Implantable Telemetry Advances Glaucoma Research
Contrasting methods for measuring intraocular pressure, developed independently in the US and Europe, lead to equally effective animal models for studying glaucoma
Accurate measurements of intraocular pressure (IOP) provide valuable information for researchers involved with glaucoma research. Christian Schnell and collaborators at Ciba Vision Ophthalmics in Basel Switzerland and Jay McLaren and collaborators at the Mayo Clinic in Rochester, MN USA independently developed techniques for monitoring (IOP) via telemetry in conscious, unrestrained rabbits.
Although several methods have been employed over the years to measure IOP, pneumatonometry (a technique involving placing a small sensor in direct contact with the eye) is currently the most commonly used for measuring IOP in animals in pharmacology and eye research. The main disadvantages of this method are that the animals must be restrained, human intervention is necessary during the measurements and the probe must contact the cornea. Therefore, a local anesthetic must be topically administered before IOP readings are obtained. The anesthesia may interfere with the activity or absorption pattern of the drug being tested. It is well known that contact with the probe increases IOP during the measurements. Indeed, McLaren et al. demonstrated this effect in their research.
The use of telemetry in research provides several benefits compared to conventional methods for monitoring IOP. Artifacts caused by restraint, local anesthesia, and human investigator intervention are eliminated. In addition, the animals are unaware that they are being monitored and they can stay in their normal environment during collection of data. With telemetry, measurements are continuous, can be obtained throughout the day, and can be performed with open or closed eyelids. By using implanted telemetry the authors were, for the first time, able to identify and quantify a clear circadian pattern of variation in IOP as well as light-induced changes in circadian phase. IOP increased after the lights were turned off and decreased after they were turned on.
Both groups of researchers adapted the DSI PA-C40 implant, originally designed for blood pressure measurements in small animals, to record IOP in freely moving rabbits. However, they followed significantly different approaches. Schnell et al. Employed a method based on an implantation of the sensor catheter into the midvitreous of the eye behind the corneoscleral junction whereas McLaren et al. opted to place their catheter into the anterior chamber through an opening made near the limbus. McLaren fixed the catheter to the sclera with three nylon and one silk suture whereas Schnell et al. employed a single drop of tissue adhesive to secure the catheter to the sclera at the site of entry. In both groups, the body of the PA-C40 telemetry implant was placed in a pocket on the neck of the rabbit with the pressure catheter routed subcutaneously to the orbit.
Both authors reported successful continuous recording of IOP in conscious, unrestrained rabbits, 24 hours a day, for several months. However, values for IOP obtained with telemetry in both groups were lower than data reported previously in the literature using pneumatonometry in trained, restrained rabbits. The lower values obtained with telemetry may be the result of a lower level of stress on the animals during measurement. It has been reported that rabbits are very sensitive to various sensory stimuli which could induce a transient rise in IOP with an amplitude as great as 5 to 10 mm Hg for several hours. By using an additional telemetry transmitter implanted in the femoral artery Schnell et al. observed that heart rate and especially mean arterial pressure remained elevated (+30 beats/min and +28 mm Hg respectively) during the entire time period a trained rabbit was placed in a restraining box when compared to the home cage situation. The lower values obtained with telemetry can also be partially explained by the fact that, as McLaren et al. noted, IOP increases by 3-5 mmHg when the pneumatonometer contacts the surface of the eye.
On most waveform traces, both authors also observed a fast, regular pressure pulse with an amplitude of 0.5-1.5 mm Hg and a rate of 180 to 300 BPM caused by blood pressure pulsation. Both groups did extended validation studies of IOP measurements obtained by telemetry or via pneumatonographic and manometric methods. High correlations were reported demonstrating an excellent concordance between methods. This indicates the accuracy and reliability of this new recording system for measuring IOP in the midvitreous as well as in the anterior chamber of the rabbit eye.
It should be pointed out that certain conditions can affect the IOP measurements obtained with implanted transmitters. First, telemetry is a preinvasive method and the implanted eye will always contain the tip of the catheter which is a foreign body. McLaren reported that mainly due to eye movements and blinking, the tip of the catheter can rotate in the anterior chamber and irritate the cornea and iris. This specific problem may be solved by using the midvitreous implantation approach, but long-term recording IOP in conscious rabbits will always be affected by the dynamic nature of the eye. Secondly, the zero offset of implanted transmitters can shift. McLaren found that telemetered measurements obtained 100 days following implantation usually differed from tonometric measurements by less than 4-5 mmHg, although relative changes observed over a few days are very stable.
In summary, both groups clearly demonstrated that IOP can be accurately and reliably measured by telemetry in freely moving conscious rabbits in their home cages. This novel telemetry research resulted in a new technique can be used to study the effects of therapeutic agents over short or extended periods of time in conscious rabbits under physiological conditions that have not been possible with previous methods. As one author stated, "the number of studies that can be designed around measuring IOP by telemetry is limited only by the imagination of the investigators."
Continuous Measurement of Intraocular Pressure in Rabbits by Telemetry McLaren, J.W. Brubaker, R.F. FitzSimon, J.S. Invest. Ophthalmol Vis Sci 1996 37 966-975
Measurement of Intraocular Pressure by Telemetry in Conscious, Unrestrained Rabbits Schnell, C.R. Debon, C. Pericott, C.L. Invest. Ophthalmol Vis Sci 1996 37 958-965