A New Contact Lens Sensor System for Continuous Intraocular Pressure Monitoring: Evaluation of Safety and Tolerability.

PURPOSE: To assess the safety and tolerability of a new contact lens sensor (CLS) system for continuous 3- and 24-hr intraocular pressure (IOP) monitoring in human eyes. METHODS: Twenty-five subjects were recruited for 3-hr IOP measurement by CLS. Corneal fluorescein staining (CFS) scores were evaluated before and after measurement. Then, 30 participants (10 normal subjects and 20 glaucoma patients) were recruited for 24-hr IOP monitoring. Ocular surface disease index (OSDI) was assessed before and one day after measurement. Contact lens dry eye questionnaire-8 was assessed immediately after measurement. Visual analog scale of discomfort was measured before, immediately after, and one day after measurement. Best-corrected visual acuity (BCVA), tear break-up time (TBUT), and CFS were assessed before, immediately after, and 1 day after measurement. RESULTS: All participants completed 3- or 24-hr IOP measurement by CLS. Corneal fluorescein staining increased from 0.6±0.7 to 2.4±1.5 after 3-hr IOP measurement ( P <0.001). For participants undergoing 24-hr IOP monitoring, OSDI increased from 9.1±9.7 to 18.0±12.4 ( P =0.001). CLDEQ-8 score was 11.6±5.8. Visual analog scale increased from 11.1±14.2 to 35.2±21.8 after measurement ( P <0.001) and decreased to 26.7±18.4 one day later ( P <0.001 compared with baseline). BCVA decreased from 1.0±0.01 to 0.8±0.1 ( P <0.001) and returned to 0.9±0.1 after one day ( P <0.001 compared with baseline). TBUT decreased from 5.1±3.9 to 2.6±1.5 s ( P =0.001) and returned to 4.8±2.5 s ( P =0.465 compared with baseline). Corneal fluorescein staining increased from 0.7±0.9 to 4.3±0.8 ( P <0.001) and dropped to 0.8±0.7 ( P =0.599 compared with baseline). No significant difference was found for all variations of indicators between normal subjects and glaucoma patients ( P >0.1 for all comparisons). CONCLUSIONS: The CLS shows a great potential for a safe and tolerable 24-hr IOP monitoring in normal subjects and glaucoma patients. Clinical attention to the worsening signs and symptoms after measurement is required.

High myopes have lower normalised corneal tangent moduli (less 'stiff' corneas) than low myopes.

PURPOSE: To compare corneal tangent moduli between low and high myopes. METHODS: Corneal hysteresis (CH) and corneal resistance factor (CRF) of 32 low and 32 high myopes were obtained using an Ocular Response Analyzer, followed by a corneal indentation device that measured corneal stiffness. Corneal topography, pachymetry, Goldmann applanation tonometry intraocular pressure (GAT-IOP), and corneal compensated intraocular pressure (IOPcc) were also obtained. Corneal tangent modulus was calculated on the basis of corneal stiffness, central corneal thickness and corneal radius. Comparisons between groups and associations between corneal biomechanical and ocular parameters were performed. RESULTS: Corneal tangent moduli were positively correlated with GAT-IOP (R2 = 0.078, p = 0.025), and IOPcc (R2 = 0.12, p = 0.006). Despite similarity in corneal thickness and radius, high myopes exhibited a significantly higher IOPcc (16.4 ± 2.51 mmHg) than low myopes (13.1 ± 1.96 mmHg; t(62) = -5.57, p < 0.0001). Both groups had similar corneal stiffness (0.063 ± 0.0085 and 0.063 ± 0.0079 N mm-1 for low and high myopes, respectively) and CRF (9.6 ± 1.58 and 9.5 ± 1.90 mmHg for low and high myopes, respectively). Moreover, high myopes exhibited a significantly lower CH (9.5 ± 1.51 mmHg) than low myopes (10.6 ± 1.38 mmHg; t(62) = 2.92, p = 0.005). After normalising corneal tangent moduli to the mean intraocular pressure in normal eyes (15.5 mmHg) using IOPcc, high myopes showed a significantly lower corneal tangent moduli (0.47 ± 0.087 MPa) than low myopes (0.57 ± 0.099 MPa; t(62) = 4.17, p < 0.0001). CONCLUSIONS: High myopes had lower normalised corneal tangent moduli than low myopes, which indicated that their corneas were less stiff. This is the first in vivo study comparing elastic moduli of the cornea in different refractive groups. Further studies are warranted to understand whether a less stiff cornea is a cause for or an outcome from myopia development.

Repeatability of a novel corneal indentation device for corneal biomechanical measurement.

PURPOSE: The aim of the study was to evaluate the repeatability of a new device for measuring corneal biomechanics. METHODS: Twenty-nine normal subjects aged 20-28 years (23.4 ± 1.7 years) underwent measurements of corneal stiffness and tangent elastic modulus using a novel corneal indentation device. Corneal topography, axial biometry and Goldmann applanation tonometry were also performed during the visit. Subjects returned after about 1 week, at approximately the same time, and with the corneal biomechanics, corneal topography and Goldmann applanation tonometry measured again. Both the intrasession and intersession repeatability was assessed. RESULTS: Both the corneal stiffness and tangent elastic modulus demonstrated good intrasession repeatability (corneal stiffness: coefficient of variation = 7.32%, intraclass correlation coefficient = 0.75; tangent elastic modulus: coefficient of variation = 7.34%, intraclass correlation coefficient = 0.84). The mean modulus after normalised to normal intraocular pressure of 15.5 mmHg was 0.755 ± 0.159 MPa. There was no significant difference between the two visits (paired t-tests: p > 0.05). The repeatability [1.96 times the standard deviation (S.D.) of the intersession difference] of the corneal stiffness and the tangent elastic modulus was 0.0022 N mm(-1) and 0.197 MPa, respectively. CONCLUSION: The corneal indentation device has good intrasession and intersession repeatability. It has good potential to measure corneal biomechanics clinically, even at different corneal regions.

Continuous 24-hour intraocular pressure monitoring in normal Chinese adults using a novel contact lens sensor system.

AIMS: To investigate the physiological nyctohemeral intraocular pressure (IOP) rhythms of normal Chinese adults using a novel contact lens sensor system (CLS) that can output IOP in millimetres of mercury (mm Hg) continuously. METHODS: Fifty-nine eyes of 59 normal Chinese adults completed 24-hour IOP monitoring using the novel CLS. A descriptive analysis was conducted on the 24-hour IOP mean, peak and acrophase, trough and bathyphase, fluctuation, and mean amplitude of intraocular pressure excursion (MAPE). The continuous data were analysed at several periods (diurnal period, 08:00-20:00 hours; nocturnal period, 22:00-06:00 hours; sleep time, 0:00-06:00 hours), and compared between right and left eyes, males and females, and different age ranges (<30, and ≥30), respectively. RESULTS: Normal adults had a lower peak, higher trough, smaller fluctuation and smaller MAPE (p<0.05 for all comparisons) but non-significantly different mean (p=0.695) in the nocturnal period or sleep time compared with the diurnal period. The 24-hour IOP peak and trough showed the frequency of occurrence ranging from 1.69% to 15.25% at an interval of 2 hours. No IOP parameter showed significant difference between right and left eyes (p>0.1 for all comparisons). The male group had larger 24-hour and diurnal IOP fluctuation and MAPE (p<0.05 for all comparisons). Subjects aged 30 or over had higher 24-hour and diurnal mean, higher peak, and larger MAPE (p<0.05 for all comparisons). CONCLUSION: Continuous 24-hour IOP output from the CLS in normal Chinese was stable with a comparable mean level between day and night, as well as scattered acrophase and bathyphase. The 24-hour IOP mean increased with age, and IOP variations were positively correlated to age and male sex.

MultiPrime: A reliable and efficient tool for targeted next-generation sequencing.

We present multiPrime, a novel tool that automatically designs minimal primer sets for targeted next-generation sequencing, tailored to specific microbiomes or genes. MultiPrime enhances primer coverage by designing primers with mismatch tolerance and ensures both high compatibility and specificity. We evaluated the performance of multiPrime using a data set of 43,016 sequences from eight viruses. Our results demonstrated that multiPrime outperformed conventional tools, and the primer set designed by multiPrime successfully amplified the target amplicons. Furthermore, we expanded the application of multiPrime to 30 types of viruses and validated the work efficacy of multiPrime-designed primers in 80 clinical specimens. The subsequent sequencing outcomes from these primers indicated a sensitivity of 94% and a specificity of 89%.

Corneal Stiffness and Modulus of Normal-Tension Glaucoma in Chinese.

PURPOSE: To assess and compare the corneal biomechanics of normal-tension glaucoma (NTG), high-tension glaucoma (HTG), and normal controls based on stiffness and modulus. The correlations among central corneal thickness (CCT), visual field, retinal nerve fiber layer (RNFL) thickness, and corneal biomechanics in glaucoma eyes were also evaluated. DESIGN: A prospective, cross-sectional, comparative study. METHODS: This study included 334 eyes of 108 NTG patients, 113 HTG patients, and 113 control subjects at Zhongshan Ophthalmic Center, Sun Yat-Sen University. Corneal biomechanics were evaluated using a corneal indentation device (CID) and corneal visualization Scheimpflug technology (Corvis ST). Visual field and RNFL thickness were obtained using standard automated perimetry and spectral-domain optical coherence tomography. One-way analyses of variance with Bonferroni post hoc tests and a multivariable linear regression analysis with adjustment were conducted. Correlations among corneal biomechanical parameters, CCT, visual field, and RNFL thickness were analyzed. RESULTS: The corneal stiffness of the NTG patients (71.0 ± 10.9 N/m) was significantly lower than that of the HTG patients (77.3 ± 15.6 N/m; P = .001) and the CCT- and IOP-matched normal controls (75.6 ± 11.0 N/m; P = .023). The patients in the NTG group had lower corneal stiffness than those in the control group (ß = -4.88, 95% CI -9.002, -0.758; P = .020) after adjusting for confounders. Stiffness was positively correlated with CCT in the NTG group (P = .028) but not in the HTG group (P = .509). There was no significant correlation (P > .05) between corneal biomechanics, visual field, or RNFL thickness. CONCLUSIONS: The corneas of NTG patients were softer than those of HTG patients and controls, as assessed by CID, which were associated with thinner CCT. These might suggest different ocular biomechanical properties in NTG and HTG.

A Novel Indentation Assessment to Measure Corneal Biomechanical Properties in Glaucoma and Ocular Hypertension.

Purpose: To evaluate the ability of the new in vivo corneal indentation device (CID) to measure corneal biomechanical properties. Methods and Results: In total, 186 eyes from 46 healthy subjects, 107 patients with primary open-angle glaucoma, and 33 patients with ocular hypertension were enrolled in a cross-sectional study. Measurements were performed using corneal visualization Scheimpflug technology (Corvis ST) and the CID. The deformation amplitude (DA), inward applanation time, inward applanation velocity (A1V), outward applanation time (A2T), outward applanation velocity (A2V), highest concavity time, DA ratio, max inverse radius (MIR), integrated radius, and stiffness parameter A1 were included as Corvis ST parameters, and stiffness and modulus were included as CID parameters. Associations between the Corvis ST and CID parameters and correlations between central corneal thickness and corneal biomechanical parameters were analyzed. The stiffness was significantly correlated with all the Corvis ST parameters (P < 0.05). The modulus was significantly correlated with the DA, A1V, A2T, A2V, highest concavity time, and MIR (P < 0.05). The DA, inward applanation time, A1V, A2T, A2V, DA ratio, MIR, integrated radius, and stiffness parameter A1 values and both CID-derived values were significantly correlated with central corneal thickness (P < 0.05). Conclusions: Parameters derived from the CID and Corvis ST demonstrated agreement in the measurement of corneal biomechanical properties. The stiffness and modulus can characterize in vivo corneal biomechanical properties. Translational Relevance: Agreeing with the Corvis ST regarding the assessment of corneal biomechanical properties, the CID can be a novel clinical tool for biomechanical evaluation of the cornea.

Dose-Response Relationship and Threshold Drug Dosage Identification for a Novel Hybrid Mechanical-Thrombolytic System with an Ultra-Low Dose Patch.

INTRODUCTION: Ischemic stroke treatment has advanced in the last two decades and intravenous thrombolysis is now considered the standard of care for selected patients. Recanalization can also be achieved by mechanical endovascular treatment for patients with large vessel occlusions. Complicating treatment-related symptomatic intracerebral hemorrhage and prolonged needle-to-recanalization times have been identified as major determinants of poor three-month functional outcomes. A hybrid mechanical-thrombolytic system with a patch imbued with an ultra-low dose of thrombolytic agents loaded onto a stent-retriever has been developed. METHODS: In this study, the in situ dose-response relationship of the thrombolytic patch imbued with up to 1000 IU of urokinase plasminogen activator (uPA) was quantified using Raman spectroscopy. RESULTS: Thrombi of up to 400 µm thickness dissolved within 15 min when patches imbued with < 1% of the conventional thrombolysis therapy dosage were applied. The results demonstrated that low-dose thrombolytic patches can dissolve normal clots compressed in the blood vessel in a short time. 500 IU is the threshold uPA dosage in the thrombolytic patch that most effectively dissolves the clots. CONCLUSION: This study suggests that a novel endovascular stent-retriever loaded with an ultra-low drug dose fibrinolytic patch may be a suitable treatment for patients who are ineligible for conventional thrombolytic therapy.

Controllable release of pirfenidone by polyvinyl alcohol film embedded soft contact lenses in vitro and in vivo.

To increase the amount of pirfenidone (PFD) loaded in polyvinyl alcohol (PVA) film embedded soft contact lens (SCL), and evaluate its function of sustaining delivery of drug in vitro and in vivo. Drug loading efficiency within PVA film and SCLs, drug release from SCLs in vitro, and the effects of parameters of SCLs and external environment on drug release in vitro were evaluated by ultraviolet-visible spectrophotometer at 312 nm. Safety of SCLs was evaluated in vitro by transformed human corneal epithelial cell. Safety in vivo was determined by optical coherence tomography and histology of anterior segment of rabbits. Drug release study in tear fluid and aqueous humor were measured by ultra-performance liquid chromatography. SCLs had smooth surface and were fit for experimental rabbits. Amount of PFD in PVA film and SCLs were 153.515 µg ± 12.508 and 127.438 µg ± 19.674, respectively, PFD in PVA film was significantly higher than SCLs (p=.006) and closed to 150 µg (targeting amount of PFD to be loaded). Thickness of SCLs, molecular weight of PVA, and amount of PVA used in SCLs affected drug release in vitro significantly. Thickness of PVA film and amount of drug in SCLs had no effect on drug release rate in vitro. SCLs were safe in vitro and in vivo, PFD released from SCLs could be detected around 12 hours in tears and aqueous humor, and the concentration of drug was higher than eye drop at all detected time points while amount of PFD in SCLs was lower than eye drop. Drug loaded PVA film embedded SCLs may be a promising ocular drug delivery system.

Extended Delivery of Pirfenidone with Novel, Soft Contact Lenses In Vitro and In Vivo.

Purpose: The aim of this study was to fabricate pirfenidone (PFD)-loaded soft contact lenses (SCLs), explore their characteristics, and evaluate their efficiency on extended delivery of PFD in vitro and in vivo. Methods: PFD-loaded SCLs were fabricated by embedding an insert of PFD and polyvinyl alcohol (PVA) into 2 layers of silicone elastomer. The optical transparency, water content, and protein deposition were measured. Transformed human corneal epithelial cells were used to test the cytotoxicity of SCLs. The release rate of PFD by SCLs in vitro was evaluated by an ultraviolet-visible spectrophotometer. Toxicity of SCLs was assessed by inspection of ocular surface irritation in rabbits before and after contact lens wear. The concentrations of PFD in tears and aqueous humor of rabbits' eyes as a function of time were determined by high-performance liquid chromatography for SCLs and 30 µL of 0.5% PFD eye drops. Results: SCLs possessed good light transmittance. Blank SCLs had poor water content (0.548% ± 0.330), and an improved water content was found in PVA film-loaded SCLs (11.022% ± 1.508, P = 0.010). No lysozyme and human serum albumin were found in SCLs. There was no significant toxicity of SCLs in vitro and in vivo. SCLs prolonged the residence time of PFD in tears and aqueous humor of rabbit eyes by 5 times compared with the eye drop instillation while around 1/10 of the eye drop dosage was loaded in SCLs. Conclusions: PFD-loaded SCLs can significantly prolong the residence time of PFD and may be a promising ocular drug delivery system.

Characterization of Corneal Biomechanical Properties and Determination of Natural Intraocular Pressure Using CID-GAT.

PURPOSE: The intraocular pressure (IOP) measured using Goldmann Applanation Tonometry (GAT) is confounded by individual corneal properties. We investigated a modified method that removes the confoundment by incorporating corneal properties into the Imbert-Fick's law is investigated. METHOD: Porcine eyes were pressurized between 10 and 40 mm Hg using a manometer. The eyes were indented using a flat cylindrical indenter. A modified corneal indentation device (CID) procedure was used to obtain the corneal moduli Eqs . The calculated IOPNC from the Imbert-Fick's Law using the corneal moduli Eqs was compared to the natural IOPN, measured using pressure sensor inserted into the eye. RESULTS: Test results showed that IOP-dependent corneal modulus Eqs is a primary confounding factor in IOP calculation. The average elastic modulus Eqs is 0.173 ± 0.018 MPa at 20 mm Hg, and increases with IOP at a linear rate of 0.0066 MPa per mm Hg (r = 0.997, P < 0.001). Incorporation of individual Eqs into IOPNC calculation showed that IOPNC are in good agreement with reference IOPN (slope = 0.999, r = 0.939, P < 0.001). CONCLUSIONS: The IOP-dependent corneal modulus Eqs is a primary confounding factor in IOP calculation. A modified CID-GAT procedure to obtain natural cornea-independent IOPNC is developed and verified in this study. The CID-GAT IOP modification may be used in place of conventional GAT when the confounding effects in eyes with atypical cornea (e.g., laser-assisted in situ keratomileusis [LASIK] thinned) are significant. TRANSLATIONAL RELEVANCE: Confoundment from corneal properties results in IOP measurement errors. The study showed that the CID-GAT method can significantly reduce the confounding corneal errors.

Association between long-term orthokeratology responses and corneal biomechanics.

Myopia is very prevalent worldwide, especially among Asian populations. Orthokeratology is a proven intervention to reduce myopia progression. The current study investigated association between baseline corneal biomechanics and orthokeratology responses, and changes of corneal biomechanics from long-term orthokeratology. We fitted 59 adult subjects having myopia between -4.00D to -5.00D with overnight orthokeratology. Corneal biomechanics was measured through dynamic bidirectional corneal applanation (in terms of corneal hysteresis, CH and corneal resistance factor, CRF) and corneal indentation (in terms of corneal stiffness, S and tangent modulus, E). Subjects with poor orthokeratology responses had lower E (mean 0.474 MPa) than subjects with good orthokeratology responses (mean 0.536 MPa). Successful orthokeratology for 6 months resulted in reducing CH (reduced by 5.8%) and CRF (reduced by 8.7%). Corneal stiffness was stable, but E showed an increasing trend. Among subjects with successful orthokeratology, a higher baseline S resulted in greater myopia reduction (Pearson correlation coefficient, r = 0.381, p = 0.02).

Model development and comparison of low hemorrhage-risk endoluminal patch thrombolytic treatment for ischemic stroke.

Clot dissolution drugs delivered into the systemic circulation can dissolve intracranial blood clots in 90 min with 20-50% hemorrhage rate. Immobilizing <5% of the intravenous dosage on an endoluminal patch can reduce the dissolution time to <20 min with negligible hemorrhage risk. The thrombus dissolution behavior in endoluminal patch thrombolytic treatment is modeled and compared with experimental results from a companion study. Analyses showed that the thrombus dissolution time decreases with increasing dosage, but the dissolution time reaches a dosage-independent minimum when uPA dosage on the patch is >800 IU. Model analyses showed that dissolution time in the plateau regime is controlled by diffusion. Further results showed that dissolution time could be reduced in this regime by reducing thrombus thickness. This suggests that a stented endoluminal thrombolytic >800 IU patch that compresses the thrombus to thin the clot thickness can help reduce dissolution time. This ultra-low transition dosage (i.e., 800 IU), compared to 0.6-2.4 million IU in conventional thrombolysis suggests that hemorrhage risk in endoluminal patch thrombolytic treatment is low. The low hemorrhagic-risk endoluminal patch can be considered for use in patients who are ineligible for conventional thrombolytic treatment because of high hemorrhagic treatment risk.

In vitro examination of the pressure effect on clot dissolution with thrombolytic patch.

Bio-kinetic thrombus dissolution model has been developed to describe the thrombus dissolution behavior during endoluminal thrombolytic patch treatment to recanalize blocked vessel in ischemic strokes. The initial model ignored the effect of pulsatile pressure in the lumen. However, pulsatile pressure in the lumen may affect molecule diffusion and bio-chemical reaction rate and accelerate clot dissolution. The effect of pressure on the dissolution rate was examined in this study. The dissolution behaviors of 100-400 µm thick blood clot specimens subject to diastolic, systolic, and pulsatile pressure were characterized using Raman spectroscopy. The results showed that dissolution time was reduced by less than 2 mins and is negligible in comparison with total treatment time. The effect of pressure may be ignored and the developed bio-kinetic model may be used in surgical applications of endoluminal thrombolytic patch to estimate treatment time in ischemic stroke.

Development of ocular viscosity characterization method.

Glaucoma is the second leading cause for blindness. Irreversible and progressive optic nerve damage results when the intraocular pressure (IOP) exceeds 21 mmHg. The elevated IOP is attributed to blocked fluid drainage from the eye. Methods to measure the IOP are widely available, but methods to measure the viscous response to blocked drainage has yet been developed. An indentation method to characterize the ocular flow is developed in this study. Analysis of the load-relaxation data from indentation tests on drainage-controlled porcine eyes showed that the blocked drainage is correlated with increases in ocular viscosity. Successful correlation of the ocular viscosity with drainage suggests that ocular viscosity maybe further developed as a new diagnostic parameter for assessment of normal tension glaucoma where nerve damage occurs without noticeable IOP elevation; and as a diagnostic parameter complimentary to conventional IOP in conventional diagnosis.

Characterization of thrombus stiffening in radio frequency (rf) Mechanical thrombectomy.

Intra-arterial mechanical thrombectomy (IAMT) for ischemic stroke has high recanalization rate, long treatment time window and low risk of symptomatic intracerebral haemorrhage (sICH), but thrombus fragments produced during treatment can lead to distal embolization. Fragmentation can be reduced if the thrombus is strengthened by increasing the thrombus's crosslink density. Radio frequency (rf) electric current commonly used in surgery to cut and coagulate tissue can induce crosslinking in thrombus. The increase in thrombus stiffness as a result of the increase in crosslinking from rf treatment is characterized in this study. Test results showed that the stiffness of thrombus is increased by more than 8 times after rf treatment. The dramatic increase in stiffness suggests that thrombus fragmentation and distal embolization can be reduced by applying rf during thrombectomy treatment.

Diurnal Variation of Corneal Tangent Modulus in Normal Chinese.

PURPOSE: The aim of this study was to investigate the diurnal variation of corneal tangent modulus, measured using a novel corneal indentation device, in healthy Chinese subjects. METHODS: The central corneal thickness (CCT), mean central corneal radius (meanK), intraocular pressure (IOP), and corneal stiffness of 25 young adults aged 21 to 25 years (23.0 ± 1.0 yrs) were measured at 3-hour intervals from 09:00 to 21:00 in the course of 1 day. Corneal tangent modulus was calculated on the basis of corneal stiffness, CCT, and meanK. Repeated-measures analyses of variance were performed to compare the diurnal changes in ocular parameters over time. RESULTS: Significant diurnal variations were observed in CCT and IOP (P < 0.001 and P = 0.025, respectively). Both parameters showed a decreasing trend throughout the day. MeanK and corneal stiffness did not show any significant diurnal changes (P = 0.251 and P = 0.516, respectively). Mean corneal tangent modulus across all measurements was 0.047 ± 0.085 MPa, and its diurnal rhythm ranged from 0.469 to 0.485 MPa. The variation was nonsignificant (P = 0.526). CONCLUSIONS: The elastic properties of the cornea in healthy Chinese subjects were stable during wake time. The present study shows that the corneal indentation device obtains stable corneal biomechanics similar to other clinical devices. Future studies investigating the differences in corneal biomechanics among patients with various ocular conditions are warranted.

In-vitro testing of RF-enabled low force mechanical thrombectomy for ischemic stroke.

Mechanical thrombectomy for ischemic stroke has high recanalization rate, long treatment time window and low hemorrhage risk. However, the clot engagement approach of caging the clot against the vessel wall can cause vessel stenosis and stroke recurrence. A device with reduced radial stenting force that reduces vessel wall friction would minimize stenosis and damage. The use of localized Radio Frequency (RF) to enable clot engagement and retrieval with minimal stenting force is explored in this study. New mechanical thrombectomy devices enabled with RF (Patent No.: US 62/172,043) were built and tested on human blood clots in vessels ex vivo. Test results showed that the RF-mechanical thrombectomy successfully and reproducibly captured and retrieved the clots without relying on stent caging of the clot against the vessel wall. Further work will be conducted on animals to compare vessel wall damage between conventional and RF-mechanical thrombectomy.

Feasibility examination of isolated zonal thrombolysis using Raman spectroscopy.

Intravenous thrombolysis for the treatment of ischemic stroke requires long treatment time and high drug dosage which increases the risk of hemorrhage. Localized zonal dosage of urokinase between 100 - 500 International Units (IU), i.e., less than 5% of typical systemic dosage (60,000 - 120,000 IU) at the thrombus can shorten the treatment time to less than 30 minutes while reducing the risk of hemorrhage. The effect of zonal-delivered urokinase on the molecular changes in a 100 µm thick by 20 mm diameter blood clot was quantified using Raman spectroscopy. In situ Raman spectra showed that the fibrin concentration in the clot decreased with time. The results verified that a zonal-delivered urokinase can dissolve the clot and reduce the treatment time. Further trials on animals will be conducted to examine the potential of zonal-delivery to accelerate clot dissolution for ischemic stroke while minimizing the risk of hemorrhage.

Individual-specific tonometry on porcine eyes.

Intraocular pressure (IOP) monitoring is important in the diagnosis and management of glaucoma. The measurement of IOP is affected by corneal properties, but the effect of corneal stiffness on IOP measurement is unaccounted for in pressure measurement instruments such as the Goldmann Applanation Tonometer (GAT). A new instrumented non-invasive indentation tonometry that can measure IOPIST, a corneal stiffness-corrected intraocular pressure is developed. The inter-individual corneal variations of 12 porcine eyes ex vivo were independently characterized; and their true intraocular pressure, IOPT's, were set using a manometer before indentation using the new indentation tonometry. Analyses of the load-displacement data showed that porcine corneal stiffness varied more than five times from 0.045 to 0.253N/mm. Analysis showed that, without individual stiffness correction, inter-individual variation of IOPGAT can vary up to 8mmHg from IOPT at 15mmHg; the error becomes larger at high IOPT. In comparison when corneal stiffness is accounted for, IOPIST has a significantly smaller error of 1.82±1.70mmHg for IOPT between 12 and 40mmHg than IOPGAT. The results showed that the new tonometry successfully accounted for inter-individual variations in IOP measurement.