This PDF file contains the front matter associated with SPIE Proceedings Volume 8567, including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

We present in vivo noninvasive retinal and choroidal perfusion maps with phase-variance optical coherence tomography (pvOCT). We acquired a pvOCT volumetric data set of a normal subject and visualized blood circulation in the retina and the choroid. En face projection views of the retina as well as the choroid were generated from a manually segmented volumetric data set. In addition, the processed pvOCT images were compared to current standard imaging modalities used for retinal and choroidal vasculature visualization in clinical settings, including fluorescein angiography (FA) and indocyanine green angiography (ICGA).

In this paper, we demonstrated that the detailed microstructure and microcirculation information of human laminar cribrosa can be in vivo visualized using an ultrahigh sensitive optical microangiography system, which is operating at 800 nm region and 500 kHz A-line capturing rate. The captured micro structure and vasculature images were first qualitatively evaluated through the maximum projection map and extracted enface images of different depth locations. Then, the pore area and elongation were statistically calculated to provide the quantitative information.

Application of femtosecond lasers to cataract surgery has added unprecedented precision and reproducibility but ocular safety limits for the procedure are not well-quantified. We present an analysis of safety during laser cataract surgery considering scanned patterns, reduced blood perfusion, and light scattering on residual bubbles formed during laser cutting. Experimental results for continuous-wave 1030 nm irradiation of the retina in rabbits are used to calibrate damage threshold temperatures and perfusion rate for our computational model of ocular heating. Using conservative estimates for each safety factor, we compute the limits of the laser settings for cataract surgery that optimize procedure speed within the limits of retinal safety.

We have developed a photovoltaic retinal prosthesis, in which camera-captured images are projected onto the retina using pulsed near-IR light. Each pixel in the subretinal implant directly converts pulsed light into local electric current to stimulate the nearby inner retinal neurons. 30 μm-thick implants with pixel sizes of 280, 140 and 70 μm were successfully implanted in the subretinal space of wild type (WT, Long-Evans) and degenerate (Royal College of Surgeons, RCS) rats. Optical Coherence Tomography and fluorescein angiography demonstrated normal retinal thickness and healthy vasculature above the implants upon 6 months follow-up. Stimulation with NIR pulses over the implant elicited robust visual evoked potentials (VEP) at safe irradiance levels. Thresholds increased with decreasing pulse duration and pixel size: with 10 ms pulses it went from 0.5 mW/mm² on 280 μm pixels to 1.1 mW/mm² on 140 μm pixels, to 2.1 mW/mm² on 70 μm pixels. Latency of the implant-evoked VEP was at least 30 ms shorter than in response evoked by the visible light, due to lack of phototransduction. Like with the visible light stimulation in normal sighted animals, amplitude of the implant-induced VEP increased logarithmically with peak irradiance and pulse duration. It decreased with increasing frequency similar to the visible light response in the range of 2 - 10 Hz, but decreased slower than the visible light response at 20 - 40 Hz. Modular design of the photovoltaic arrays allows scalability to a large number of pixels, and combined with the ease of implantation, offers a promising approach to restoration of sight in patients blinded by retinal degenerative diseases.

Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a “biofactory” that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.

Collagen crosslinking (CXL) has shown promising results in the prevention of the progression of keratoconus and corneal ectasia. However, techniques for in vivo and in situ assessment of the treatment are limited. In this study, ex vivo porcine eyes were treated with a chemical CXL agent (glutaraldehyde), during which polarization sensitive optical coherence tomography (PS-OCT) recordings were acquired simultaneously to assess the sensitivity of the technique to assess changes in the cornea. The results obtained in this study suggest that PSOCT may be a suitable technique to measure CXL changes in situ and to assess the local changes in the treated region of the cornea.

We use phase-sensitive optical coherence tomography (OCT) to measure the deformation of the optic nerve head during the pulse cycle, motivated by the possibility that these deformations might be indicative of the progression of glaucoma. A spectral-domain OCT system acquired 100k A-scans per second, with measurements from a pulse-oximeter recorded simultaneously, correlating OCT data to the subject’s pulse. Data acquisition lasted for 2 seconds, to cover at least two pulse cycles. A frame-rate of 200–400 B-scans per second results in a sufficient degree of correlated speckle between successive frames that the phase-differences between fames can be extracted. Bulk motion of the entire eye changes the phase by several full cycles between frames, but this does not severely hinder extracting the smaller phase-changes due to differential motion within a frame. The central cup moves about 5 μm/s relative to the retinal-pigment-epithelium edge, with tissue adjacent to blood vessels showing larger motion.

Spectral-domain optical coherence tomography (SD-OCT) is a 3-D imaging technique, allowing direct visualization of retinal morphology and architecture. The various layers of the retina may be affected differentially by various diseases. In this study, an automated graph-based multilayer approach was developed to sequentially segment eleven retinal surfaces including the inner retinal bands to the outer retinal bands in normal SD-OCT volume scans at three different stages. For stage 1, the four most detectable and/or distinct surfaces were identified in the four-times-downsampled images and were used as a priori positional information to limit the graph search for other surfaces at stage 2. Eleven surfaces were then detected in the two-times-downsampled images at stage 2, and refined in the original image space at stage 3 using the graph search integrating the estimated morphological shape models. Twenty macular SD-OCT (Heidelberg Spectralis) volume scans from 20 normal subjects (one eye per subject) were used in this study. The overall mean and absolute mean differences in border positions between the automated and manual segmentation for all 11 segmented surfaces were -0.20 ± 0.53 voxels (-0.76 ± 2.06 μm) and 0.82 ± 0.64 voxels (3.19 ± 2.46 μm). Intensity and thickness properties in the resultant retinal layers were investigated. This investigation in normal subjects may provide a comparative reference for subsequent investigations in eyes with disease.

Recent advances in swept-source / Fourier domain optical coherence tomography (SS-OCT) technology enable in vivo ultrahigh speed imaging, offering a promising technique for four-dimensional (4-D) imaging of the eye. Using an ultrahigh speed tunable vertical cavity surface emitting laser (VCSEL) light source based SS-OCT prototype system, we performed imaging of human eye dynamics in four different imaging modes: 1) Pupillary reaction to light at 200,000 axial scans per second and 9 μm resolution in tissue. 2) Anterior eye focusing dynamics at 100,000 axial scans per second and 9 μm resolution in tissue. 3) Tear film break up at 50,000 axial scans per second and 19 μm resolution in tissue. 4) Retinal blood flow at 800,000 axial scans per second and 12 μm resolution in tissue. The combination of tunable ultrahigh speeds and long coherence length of the VCSEL along with the outstanding roll-off performance of SS-OCT makes this technology an ideal tool for time-resolved volumetric imaging of the eye. Visualization and quantitative analysis of 4-D OCT data can potentially provide insight to functional and structural changes in the eye during disease progression. Ultrahigh speed imaging using SS-OCT promises to enable novel 4-D visualization of realtime dynamic processes of the human eye. Furthermore, this non-invasive imaging technology is a promising tool for research to characterize and understand a variety of visual functions.

A digital light projector is implemented as an integrated illumination source and scanning element in a confocal nonmydriatic retinal camera, the DLP-Cam. To simulate scanning, a series of illumination lines are rapidly projected on the retina. The backscattered light is imaged onto a 2-dimensional rolling shutter CMOS sensor. By temporally and spatially overlapping the illumination lines with the rolling shutter, confocal imaging is achieved. This approach enables a low cost, flexible, and robust design with a small footprint. Qualitative image comparison with commercial non-mydriatic SLOs and fundus cameras shows comparable fine vessel visibility and contrast.

We have used a swept-source optical coherence tomography (OCT) system to study the development of eyes in mice embryo in utero at different development stages from E13.5 - 18.5. Obtained results demonstrate capability of OCT technology for high-resolution imaging of ocular tissues in utero and capability of assessing key developmental characteristics of the eye during embryonic development.

We extend nonlinear pump-probe microscopy, recently demonstrated to image the microscopic distribution of eumelanin and pheomelanin in unstained skin biopsy sections, to the case of melanocytic conjunctival lesions. The microscopic distribution of pigmentation chemistry serves as a functional indicator of melanocyte activity. In these conjunctival specimens (benign nevi, primary acquired melanoses, and conjunctival melanoma), we have observed pump-probe spectroscopic signatures of eumelanin, pheomelanin, hemoglobin, and surgical ink, in addition to important structural features that differentiate benign from malignant lesions. We will also discuss prospects for an in vivo ‘optical biopsy’ to provide additional information before having to perform invasive procedures.

Measuring retinal hemodynamics in response to flicker stimulus is important for investigating pathophysiology in small animal models of diabetic retinopathy, because a reduction in the hyperemic response is thought to be one of the earliest changes in diabetic retinopathy. In this study, we investigated functional imaging of retinal hemodynamics in response to flicker stimulus in the rat retina using an ultrahigh speed spectral / Fourier domain OCT system at 840nm with an axial scan rate of 244kHz. At 244kHz the nominal axial velocity range that could be measured without phase wrapping was +/-37.7mm/s. Pulsatile total retinal arterial blood flow as a function of time was measured using an en face Doppler approach where a 200μm × 200μm area centered at the central retinal artery was repeatedly raster scanned at a volume acquisition rate of 55Hz. Three-dimensional capillary imaging was performed using speckle decorrelation which has minimal angle dependency compared to other angiography techniques based on OCT phase information. During OCT imaging, a flicker stimulus could be applied to the retina synchronously by inserting a dichroic mirror in the imaging interface. An acute transient increase in total retinal blood flow could be detected. At the capillary level, an increase in the degree of speckle decorrelation in capillary OCT angiography images could also be observed, which indicates an increase in the velocity of blood at the capillary level. This method promises to be useful for the investigation of small animal models of ocular diseases.

Recently, a method to determine the retinal nerve fiber layer (RNFL) attenuation coefficient, based on normalization on the retinal pigment epithelium, was introduced. In contrast to conventional RNFL thickness measures, this novel measure represents a scattering property of the RNFL tissue. In this paper, we compare the RNFL thickness and the RNFL attenuation coefficient on 10 normal and 8 glaucomatous eyes by analyzing the correlation coefficient and the receiver operator curves (ROCs). The thickness and attenuation coefficient showed moderate correlation (r=0.82). Smaller correlation coefficients were found within normal (r=0.55) and glaucomatous (r=0.48) eyes. The full separation between normal and glaucomatous eyes based on the RNFL attenuation coefficient yielded an area under the ROC (AROC) of 1.0. The AROC for the RNFL thickness was 0.9875. No statistically significant difference between the two measures was found by comparing the AROC. RNFL attenuation coefficients may thus replace current RNFL thickness measurements or be combined with it to improve glaucoma diagnosis.

The aqueous outflow system (AOS), including the trabecular meshwork (TM), the collector channels (CC) and the Schlemm’s canal (SC), regulates intraocular pressure (IOP) through the drainage of the aqueous humor (AH). Abnormal IOP elevation leads to increased pressure stress to retinal ganglion cells, resulting in cell loss that can ultimately lead to complete loss of eyesight. Therefore, development of imaging tools to detect abnormal structural and functional changes of the AOS is important in early diagnosis and prevention of glaucoma. Multiphoton microscopy (MPM), including twophoton autofluorescence (TPAF) and second harmonic generation (SHG), is a label-free microscopic technique that allows molecular specific imaging of biological tissues like the TM. Since the TM and other AOS structures are located behind the highly scattering scleral tissue, transscleral imaging of the TM does not provide enough optical resolution. In this work, a gonioscopic lens is used to allow direct optical access of the TM through the cornea for MPM imaging. Compared to transscleral imaging, the acquired MPM images show improved resolution as individual collagen fiber bundles of the TM can be observed. MPM gonioscopy may have the potential to be developed as a future clinical imaging tool for glaucoma diagnostics.

Structural properties of the cornea determine the shape and optical quality of the eye. Keratoconus, a structural degeneration of the cornea, is often treated with UV-induced collagen cross-linking to increase tissue resistance to further deformation and degeneration. Optimal treatments would be customized to the individual and consider preexisting structural properties as well as the effects induced by treatment and this requires the capability to noninvasively measure tissue properties. The purpose of this study is to use novel methods of optical elastography to study the effects of UV-induced corneal collagen cross-linking in the rabbit eye. Low-amplitude (<1μm) elastic flexural waves were generated using focused air-pulse stimulation. Elastic wave propagation was measured over a 10x10mm area using Phase Stabilized Swept Source Optical Coherence Elastography (PhS-SSOCE) with a sensitivity of ~ 10 nm. Wave amplitude and velocity were computed and compared in tissues before and after UV cross-linking. Wave amplitude was decreased by the cross-linking treatment, while wave velocity was greater in cross-linked tissue than it was in the untreated cornea. Decreased wave amplitude and increased wave velocity after cross-linking is consistent with increased tissue stiffness. This was confirmed by conventional mechanical tension testing. These results demonstrate that the combination of the PhS-SSOCE and focused air pulse stimulation is capable of measuring low amplitude tissue motion and quantifying corneal stiffness.

The International Commission on Non-Ionizing Radiation Protection (ICNIRP) establishes that the safe limits regarding ultraviolet radiation exposure in the spectral region 180nm–400nm incident upon the unprotected eye(s) should not exceed 30 Jm^-2 effective spectrally weighted (spectral weighting factors are provided by ICNIRP); and the total (unweighted) ultraviolet radiant exposure in the spectral region 315nm–400nm should not exceed 10⁴ Jm^-2. However, it should be considered that the spectral range from 180nm–280nm does not reach the surface of the Earth, since it is absorbed by the ozone layer of the atmosphere. The Brazilian Standard for sunglasses protection, NBR15111(2004), as well as the British Standard BSEN1836(2005) and American Standard ANZI Z80.3(2009), requires the UV protection in the spectral range 280nm–380nm, but does not take into account the total (unweighted) UVA radiant exposure. These limits are discussed in this work and calculations have been made for 27 state capitals of Brazil to understand the limits that should be involved in order to protect the eyes of the Brazilian population. These calculations and considerations may be extended to other countries as well. As a conclusion, we show that the upper limit for the UVA protection of 400nm should be included in the Brazilian standard, as well as the irradiance limits. Furthermore, the parameters for the resistance to irradiance test required on the Brazilian standard are also discussed herein as well the significance of this test. We show that the test should be performed by the sun simulator for a longer period than currently required.

The use of polarizing filters in sunglasses has become increasingly common worldwide. Although the Brazilian standard NBR15111 has specific requirements for its use (position and efficiency), there is not a proper machine to make the specified measures. This paper describes the development of an equipment according to NBR15111. A study was made using a 120,000 lx white LED light source, and an analyzer, which is an assembly of two polarizing filters with its polarization axis orthogonally aligned, both in front a light sensor with 16 bit resolution. The proposed system was able to measure the polarization efficiency of all the sunglasses categories, including the critical situation of the category 4, 3% of light transmittance, and efficiency of 8:1. The direction of the polarization plane is determined with the resolution of 0.056°in this critical situation. The results meet the standard requirements of 0.5° for angle measures and 8:1 for filters efficiency, which shown that the proposed equipment is able to check the quality of the polarizing filters used in sunglasses, that are commercialized in the Brazilian market.

Light transmittance measurements through sunglasses lenses is one of the required tests of the Brazilian Standard NBR15111(2004). Its measurement establishes the category of the sample and determines the required ultraviolet, visible and infrared protection, as well as the attenuation coefficient for signal light recognition. However, these measurements are usually performed by spectrophotometers and educated users, who are acknowledged to manage the equipment, use the weighting functions (WF) and interpret the data. We propose an alternative method, which consists in having matching optics and electronics to obtain a close WF to be used in transmittance measurements, and create an accessible device, for public self-use, providing a simple way for measuring and educating the public about sunglasses protection. Measurements were made in 30 samples for UV test, performed for the 280 – 400nm range, where UVA and UVB light sources and two photodiode sensors with Erythema action response are assembled, and for traffic signal a visible light sensor was used with spectral human eye response and different LEDs. As for the visible test, the visible light sensor was used for different light sources: incandescent, fluorescent, and a set of LEDs, while the infrared test is performed by several LEDs that provide the 780 – 2000nm range, and an infrared sensor. For these tests, only the samples spectrum were used. The transmittances were within the deviation limit required by NBR15111. The results have led us to build a self service kiosk for public use providing the category, UV protection and IR protection of the sunglasses as well as the information regarding its use for driving.

As cataracts are the most common reason for loss of vision with an age over 55, the implantation of intraocular intraocular lenses is one of the most common surgical interventions. The quality measurement and test instructions for the patients. Therefore more efforts are put into the individualization of IOL in order to achieve better imaging properties. Two examples of typical quality standards for IOL are the modulated transfer function (MTF) and the Strehl ratio which can be measured in vivo or also in mechanical eye models. A mechanical eye model in the scale 1:1 is presented. It has been designed to allow the measurement of the MTF and Strehl ratio and simultaneous evaluation of physiological imaging quality. The eye model allows the automatic analysis of the IOL especially focused on the tolerance for tilting and decentering. Cornea, iris aperture and IOL type are interchangeable, because all these parts are implemented by the use of separated holders. The IOL is mounted on a shift plate. Both are mounted on a tilt plate. This set-up guarantees an independent decentration and tilt of the IOL, both moved by electrical drives. This set–up allows a two–dimensional tolerance analysis of decentration and tilt effects. Different 100×100 point (decentration×tilt) analyzes for various iris apertures, needing only approximately 15 minutes, are presented.

Diode laser welding of ocular tissues is a procedure that enables minimally invasive closure of a corneal wound. This procedure is based on a photothermal effect: a water solution of Indocyanine Green (ICG) is inserted in the surgical wound, in order to stain the corneal tissue walls. The stained tissue is then irradiated with a low power infrared diode laser, delivering laser light through a 300-μm core diameter optical fiber. This procedure enables an immediate closure of the wounds: it is thus possible to reduce or to substitute the use of surgical threads. This is of particular interest in children, because the immediate closure improves refractive outcome and anti-amblyopic effect; moreover this procedure avoids several general anaesthesia for suture management. In this work, we present the first use of diode laser welding procedure in paediatric patients. 5 selected patients underwent cataract surgery (Group 1), while 4 underwent fs-laserassisted penetrating keratoplasty (Group 2). In Group 1 the conventional surgery procedure was performed, while no stitches were used for the closure of the surgical wounds: these were laser welded and immediately closed. In Group 2 the donor button was sutured upon the recipient by 8 single stitches, instead of 16 single stitches or a running suture. The laser welding procedure was performed in order to join the donor tissue to the recipient bed. Objective observations in the follow up study evidenced a perfect adhesion of the laser welded tissues, no collateral effects and an optimal restoration of the treated tissues.

We present a femtosecond solid-state Yb:KGW laser system capable of performing the complete laser-assisted in situ keratomileusis (LASIK) ophthalmic procedure. The fundamental infrared radiation (IR) is used to create the corneal flap, and subsequently the corneal stromal ablation is performed using the ultraviolet (UV) pulses of the fifth harmonic. The heating of cornea, ablated surface quality, and healing outcomes of the surgeries performed using the femtosecond laser system are investigated by both ex vivo and in vivo experiments and compared to the results of conventional clinical ArF excimer laser application. The results of this research indicate the feasibility of clinical application of femtosecond UV lasers for LASIK procedure.

It was revealed correlation between the optical density of the lens’s nucleus in terahertz range with its density, determined according to the L. Buratti classification. Consolidation of the lens fibers caused by senile cataract, increases the reflectivity of the lens in the THz range. The temporal structure of reflected THz signals allows to determine the spatial distribution of density in the lens.

We present a symbolic approach based on matrix methods that allows for the analysis and computation of intraocular lens power following cataract surgery. We extend the basic matrix approach corresponding to paraxial optics to include astigmatism and other aberrations. The symbolic approach allows for a refined analysis of the potential sources of errors (“refractive surprises”). We demonstrate the computation of lens powers including toric lenses that correct for both defocus (myopia, hyperopia) and astigmatism. A specific implementation in Mathematica allows an elegant and powerful method for the design and analysis of these intraocular lenses.

We developed an optical coherence tomography (OCT) prototype with a sample arm that uses a 3.4 mm beam, which is considerably larger than the 1.2 to 1.5 mm beam that is used in commercialized OCT systems. The system is equipped with adaptive optics (AO), and to distinguish it from traditional AO-OCT systems with a larger 6 mm beam we have coined this concept AO-assisted OCT. Compared to commercialized OCT systems, the 3.4 mm aperture combined with AO improves light collection efficiency and imaging lateral resolution. In this paper, the performance of the AOa-OCT system was compared to a standard OCT system and demonstrated for imaging of age-related macular degeneration (AMD). Measurements were performed on the retinas of three human volunteers with healthy eyes and on one eye of a patient diagnosed with AMD. The AO-assisted OCT system imaged retinal structures of healthy human eyes and a patient eye affected by AMD with higher lateral resolution and a 9° by 9° field of view. This combination of a large isoplanatic patch and high lateral resolution can be expected to fill a gap between standard OCT with a 1.2 mm beam and conventional AO-OCT with a 6 mm beam and a 1.5° by 1.5° isoplanatic patch.

Differential OTF (dOTF) is is a new image-based non-iterative technique for measuring the complex pupil field. When used with a collection of point sources that exhibit position-dependent PSFs, dOTF allows the 3-D tomographic reconstruction of transmission and aberrating structures between the source and the camera. We explore the potential of using dOTF with a pattern of laser spots projected onto the retina to map the 3-D complex transmission between the cornea to some distance into the vitreous. We present the concept, systems-level analysis, simulations, and initial laboratory experiments to validate this approach.

We propose a method that allows an inexperienced observer, through the examination of the digital fundus image of a retina on a computer screen, to simply determine the presence of a cataract and the necessity to refer the patient for further evaluation. To do so, fundus photos obtained with a non-mydriatic camera were presented to an inexperienced observer that was briefly instructed on fundus imaging, nature of cataracts and their probable effect on the image of the retina and the use of a computer program presenting fundus image pairs. Preliminary results of pair testing indicate the method is very effective.

We present a new design for a reflective afocal AO-OCT retinal imaging system. The optical performance of this instrument is compared to our previous multimodal AO-OCT/AO-SLO retinal imaging system. The feasibility of new instrumentation for improved visualization of microscopic retinal structures will be discussed. Examples of images acquired with this new AO-OCT instrument will be presented.

Accurate diagnosis and treatment of disease is a function of how well the pathology can be imaged. Coregistering images from different modalities can offer significant advantages. Multi-modal imaging is finding its place in Ophthalmology and we illustrate and analyze its use in macular disease. New technologies have provided the ability to simultaneously capture FA and OCT images, allowing dynamic analysis at the exact point of interest. We establish that the combined imaging protocol is easier and faster for both patient and technician, and ultimately and most importantly more capable of guiding the physician to a diagnosis and treatment.

Lasers have been shown to be successful in certain medical procedures and they have been identified as potentially making a major contribution to the development of minimally invasive procedures. However, the uptake is not as widespread and there is scope for many other applications where laser devices may offer a significant advantage in comparison to the traditional surgical tools. The purpose of this research is to assess the potential of using a picosecond laser for minimally invasive laser sclerostomy. Experiments were carried out on porcine scleral samples due to the comparable properties to human tissue. Samples were prepared with a 5mm diameter trephine and were stored in lactated Ringer’s solution. After laser machining, the samples were fixed in 3% glutaraldehyde, then dried and investigated under SEM. The laser used in the experiments is an industrial picosecond TRUMPF TruMicro laser operating at a wavelength of 1030nm, pulse length of 6ps, repetition rate of 1 kHz and a focused spot diameter of 30μm. The laser beam was scanned across the samples with the use of a galvanometer scan head and various ablation patterns were investigated. Processing parameters (pulse energy, spot and line separation) which allow for the most efficient laser ablation of scleral tissue without introducing any collateral damage were investigated. The potential to create various shapes, such as linear incisions, square cavities and circular cavities was demonstrated.

We describe a novel common-path optical coherence tomography (CP-OCT) fiber probe design using a sapphire ball lens for cross-sectional imaging and sensing in retina vitrectomy surgery. Single mode Gaussian beam (TEM⁰⁰) simulation was used to optimize lateral resolution and working distance (WD) of the common-path probe. A theoretical sensitivity model for CP-OCT was prosed to assess its optimal performance based an unbalanced photodetector configuration. Two probe designs with working distances (WD) 415μm and 1221μm and lateral resolution 11μm and 18μm, respectively were implemented with sensitivity up to 88dB. The designs are also fully compatible with conventional Michelson interferometer based OCT configurations. The reference plane of the probe, located at the distal beam exit interface of the single mode fiber (SMF), was encased within a 25-gauge hypodermic needle by the sapphire ball lens facilitates its applications in bloody and harsh environments. The performances of the fiber probe with 11μm of lateral resolution and 19μm of axial resolution were demonstrated by cross-sectional imaging of a cow cornea and retina in vitro with a 1310nm swept source OCT system. This probe was also attached to a piezoelectric motor for active compensation of physiological tremor for handheld retinal surgical tools.

Visualization and measurement of retinal blood flow (RBF) is important to the diagnosis and management of different eye diseases, including diabetic retinopathy. Optical microangiography (OMAG) is developed for generating 3D dynamic microcirculation image and later refined into ultra-high sensitive OMAG (UHS-OMAG) for true capillary vessels imaging. Here, we present the application of OMAG imaging technique for visualization of depth-resolved vascular network within retina and choroid as well as measurement of total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was developed to image mouse posterior eye. By applying UHS-OMAG scanning protocol and processing algorithm, we achieved true capillary level imaging of retina and choroid vasculature in mouse eye. The vascular pattern within different retinal layers and choroid was presented. An en face Doppler OCT approach [1] without knowing Doppler angle was adopted for the measurement of total retinal blood flow. The axial blood flow velocity is measured in an en face plane by raster scanning and the flow is calculated by integrating over the vessel area of the central retinal artery.

Vitreoretinal surgery is performed using mechanical dissection that sometimes results in iatrogenic complications, including vitreous hemorrhage, retinal breaks, incomplete membrane delamination, retinal distortion, microscopic damage, etc. The laser probe would be an ideal tool for cutting away pathologic membranes, however the depth of surgery should be precisely controlled to protect the retina. In this study, we optimized the design of such ultraprecise surgical microprobe formed by chains of dielectric spheres assembled directly inside the cores of the mid-infrared flexible delivery systems used in such surgeries. Specifically, our design is optimized for use of Erbium:YAG laser sources with extremely short optical penetration depth in tissue. By using numerical modeling, we demonstrate a potential advantage of five-sphere focusing chains of sapphire or ruby spheres with index n=1.71 for ablating the tissue with self-limited depth around 10-20 μm. We fabricated and tested such optimized structures formed by 300 μm ruby spheres with ophthalmic tissues, ex vivo. Single Er:YAG pulses of 0.2 mJ and 75 μs duration produced ablation craters in cornea epithelium for one, three, and five sphere structures with the latter generating the smallest crater depth (10 μm) with the least amount of thermal damage depth (30 μm). We show that integration of the ultraprecise laser ablation capability with illumination and suction tools would produce a single headpiece with versatile functionality in ultraprecise intraocular surgery.

The use of femtosecond lasers (FSL) in ophthalmic procedures, such as LASIK, lens replacement (cataract surgery), as well as several other treatments, is growing rapidly. The treatment effect is based on photo ablation of ocular tissues by a series of ultra-short laser pulses. However, the laser beam characteristics change dynamically due to interactions with birefringent corneal tissue, which may affect the outcome of the laser treatment. To better understand the effect the cornea has on the laser characteristics, we developed a system for measuring retardation and validated it with precise, standard phase retarders. Then we measured the phase retardation of FSLs through bovine corneas and found that there is a considerable, location dependent, variation in retardation values. This information can potentially help optimize FSL parameters to make their application in ophthalmic procedures safer and more effective.

A spectral domain optical coherence tomography system is integrated with an optical reflectometer to provide dualfunctional eye measurement. The system is capable of performing anterior segment imaging and tear film thickness evaluation at the same time. The axial resolution of the anterior segment imaging is 6μm while for tear film thickness measurement the resolution is about 21 nm. We use the integrated device to examine a model eye with artificial tear film. Structures such as the cornea, the ciliary muscle, and the front boundary of the crystalline lens are clearly visible. Artificial tear film thickness is determined simultaneously with anterior segment imaging. The integrated device is also flexible for separated anterior segment imaging or tear thickness evaluation.

In ophthalmic microsurgery tissue dissection is achieved using femtosecond laser pulses to create an optical breakdown. For vitreo-retinal applications the irradiance distribution in the focal volume is distorted by the anterior components of the eye causing a raised threshold energy for breakdown. In this work, an adaptive optics system enables spatial beam shaping for compensation of aberrations and investigation of wave front influence on optical breakdown. An eye model was designed to allow for aberration correction as well as detection of optical breakdown. The eye model consists of an achromatic lens for modeling the eye’s refractive power, a water chamber for modeling the tissue properties, and a PTFE sample for modeling the retina’s scattering properties. Aberration correction was performed using a deformable mirror in combination with a Hartmann-Shack-sensor. The influence of an adaptive optics aberration correction on the pulse energy required for photodisruption was investigated using transmission measurements for determination of the breakdown threshold and video imaging of the focal region for study of the gas bubble dynamics. The threshold energy is considerably reduced when correcting for the aberrations of the system and the model eye. Also, a raise in irradiance at constant pulse energy was shown for the aberration corrected case. The reduced pulse energy lowers the potential risk of collateral damage which is especially important for retinal safety. This offers new possibilities for vitreo-retinal surgery using femtosecond laser pulses.