A Wireless Pressure Sensor for Continuous Monitoring of Intraocular Pressure in Conscious Animals

Abstract

An important aspect of eye health in humans and animal models of human diseases is intraocular pressure (IOP). IOP is typically measured by hand with a tonometer, so data are sparse and sporadic and round-the-clock variations are not well characterized. Here we present a novel system for continuous wireless IOP and temperature measurement in small animals. The system consists of a cannula implanted in the anterior chamber of the eye connected to pressure sensing electronics that can be worn by rats or implanted in larger mammals. The system can record IOP with 0.3 mmHg accuracy and negligible drift at a rate of 0.25 Hz for 1-2 months on a regulated battery or indefinitely at rates up to 250 Hz via RF energy harvesting. Chronic recordings from conscious rats showed that IOP follows a diurnal rhythm, averaging 16.5 mmHg during the day and 21.7 mmHg at night, and that the IOP rhythm lags a diurnal rhythm in body temperature by 2.1 h. IOP and body temperature fluctuations were positively correlated from moment-to-moment as well. This technology allows researchers to monitor for the first time the precise IOP history of rat eyes, a popular model for glaucoma studies.

Keywords: Energy harvesting; Eye; Glaucoma; Rat; Telemetry; Wireless.

Figure 1.

IOP telemetry system. (A) Component illustration. a: cannula implanted in anterior chamber of eye, b: coupler affixed to skull, c: spring-encased tubing, d: pressure sensor electronics, e: vest on which sensor mounts. (B) Electronics diagram. IOP signal is conducted by the cannula to a pressure transducer, amplified, digitized by a microcontroller, and transmitted wirelessly with temperature data to a PC. The electronics are powered by two different circuits. For the BRS version of the system the powering circuitry is a regulated coin-cell battery. For the WPS version it consists of a RF antenna, RF harvester, and energy storage unit. (C) Picture of coupler affixed to a rat skull with screws. The cannula is inserted in the front port, the tubing is connected to the back port, and the coupler is covered in bone cement. (D) Picture of the wireless pressure sensor. The WPS version is shown but the BRS version has the same size and look. (E) Picture of an implanted rat outfitted with the BRS. (F) Illustration of the WPS setup. Two RF emitters atop the rat’s cage provide constant power to sensor electronics via the RF energy harvesting circuit. The BRS setup is the same without the RF emitters. IOP data from up to 8 rats can be sent wirelessly via Bluetooth to a nearby PC.

Figure 2.

Telemetry system powering. Constant hydrostatic pressure of 40 mmHg was applied to the system powered by: (A) unregulated 3V battery [BUS], (B) circuit-regulated 3V battery [BRS], and (C) wireless energy harvesting circuit [WPS]. Stored voltage (top) and pressure sensor output (bottom) of the system were recorded every 4 sec for several weeks. Linear regression of pressure data in B and C gave an offset of 40.1 and 40.4 mmHg and a slope of 0.119 and 0.002 mmHg/week, respectively. Crosses indicate battery failure and system shut down, which happened at 39 days in A and 30 days in B. The shutdown time depends on data collection rate. Batteryless system in C harvests energy from an external plugged-in RF emitter (height = 20 cm) and only shuts down if stored voltage falls below a minimum level (dashed line) needed for circuit operation.

Figure 3.

Power transfer characteristics of WPS. (A) Power consumption profile during collection of one IOP and temperature measurement, given by the average of 20 readings in a 0.4 s period. (B) Consumption profile during wireless transmission of IOP and temperature data. (C) Map of minimum power reception level of the WPS across space with RF emitters centered 20 cm above. Thick line outlines the cage walls. (D) Map of maximum power reception level of the WPS with RF emitters in the same location. (E) Stored voltage level over a 2-week period with the system on an awake behaving rat. IOP data were collected every 4 s during the recording. Figure inset shows a 7-min segment of the voltage record. Dashed line marks the minimum voltage level needed to run system.

Figure 4.

System properties in live animals. (A) Pressure measured by the wireless sensor as IOP of an anesthetized rat was stepped to different levels by manometry via a needle inserted in the eye. Solid line is a linear regression fit of the data (n=3). (B) Pressure recorded by the wireless sensor over a 48-hr period in an awake behaving animal (rat j29). (C) Pressure record from the same animal in B after cutting the cannula outside the eye and opening it to air. Residual variations in the pressure record reflect hydrodynamic changes caused by head elevation and rotation. (D) Autocorrelation of the pressure signals in B (black) and C (grey). Bar marks ±30 min interval during which signals show strong positive correlation.

Figure 5.

Round-the-clock IOP recording in awake behaving rats. (A) Smoothed IOP record obtained with the telemetry system from an animal implanted over a month (rat j26). (B) IOP of the implanted (solid circles) and non-implanted (open circles) eye measured by tonometry from animal in A. Error bars give SD of 6 tonometry measurements. (C) Comparison of mean tonometer and telemetry data while tonometry data were collected (R = 0.5). (D, E) Smoothed IOP records from animal eyes that exhibited little temporal patterning (rat j22) and pronounced rhythmicity (rat j39), respectively

Figure 6.

Circadian IOP rhythm in rats. (A) Raw (thin line) and smoothed (thick line) IOP record over a 24-hr period from an awake behaving animal (rat j18) (B) Average IOP rhythm in one-hour bins (n = 7 days). Grey and black bars in A and B indicate timing of light-dark cycle to which the animal was exposed. (C) Average IOP during day (grey) and night (black) phases of the light-dark cycle for all implanted animals. Asterisks indicate daytime and nighttime IOP levels that differed significantly.

Figure 7.

Temperature measurements with the telemetry system. (A) Calibration data relating system sensor readings (T_sensor) to core body temperature (T_body) measured with a rectal thermometer from anesthetized rats outfitted with the system. Bars give standard deviation. (B,C) Temperature data recorded over two weeks from conscious rats by the BRS and WPS. Data were calibrated as shown in A to estimate body temperature (T*_body). Bars indicate times when the rat was briefly anesthetized. (D) Auto-correlation of temperature record in C (rat j18). Grey line is sinewave fit to data (amplitude: 0.18, period: 24.64, phase: 1.57). (E) Cross-correlation of temperature record with IOP record of the same rat. Grey line gives correlation with randomly shuffled IOP record. (F) Cross-correlation data in E expanded in time scale. Positive lag corresponds to a lead in temperature.