Nanoarray-Enhanced Micromechanical Pressure Sensor with Remote Optical Readout

We demonstrate a compact implantable intraocular pressure (IOP) sensor with remote optical readout for glaucoma research and patient management. Using non-invasive white light, we excite the sensor’s pressure-sensitive optomechanical cavity and detect the reflected light, whose optical signature changes as a function of IOP. The sensor has provided robust measurements of hydrostatic pressure between 10-60 mmHg with an accuracy of 0.15 mmHg

Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo IOP monitoring. The ANN converts captured optical spectra into corresponding IOP levels. We achieved an IOP-measurement accuracy of ±0.1 mmHg at a measurement rate of 100 Hz, which represents a ten-fold improvement from previously reported values. This technique allowed real-time tracking of artificially induced sub-1 s transient IOP elevations and minor fluctuations induced by the respiratory motion of the rabbits during in vivo monitoring. All in vivo sensor readings paralleled those obtained concurrently using a commercial tonometer and showed consistency within ±2 mmHg. Real-time processing is highly useful for IOP monitoring in clinical settings and home environments and improves the overall practicality of the optical IOP-monitoring approach

Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo IOP monitoring. The ANN converts captured optical spectra into corresponding IOP levels. We achieved an IOP-measurement accuracy of ±0.1 mmHg at a measurement rate of 100 Hz, which represents a ten-fold improvement from previously reported values. This technique allowed real-time tracking of artificially induced sub-1 s transient IOP elevations and minor fluctuations induced by the respiratory motion of the rabbits during in vivo monitoring. All in vivo sensor readings paralleled those obtained concurrently using a commercial tonometer and showed consistency within ±2 mmHg. Real-time processing is highly useful for IOP monitoring in clinical settings and home environments and improves the overall practicality of the optical IOP-monitoring approach

In Vivo Intraocular Pressure Measurements Using A Miniaturized Nano-Photonic Sensor Implant

Purpose : We have been developing a nanophotonic pressure sensor whose optical resonance is directly related to intraocular pressure (IOP). Bench testing has demonstrated sensor near-infrared (NIR) reflectance to accurately track pressures from 0-50 mmHg. The current study examined sensor performance following implantation into rabbit eyes for up to one month

A microscale optical implant for continuous in vivo monitoring of intraocular pressure

Intraocular pressure (IOP) is a key clinical parameter in glaucoma management. However, despite the potential utility of daily measurements of IOP in the context of disease management, the necessary tools are currently lacking, and IOP is typically measured only a few times a year. Here we report on a microscale implantable sensor that could provide convenient, accurate, on-demand IOP monitoring in the home environment. When excited by broadband near-infrared (NIR) light from a tungsten bulb, the sensor’s optical cavity reflects a pressure-dependent resonance signature that can be converted to IOP. NIR light is minimally absorbed by tissue and is not perceived visually. The sensor’s nanodot-enhanced cavity allows for a 3–5 cm readout distance with an average accuracy of 0.29 mm Hg over the range of 0–40 mm Hg. Sensors were mounted onto intraocular lenses or silicone haptics and secured inside the anterior chamber in New Zealand white rabbits. Implanted sensors provided continuous in vivo tracking of short-term transient IOP elevations and provided continuous measurements of IOP for up to 4.5 months

Biocompatible Multifunctional Black-Silicon for Implantable Intraocular Sensor

Multifunctional black-silicon (b-Si) integrated on the surface of an implantable intraocular pressure sensor significantly improves sensor performance and reliability in six-month in vivo studies. The antireflective properties of b-Si triples the signal-to-noise ratio and increases the optical readout distance to a clinically viable 12 cm. Tissue growth and inflammation response on the sensor is suppressed demonstrating desirable anti-biofouling properties

Biocompatible Multifunctional Black-Silicon for Implantable Intraocular Sensor

Multifunctional black-silicon (b-Si) integrated on the surface of an implantable intraocular pressure sensor significantly improves sensor performance and reliability in six-month in vivo studies. The antireflective properties of b-Si triples the signal-to-noise ratio and increases the optical readout distance to a clinically viable 12 cm. Tissue growth and inflammation response on the sensor is suppressed demonstrating desirable anti-biofouling properties

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices

Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si3_N_4 substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices

Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si3_N_4 substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation

Ectopic Vesicular Glutamate Release at the Optic Nerve Head and Axon Loss in Mouse Experimental Glaucoma

Although clinical and experimental observations indicate that the optic nerve head (ONH) is a major site of axon degeneration in glaucoma, the mechanisms by which local retinal ganglion cell (RGC) axons are injured and damage spreads among axons remain poorly defined. Using a laser-induced ocular hypertension (LIOH) mouse model of glaucoma, we found that within 48 h of intraocular pressure elevation, RGC axon segments within the ONH exhibited ectopic accumulation and colocalization of multiple components of the glutamatergic presynaptic machinery including the vesicular glutamate transporter VGLUT2, several synaptic vesicle marker proteins, glutamate, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex and active zone cytomatrix components, as well as ultrastructurally identified, synaptophysin-containing vesicles. Ectopic vesicle exocytosis and glutamate release were detected in acute preparations of the LIOH ONH. Immunolocalization and analysis using the ionotropic receptor channel-permeant cation agmatine indicated that ONH axon segments and glia expressed glutamate receptors, and these receptors were more active after LIOH compared with controls. Pharmacological antagonism of glutamate receptors and neuronal activity resulted in increased RGC axon sparing in vivo. Furthermore, in vivo RGC-specific genetic disruption of the vesicular glutamate transporter VGLUT2 or the obligatory NMDA receptor subunit NR1 promoted axon survival in experimental glaucoma. As the inhibition of ectopic glutamate vesicular release or glutamate receptivity can independently modify the severity of RGC axon loss, synaptic release mechanisms may provide useful therapeutic entry points into glaucomatous axon degeneration