A Circadian and Cardiac Intraocular Pressure Sensor for Smart Implantable Lens.

This paper presents a new system to measure the Intraocular Pressure (IOP) with very high accuracy (0.036 mbar) used for monitoring glaucoma. The system not only monitors the daily variation of the IOP (circadian IOP), but also allows to perform an spectral analysis of the pressure signal generated by the heartbeat (cardiac IOP). The system comprises a piezoresistive pressure sensor, an application-specific integrated circuit (ASIC) to read out the sensor data and an external reader installed on customized glasses. The ASIC readout electronics combines chopping modulation with correlated double sampling (CDS) in order to eliminate both the amplifier offset and the chopper ripple at the sampling frequency. In addition, programmable current sources are used to compensate for the atmospheric pressure ( 800-1200 mbar ) and the circadian component (± 7 mbar) thus allowing to read out the very weak cardiac signals (± 1.6 mbar) with a maximum accuracy of 0.036 mbar.

Correlation between protoporphyrin IX fluorescence intensity, photobleaching, pain and clinical outcome of actinic keratosis treated by photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) with Metvix® is a good therapeutic option to treat actinic keratosis, but it presents drawbacks (pain, lesion recurrences, heterogeneous outcome), emphasizing the possible need to individualize treatment. OBJECTIVE: We assessed whether PDT clinical outcome and pain during treatment were correlated with protoporphyrin IX fluorescence intensity and photobleaching. METHODS: 25 patients were treated by Metvix PDT. The outcome was evaluated after 1.3 (±0.4), 7.6 (±1.8), 13.2 (±1.2) and 33.6 (±3.0) months. After administration of Metvix, red light (632 ± 10 nm) was delivered with a light-emitting diode panel device. The outcome was assessed on a cosmetoclinical scale. RESULTS: All patients who showed a fluorescence level before PDT treatment above a certain threshold had a complete recovery at 33.6 (±3.0) months. CONCLUSION: Our approach could be used to individualize PDT treatment based on the pretreatment fluorescence level, and to predict its long-term outcome.

Rollable and implantable intraocular pressure sensor for the continuous adaptive management of glaucoma.

We designed and tested a new rollable and implantable medical device to directly and continuously measure intraocular pressure. Since high intraocular pressure is a leading risk factor for glaucoma, such a system could solve the difficulties encountered in the management of this condition. In fact, glaucoma is one among those pathologies that could most benefit of an adaptive patient-specific medicine device. The presented prototype was realized with standard industrial microelectronic technologies (Flip-Chip on Kapton flexible PCB) and off-the-shelf IC components. Detailed system description and measurements, obtained during in-vitro and laboratory characterizations, are reported.

Real-time, in vivo measurement of tissular pO2 through the delayed fluorescence of endogenous protoporphyrin IX during photodynamic therapy.

Tissular oxygen concentration plays a key role during photodynamic therapy (PDT). Therefore, monitoring its local oxygen partial pressure (pO2) may help predict and/or control the outcome of a PDT treatment. The first real-time, in vivo measurements of the pO2 in the chicken egg's chorioallantoic membrane, using the delayed fluorescence of photoactivable porphyrins (PAPs), including protoporphyrin IX (PpIX), as monitored with a dedicated optical, fiber-based, time-resolved spectrometer, are reported here. The formation of PAPs/PpIX, photosensitizers of extensive clinical use, was induced in the chicken egg's chorioallantoic membrane (CAM) with aminolevulinic acid. An excellent correlation between the vascular damage induced by PDT and the reduction in tissular pO2 is found. This study suggests that clinical measurement of the pO2 using the PAPs'/PpIX's delayed fluorescence (DF) may be used to individualize in real time the PDT light dose applied.

Reflectance imaging of the human retina at 810 nm does not suffice to optimize the parameters of hydrodynamic rebalancing laser treatment.

The hydrodynamic rebalancing laser (HRL) procedure is an ophthalmic therapy based on the administration of subthreshold infrared (810 nm) laser light to selected areas on the retina to treat various retina diseases. Heterogeneities of tissue response are observed, including undesired retinal damages. Variations of tissue absorbance were hypothesized to cause this uneven response. Irradiation parameters (diameter = 100 µm; power = 1 W; irradiation time: 50 to 200 ms), location and tissue response were studied in 16 patients (20 eyes, 2535 laser spots) to discover any correlation between tissue response and normalized fundus reflectance at 810 nm. The results demonstrate a complex relationship between some pathologies and occurrences of retinal damage, but no clear correlation. One possible reason is that the resolution of reflectance images is insufficient to see "small" (40 µm or less) absorption centers, particularly deep-seated ones. Additionally, tissue parameters other than variations of the fundus optical absorption influence heat diffusion and temperature increases. Monitoring or individualizing the light dose in HRL therapy, or any similar infrared diode laser-based therapy will require more sophisticated technologies, including imaging the retina's reflectance with an improved resolution, as well as refined methods to detect complex correlations between retinal damage and specific pathologies.

Optical fiber-based setup for in vivo measurement of the delayed fluorescence lifetime of oxygen sensors.

A new optical-fiber-based spectrofluorometer for in vivo or in vitro detection of delayed fluorescence is presented and characterized. This compact setup is designed so that it can be readily adapted for future clinical use. Optical excitation is done with a nitrogen laser-pumped, tunable dye laser, emitting in the UV-vis part of the spectrum. Excitation and luminescence signals are carried to and from the biological tissues under investigation, located out of the setup enclosure, by a single optical fiber. These measurements, as well as measurements performed without a fiber on in vitro samples in a thermostable quartz cell, in a controlled-atmosphere enclosure, are possible due to the efficient collection of the laser-induced luminescence light which is collected and focused on the detector with a high aperture parabolic mirror. The detection is based on a gated photomultiplier which allows for time-resolved measurements of the delayed fluorescence intensity. Thus, relevant luminescence lifetimes, typically in the sub-microsecond-to-millisecond range, can be measured with near total rejection of the sample's prompt fluorescence. The instrument spectral and temporal resolution, as well as its sensitivity, is characterized and measurement examples are presented. The primary application foreseen for this setup is the monitoring and adjustment of the light dose delivered during photodynamic therapy.