Diabetic retinopathy (DR) and other eye diseases can affect artery and vein differently. Therefore, differential artery-vein analysis can improve disease detection and treatment assessment. This study aims to establish color fundus image analysis guided artery-vein differentiation in OCTA, and to verify that differential artery-vein analysis can improve the sensitivity of OCTA detection and classification of DR. Briefly, optical density ratio (ODR) analysis and blood vessel tracking were combined to identify artery-vein in color fundus images. The fundus artery-vein map was used to register arteries and veins in corresponding OCTA images. Based on the fundus image guided artery-vein differentiation, quantitative analysis of arteries and veins in control and NPDR OCTA images were performed. The sensitivities of traditional mean blood vessel caliber (m-BVC) and artery-vein ratio of BVC (AVR-BVC) were quantitatively compared for DR classification. One way, multi-label analysis of variance (ANOVA) with Bonferroni’s test and Student t-test was employed for evaluating classification performance. Images from 20 eyes of 18 control subjects and 48 eyes of 35 NPDR patients (18 mild, 16 moderate and 14 severe NPDR) were used for this study. Compared to m-BVC, AVR-BVC provided enhanced sensitivity in differentiating NPDR stages. AVR-BVC was able to differentiate among control and three different NPDR groups. AVR-BVC could also differentiate control from mild NPDR, promising a unique OCTA biomarker for detecting early onset of NPDR.

We propose a cross-scanning OCT (CS-OCT) system for motion-free OCT angiography without SLO or additional devices eye tracking devices. The CS-OCT system employs dual illumination configuration with orthogonally polarized beams, with the scanning directions of the two beams being perpendicular to each other. It scans the retina from two directions and provides two cross-sectional images simultaneously. In this way, the degree of eye movement can be easily identified and the two angiography images compensate each other for motion correction. Finally, we perform a non-rigid registration of the two images to obtain the motion-corrected image.

A high-resolution, motion-free, multi-contrast optical coherence tomography (OCT) method was developed for imaging posterior eye. The modified scan pattern from a Lissajous trajectory was applied to scan probing beam. Long imaging duration enables to acquire multiple samples with slight displacement due to eye motion. The high-dense sampling image can be obtained by re-mapping these data. Optical coherence tomography (OCT) signals are acquired using polarization-sensitive OCT system. The OCT angiography (OCT-A) signal were calculated and used to estimate eye motion. After motion correction of OCT, OCT-A, and degree-of-polarization uniformity (DOPU) images, capillary network and small abnormality were visualized without motion artifacts.

We demonstrate the advantages of optical coherence tomography (OCT) imaging for investigation of spontaneous retinal venous pulsation (SRVP). The pulsatile changes in venous vessel caliber are analyzed qualitatively and quantitatively using conventional intensity based OCT as well as the functional extension Doppler OCT. Single-channel and double-channel line scanning protocols of our time-encoded multi-channel OCT prototype are employed to investigate venous caliber oscillations as well as venous flow pulsatility in the eyes of healthy volunteers. A comparison to recordings of scanning laser ophthalmoscopy – a standard en-face imaging modality for evaluation of SRVP – is provided, emphasizing the advantages of tomographic image acquisition.

Oblique scanning laser ophthalmoscopy (oSLO) is a recently developed technique that offers high speed volumetric fluorescence imaging on retina in vivo. Unique from existing ophthalmoscopy, oSLO uses oblique illumination and detection, enabling 3D imaging over a large field of view without the need for depth scanning, essentially a fluorescence version of optical coherence tomography. In this presentation, we report the application of oSLO on volumetric fluorescein angiography in vivo on mouse retina. With the 3D capability and high speed, we provides quantitative metrics to measure spatially resolved capillary hematocrit and speed.

Adaptive Optics (AO) enables single-cell imaging in the retina of living animals. For small animal eyes, Sensorless AO can provide depth-resolved aberration correction with low system complexity. We present a multi-modal Sensorless AO retina imaging system that includes Optical Coherence Tomography (OCT), OCT-Angiography, confocal Scanning Laser Ophthalmoscopy (cSLO), and fluorescence detection. Our results demonstrate the system performance on wild type mice and transgenic mice with GFP labeled cells, including volumetric imaging of microglia throughout the inner retina. Dynamics of the microglia branches were clearly observed with time-lapse imaging over 1 hour.

There are two general types of photoreceptors, called rods and cones. Rods allow us to see in dim and dark light, cones allow us to perceive fine visual detail and color. The detailed structure and function of these specialized type of neurons that convert light into signals that can stimulate biological processes vary between species. Optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) are two main imaging technologies commonly used to study retina. Adaptive Optics (AO) is an “enabling” technology that provides high-fidelity correction of ocular aberrations in retinal imaging, resulting in improved resolution and sensitivity for both SLO and OCT systems. Here we present work integrating two recently developed technologies with our AO-OCT system to visualize mouse cone photoreceptors in vivo.

A multi-functional optical coherence tomography (OCT) approach, featuring polarization-sensitivity and angiography, was used to describe the retinal phenotype of a mouse model of age-related macular degeneration. Superoxide dismutase 1 (SOD1) knock-out mice were imaged in an age range from 159 to 368 days. Retinal thickness analysis revealed a thinner total and outer retina in the SOD1 mice compared to an age-matched control group. Hyper-reflective spots in the outer retina were found anterior to the retinal pigment epithelium in the proximity of the photoreceptors. The lesions showed a pseudodrusen-like appearance in the reflectivity and polarization contrast channels.

Currently, the only way to identify leaky vasculature, a key feature of several retinal diseases, is through fluorescence angiography, which lacks depth resolution. Here we present the first 4D tracking of leaky vasculature in a mouse model of sub-retinal neovascularization using contrast-enhanced OCT. OCT angiograms were acquired following intravenous injection of Intralipid 20%, an OCT contrast agent. Compared to healthy vessels, leaky vessels became broader over time. By fitting a model, the apparent width of the vessels was quantified as an indicator of leakage. A clear trend of increased leakage was observed in vessels that derive from retinal lesions.

The cornea is the clear outer window of the eye directly accessible using light-based approaches, providing us with a unique window into the physiology of the body. At the same time, the cornea is a model tissue from which we have acquired much knowledge about light-tissue interactions. Finally, and importantly, diseases of the cornea compromising its transparency are responsible for millions of cases of corneal blindness globally, so there is much to gain from technological advancements in the field. Here, a need for new technological solutions is presented, that is not primarily technology-driven but instead motivated by real and pressing medical needs in the research, diagnosis and treatment of corneal blindness.

We created a time-domain full-field OCT (FFOCT)-based device, capable of volumetric imaging in in vivo human eye. Testing on a steadily moving ex vivo cornea and a randomly moving in vivo human eye we were able to consistently acquire high-SNR images from different corneal layers, which altogether formed a 3D image. This consistent acquisition became possible by implementing a real-time defocus correction in FFOCT, which used the data about the corneal position from a Spectral-domain OCT as a feedback. Possibilities of real-time and volumetric corneal viewing make FFOCT instrument a promising candidate for becoming a new tool in ophthalmological diagnostics.

High speed optical coherence (OCT) systems allow for 4D visualizations in applications such as intraoperative OCT. However, traditional raster scan patterns often lead to distorted scans either due to the high frequency content or nonlinearity in the input signal. They also introduce significant acquisition dead time between scans. Continuous scan patterns no longer have acquisition dead times, but suffer from non-uniform sampling across the field of view. We introduce a new processing pipeline for constant linear velocity (CLV) spiral scanning to maximize the data acquisition efficiency, demonstrated real-time visualization of mock microsurgical procedures which can be viewed in virtual reality.

Optical coherence tomography (OCT) is currently recognized as the gold standard for identifying retinal structural abnormalities in ophthalmology. However, its availability is limited to large eye centers and research labs due to its high cost and lack of portability. We present a low-cost, portable OCT system with a total cost of materials under $6,000. Compared to current commercial systems, our design offers 50% size reduction and over 80% cost reduction. Image acquisition interface is incorporated and displayed onto a mounted 7-inch touchscreen. Human retinal imaging is demonstrated, and performance is compared with a commercial OCT system.

Imaging the entire human cornea with OCT usually requires trade-offs between resolution and depth-of-focus because of corneal curvature and the relatively deep anterior chamber. These trade-offs result in SNR variations such as decreasing intensity away from the apex. Here, we describe the development of an axial motion corrected dynamically focusing corneal OCT system coupled with constant linear velocity (CLV) spiral scanning that better maintains focus from the apex to corneal periphery during a scan. A subject was imaged with this system demonstrating increased intensity from the corneal apex to anterior chamber angle.

We describe the application of the Ray-Tracing Aberrometry to the measurement of lens spherical aberration using a recently developed instrument (Ruggeri et al. 2018). Fifty-four isolated human lenses were sampled with an 880 nm SLD in a raster scan pattern. Exit ray slopes over a 6 mm pupil were used to determine Zernike wavefront coefficients. The 4th order Zernike coefficient Z[4,0] was used to measure primary spherical aberration. The results suggest that spherical aberration of the growing lens becomes more negative before adulthood and less negative after ~30 years.

Our recent work has demonstrated viability of use of femtosecond oscillators to crosslink corneal tissue in absence of photosensitizers to correct refractive errors and enhance corneal mechanical properties. In this study we have shown that adjustment of the corneal curvature can be controlled through variation of the lasing and beam delivery parameters, which may correct the refractive errors with a resolution of approximately 0.75 diopter. Meanwhile corneal inflation tests showed statistically significant increase in stiffness in contrast to controls, in which no change has been observed. Furthermore, a new system design is proposed to reduce the procedure time to clinically acceptable duration.

Corneal ectasias lead to impaired vision and may require corneal transplantation. Corneal crosslinking (CXL) is used to treat ectasias by photochemically crosslinking the cornea. In this work, phase-decorrelation optical coherence tomography (PhD-OCT) is used as a tool to compare CXL protocols. There is interest in accelerating the CXL protocol, but efficacy of these treatments is unclear. Using PhD-OCT, it was observed in ex vivo porcine corneas that accelerated treatment crosslinks remain superficial. Additionally, there is interest in spatially patterned CXL to reduce astigmatism. When patterned CXL was performed on ex vivo porcine corneas, PhD-OCT volumes clearly show where crosslinking occurred.

There has been a large amount of research focused on the biomechanical properties of the lens and the related conditions such as presbyopia. However, the relationship between eye-globe intraocular pressure (IOP) and lenticular biomechanical properties is relatively unknown. In addition, the storage medium of the lenses may affect the biomechanical evaluation during in vitro measurements, which has been demonstrated with other tissues such as the cornea. In this work, we utilized optical coherence elastography (OCE) to measure acoustic radiation force induced elastic waves in in situ porcine lenses (N=3) at various IOPs. Additional OCE measurements were performed on excised lenses (N=3) stored at various temperatures (4°C, 22°C and 37°C) in Dulbecco's Modified Eagle Medium (DMEM).

The three spectral types of cone photoreceptors set fundamental limits on color perception. Classifying cone type is of significant clinical interest as absence of a type causes color blindness and type-specific dysfunction is associated with aging and retinal disease. In vivo mapping of the trichromatic cone mosaic provides the most direct and quantitative means to assess the role photoreceptors play in color vision and disease, but current methods have important limitations. We present a new method for classifying cones that achieves unprecedented efficiency and accuracy by using the unique phase response of cones to flashes of light.

The ganglion cell (GC) is the primary cell type damaged by diseases of the optic nerve such as glaucoma. Assessment of individual glaucoma risk is limited by our inability to accurately measure GC degeneration and loss. Recently, adaptive optics optical coherence tomography (AO-OCT) has enabled visualization and quantification of individual GC layer somas. We assess the ability of our AO-OCT method to track individual GCL somas over a period of one year and of our post processing methods to reliably measure soma loss rates associated with normal aging and glaucomatous progression.

Using phase-sensitive full-field swept-source optical coherence tomography we already showed that morphological changes in the photoreceptor outer segments are detectable. Those signals manifest themselves by an elongation of the optical path length. Using an improved post processing we are now able to detect those signals in the ganglion cell layer as well. The spatially resolved signals showed a characteristic time course. Combining this with the previous results we were able to generate a wiring map of the neuronal retina.

Retinal ganglion cells (RGC) and photoreceptors play a vital role in retinal neural circuitry. Much remains unknown about the morphological correspondence between the two in living human eyes. A major bottleneck has been our inability to observe both neurons simultaneously. We present a novel method based on multimodal adaptive optics to simultaneously image both cell types. In one subject, we identified a region of photoreceptor loss that corresponded to RGC enlargement and decreased density. The method may eventually provide a useful tool to noninvasively examine signal transduction pathways along retinal neural circuitry in the living human eyes.

AO-OCT enables cellular-level imaging of human retina, and offers the potential for improved disease detection. A semi-automated AO-OCT cone identification routine was developed and its performance on images from healthy retina and dry age-related macular degeneration (AMD) are presented here. In AMD, results indicate that cone outer segments become more deformed over drusen than inner segments. Application of this procedure and a quantitative analysis of cone outer segment tip layer variation were applied to the detection of emerging drusen too small to be visualized in clinical OCT.

We propose a study to better understand the impact of dynamic ocular aberrations in the axial resolution of nonconfocal adaptive optics (AO) ophthalmoscopes via a simulation of the 3D PSF in the retina for various AO-loop rates. We then use Optical Incoherence Tomography (OIT), a method enabling the generation of tomographic retinal cross-sections in incoherent imaging systems, to evaluate the benefits of a fast AO-loop rate on axial resolution and consequently on AO-corrected retinal image quality. We used the PARIS AO flood-illumination ophthalmoscope (FIO) for this study, where retinal images from different focal planes at an AO-loop rate of 10 Hz and 50 Hz were acquired.

A Swept Source-Optical Coherence Tomography system was developed for imaging the ciliary muscle with faster speed and greater contrast to enable full characterization of the dynamics of accommodative behavior of the muscle. A dynamic response from a 30 year old subject at 50 Hz with incident power of 22 mW is shown as a proof-of-concept. Improved visualization of the muscle will allow future studies to determine the exact role of the ciliary muscle in the age related conditions such as presbyopia.

Knowledge about tumor stage and grade is paramount for decision making in tumor treatment. Here we present a quantitative study of tumor growth assessed by observing the change in its micro-vascularization. To extract tumor vasculature, we have applied phase variance-based OCT Angiography (OCTA) method, an optical non-invasive imaging technique, that relies on the change in optical phase due to Red Blood Cells (RBC) flow within the vasculature of a tumor. However, the adopted technique is deteriorated due to the speckle noise, an inherent artifact of any coherence imaging technique, that influences significantly the transversal resolution of OCT. To address this problem, we present an enhanced visualization of tumor neovascularization through averaging of multiple OCT volumes. Several results comparing images obtained with number of average volumes will be presented and analyzed for improvement in image quality.

The ambitious goal of this project is to show ability of detection of ocular motions like eye drifts, saccades and microsaccades with an ultrafast optoelectronic device that provides up to 1200 images/s from the living human eye. Data registered by the FreezEye tracker may be then used for image stabilization purpose or early detection diseases related with eye movements disorders: central nervous system diseases or injures, ocular tumor, diabetes or general hypertension disease).

Recently, in vivo trans-conjunctiva optical coherence tomography (OCT) imaging of the lacrimal canaliculus (LC) using a commercial eye drop as an extrinsic contrast agent was reported. The extrinsic contrast agent, including light-scattering particles that flow and undergo Brownian motion, can be used for dynamic OCT to enhance LC image, enabling unambiguous segmentation. We characterized the dynamic OCT properties of the eye drop, and then performed unambiguous segmentation of the lumen of the LC by comparing three kinds of dynamic OCT images as well as a static OCT image. Three-dimensional volumetric images of LC embedded under the conjunctiva were demonstrated.

We report that a large field of view (FOV) retinal image can be acquired by a low-cost smart fundus camera. This handheld system includes a Raspberry Pi board, a touch screen display, a customized optical lens group, a ring LED light, and a Li-battery. Based on the open hardware platform and Linux operating system, we have integrated the portable system with component switching and image processing functions. Wide FOV has been realized using image stitching and structure from motion algorithms. This customized low-cost handheld fundus camera provides better image quality than cellphone-based fundus imaging solutions and offers more operational features than traditional portable fundus cameras. It may benefit field portable ophthalmic diagnostic applications.

Sunglasses standards only require ultraviolet protection in the spectral range of 280- 380nm to ensure the limits for effective spectrally weighted radiant exposure. None of them take into account the World Health Organization safe limits for unweighted. Calculations of limits for 27 Brazilian state capitals show that for the 280-400 nm range the ultraviolet radiant exposure is 49 % greater than WHO’s limit for the 280- 380 nm range. The condition is similar to countries in Europe and in the US. Inclusion of safe limits in sunglasses standards for ocular health safety. Blue light limits should be included as well.

Optical Coherence Tomography Angiography (OCTA) is a powerful tool that allows in-vivo visualization of 2D and 3D retinal microvascular networks at micrometer-level resolution. However, quality of OCTA images are often hindered by the noise and poor contrast. Hessian based enhancement filters have been reported to be a promising tool allowing enhancement of vascular structures. In this paper, a modified enhancement filter based on the ratio of multiscale Hessian eigenvalues have been demonstrated to improve OCTA images quality. The enhanced performance of the proposed filter was evaluated and compared to the reported state-of-the art filters using an OCTA images of a mouse retina.

Differential artery-vein analysis is valuable for early detection of diabetic retinopathy (DR) and other eye diseases. As a new optical coherence tomography (OCT) imaging modality, emerging OCT angiography (OCTA) provides capillary level resolution for accurate examination of retinal vasculatures. However, differential artery-vein analysis in OCTA, particularly for macular region in which blood vessels are small, is challenging. In coordination with an automatic vessel tracking algorithm, we report here the feasibility of using near infrared OCT oximetry to guide artery-vein classification in OCTA of macular region.

Modern day ophthalmologists and eye care professionals feel an urgent need for more cost effective and smarter instrumentation for the early diagnosis of Glaucoma, a leading disease in the cause of blindness worldwide. One of the methods for precise diagnosis of Glaucoma is measuring the optic disc nerve excavassion progress. In this work we have developed the instrumentation and algorithms for a cost-effective 3D retinal camera that uses the stacking technique for focus improvement of stereo. We demonstrate here that this technique improves depth computation algorithm in up to 20%.

The hyaloid vascular system (HVS) is a transient capillary network nourishing developing eye. Currently, there is a lack of noninvasive imaging techniques for functional investigation of the HVS with high spatial and temporal resolutions. In this study, we demonstrated the feasibility of longitudinal optical coherence tomography angiography (OCTA) observation of the HVS regression in C57BL/6J mice. Longitudinal 3D OCT/OCTA measurements were conducted at 2-week, 3-week, and 4-week age by using a custom-designed OCT system. Three-dimensional OCT volume was acquired over 1.2 mm x 1.2 mm x 1.05 mm, containing a part of the lens tip, vitreous chamber, and the retina. Both OCT and OCTA successfully detected the hyaloid vessels, but OCTA benefits visualizing functional preservation of the blood vessels. OCTA images at 4-week age revealed functional loss of hyaloid vessels; while the OCT images still showed vascular remnants. We anticipate that longitudinal OCT/OCTA observation will be helpful to unravel the complex mechanism of the involution of the HVS correlated with eye development.

Photoacoustic microscopy (PAM) represents a powerful imaging technique for biomedical imaging and diagnosis due to non-invasive, nonionizing, high-resolution, and excellent sensitivity. Colloidal gold nanoparticles have been applied as exogenous contrast agent To boost the sensitivity, increase contrast, and allow molecular imaging and combined therapy (theranostics). However, their low photoacoustic efficiency in the tissue transparent window limits their clinical application. The current study presents biocompatible cluster blue gold nanoparticles as a novel photoabsorbing agent for dual-functional PAM and photodynamic therapy (PDT) due to its strong near-infrared absorption and high efficiency of photothermal conversion. Ultra-pure functionalized blue gold nanoparticles (GNPs) were synthesized by femtosecond laser, clustering a group of 3-4 colloidal nanoparticles, conjugated with RGD ligands, and delivered to 18 New Zealand rabbits. Retinal neovascularization was achieved through an intravitreal injection of vascular endothelial growth factor. All the rabbits were irradiated with laser light at a wavelength of 650 nm, and laser irradiance of 50, 75 and 100 mg/cm2 for 20 min. The functionalized GNPs, particle size of 60 nm, peak absorption at 650nm, were demonstrated to have excellent biocompatibility in bovine retinal endothelial cells and HeLa cells. The PA amplitudes from the retinal neovascularization (RNV) was enhanced by up to 4-fold after injection of GNPs at concentration of 1 mL/kg. In vivo PDT experiment exhibited that the RNV vessels were significantly reduced at day 2 post-treatment with a GNPs-assisted laser in comparison with rabbit treated with laser only. Blue GNPs can serve as efficient and safe multi-functional agents for visualization and treatment of neovascularization.

Afterimages are artifacts produced on the retina after an exposure to a bright light or image. The number of positive afterimages produced was determined among eight subjects based on LED array distance and monocular vs. binocular vision. It was found that significant changes in the quantity of afterimages produced was observed only when the LED array panel was opposite to the eye being exposed in a monocular test condition as opposed to when the test panel was adjacent to the eye being tested. Significant changes also occurred between distances within the binocular testing condition.

Spectral domain optical coherence tomography (SD-OCT), infra-red and multicolor fundus imaging were used to monitor efficacy and safety of therapeutics into the suprachoroid of domestic pigs. Vital dyes and triamcinolone acetonide were injected into the suprachoroid using a novel minimally-invasive adjustable-depth blunt injector. Imaging analysis demonstrated that injected therapeutics covered over 80% of the posterior eye surface with no retinal detachment, hemorrhages or inflammation up to one month following injection. Multimodal imaging enables longitudinal monitoring of safety and efficacy of therapeutics delivery into the EVSC in pig eyes.

Studying the optical properties of the human, bald eagle, and cat eyes allowed us to model them in Zemax OpticStudio™. Using the CAGE model, the reduced human eye is modelled through Zemax. Upon completion, we worked on modeling the bald eagle’s and cat’s eyes individually by looking for data regarding the dimensions of said eyes and putting it into our models. We analyzed these models using the ‘image simulation’ feature to compare the visual acuity and color vision between each model. The Bald Eagle has the highest visual acuity with the widest range of color vision, the cat has the lowest in both regards, and the human eye falls between the two.

We have developed a line-field, spectral domain optical coherence tomography (LF-OCT) system for in-vivo, non-contact imaging of the cellular structure of the human cornea. The LF-OCT offers ~ 2 µm axial and ~ 5 lateral resolution. A high speed 2D camera allowed for a line scan rate of ~2,500 B-scans/s. The systems’s SNR was ~ 90 dB close to the zero-delay line for 4.5 mW with ~ 20 dB roll-off over a scanning range of 1 mm. Images of the human cornea acquired in-vvio with the LF-OCT showed the cellular structure of the corneal epithelium.

Purpose: To define the optical properties of 12 models of commercially available multifocal contact lenses when interacting with the higher order aberrations naturally occurring in 65 eyes by using the visual Strehl Ratio in the Frequency space (VSOTF) metric. Methods: The optical profiles of 12 models of multifocal contact lenses were measured by using the NIMO instrument (Lambda-X). Three corrections (-6 D, -3 D, and +1 D) of each model were measured. The lenses measured included: two Ultra lens models (B&L), three models of the Air Optix Aqua (Alcon), four models of the Biofinity lens (Cooper Vision), and three models of the Oasys lens (J&J). The optical profiles obtained from the NIMO contained 28 points per mm and were translated to their corresponding wavefronts by locally segmenting the pupil. Once the multifocal wavefronts were created, a standard Fourier procedure was applied to obtain the VSOTF through focus between -1 and 5 D. Two values were obtained to compare the optical properties (between optical infinity and a working distance of 20 cm) of the 13 designs: the area under the through focus VSOTF (normalized by the area obtained for the monofocal design) and the interval of acceptable quality through focus. Results: The area under the through focus VSOTF ranges from 0.80 (Oasys L) to 1.42 (Ultra H) and the range through focus varies from 0.93 D (Oasys L) to 2.73 D (Ultra H). The optical performance of the Oasys M and the Oasys L is comparable to the one produced by a monofocal lens. The contact lenses manufactured by B&L, Alcon, and Cooper Vision, shift the VSOTF towards more positive values when the myopic correction increases. Conclusions: A new method to evaluate the optical profiles of multifocal contact lenses has been presented. With this method it is possible to observe how designs for old presbyopes - Ultra H, AOA H, Oasys H - spread the VSOTF across around 2.5 D through focus. The peak performance of these designs, however, is lower than the one obtained for lenses that are used by young presbyopes – Ultra L, AOA M and L, Bio 1.50 and 1.00. Designs intended for young presbyopes do not extend the VSOTF more than 2 D but do conserve a higher peak performance that young presbyopes move through focus by using the partial accommodation they still conserve.

Images from recently introduced ultra-wide field of view fundus cameras have shown that examining the peripheral regions of the retina may influence the assessment of severity of disease. In this study we increased the field of view (FOV) of swept source optical coherence tomography (SSOCT) to match that of such wide field fundus cameras. We present single shot structural and OCT angiography images of healthy and diseased eyes with a FOV of up to 90 degree without significant degradation of signal or resolution in the periphery. Aside from the diagnostic benefit of being able to detect pathological changes in the periphery, the large field of view allows to study the connection between retinal diseases, eye shape and myopia. We present a dewarping algorithm, which uses computer modeling and patient specific biometric data to estimate the true geometry of a patient’s eye.

The corneal undergoes dramatic structural changes during the developmental process. From being fragile and opaque, it transforms into a strong and transparent structure. To be fully functional, the mature tissue must be able to transmit incident light in the visible part of spectrum. In this work, we applied second harmonic generation microscopy to image developing chick corneas. Specifically, three-dimensional images throughout the cornea lamella were obtained and analyzed by fast Fourier transform analysis. This approach may be used to characterize and analyze the development process of collagen-rich connective tissues.

We present first results imaging patients with various eye diseases with an Off-Axis Full-Field Time-Domain OCT (OA-FF-TD-OCT) setup. OA-FF-TD-OCT is a promising novel technology for a simple and robust retina imaging system. It allows the design of a handheld OCT and opens the path towards a home care OCT device for AMD patients. First measurements showed that the majority of patients can use the clinical device autonomously. Although inferior compared to FD OCT systems the image quality is sufficient to determine the relevant disease marker of wet AMD.

In clinical practice, ectatic disorders, such as keratoconus, are treated by accelerated corneal collagen crosslinking (ACXL). The treatment is based on the photodynamic reaction of riboflavin with ultraviolet A (UVA) light and increases the cornea’s mechanical stability. The clinical outcome of ACXL is usually evaluated several weeks post-treatment. An earlier evaluation could lead to a faster re-intervention in case of failure which could avoid additional discomfort and pain for the patient. We propose multiphoton tomography (MPT) to evaluate the outcome of ACXL soon after treatment. In this study, we investigate ACXL-induced changes to the cornea autofluorescence (AF) using MPT. ACXL was performed in de-epithelialized corneal donor buttons and keratoconus corneas by infusing the samples with 0.1% riboflavin solution followed by UVA irradiation using either an in-house adapted system or a commercial ACXL system. AF lifetime images of the tissue were acquired prior and after treatment using MPT. As a control, corneas without treatment were monitored at the same time points. Higher AF lifetimes were observed in the stroma of treated corneas than in control samples. The stroma AF lifetime was higher anteriorly, corresponding to the area where ACXL was most effective. First changes were observed as soon as 2 h after treatment. We demonstrate that MPT can be used to follow-up the outcome of ACXL and that ACXL-induced changes can be detected sooner than with conventional methods and non-invasively.

Hyperspectral images of the human iris, containing spectral and spatial information of the iris, are acquired by a custom developed instrument. We developed this instrument specifically to perform in-vivo spectral reflectance measurements of the human iris. The significance of the data cube acquired is strictly related to the acquisition system performance. This paper analyzes the qualitative and quantitative in-vivo performances of our instrument considering in-vivo repeatability tests and comparing left and right irises of normal subjects, without visually assessed heterochromia of the irises.

Retinoblastoma is a rare form of cancer of the retina mostly occurring in the eye of young children. We successfully show that gold plasmonic nanoparticle-mediated hyperthermia is a potential efficient therapy to kill the cancerous cells. The proof of concept is demonstrated in vitro on cultured Y79 retinoblastoma cancer cells. Hyaluronan was then used to perform studies in a phantom of the vitreous, characterized by its viscosity. Several parameters such as laser fluence, concentration of NPs and hyaluronan are investigated and optimized.

Initial study found that depth-resolved refractive index variations encoded in retinal optical coherence tomography (OCT) exhibits multifractality. Interestingly, automated segmented different layers of the retina exhibited different degree of multifractality in a human eye. In an advanced study, we have adopted nano sensitive study of spectral contents of OCT signals before retinal image construction of a human eye. We have identified and constructed most contributed submicron structural spatial period OCT images. We have quantified nano structural morphological alteration in human retinal layers as deformation progress. This innovative approach promises to develop nano sensitive diagnostic tool for early disease detection in the human eye.

The corneal sub-basal nerve plexus (SNP) is a network of thin, unmyelinated nerve fibers located between the basal epithelium and the Bowman’s membrane. Both corneal and systemic diseases such as keratoconus and diabetic can alter the nerve fiber density, thickness and tortuosity. Recent developments of cellular resolution OCT technology allowed for in-vivo visualization and mapping of the corneal SNP. We have developed a fully automated algorithm for segmentation of corneal nerves. The performance of the algorithm was tested on a series of enface UHR-OCT images acquired in-vivo from healthy human subjects. The proposed algorithm traces most of the sub-basal corneal nerves correctly. The achieved processing time and tracing quality are the major advantages of the proposed method. Results show the potential application of proposed method for nerve analysis and morphometric quantification of human sub-basal corneal nerves which is an important tool in corneal related diseases.

We propose a novel concept of presbyopia-correcting adaptive eyeglasses for people who do no accept current corrective solutions. Our eyeglasses provide clear vision at all distances automatically and feature enhanced field of vision and high optical quality. The adaptive technology relies on an original fluid-filled lens whose focusing power is set by a low-power micro-fluidic pump inserted in the eyeglass temples. We present our prototype and demonstrate the viability of our technology through its characterization.

Current systems of retinal laser photocoagulation suffer from a lack of control of the depth confinement of the laser and the eye constant motion, leading to reduced performance and risks of permanent damage on healthy neighboring tissues. We evaluate here how laser photocoagulation could benefit from Adaptive Optics in terms of 3D confinement and stabilization of the laser impact on the therapeutic target, in the prospect of an AO based, multimodal, compact and high performance prototype of laser photocoagulation clinical tool.

In femtosecond laser assisted keratoplasty different surgical wound profiles can be performed: the cut shape is chosen on the basis of patient’s needs and surgeon’s experience. This work aims to evaluate the biomechanical load resistance of the different configurations that are used in keratoplasty. A 2D and a 3D finite-element model of the human cornea was developed and different graft geometries were designed. The internal pressure was raised until the wound misaligned. The anvil profile resulted highly resistant, confirming the clinical evidences observed in previously treated patients.

Blood flow in the microcirculation plays an essential role in oxygen and nutrients delivery, and it is a prerequisite for normal perfusion and functions of cells and organs. In critical illnesses, microcirculation is often impaired, and microcirculatory dysfunction occurs. In this study, we have developed and utilized a high-speed rodent retinal OCT angiography system for investigating hemodynamic changes of retinal and choroidal blood flows in rat sepsis and hemorrhagic shock models, and evaluated feasibility of OCTA for assessing the critical illness.

The QuantifEye-Macular Pigment Reflectometer (MPR) is a near commercial prototype developed by ZeaVision. It objectively measures lutein optical density, zeaxanthin optical density and overall macular pigment optical density (MPOD). Here we evaluate the repeatability obtained using the MPR and compare it with the current gold-standard (MPSII). The QuantifEye-MPR shows better repeatability at MPOD measurements than the MPSII. Pupillary dilation is not necessary to obtain repeatable MPOD from the QuantifEye-MPR

The market for retinal cameras is now dominated by lower-cost, smaller foot print cameras. The performance of these cameras generally produce inferior quality images. Two cameras (Canon CR2AF and Volk’s Pictor Plus) were used to evaluate the impact of an image quality analyzer (IQA) for mitigating user-caused low-quality. 2,000 images from each camera were used to test the effect of the IQA in improving quality. At the initial introduction of each camera to the different clinics, the number of unreadable images was as high as 50 percent. After 2 months, the unreadable images dropped to around 20 percentage.

Eye imaging techniques involving light beam scanning are vulnerable to motion artifacts. To solve this issue we have constructed an ultrafast imaging device that we called Freeze-Eye Tracker (FET). It allows tracking eye of retinal movements at framerate of up to 1200 Hz provided proper algorithms are used. There are two main features crucial for algorithms to track retinal motion in vivo: the accuracy and the speed. Both are achieved using algorithms based of cross correlation between a number of acquired images combined with smart averaging of obtained displacements. As a result, the information on retinal trajectory can be extracted.

We demonstrated the feasibility of capturing the dynamics of lens thickness changes during accommodation and disaccommodation at high speed using OCT. The left eye of 6 subjects (23.3 ± 5.4 years old) were imaged during accommodation and disaccommodation in response to 2D and 4D step stimuli using a spectral domain OCT. Images were recorded over the central 1mm of the lens with 40 A-lines/frame and 400 B-scans. The velocity from the linear fit of the initial phases of the response and the minimum acquisition rate were calculated. The accommodation and disaccommodation velocity can be accurately quantified using OCT imaging.

Conventional Laser surgery for hyperopia correction on the cornea pose a higher risk when compared to myopia. We pre-clinically evaluated a new technique, using a transparent filler material injected into a femtosecond laser created intrastromal pocket for corneal curvature re-shaping. In 187 rabbit eyes and 10 living rabbits we were able to show that the induced magnitude of refractive correction, was dependent on volume injected, pocket depth and individual biomechanics. A stable filler volume, a clear cornea and no adverse reactions could be shown in rabbits in-vivo and in-vitro. This first promising results suggest a new clinical application.

We have conducted measurements of the group refractive index of hydrogel contact lenses at different wavelengths (from 530 to 670 nm), using time-domain low-coherence interferometer (LCI), based on the super-continuum light source (SCLS). Accurate refractive index of the contact lenses is one of the most important parameters needed to properly evaluate the performance of the lens. Measurements of the refractive power and other optical properties of the lenses are typically conducted in solution, and converted to in-air performance. Such approach is very sensitive to errors in the refractive indices of both the lens and the solution. Efforts to accurately measure the phase refractive index a contact lens directly have for the most part been unsuccessful due to a curved shape of the lens and lens material properties. In this paper we describe a different approach of obtaining group index dispersion curve with high accuracy of 0.003 or better, and discuss practical implications.

Here we present non-invasive, in-vivo, high-resolution images of the non-human primates choriocapillaris using OCTA. Images were acquired with a prototype swept-source OCTA (SS-OCTA) system with 100kHz A-scan/s rate, over regions of 3×3 mm2 and 12×12 mm2. The non-perfusion area, also called flow voids, were segmented with an intensity damped, illuminance-compensated algorithm. The optimized quantification of the choriocapillaris flow voids may have applications in a wide array of eye diseases including age-related macular degeneration (AMD) and visualization of choriocapillaris in animal models could aid future studies on choroid involvement in models of eye disease.

We exploit the intrinsic phase stability of akinetic swept source optical coherence tomography to demonstrate digital defocus correction in-vivo at a center wavelength of 1060nm. The high speed of 500kHz enables digital adaptive optics (AO) correction across a field of view of 1.8x1.5deg, currently limited by the employed galvo scanners. The source operates in a previously presented dual resolution mode OCT system (wide field >40deg, AO >3deg) with hardware based adaptive optics. The latter allows to efficiently combine hardware and digital AO, and to further optimize the AO imaging results. We demonstrate the digitally assisted AO performance for both structural imaging as well as for OCT angiography imaging across the full retina down to the choriocapillaris.

We present Doppler angiography of retinoblastoma tumors with a novel handheld 1050nm OCT clinical system specifically developed for retinoblastoma tumors in children under anesthesia. Probing 3D morphology at OCT resolution coupled with angiography by flow detection at every pixel improves quality of diagnosis. Specifically, visualizing the precise localization and geometry of tumors and non-malignant disorders facilitates the optimal choice of treatment, as well as differential diagnosis in-vivo and in real time. The design and performance of the patient interface, and the findings of the ongoing clinical study will be discussed, including the images of early, active, and treated retinoblastoma tumors.

We describe the development of a non-contact, handheld optical coherence tomography angiography (HH-OCTA) probe for imaging of young children and infants in the operating room. This probe uses a novel optical design that improves performance and has an ergonomic design to facilitate alignment and stabilization. Imaging was performed in 9 children and infants during exams under anesthesia. The probe used a 200 kHz OCT engine, has a motorized stage that provides +10 to -10 D refractive error correction, and weighs 700g. The HH-OCTA images provided visualization of the retinal microvasculature in both normal and pathological eyes.

Conventional Selective Laser Trabeculoplasty (SLT) is a well-established, safe, and effective glaucoma therapy involving manual beam targeting of the trabecular meshwork through a goniolens placed in physical contact with the cornea. Due to the skill level required, this procedure, although effective in lowering intra-ocular pressure (IOP), has not achieved significant penetration as a first line glaucoma treatment. We describe a very rapid automatic Direct Selective Laser Trabeculoplasty (DSLT) delivery system based on trans-scleral application of the laser to the trabecular meshwork and report on the preliminary results of our first-in-human clinical study.

We demonstrate direct integration of a fiber-optic Fabry-Perot pressure sensor into an artificial cornea, named Boston Keratoprosthesis (B-KPro), to facilitate quantitative intraocular pressure monitoring and improve glaucoma managements. The sensor-integrated B-KPros are illuminated and probed with an external multimode fiber and a commercial optical correlator module for white-light interferometry. To achieve efficient optical coupling robust against saccades and tremor during clinical measurements, we implemented a novel fiber-optic self-alignment scheme by fitting NdFeB micro-magnets over the probing fibers and the sensors. We validated the device against a reference sensor which showed a coupling-induced pressure variation of ±1.4 mmHg after offset adjustment.

The proposed new technique addresses the current void in efficient, cell-specific, retinal drug delivery systems. Here we show that we can selectively optoporate retinal cells in vivo using a 800nm fs laser irradiation and functionalized gold nanoparticles (AuNPs). The cell-surface Kv1.1 voltage-gated channel was chosen to selectively target retinal ganglion cells (RGCs) in the rat retina. Following intravitreal injection and incubation, irradiation resulted in siRNA uptake by retinal cells. Importantly, neither AuNP intravitreal injection nor irradiation resulted in RGC death. This non-invasive and non-viral gene therapy tool may provide a safe, cost effective approach to selectively target retinal cells.

Photovoltaic retinal prosthesis is designed to restore sight in patients who lost central vision due to age-related macular degeneration. Subretinal photovoltaic pixels convert pulsed NIR light projected from video goggles into electric current, stimulating the nearby inner retinal neurons. This wireless design greatly reduces the surgical complexity and allows scaling the number of pixels to thousands. In rats, photovoltaic arrays with 55um pixels provided grating acuity up to a pixel pitch, corresponding to about 20/200 acuity in a human eye. In patients with geographic atrophy, implants with 100um pixels elicited retinotopically correct pattern perception with resolution matching the pixel size.

We developed an analytical method to quantify the composition of heterogeneous blood cell mixtures, like those presenting pathologically in the anterior chamber (AC), utilizing spectroscopic OCT. Mie theory was used to correlate the spectrum extracted from individual cells to their characteristic sizes. We estimated cell-type composition of a sample blood cell mixture by fitting the distribution of individual cell sizes with a weighted combination of reference lymphocytes and neutrophils size distributions. These results were then compared to reference methods. This proposed method can potentially characterize the AC cell profile of intraocular inflammation non-invasively and provide additional diagnostic information for treatment.

Optical coherence tomographic angiography (OCT-A) technologies have been primarily demonstrated on slit-lamp systems, which preclude imaging in infants, bedridden patients, or patients who are otherwise unable to be imaged upright. Current-generation OCT-A requires densely-sampled volumetric datasets for high vascular resolution imaging, but bulk motion artifacts, resulting from saccades or eye drifts, often distort anatomic features during long acquisitions. We demonstrate handheld OCT-A using spectrally encoded coherence tomography and reflectometry (SECTR). OCT and OCT-A images were motion-corrected using motion information from en face spectrally encoded reflectometry and cross-sectional OCT images. We believe our probe will enable point-of-care functional ophthalmic imaging.

A white light optical coherence tomography (OCT) system was utilized to measure the absolute melanin concentration of the mouse retinal pigment epithelium (RPE) in vivo. As a calibration step, phantoms were created from small ellipsoidal melanin particles in silicone solutions (at known concentrations). Using additional post-processing of OCT images of these phantoms, a wavelength-dependent calibration map was created. This map can be used to calculate the melanin concentration of an unknown sample, given its hyperspectral signature. A first attempt was then made to measure the RPE melanin concentration in vivo in the mouse using this technique.

We used laser Doppler holography to image qualitatively blood flow in retinal and choroidal vessels with a temporal resolution down to a few milliseconds. Ultrafast wideband measurements of the optical Doppler broadening were performed with a 75 kHz camera over a full-field thanks to digital holography. The beat frequency of the recorded holograms was analyzed with a short-time Fourier transform analysis to reveal the pulsatile flow which allowed to investigate the blood flow profile in arteries and veins. Additionally we showed that laser Doppler holography allows to reveal choroidal vasculature non-invasively in young and healthy subjects.

The inner plexiform layer (IPL) of the retina comprises sublaminae with connections between bipolar cells, amacrine cells, and ganglion cells. Here, we demonstrate imaging of lamination in the IPL using achromatized visible light Optical Coherence Tomography (OCT). In vivo retinal images acquired from human subjects show that the IPL consists of 3 hyper-reflective bands and 2 hypo-reflective bands, which correspond well with the standard anatomical division of the IPL into 5 layers. Possible explanations for the ability of visible light OCT to visualize IPL sublaminae, based only on backscattering or backreflection contrast, and implications for glaucoma progression monitoring, are discussed.

Research in neurobiology has identified a new ocular photoreceptor (melanopsin or ipRGC) which mediates a variety of light-based, non-visual effects on human physiology. One way to isolate the stimulation of ipRGCs is the silent substitution technique. We have built a Maxwellian view device capable of 85% ipRGCs contrast excitation with a large FOV (52°). Four modulated LED light sources, illuminate a diffusing sphere, which exit aperture is imaged into the pupil of the eye. A camera with a 900 nm illumination capture the pupil. Without luminance changes (510±2 lm/m2 ), we increased ipRGC excitation from low to high level on three subjects. We observed a pupil constriction increasing with the ipRGC contrast. This suggests that we excite melanopsin silently. However, further experiments with electrophysiological and pupil recording needs to be done to completely validate our silent substitution device.

We propose a MEMS-based approach for retinal eye tracking (FET – FreezEye Tracker). The device allows for acquisition of small images of the retina at the rate of 1.2 kHz. We show that despite relatively low SNR the quality of the images is sufficient to serve as the input data for the inter-frames correlation algorithms for quantitative measurement of the retinal motion. The accessible high temporal resolution allows for effective and detailed analysis of the saccadic movements in the broad spectrum of frequencies. It can be used for both: medical diagnosis and providing optical stabilization of the ophthalmic imaging modalities.

Retinal diseases are the major cause of blindness in industrialized countries. While tremendous effort is made to develop novel therapeutic strategies to rescue retinal neurons and retinal pigment epithelium (RPE), optimal means to diagnose the disease are still missing. We developed an imaging modality, called transscleral optical phase imaging (TOPI), which is able to resolve the individual human RPE cells in-vivo with the help of adaptive optics. The resulting 5.7°×5.7° field-of-view system allows for the visualization of the RPE cells within 2 seconds. We demonstrated the quantification of the RPE cells via TOPI modality on seven healthy subjects.

We have developed a method to image the ocular fundus in transmission using a commercial non-mydriatic fundus camera. The method is based on deeply penetrating near-infrared light delivered transcranially near the subject’s temple. A portion of this light diffuses through bone and illuminates the posterior eye not from the front, as with conventional methods, but rather mostly from behind. As such, we image light transmitted through the fundus rather than back-reflected off multiple fundus layers. This single-pass geometry simplifies absorption pathlength considerations and provides complementary information to fundus reflectometry. The use of near-infrared light enables imaging as deep as the choroid.

Macular pigment is a yellowish pigment of dietary origin lying mainly at the fovea and it is thought to have a protective role to the retina. Recently, it has been related to Age-related Macular Degeneration. In this work we present a novel, non-midriatic, compact and fast optical system for the objective measurement of the optical density of the macular pigment. The method has been tested in a group of young, healthy subjects, and showed high repeatability and accuracy as well as high right-left eye correlation.

MRI brain imaging, cognitive function testing, infra-red (IR) and multicolor fundus imaging and spectral domain optic coherence tomography (SD-OCT) were performed in 108 non-symptomatic offspring of AD patients (FH+) and 44 age-matched controls (FH-). In FH+ subjects, lower performance in memory was associated with thicker peri-papillary temporal-superior Retinal Nerve Fiber Layer (RNFL). In FH+ subjects, left hippocampal volume was associated with larger total thickness of macular inner layers. Taken together the thickness of macular layers and peripapilary RNFL may present a novel biomarker for very early detection of AD.

We propose the approaches to solve hardware complexity and poorly established methods for clinical interpretation of jones matrix OCT (JM-OCT). To reduce the hardware complexity, we employ encapsulated modules to build full-function JM-OCT and simplified JM-OCT. For the clinical interpretation, we developed a pixel-wise segmentation method for retinal pigment epithelium (RPE) and choroidal stroma which exploits multiple types of images obtained by the JM-OCT. In a pigment epithelial detachment subject obtained by simplified JM-OCT, thickened RPE, hyper-reflective foci, and damaged RPE are correctly detected by RPE segmentation. In addition, created melano-layer thickness map has similar patterns to infrared fundus autofluorescence.

We assess the impact of utilizing a deep learning-based algorithm for automatic evaluation of ellipsoid zone (EZ) defects on optical coherence tomography images in a real-world macular telangiectasia type 2 clinical trial. The changes in EZ defects areas in participants receiving different treatments over a two-year period in a phase 2 clinical trial for a novel therapeutic agent are assessed manually and with a fully-automated algorithm. We demonstrate that our fully-automatic approach is as accurate as manual segmentation by expert Readers, and that it is able to faithfully replicate the outcome of the clinical trial.

We will demonstrate a novel operational modality of long-depth-range imaging that aims at in vivo enhanced visualization of vitreous opacities using an optimized SS-OCT instrument. The platform implements focus tunable optics to account for the eye refraction and to maximize the field of view, and is able to obtain images through the entire axial length of the vitreous body (from lens to retina). We will demonstrate enhanced visualization of different types of vitreous opacities in vivo that commonly cause floaters. SS-OCT can be a useful tool in the high-resolution 3-D evaluation and surgical management of vitreous opacities.

TThe present study aimed to develop a strategy for evaluation of instant PIMD-2Pi measurements as a basis for clinical monitoring of glaucoma. PIMD-2Pi is a morphometric measure of the waist of the nerve fiber layer at the optic nerve head (ONH). Clinical measurements of PIMD-2Pi in patients with early to moderate stage glaucoma demonstrated a high variability among subjects. The high variability among subjects renders comparison of instant PIMD-2Pi measurements to tolerance limits for normality derived from a normative database inefficient. It is suggested to instead compare sequential measurements of PIMD-2Pi within a patient. Initially, the difference between an instant measurement and the average of previous measurements can be compared to tolerance limits for difference between measurements within subject. Once, a potential loss of PIMD-2Pi is detected, a sufficient number of measurements within a sufficiently wide time interval can be used to estimate the PIMD-2Pi loss rate with regression and the deviation of the estimated loss rate can be evaluated as a 95 % confidence interval for the loss rate. If the upper confidence limit excludes 0, a significant loss rate has been detected. The currently proposed strategy has the potential to detect glaucoma earlier than the current gold standard, computer perimetry, with less inconvenience for the patient.

We demonstrate the potential of polarization-sensitive optical coherence tomography (PS-OCT) using a conical scan pattern for mapping the thicknesses of individual corneal layers. Combining the additional contrast provided by PS-OCT and the good signal quality from limbus to limbus achieved by conical scanning enables the segmentation and mapping of individual layer thicknesses. Compared to healthy eyes, keratoconic eyes showed a “doughnut profile” in the epithelial thickness map and substantial irregularities in Bowman’s layer thickness. Both epithelial and Bowman’s layer thicknesses showed statistically significant differences between healthy and keratoconic eyes and therefore clearly prove their benefit in the diagnosis of keratoconus.