This PDF file contains the front matter associated with SPIE Proceedings Volume 7163, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.

Noninvasive monitoring of blood flow in retinal circulation will reveal the progression and treatment of ocular disorders, such as diabetic retinopathy, age-related macular degeneration and glaucoma. A non-invasive and direct BF measurement technique with high spatial-temporal resolution is needed for retinal imaging. Laser speckle imaging (LSI) is such a method. Currently, there are two analysis methods for LSI: spatial statistics LSI (SS-LSI) and temporal statistical LSI (TS-LSI). Comparing these two analysis methods, SS-LSI has higher signal to noise ratio (SNR) and TSLSI is less susceptible to artifacts from stationary speckle. We proposed a hybrid temporal and spatial analysis method (HTS-LSI) to measure the retinal blood flow. Gas challenge experiment was performed and images were analyzed by HTS-LSI. Results showed that HTS-LSI can not only remove the stationary speckle but also increase the SNR. Under 100% O2, retinal BF decreased by 20-30%. This was consistent with the results observed with laser Doppler technique. As retinal blood flow is a critical physiological parameter and its perturbation has been implicated in the early stages of many retinal diseases, HTS-LSI will be an efficient method in early detection of retina diseases.

A high speed (47,000 A-scan/s), high resoluiton FD-OCT system, operating in the 1060nm wavelength range was used to acquire in-vivo 3D image of healthy and pathological rat retinas. The images were acquired with ~4.3µm axial and ~5µm lateral resolution in the rat eye and 102dB sensitivity at 1.3mW optical power of the imaging beam. The images of the healthy rat retinas show increased penetration into the choroid, clear visualization of all intra-retinal layers and the choroidal blood network, as well as part of the underlying sclera. The high imaging resolution of the OCT system is also sufficient for resolving tiny capillaries imbedded in the inner - and outer plexiform layers of the retina. The high data acquisition rate of the FD-OCT system combined with the high axial resolution is also suitable for probing light induced physiological processes in the retina simultaneously with the morphological imaging.

Ultrahigh speed spectral / Fourier domain optical coherence tomography (OCT) imaging using a CMOS line scan camera with acquisition rates of 70,000 - 312,500 axial scans per second is investigated. Several design configurations are presented to illustrate trade-offs between acquisition speed, sensitivity, resolution and sensitivity roll-off performance. We demonstrate: extended imaging range and improved sensitivity roll-off at 70,000 axial scans per second , high speed and ultrahigh resolution imaging at 106,382 axial scans per second, and ultrahigh speed imaging at 250,000-312,500 axial scans per second. Each configuration is characterized through optical testing and the trade-offs demonstrated with in vivo imaging of the fovea and optic disk in the human retina. OCT fundus images constructed from 3D-OCT data acquired at 250,000 axial scans per second have no noticeable discontinuity of retinal features and show that there are minimal motion artifacts. The fine structures of the lamina cribrosa can be seen. Long cross sectional scans are acquired at 70,000 axial scans per second for imaging large areas of the retina, including the fovea and optic disk. Rapid repeated imaging of a small volume (4D-OCT) enables time resolved visualization of the capillary network surrounding the INL and may show individual red blood cells. The results of this study suggest that high speed CMOS cameras can achieve a significant improvement in performance for ophthalmic imaging. This promises to have a powerful impact in clinical applications by improving early diagnosis, reproducibility of measurements and enabling more sensitive assessment of disease progression or response to therapy.

We present applicability of the high speed swept-source optical coherence tomography for in vivo imaging of the anterior segment of the human eye. Three dimensional imaging of the cornea with reduced motion artifacts is possible by using swept source with Fourier domain mode locking operating at 200kHz with 1300nm central wavelength. High imaging speeds allow for assessment of anterior and posterior corneal topography and generation of thickness and elevation maps.

We present in vivo frequency domain optical coherence tomography of the human retina and choroid in the 1060 nm water transmission window with 72 nm optical bandwidth (<8 &mgr;m axial resolution in tissue) and up to 74 frames per second (`a 512 x 512 pixels). A novel InGaAs stripe array with 1024 pixels and 47000 lines/s read out rate is utilized in combination with an all reflective spectrometer to enable densely sampled wide field scans (35°x°35), i.e. ~­10x10 mm²) acquired in less than 7 seconds. At this speed numerical motion artifact removal algorithms are sufficient to compensate remaining involuntary drifts of the subject's eye. Enhanced penetration beyond the retina enables for the first time highly isotropically sampled, three-dimensional visualization of all three layers of the choroidal vasculature without the need of contrast agents, the choroidal-scleral interface as well as the first scleral layer, the absorbing lamina fusca sclerae. Furthermore the choroidal thickness was quantified in 30 healthy subjects and correlated with axial eye length. First results indicate an decrease in choroidal thickness with increasing axial eye length.

An improved digital interference holography (DIH) technique suitable for fundus images is proposed. This technique incorporates a dispersion compensation algorithm to compensate for the unknown axial length of the eye. Using this instrument we acquired successfully tomographic fundus images in human eye with narrow axial resolution less than 5μm. The optic nerve head together with the surrounding retinal vasculature were constructed. We were able to quantify a depth of 84μm between the retinal fiber and the retinal pigmented epithelium layers. DIH provides high resolution 3D information which could potentially aid in guiding glaucoma diagnosis and treatment.

We describe a novel instrument that combines adaptive optics - Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO). Both systems share a common AO sub-system and vertical scanner to permit simultaneous acquisition of retinal images from both OCT and SLO. One of the benefits of combining OCT with SLO includes automatic co-registration between the two imaging modalities and potential for correcting lateral and transversal eye motion resulting in motion artifact-free volumetric retinal imaging. Results of using this system for eye model imaging are presented. Feasibility for clinical application is briefly discussed as well as potential further improvements of the current system.

Retinal pathologies, like ARMD or glaucoma, need to be early detected, requiring imaging instruments with resolution at a cellular scale. However, in vivo retinal cells studies and early diagnoses are severely limited by the lack of resolution on eye-fundus images from classical ophthalmologic instruments. We built a 2D retina imager using Adaptive Optics to improve lateral resolution. This imager is currently used in clinical environment. We are currently developing a time domain full-field optical coherence tomograph. The first step was to conceive the images reconstruction algorithms and validation was realized on non-biological samples. Ex vivo retina are currently being imaged. The final step will consist in coupling both setups to acquire high resolution retina cross-sections.

An adaptive optics scanning laser ophthalmoscope (AOSLO) corrects ocular aberrations to provide clear retinal images in vivo with high lateral resolution. In this study, we developed an AOSLO system with a 1 μm wavelength probe beam. This wavelength band is effective in improving the retinal imaging capability of AO systems. Because of the long wavelength, the AOSLO system has high tolerance to a mechanical deformation of mirror surfaces; further, it is easier to achieve diffraction limit of the system. To visualize individual photoreceptors, parafoveal regions of retinas of two normal subjects were examined using the 1 μm wavelength AOSLO system. Ocular aberrations were measured using a Shack-Hartmann wavefront sensor and an 840 nm superluminescent diode light source as an AO beacon. A magnetic deformable mirror was used for the correction of ocular aberrations. When AO correction was carried out, the residual RMS wavefront error was measured to be less than 0.1 μm. This residual aberration resulted in a lateral resolution of 3.6 μm of the retinal image. Despite the relatively low transform-limited resolution due to the longer wavelength, the AOSLO could successfully be used to visualize individual photoreceptors, flow of blood cells, and nerve fibers. It was found that the developed AOSLO system with a center wavelength of 1 μm can effectively visualize individual photoreceptors.

We have developed a compact retinal imager that integrates adaptive optics (AO) into a line scanning laser ophthalmoscope (LSLO). The bench-top AO-LSLO instrument significantly reduces the size, complexity, and cost of research AOSLOs, for the purpose of moving adaptive optics imaging more rapidly into routine clinical use. The AO-LSLO produces high resolution retinal images with only one moving part and a significantly reduced instrument footprint and number of optical components. The AO-LSLO has a moderate field of view (5.5 deg), which allows montages of the macula or other targets to be obtained more quickly and efficiently. In a preliminary human subjects investigation, photoreceptors could be resolved and counted within ~0.5 mm of the fovea. Photoreceptor counts matched closely to previously reported histology. The capillaries surrounding the foveal avascular zone could be resolved, as well as cells flowing within them. Individual nerve fiber bundles could be resolved, especially near the optic nerve head, as well as other structures such as the lamina cribrosa. In addition to instrument design, fabrication, and testing, software algorithms were developed for automated image registration, cone counting, and montage stitching.

Polarization sensitive optical techniques such as Scanning Laser Polarimetry (SLP) or Polarization Sensitive Optical Coherence Tomography (PS-OCT) must take into account corneal polarization changes when imaging the eye fundus. Information about corneal structure is also basic in the diagnosis of corneal disorders. Histological analysis shows that cornea is layered, with fibrils oriented at varying angles. However, this information does not refer to fibril orientation in a macrostructural sense. In this work, we propose a corneal structural model with different fibril arrangements and compare them with in vivo and in vitro PS-OCT measurements. The model is based on a stack of lamellae, represented by Jones theory. Each lamella has a preferred fast axis orientation according to the fibril structure and a birefringence. Optical radiation is parallel to the eye optical axis. A third of the lamellae are arbitrarily oriented. Several fibril configurations were modeled: preferentially horizontal and vertical fibrils; preferentially vertical and radial fibrils; circularly and radially oriented fibrils; and a configuration in which fibrils form arcs that join opposite points of a cross defined over the corneal surface. We also modeled the rotation of the previous configurations and compared them with PS-OCT measurements of in vitro tilted corneas.

GDx VCC is a confocal scanning laser polarimeter (SLP) developed to assess the retinal nerve fiber layer (RNFL) of the eye based on measurement of the phase retardation in the backscattered light from the fundus. In addition to the phase retardation measurement, a depolarization measurement is readily available from the same image series. We hypothesize that the depolarized light in the GDx signal consists of backscattering from the retinal pigment epithelium (RPE) and the RPE-Bruch's membrane junction, and further, that subRPE deposits contribute to the depolarized backscattered light in proportion to their thickness. Therefore, a quantitative macular depolarization map will provide information about both spatial distribution and heterogeneity of the RPE structure and deposit thickness. Ultimately we predict that depolarization mapping will significantly increase the positive predictive power to identify early dry AMD eyes. In this paper, depolarization measurements in normal eyes and age related changes are reported. Data collection was performed at the Duke University Eye Center. A commercial GDx VCC system was modified with a central fixation target and, instead of depolarized light intensity images, normalized depolarization images were derived and saved in the database. Macular depolarization was observed to increase with age in normal eyes at a rate of 0.27%/yr.

Corneal and anterior segment optical coherence tomography has been developed to measure cross-sectional images of the anterior eye segment non-invasively. Since conventional OCT measures only the backscattering intensity, it is often difficult to discriminate the tissues of the anterior eye segment to each other, such as conjunctiva, sclera, trabecular meshwork and small blood vessels. To enhance the contrast of these tissues, we develop a multi-functional swept-source OCT that can measure intensity, birefringence and Doppler flow images simultaneously. In addition to the structural intensity images, characteristic birefringence and Doppler flow of these tissues are imaged.

Polarization-sensitive (PS) optical coherence tomography (OCT) allows for depth-resolved measurement of light polarizing properties of different layers in the human retina. Since their inherent polarizing properties are different, the retinal structures can be identified using PS-OCT. We present an improved PS-OCT instrument for in vivo imaging of healthy and diseased human retinas. The system is based on spectral-domain (SD) PS-OCT operating at an A-line rate of 20 kHz. Different scan patterns and trigger signals are controlled by a field-programmable gate array (FPGA). By integration of an additional detection channel in the source arm of the OCT system, scanning laser ophthalmoscope (SLO) images can be recorded. Images of healthy and diseased human retinas are presented.

An application of swept-source polarization sensitive optical coherence tomography (PS-OCT) to anterior eye is presented. The image properties of anterior eye segments in PS-OCT images are discussed. The ability of PS-OCT to visualize trabecular meshwork is evaluated. For this evaluation, 25 normal subjects were involved. The visibility of trabecular meshwork in PS-OCT images of the subjects were scored by 2 graders. The grading score were then statistically analyzed. This analysis shows a statistically significant improvement of the visibility of trabecular meshwork in PS-OCT images against conventional intensity OCT images. A birefringent artifact appeared in anterior eye segment OCT image is also discussed.

The oxygen saturation of blood inside retinal vessels is an essential measure for the estimation of oxygen supply to the tissue as well as its oxygen consumption. In the current approach, the blood oxygenation is measured by a dual-wavelength technique. Using a fundus camera, equipped with a special dual wavelength transmission filter and a color CCD camera, two monochromatic fundus images at 548 nm and 610 nm were recorded simultaneously. The optical densities of retinal vessels for both wavelengths and their ratio, which is known to be proportional to the oxygen saturation, were calculated. From a health control population, mean arterial and venous oxygen saturations were measured of 98±10.1% and 65±11.7% with reproducibility of 2.52% and 3.25% respectively. In 10 patients with arterial occlusion, a reduction of the arterial oxygen saturation to 78 ±17% (mean ± standard deviation, branch arterial occlusion) and 91±11% (central arterial occlusion) respectively was found in the occluded vessel. After 5 days on pentoxifilin therapy, the arterial saturation increased to an average of 93±12% or 103 ±6% respectively. In 70 eyes of 42 patients suffering from diabetic retinopathy, an increase of the venous oxygen saturation with the severity of the retinopathy was found (mild nonproliferative retinopathy: 68.4±8.2%, moderate non-proliferative retinopathy: 70.5±6.8%, severe non-proliferative retinopathy: 72.4±7.6%, proliferative retinopathy 75.7±8.3%) due to vessel shunting and diabetic changes of the permeability of vessel walls. These first clinical results demonstrate the ability of an accurate measurement of retinal vessel oxygenation with a very simple setup just requiring a special filter in the illumination path of a fundus camera and dedicated software.

In this submission we demonstrate a new application of the joint Spectral and Time domain Optical Coherence Tomography (STdOCT) technique for segmenting and measuring the retinal blood flow velocity in three dimensions. The method is based on direct detection of Doppler shift that arises in time during the measurement. New scanning protocols and analysis tools are proposed to create velocity distribution maps of the retina and to segment and visualize 3D vasculature of human eye in-vivo. STdOCT segmentation is more sensitive than methods based on phase measurements and calculations are more straightforward than other techniques, which require more complex experimental setup and more sophisticated numerical tools. The usage of ultra-fast line scan camera allows to broaden the axial velocity range up to ±24mm/s, thus all high flows in human retina can be registered.

The purpose of this study is to explore the possibility that oxygen (O2) diffusion out of the retinal artery (RA) can explain the observed significant (P<0.001) decrease of oxygen saturation (O2Sat) in RA as intraocular pressure (IOP) is raised from 10 to 55 mmHg. Hyperspectral image data from normal monkeys' optic nerve head (ONH) and overlying retinal blood vessels were recorded at IOP settings of 10, 30, 45 and 55 mmHg. Average percent O2Sat values of the RAs were found from the recorded blood spectra by comparing to reference spectra from saturated and desaturated red cell suspensions. Percent O2Sat of the RAs was 78.9% at IOP of 10 mmHg. This decreased to 74.1% at 45 mmHg (P=0.01); and further decreased to 51.5% at IOP = 55 mmHg (P<0.0001). To interpret these results, we developed a simple diffusion model assuming that the RA is surrounded by tissues in equilibrium with venous oxygen tension (PO2). O2 flux across the arterial wall was calculated by Fick's law. The percentage of O2 diffusing out of the RA were 0.6% at IOP of 10 mmHg, and 38% at IOP of 55 mmHg. Confirmation still requires measurement of blood velocity.

In patterned scanning laser photocoagulation, shorter duration (< 20 ms) pulses help reduce thermal damage beyond the photoreceptor layer, decrease treatment time and minimize pain. However, safe therapeutic window (defined as the ratio of rupture threshold power to that of light coagulation) decreases for shorter exposures. To quantify the extent of thermal damage in the retina, and maximize the therapeutic window, we developed a computational model of retinal photocoagulation and rupture. Model parameters were adjusted to match measured thresholds of vaporization, coagulation, and retinal pigment epithelial (RPE) damage. Computed lesion width agreed with histological measurements in a wide range of pulse durations and power. Application of ring-shaped beam profile was predicted to double the therapeutic window width for exposures in the range of 1 - 10 ms.

We report the evaluation of a system which delivers the 5th harmonic of an Nd:YAG (213nm) via optical fibre to ocular tissue sites. The 213nm beam is concentrated, using a hollow glass taper, prior to launch into 200 μm or 600 μm core diameter silica/silica optical fibre. The fibre tip was tapered to enhance the fluence delivered. An operating window of fluence values that could be delivered via 330 - 1100mm lengths of optical fibre was determined. The lower value of 0.2J/cm² determined by the ablation threshold of the tissue and the upper value of 1.3J/cm² by the launch, transmission and tip characteristics of the optical fibre. The fluence output decreased as a function of both transmitted pulse energy and number of pulses transmitted. Fresh retinal tissue was cleanly ablated with minimal damage to the surrounding tissue. Lesions were generated using 1, 3 and 10 pulses with fluences from 0.2 to 1.0J/cm². The lesion depth demonstrated clear dose dependence. Lesions generated in ex vivo preparations of human trabecular meshwork in a fluid environment also demonstrated dose dependence, 50 pulses being sufficient to create a hole within the trabecular meshwork extending to Schlemm's canal. The dose dependence of the ablation depth combined with the ability of this technique to create a conduit through to Schlemm's canal demonstrates the potential of this technique for ophthalmological applications requiring precise and controlled intraocular tissue removal and has potential applications in the treatment and management of glaucoma.

The structural modifications of the collagen lattice induced in corneal stroma by laser welding were investigated with second-harmonic-generation (SHG) imaging. Corneal laser welding lies in the staining of the wound with a saturated solution of ICG followed by irradiation with a near-infrared-laser operated in continuous (CWLW) or pulsed (PWL) mode. After CWLW the lamellar arrangement was lost although a densely packing of collagen bundles increasingly disordered remained still clearly visible pointing out the lack of complete collagen denaturation. PLW produced welding spots which were characterized by a severe loss of SHG signal suggesting the occurrence of a complete collagen denaturation.

Conclusion: The current data are consistent with a potential photochemical effect of in vivo exposure of the crystalline lens to near infrared radiation since the onset of cataract after in just above threshold dose was at least 18 hrs delayed after the exposure. Materials and methods: The eyes of 6 weeks old Sprague-Dawley rats were exposed unilaterally in vivo to 1090 nm, 6.2 W quasi-top hat spatial distribution with a 3 mm spot on the anterior lens surface within the dilated pupil. First, four exposure time groups of rats were exposed to increasing exposure times. At 24 hrs after exposure, the difference of light scattering between the lenses from the same animal was measured. Then, based on the first experiment, four post-exposure time groups were exposed unilaterally in vivo to 8 s of 1090 nm, 6.2 W quasi-top hat spatial distribution with a 3 mm spot on the anterior lens surface within the dilated pupil. After, the intended post-exposure time, the difference of light scattering between the lenses from the same animal was measured. Results: A 3 mm spot of 6.2 W induces light scattering in the lens with exposures of at least 8 s. Further, after 8 s of 6.2 W within a 3 mm spot on the lens surface, the light scattering increase in the lens was delayed at least 18 hrs after the exposure.

We describe and compare two volume visualization methods for Optical Coherence Tomography (OCT) retinal data sets. One of these methods is CPU-slicing, which is previously reported and used in our visualization engine. The other is GPU-ray casting. Several metrics including image quality, performance, hardware limitations and perception are used to grade the abilities of each method. We also discuss how to combine these methods to make a scalable volume visualization system that supports advanced lighting and dynamic volumetric shadowing techniques on a broad range of hardware. The feasibility of each visualization method for clinical application as well as potential further improvements are discussed.

Presbyopia is the age related, gradual loss of accommodation, mainly due to changes in the crystalline lens. As part of research efforts to understand and cure this condition, ex vivo, cross-sectional OCT images of crystalline lenses were obtained and analyzed to extract their physical and optical properties. The raw OCT images are distorted, as the probing beam passing through media of different refractive indices and refraction on curved surfaces. In a first step, various filters, edge detection and pattern matching methods are applied to isolate the edge contour. An ellipse is fitted to the lens outline to obtain central reference point for transforming the pixel data into the analysis coordinate system. This allows for the fitting of high order equation to obtain a mathematical description of the edge contour, which obeys constraints of continuity as well as zero to infinite surface slopes from apex to equator. Robustness of these algorithms are tested by analyzing the images at various contrast levels. Gradient refractive index of the lens is determined and the physical shape is reconstructed. In a further refinement, the refraction on the curved anterior surface is compensated to obtain the actual shape of the posterior surface. Once the physical shape is fully reconstructed, the optical properties are determined by fitting conic sections to both surfaces and calculating the power profile across the lens. The relative contribution of each of these refinement steps is investigated by comparing their influence on the effective power of the lens.

The corneal endothelium serves as the posterior barrier of the cornea. Factors such as clarity and refractive properties of the cornea are in direct relationship to the quality of the endothelium. The endothelial cell density is considered the most important morphological factor. Morphometry of the corneal endothelium is presently done by semi-automated analysis of pictures captured by a Clinical Specular Microscope (CSM). Because of the occasional need of operator involvement, this process can be tedious, having a negative impact on sampling size. This study was dedicated to the development of fully automated analysis of images of the corneal endothelium, captured by CSM, using Fourier analysis. Software was developed in the mathematical programming language Matlab. Pictures of the corneal endothelium, captured by CSM, were read into the analysis software. The software automatically performed digital enhancement of the images. The digitally enhanced images of the corneal endothelium were transformed, using the fast Fourier transform (FFT). Tools were developed and applied for identification and analysis of relevant characteristics of the Fourier transformed images. The data obtained from each Fourier transformed image was used to calculate the mean cell density of its corresponding corneal endothelium. The calculation was based on well known diffraction theory. Results in form of estimated cell density of the corneal endothelium were obtained, using fully automated analysis software on images captured by CSM. The cell density obtained by the fully automated analysis was compared to the cell density obtained from classical, semi-automated analysis and a relatively large correlation was found.

Our aim was to fabricate a bench-top physical model eye that closely replicates anatomical and optical properties of the average human eye, and to calibrate and standardize this model to suit normal viewing conditions and subsequently utilize it to understand the optical performance of corrective lens designs; especially multifocal soft contact lenses. Using available normative data on ocular biometrics and Zemax ray-tracing software as a tool, we modeled 25, 45 and 55 year-old average adult human eyes with discrete accommodation levels and pupil sizes. Specifications for the components were established following manufacturing tolerance analyses. The cornea was lathed from an optical material with refractive index of 1.376 @ 589 nm and the crystalline lenses were made of Boston RGP polymers with refractive indices of 1.423 (45 & 55yr) and 1.429 (25yr) @ 589 nm. These two materials served to model the equivalent crystalline lens of the different age-groups. A camera, the acting retina, was hosted on the motor-base having translatory and rotary functions to facilitate the simulation of different states of ametropia and peripheral refraction respectively. We report on the implementation of the first prototype and present some simulations of the optical performance of certain contact lenses with specific levels of ametropia, to demonstrate the potential use of such a physical model eye. On completion of development, calibration and standardization, optical quality assessment and performance predictions of different ophthalmic lenses can be studied in great detail. Optical performance with corrective lenses may be reliably simulated and predicted by customized combined computational and physical models giving insight into the merits and pitfalls of their designs

Recent research showed that the peripheral refractive state is a sufficient stimulus for myopia progression. This finding led to the suggestion that devices that control peripheral refraction may be efficacious in controlling myopia progression. This study aims to understand whether the optical effect of such devices may be affected by near focus. In particular, we seek to understand the influence of accommodation on peripheral refraction and curvature of field of the eye. Refraction was measured in twenty young subjects using an autorefractor at 0° (i.e. along visual axis), and 20°, 30° and 40° field angles both nasal and temporal to the visual axis. All measurements were conducted at 2.5 m, 40 cm and 30 cm viewing distances. Refractive errors were corrected using a soft contact lens during all measurements. As field angle increased, refraction became less hyperopic. Peripheral refraction also became less hyperopic at nearer viewing distances (i.e. with increasing accommodation). Astigmatism (J180) increased with field angle as well as with accommodation. Adopting a third-order aberration theory approach, the position of the Petzval surface relative to the retinal surface was estimated by considering the relative peripheral refractive error (RPRE) and J180 terms of peripheral refraction. Results for the estimated dioptric position of the Petzval surface relative to the retina showed substantial asymmetry. While temporal field tended to agree with theoretical predictions, nasal response departed dramatically from the model eye predictions. With increasing accommodation, peripheral refraction becomes less hyperopic while the Petzval surface showed asymmetry in its change in position. The change in the optical components (i.e. cornea and/or lens as opposed to retinal shape or position) is implicated as at least one of the contributors of this shift in peripheral refraction during accommodation.

We propose a novel theoretical design of gradient index (GRIN) multifocal contact lens (MFCL) to compensate presbyopia and make predictions regarding its performance on a schematic model eye and to compare its performance with conventional aspheric progressive MFCL.

Electronic retinal prostheses seek to restore sight in patients with retinal degeneration by delivering pulsed electric currents to retinal neurons via an array of microelectrodes. Most implants use inductive or optical transmission of information and power to an intraocular receiver, with decoded signals subsequently distributed to retinal electrodes through an intraocular cable. Surgical complexity could be minimized by an "integrated" prosthesis, in which both power and data are delivered directly to the stimulating array without any discrete components or cables. We present here an integrated retinal prosthesis system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a video goggle projection system operating at near-infrared wavelengths (~ 900 nm). Photodiodes convert light into pulsed electric current, with charge injection maximized by specially optimized series photodiode circuits. Prostheses of three different pixel densities (16 pix/mm², 64 pix/mm², and 256 pix/mm²) have been designed, simulated, and prototyped. Retinal tissue response to subretinal implants made of various materials has been investigated in RCS rats. The resulting prosthesis can provide sufficient charge injection for high resolution retinal stimulation without the need for implantation of any bulky discrete elements such as coils or tethers. In addition, since every pixel functions independently, pixel arrays may be placed separately in the subretinal space, providing visual stimulation to a larger field of view.

Subretinal neovascular membranes (SRNM) are a deleterious complication of laser eye injury and retinal diseases such as age-related macular degeneration (AMD), choroiditis, and myopic retinopathy. Photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) drugs are approved treatment methods. PDT acts by selective dye accumulation, activation by laser light, and disruption and clotting of the new leaky vessels. However, PDT surgery is currently not image-guided, nor does it proceed in an efficient or automated manner. This may contribute to the high rate of re-treatment. We have developed a multimodal scanning laser ophthalmoscope (SLO) for automated diagnosis and image-guided treatment of SRNMs associated with AMD. The system combines line scanning laser ophthalmoscopy (LSLO), fluorescein angiography (FA), indocyanine green angiography (ICGA), PDT laser delivery, and retinal tracking in a compact, efficient platform. This paper describes the system hardware and software design, performance characterization, and automated patient imaging and treatment session procedures and algorithms. Also, we present initial imaging and tracking measurements on normal subjects and automated lesion demarcation and sizing analysis of previously acquired angiograms. Future pre-clinical testing includes line scanning angiography and PDT treatment of AMD subjects. The automated acquisition procedure, enhanced and expedited data post-processing, and innovative image visualization and interpretation tools provided by the multimodal retinal imager may eventually aid in the diagnosis, treatment, and prognosis of AMD and other retinal diseases.

A new instrument has been developed and built to measure the spatially resolved optical power of intra-ocular and contact lenses. Currently available instruments are based on either Hartmann Shack or Moiré Fringe techniques, which both have inherent limitations in terms of measurement range, sensitivity and achievable lateral resolution. Our new method uses a narrow laser beam which is scanned paraxially across the surface of the lens. The angle of the deflected beam is determined by capturing the lateral laser spot position at two different axial locations by means of a beam-splitter and two position sensitive, optical detectors. From the matrix of deflection angles, the spherical and cylindrical power components as well as higher order aberrations can be extracted and displayed as spatially resolved power maps. While measurement speed is compromised due to the scanning operation, the achievable lateral resolution can be as high as 20μm and the power accuracy in the order of milli-diopters. Soft contact lenses and foldable IOLs can be placed in wet cells to maintain hydration and form stability. Sample measurements of contact and intra ocular lenses are presented.

As the use of lasers proliferate in military and civilian applications, the importance of laser eye protection becomes increasingly significant. Of particular relevance is protection from non-visible laser sources operating in the near-infrared, as it is impossible to determine when the eye is being exposed to such harmful radiation. Current technologies for laser eye protection, such as dyes or reflective coatings of visors/glasses, are generally bulky, which presents a challenge for use and integration with oxygen masks, helmets and night vision apparatus. A contact-lens based laser eye protection system would offer the advantage of minimal modification of current equipment to provide protection against laser exposure. A laser eye protection system has been developed based on the unique optical properties of gold nanoshells. Gold nanoshells consist of a dielectric silica core, surrounded by a thin (nm) shell of gold. By adjusting the core size and the shell thickness, these nanoparticles can provide high extinction levels throughout the near-infrared region of the spectrum. Unlike some organic dyes, the particles are photostable and non-toxic, increasing the practical life of the lens. The design and fabrication of a soft contact lens containing nanoshells is described. The optical and physiochemical properties are compared to a standard soft contact control. The results of preliminary toxicity studies are also presented

Hypoxia induced corneal swelling was observed and evaluated in healthy human volunteers by use of high speed, ultrahigh resolution optical coherence tomography (UHROCT). Two dimensional corneal images were acquired at a speed of 47,000 A-scans/s with 3µm x 10µm (axial x lateral) resolution in corneal tissue. The UHROCT tomograms showed clear visualization of all corneal layers, including the Bowman's layer and the Descemet's membrane - Endothelium complex. A segmentation algorithm was developed and used for automatic detection of the boundaries of the different corneal layers and evaluation the individual layer thickness as a function of location. Corneal hypoxia was induced by wear of a soft contact lens (SCL) and an eye patch by 2 healthy volunteers for duration of 3 hours. The thickness of all corneal layers was measured as a function of time, prior to, with and after removal of the SCL. Results from the hypoxia study showed different rates of swelling and de-swelling of the individual corneal layers. About 10% increase in the total cornea thickness was observed, similar to the changes in the stroma, the Bowman's membrane swelled by 20%, while no significant change in the thickness was observed in the Descemet's - Endothelium complex.

Aside from other ocular drug delivery methods, topical application and follow up drug diffusion through the cornea and sclera of the eye remain the favored method, as they impose the least pain and discomfort to the patient. However, this delivery route suffers from the low permeability of epithelial tissues and drug washout, thus reducing the effectiveness of the drug and ability to reach its target in effective concentrations. In order to better understand the behavioral characteristics of diffusion in ocular tissue, a method for noninvasive imaging of drug diffusion is needed. Due to its high resolution and depth-resolved imaging capabilities, optical coherence tomography (OCT) has been utilized in quantifying the molecular transport of different drugs and analytes in vitro in the sclera and the cornea. Diffusion of Metronidazole (0.5%), Dexamethasone (0.2%), Ciprofloxacin (0.3%), Mannitol (20%), and glucose solution (20%) in rabbit sclera and cornea were examined. Their permeability coefficients were calculated by using OCT signal slope and depth-resolved amplitude methods as function of time and tissue depth. For instance, mannitol was found to have a permeability coefficient of (8.99 ± 1.43) × 10^-6 cm/s in cornea (n=4) and (6.18 ± 1.08) × 10^-6 cm/s in sclera (n=5). We also demonstrate the capability of OCT technique for depth-resolved monitoring and quantifying of glucose diffusion in different layers of the sclera. We found that the glucose diffusion rate is not uniform throughout the tissue and is increased from approximately (2.39 ± 0.73) × 10^-6 cm/s at the epithelial side to (8.63 ± 0.27) × 10^-6 cm/s close to the endothelial side of the sclera. In addition, discrepancy in the permeability rates of glucose solutions with different concentrations was observed. Such diffusion studies could enhance our knowledge and potentially pave the way for advancements of therapeutic and diagnostic techniques in the treatment of ocular diseases.

Probing the retina with flicker light of defined frequencies allowed to offset the detection for intrinsic signals from proband motion artifacts as well as blood flow. In addition the fast imaging sequence capability of FDOCT is promising for the assessment of fast physiologic changes within retinal structures. For the present study two measurement protocols are evaluated: first, taking fast tomogram series across a flickered region, and then constructing via frequency analysis and bandpass filtering a functional OCT tomogram similar to fMRI. The second protocol consists of a fast local A-scan series at 17kHz rate with 1Hz flicker. 'Light-on' time is 250ms. 'Lights off' time is 750ms. 500ms before 'light-on' is used for calculating the baseline. Finally the average over 5 cycles is taken. A clear negative response is found at the outer photoreceptor segment for both 'light-on' and 'light-off' edge. The response appears to be stronger for the 'light off' edge. The shape of the responses is analysed and might eventually be used in linear regression models to enhance the sensitivity of our fOCT approach.

A system for ophthalmic surgery support has been developed in order to minimize the residual astigmatism due to the induced irregular shape of the cornea by corneal suture. The system projects 36 light spots, from LEDs, displayed in a precise circle at the lachrymal film of the examined cornea. The displacement, the size and deformation of the reflected image of these light spots are analyzed providing the keratometry and the circularity of the suture. Measurements in the range of 32D - 55D (up to 23D of astigmatism are possible to be obtained) and a self-calibration system has been designed in order to keep the system calibrated. Steel precision spheres have been submitted to the system and the results show 99% of correlation with the fabricant's nominal values. The system has been tested in 13 persons in order to evaluate its clinical applicability and has been compared to a commercial keratometer Topcon OM-4. The correlation factors are 0,92 for the astigmatism and 0.99 for the associated axis. The system indicates that the surgeon should achieve circularity ≥98% in order to do not induce astigmatisms over 3D.

According to recent studies, an increase in corneal stiffness is a promising alternative for avoiding ectasias and for stagnating keratoconus of grades 1 and 2. The clinical treatment consists essentially of instilling Riboflavin (vitamin B2), in the cornea and then irradiating the corneal tissue, with UVA (365nm) radiation at 3mW/cm2 for 30min. This procedure provides collagen cross-linking in the corneal surface, increasing its stiffness. This work presents a system for UVA irradiation of the corneas at a peak wavelength of 365nm with adjustable power up to 5mW. The system has closed loop electronics to control the emitted power with 20% precision from the sated power output. The system is a prototype for performing corneal cross-linking and has been clinically tested. The closed loop electronics is a differential from the equipments available on the market.

We present novel technology for extension in depth of focus of imaging lenses for use in ophthalmic lenses correcting myopia, hyperopia with regular/irregular astigmatism and presbyopia. This technology produces continuous focus without appreciable loss of energy. It is incorporated as a coating or engraving on the surface for spectacles, contact or intraocular lenses. It was fabricated and tested in simulations and in clinical trials. From the various testing this technology seems to provide a satisfactory single-lens solution. Obtained performance is apparently better than those of existing multi/bifocal lenses and it is modular enough to provide solution to various ophthalmic applications.

A new automatic visualization procedure for the oxygen saturation imaging from multi-spectral imaging of human retinal vessels has been proposed. Two-wavelength retinal fundus images at 545 and 560 nm, which were oxygen insensitive and oxygen sensitive, respectively, were captured by CCD cameras simultaneously through a beam splitter and interference filters. We applied a morphological processing technique to presume a distribution of incident light including the vessel parts and an optical density (OD) image of each wavelength image. And the OD ratio (OD₅₆₀/OD₅₄₅) image was calculated as a relative indicator of oxygen saturation. Furthermore, processing of line convergence index filter was adopted to identify the retinal vessels. Clear difference between retinal arteries and veins was observed in the automated imaging method. In addition, the decrease of oxygen saturation in the retinal artery without breathing could be monitored by the ODR. This method is possible to be applied to real-time monitoring for oxygen saturation of retinal vessels.

We used one of cyanine dyes as a spectral and fluorescent probe in the study of the composition of the extracellular matrix of the human eye (its vitreous body). Owing to the unique ability of the dye to bind to collagens and human serum albumin, we revealed the simultaneous presence of both types of biomacromolecules in the vitreous body. The formation of the dye complex with human serum albumin leads to appearance of a long-wavelength absorption band (~612 nm) and a steep rise of fluorescence, whereas in the presence of collagens the dye forms J-aggregates with a longer-wavelength absorption band (640-660 nm) and moderate fluorescence. In this work we studied the composition of the human fetus vitreous body and its dynamics from 9 to 31 gestation weeks. On the basis of the data obtained by this method, we may assume that albumin, being a carrier protein, probably provides the vitreous body and surrounding tissues with necessary growth factors, hormones, lipids, vitamins, and some other biomolecules. The data show that the dye is promising not only for study of albumin functions in eye development, but also for characterization of some eye diseases and for analysis of other extracellular media.

We developed an orange fiber laser as the light source for an ophthalmic photocoagulator with superior beam quality and focusing ability. An optical system was also fabricated to verify the spot size of the newly developed laser. It is a simple optical system without the zoom lenses of a conventional delivery system. The laser focal spot has a diameter of 6.8 μm as measured by the knife-edge method. We verified that the laser spot could be reduced to less than that of conventional systems by removing optical system aberrations using wavefront analysis and knife-edge method. However, the effect of laser irradiation cannot be verified with a conventional observation system of photocoagulator. Therefore, we fabricated a laser irradiation device to examine micro spots by modifying an optical microscope. We used our unique pseudo-biological tissue to verify the effect of high-brightness laser irradiation on a human eye. The pseudobiological tissue is comprised of albumin and human gelatin. The laser irradiation caused coagulation and heat denaturation to the pseudo-biological tissue. We evaluated the relationship of the irradiated area with the power intensity and irradiation time. As a result, the coagulation spot size was only slightly dependent on power intensity and irradiation time while the heat denaturation size was strongly dependent on them, especially on irradiation time. The effects of highbrightness laser irradiation will be thermally analyzed in a future paper.

The structural modifications in the stromal matrix induced by low-temperature corneal laser welding were investigated by atomic force microscopy (AFM). This procedure consists of staining the wound with Indocyanine Green (ICG), followed by irradiation with a near-infrared laser operated at low-power densities. This induces a local heating in the 55-65 °C range. In welded tissue, extracellular components undergo heat-induced structural modifications, resulting in a joining effect between the cut edges. However, the exact mechanism generating the welding, to date, is not completely understood. Full-thickness cuts, 3.5 mm in length, were made in fresh porcine cornea samples, and these were then subjected to laser welding operated at 16.7 W/cm² power density. AFM imaging was performed on resin-embedded semi-thin slices once they had been cleared by chemical etching, in order to expose the stromal bulk of the tissue within the section. We then carried out a morphological analysis of characteristic fibrillar features in the laser-treated and control samples. AFM images of control stromal regions highlighted well-organized collagen fibrils (36.2 ± 8.7 nm in size) running parallel to each other as in a typical lamellar domain. The fibrils exhibited a beaded pattern with a 22-39 nm axial periodicity. Laser-treated corneal regions were characterized by a significant disorganization of the intralamellar architecture. At the weld site, groups of interwoven fibrils joined the cut edges, showing structural properties that were fully comparable with those of control regions. This suggested that fibrillar collagen is not denatured by low-temperature laser welding, confirming previous transmission electron microscopy (TEM) observations, and thus it is probably not involved in the closure mechanism of corneal cuts. The loss of fibrillar organization may be related to some structural modifications in some interfibrillar substance as proteoglycans or collagen VI. Furthermore, AFM imaging was demonstrated to be a suitable tool for attaining three-dimensional information on the fibrillar assembly of corneal stroma. The results suggested that AFM analyses of resin-embedded histological sections subjected to chemical etching provide a rapid and cost-effective response, with an imaging resolution that is quite similar to that of TEM.

We present experimental results of investigation of the optical properties of the human eye sclera controlled by administration of osmotically active chemical, such as 40%-glucose solution. Administration of the chemical agent induces diffusion of matter and as a result equalization of the refractive indices of collagen and ground material. Results of the experimental study of influence of the glucose solution on the absorption and scattering properties of human sclera are presented. In vitro reflectance and transmittance spectra of the human sclera samples were measured by commercially available spectrophotometer CARY-2415 in the spectral range from 400 to 1800 nm. The reduced scattering coefficient of human sclera samples is significantly decreased under action of the osmotical solution were demonstrated.

Background and Objective: To evaluate the effect of an acute elevated intraocular pressure (IOP) on oxygen saturation of structures of the optic nerve head. Study Design/Materials and Methods: In the cynomolgus monkey eye, IOP was set to 10 mm Hg, and then raised to 30, 45, and 55 mm Hg. The ONH and overlying vessels were imaged using a fundus camera attached to a hyperspectral imaging system (HSI) at 10 and 30 minutes after IOP elevation. Results: Raising IOP from 10 to 30 mm Hg did not significantly (P < 0.0001) change saturation in vessels or ONH tissue structures but at 55 mm Hg, all structures showed significant reduction. Conclusions: Quantitative assay of the blood oxygen saturation in structures on the surface and overlying the optic nerve head is possible using hyperspectral imaging techniques.

When the iris of the Bottlenose dolphin (Tursiops truncatus) contracts it constrains the path of light that can focus onto the two areas of the retina having a finer retinal mosaic. Under high ambient light conditions the operculum of the iris shields the lens and forms in the process two asymmetrically shaped, sized and positioned slit pupils. Tracing rays of light in the reverse direction through the pupils from the retinal regions associated with higher resolution confirm behaviorally observed preferred aerial and underwater viewing directions. In the forward and downward viewing direction, the larger temporal pupil admits light that is focused by the weakly refractive margin of a bifocal lens onto the temporal area centralis compensating for the addition of the optically strong front surface of the cornea in air. A schematic dolphin eye model incorporating a bifocal lens offers an explanation for a dolphin's comparable visual acuities in air and water for both high and low ambient light conditions. Comparison of methods for curve fitting psychometric ogive functions to behavioral visual acuity and spectral sensitivity data are discussed.