IOP Reduction in Nonhuman Primates by Microneedle Injection of Drug-Free Hydrogel to Expand the Suprachoroidal Space.

Purpose: Expansion of the suprachoroidal space (SCS) by a hydrogel injection has been shown to reduce intraocular pressure (IOP) in rabbits as a potential treatment for ocular hypertension in glaucoma. Here, we evaluate the safety and efficacy of this approach in hypertensive and normotensive eyes in nonhuman primates. Methods: A microneedle was used to inject a hyaluronic acid-based hydrogel or saline solution (control) into the SCS of cynomolgus monkey eyes that were either normotensive (n = 7 experimental; n = 2 control eyes) or had induced ocular hypertension (n = 6 experimental; n = 3 control eyes). IOP and the degree of SCS expansion were monitored over time by tonometry and ultrasound biomicroscopy, respectively. Safety was evaluated through slit lamp, fundus, and histology examinations. Results: In hypertensive eyes, SCS injection with hydrogel initially reduced IOP by 47.5 ± 16.7%, and IOP returned to baseline in 38 days. In normotensive eyes, hydrogel injection initially reduced IOP by 38.8 ± 8.1% and IOP gradually returned to baseline also in 39 days. Sham injections resulted in mild IOP reduction in hypertensive eyes and normotensive eyes. The hydrogel injections were well tolerated by clinical assessments. Conclusions: IOP was reduced in nonhuman primates for over one month by sustained SCS expansion. This procedure was safe and simple to perform. These data confirm the translational potential of this treatment method. Further optimization of the hydrogel may provide longer durations of IOP reduction. Translational Relevance: A microneedle injection of hydrogel into the suprachoroidal space may provide a non-surgical, non-pharmacologic treatment for ocular hypertension in glaucoma patients.

Compact dual-mode diffuse optical system for blood perfusion monitoring in a porcine model of microvascular tissue flaps.

In reconstructive surgery, the ability to detect blood flow interruptions to grafted tissue represents a critical step in preventing postsurgical complications. We have developed and pilot tested a compact, fiber-based device that combines two complimentary modalities-diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy-to quantitatively monitor blood perfusion. We present a proof-of-concept study on an in vivo porcine model (n=8). With a controllable arterial blood flow supply, occlusion studies (n=4) were performed on surgically isolated free flaps while the device simultaneously monitored blood flow through the supplying artery as well as flap perfusion from three orientations: the distal side of the flap and two transdermal channels. Further studies featuring long-term monitoring, arterial failure simulations, and venous failure simulations were performed on flaps that had undergone an anastomosis procedure (n=4). Additionally, benchtop verification of the DCS system was performed on liquid flow phantoms. Data revealed relationships between diffuse optical measures and state of occlusion as well as the ability to detect arterial and venous compromise. The compact construction of the device, along with its noninvasive and quantitative nature, would make this technology suitable for clinical translation.

Novel diffuse optics system for continuous tissue viability monitoring - extended recovery in vivo testing in a porcine flap model.

In reconstructive surgery, tissue perfusion/vessel patency is critical to the success of microvascular free tissue flaps. Early detection of flap failure secondary to compromise of vascular perfusion would significantly increase the chances of flap salvage. We have developed a compact, clinically-compatible monitoring system to enable automated, minimally-invasive, continuous, and quantitative assessment of flap viability/perfusion. We tested the system's continuous monitoring capability during extended non-recovery surgery using an in vivo porcine free flap model. Initial results indicated that the system could assess flap viability/perfusion in a quantitative and continuous manner. With proven performance, the compact form constructed with cost-effective components would make this system suitable for clinical translation.

In vivo preclinical verification of a multimodal diffuse reflectance and correlation spectroscopy system for sensing tissue perfusion.

In reconstructive surgery, impeded blood flow in microvascular free flaps due to a compromise in arterial or venous patency secondary to blood clots or vessel spasms can rapidly result in flap failures. Thus, the ability to detect changes in microvascular free flaps is critical. In this paper, we report progress on in vivo pre-clinical testing of a compact, multimodal, fiber-based diffuse correlation and reflectance spectroscopy system designed to quantitatively monitor tissue perfusion in a porcine model's surgically-grafted free flap. We also describe the device's sensitivity to incremental blood flow changes and discuss the prospects for continuous perfusion monitoring in future clinical translational studies.

Design verification of a compact system for detecting tissue perfusion using bimodal diffuse optical technologies.

It is essential to monitor tissue perfusion during and after reconstructive surgery, as restricted blood flow can result in graft failures. Current clinical procedures are insufficient to monitor tissue perfusion, as they are intermittent and often subjective. To address this unmet clinical need, a compact, low-cost, multimodal diffuse correlation spectroscopy and diffuse reflectance spectroscopy system was developed. We verified system performance via tissue phantoms and experimental protocols for rigorous bench testing. Quantitative data analysis methods were employed and tested to enable the extraction of tissue perfusion parameters. This design verification study assures data integrity in future in vivo studies.