. Importantly, our preliminary study demonstrates extensive hypoxia within the injured eye in a mouse model of open globe injury. We thus propose to test the effect of optimized local oxygen supplementation at the time of injury in preserving ocular tissues and preventing PVR after open globe injury, using our recently developed technology Supersaturated Oxygen Emulsion (SSOE), which is a portable and biocompatible emulsion, stable in storage and transport, and can be directly dispensed to the eye without the need for additional tools or trained medical skills, providing immediate and constant oxygen supply to the wound at a physiological level close to that inside the normal eye. Our initial testing on SSOE has shown biocompatibility with mouse ocular tissues, and inhibition on excessive inflammation and scar formation, as summarized in the application. Objectives: In this proposal, we will establish the full safety profiles of SSOE in ophthalmic application and determine the therapeutic potential of SSOE in mitigating open globe injury. Aims: We will test the product s biocompatibility with human-derived eye cells grown outside the body, and evaluate toxicity on visual function in live animals. Next, we will mimic the EMT process using human retinal cells grown outside the body and evaluate the inhibitory effect of SSOE on the human cell models. Lastly, we will mimic open globe injury in animals and apply SSOE to their eyes right after injury to determine how SSOE preserves eye tissues and prevents PVR development. Expected Outcomes and Impact: When the proposal is compl
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210889
Entities
People
- Yihe Chen
Organizations
- Schepens Eye Research Institute
- United States Army