Tueng T. Shen

Volumetric and quantitative imaging of retinal blood flow in rats with optical microangiography

In this paper, we present methods for 3D visualization and quantitative measurements of retinal blood flow in rats by the use of optical microangiography imaging technique (OMAG). We use ultrahigh sensitive OMAG to provide high-quality 3D RBF perfusion maps in the rat eye, from which the Doppler angle, as well as the diameters of blood vessels, are evaluated. Estimation of flow velocity (i.e. axial flow velocity) is achieved by the use of Doppler OMAG, which has its origins in phase-resolved Doppler optical coherence tomography. The measurements of the Doppler angle, vessel size, and the axial velocity lead to the quantitative assessment of the absolute flow velocity and the blood flow rate in selected retinal vessels. We demonstrate the feasibility of OMAG to provide 3D microangiograms and quantitative assessment of retinal blood flow in a rat model subjected to raised intra-ocular pressure (IOP). We show that OMAG is capable of monitoring the longitudinal response of absolute blood velocity and flow rate of retinal blood vessels to increased IOP in the rat, demonstrating its usefulness for ophthalmological research.

High speed spectral domain optical coherence tomography for retinal imaging at 500,000 A‑lines per second

We present a new development of ultrahigh speed spectral domain optical coherence tomography (SDOCT) for human retinal imaging at 850 nm central wavelength by employing two high-speed line scan CMOS cameras, each running at 250 kHz. Through precisely controlling the recording and reading time periods of the two cameras, the SDOCT system realizes an imaging speed at 500,000 A-lines per second, while maintaining both high axial resolution (~8 μm) and acceptable depth ranging (~2.5 mm). With this system, we propose two scanning protocols for human retinal imaging. The first is aimed to achieve isotropic dense sampling and fast scanning speed, enabling a 3D imaging within 0.72 sec for a region covering 4x4 mm2. In this case, the B-frame rate is 700 Hz and the isotropic dense sampling is 500 A-lines along both the fast and slow axes. This scanning protocol minimizes the motion artifacts, thus making it possible to perform two directional averaging so that the signal to noise ratio of the system is enhanced while the degradation of its resolution is minimized. The second protocol is designed to scan the retina in a large field of view, in which 1200 A-lines are captured along both the fast and slow axes, covering 10 mm2, to provide overall information about the retinal status. Because of relatively long imaging time (4 seconds for a 3D scan), the motion artifact is inevitable, making it difficult to interpret the 3D data set, particularly in a way of depth-resolved en-face fundus images. To mitigate this difficulty, we propose to use the relatively high reflecting retinal pigmented epithelium layer as the reference to flatten the original 3D data set along both the fast and slow axes. We show that the proposed system delivers superb performance for human retina imaging.

Using ultrahigh sensitive optical microangiography to achieve comprehensive depth resolved microvasculature mapping for human retina

This paper presents comprehensive and depth-resolved retinal microvasculature images within human retina achieved by a newly developed ultrahigh sensitive optical microangiography (UHS-OMAG) system. Due to its high flow sensitivity, UHS-OMAG is much more sensitive to tissue motion due to the involuntary movement of the human eye and head compared to the traditional OMAG system. To mitigate these motion artifacts on final imaging results, we propose a new phase compensation algorithm in which the traditional phase-compensation algorithm is repeatedly used to efficiently minimize the motion artifacts. Comparatively, this new algorithm demonstrates at least 8 to 25 times higher motion tolerability, critical for the UHS-OMAG system to achieve retinal microvasculature images with high quality. Furthermore, the new UHS-OMAG system employs a high speed line scan CMOS camera (240 kHz A-line scan rate) to capture 500 A-lines for one B-frame at a 400 Hz frame rate. With this system, we performed a series of in vivo experiments to visualize the retinal microvasculature in humans. Two featured imaging protocols are utilized. The first is of the low lateral resolution (16 μm) and a wide field of view (4 × 3 mm(2) with single scan and 7 × 8 mm(2) for multiple scans), while the second is of the high lateral resolution (5 μm) and a narrow field of view (1.5 × 1.2 mm(2) with single scan). The great imaging performance delivered by our system suggests that UHS-OMAG can be a promising noninvasive alternative to the current clinical retinal microvasculature imaging techniques for the diagnosis of eye diseases with significant vascular involvement, such as diabetic retinopathy and age-related macular degeneration.

Sustained release of antibiotic from poly(2-hydroxyethyl methacrylate) to prevent blinding infections after cataract surgery.

Intraocular lens implantation after opacified natural lens removal is the primary treatment for cataracts in developed countries. Cataract surgery is generally considered safe, but entails significant risks in countries where sophisticated sterile operating theaters are not widely available. Post-operative infection (endophthalmitis) is a potential blinding complication. Infection often results from bacterial colonization of the new lens implant and subsequent antibiotic-tolerant biofilm formation. To combat this risk, we developed a polymeric hydrogel system that can deliver effective levels of antibiotic over an extended period of time within the globe of the eye. Norfloxacin antibiotic was loaded into cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA) gels, which were subsequently surface-modified with octadecyl isocyanate to produce a hydrophobic rate-limiting barrier controlling norfloxacin release. Octadecyl surface modification was characterized using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A 15-min modification leads to a uniform surface coating and near zero order release of norfloxacin from the matrix. Norfloxacin released from coated pHEMA kills Staphylococcus epidermidis in suspension and on a simulated medical implant surface. With these data, we demonstrate a new and effective system for sustained drug release from a hydrogel matrix with specific application for intraocular lens surgery.

In vivo microstructural and microvascular imaging of the human corneo-scleral limbus using optical coherence tomography

The corneo-scleral limbus contains several biological components, which are important constituents for understanding, diagnosing and managing several ocular pathologies, such as glaucoma and corneal abnormalities. An anterior segment optical coherence tomography (AS-OCT) system integrated with optical microangiography (OMAG) is used in this study to non-invasively visualize the three-dimensional microstructural and microvascular properties of the limbal region. Advantages include first the ability to correct optical distortion of microstructural images enabling quantification of relationships in the anterior chamber angle. Second, microvascular images enable the visualization of the microcirculation in the limbal area without the use of exogenous contrast agents. Third, by combining the microstructural and microvascular information, the aqueous outflow pathway can be identified. The proposed AS-OCT can serve as a useful tool for ophthalmological research to determine normal and pathologic changes in the outflow system. As a clinical tool it has the potential to detect early aqueous outflow system abnormalities that lead to the pressure elevation in glaucoma. Recent surgical innovations and their implementations also rely on an assessment of outflow system structure and function, which can be revealed by AS-OCT.

Functional Contact Lenses for Remote Health Monitoring in Developing Countries

The opportunities afforded by using a functional contact lens for remote wireless health status monitoring are discussed and the progress to date in the development of this technology platform is presented. A functional contact lens complete with sensors and embedded circuitry can be used to monitor the composition of tear fluid and, by extension, a number of health-status related parameters in the body in a noninvasive and continuous fashion. The data collected by the disposable contact lens may be sent wirelessly to a mobile phone that, in turn, can relay the information to a medical practitioner via the cellular phone network. If successfully developed and deployed, such a system can be used for monitoring a variety of health indicators over a large geographic area and population distribution with minimal need for the physical presence of health care providers.

Wavefront analysis in normal refractive surgery candidates

PURPOSE To quantify the higher order aberrations of refractive surgery candidates and compare the wavefront-determined refractions with manifest refractions refined with a +/- 0.25 Jackson cross cylinder. METHODS Results of 226 consecutive patients (418 eyes) were analyzed with the WaveScan WavePrint system (VISX, Santa Clara, Calif). Only patients with normal eyes without previous surgery were included. RESULTS The mean spherical equivalent refraction determined with wavefront analysis was -3.40 +/- 3.14 diopters (D) (range: -10.72 to +5.41 D). The largest amount of higher order aberrations was detected with : a 6-mm pupil diameter (coma 0.14 +/- 0.08 microm; trefoil 0.10 +/- 0.07 microm; spherical aberrations 0.09 +/- 0.07 microm). The mean root-mean-square of higher order aberrations and total aberrations were 0.23 +/- 0.11 microm and 4.00 +/- 2.45 microm, respectively. No statistically significant correlation was noted between higher order aberrations and gender (P = 0.7) or between higher order aberration and refractive level (P > .59). The mean differences in spherical equivalent refraction, sphere, and cylinder between WaveScan measurements and manifest refraction were 0.36 +/- 0.41 D, 0.40 +/- 0.44 D, and 0.28 +/- 0.32 D, respectively. CONCLUSIONS This study provides reference values for higher order aberrations in normal refractive surgery candidates. Wavefront analysis also proved to be a valuable tool for objectively measuring preoperative refractive error.

A 2.3

We present the design of an ultra-low power, wireless capacitance/temperature sensing device for continuous intraocular pressure monitoring. The device is wirelessly powered and demonstrates a power consumption of 2.3μW at 1.5V during continuous reading. The chip converts both capacitance and temperature to frequency using a time-interleaved relaxation oscillator, which modulates RF backscatter to a reader for computation of measured samples. The chip exhibits measured capacitance and temperature standard deviations of 1.4fF and 0.4°C, respectively.

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Glaucoma is a blinding disease for which intraocular pressure (IOP) is the only treatable risk factor. The mean IOP is regulated through the aqueous outflow system, which contains the trabecular meshwork (TM). Considerable evidence indicates that trabecular tissue movement regulates the aqueous outflow and becomes abnormal during glaucoma; however, such motion has thus far escaped detection. The purpose of this study is to describe anovel use of a phase-sensitive optical coherence tomography (PhS-OCT) method to assess pulse-dependent TM movement. For this study, we used enucleated monkey eyes, each mounted in an anterior segment holder. A perfusion system was used to control the mean IOP as well as to provide IOP sinusoidal transients (amplitude 3 mmHg, frequency 1 pulse/second) in all experiments. Measurements were carried out at seven graded mean IOPs (5, 8, 10, 20, 30, 40, and 50 mm Hg). We demonstrate that PhS-OCT is sensitive enough to image/visualize TM movement synchronous with the pulse-induced IOP transients, providing quantitative measurements of dynamic parameters such as velocity, displacement, and strain rate that are important for assessing the biomechanical compliance of the TM. We find that the largest TM displacement is in the area closest to Schlemms canal (SC) endothelium. While maintaining constant ocular pulse amplitude, an increase of mean IOP results in a decrease of TM displacement and mean size of the SC. These results demonstrate that the PhS-OCT is a useful imaging technique capable of assessing functional properties necessary to maintain IOP in a healthy range, offering a new diagnostic alternative for glaucoma.

W Wireless Intraocular Pressure/Temperature Monitor

Aqueous leaves the anterior chamber of eye by passing through the trabecular meshwork (TM), a tissue thought to be responsible for increased outflow resistance in glaucoma. Motion assessment could permit characterization of TM biomechanical properties necessary to maintain intra-ocular pressure (IOP) within a narrow homeostatic range. In this paper, we report the first in vivo identification of TM motion in humans. We use a phase-sensitive optical coherence tomography (PhS-OCT) system with sub-nanometer sensitivity to detect and image dynamic pulse-induced TM motion. To permit quantification of TM motion and relationships we develop and apply a phase compensation algorithm permitting removal of the otherwise evitable confounding effects of bulk motion. Twenty healthy human eyes from 10 subjects are imaged. The results permit visualization of pulsatile TM motion visualization by PhS-OCT; correlation with the digital/cardiac pulse is highly significant. The correlation permits assessment of the phase lag and time delay between TM motion and the cardiac pulse. In this study, we find that the digital pulse leads the pulsatile TM motion by a mean phase of 3.53 ± 0.48 rad and a mean time of 0.5 ± 0.14 s in the fundamental frequency. A significant linear relationship is present between the TM phase lag and the heart rate (p value < 0.05). The TM phase lag is also affected by age, the relationship not quite reaching significance in the current study. PhS-OCT reveals pulse-induced motion of the TM that may provide insights into the biomechanics of the tissues involved in the regulation of IOP.