Proceedings Volume 6844

Ophthalmic Technologies XVIII

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Proceedings Volume 6844

Ophthalmic Technologies XVIII

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Volume Details

Date Published: 21 March 2008
Contents: 13 Sessions, 36 Papers, 0 Presentations
Conference: SPIE BiOS 2008
Volume Number: 6844

Table of Contents

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Table of Contents

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  • Ophthalmic Imaging I: Animal Models
  • Ophthalmic Imaging II: Adaptive Optics
  • Optical Coherence Tomography I: Instrumentation and Image Processing
  • Keynote Lecture
  • Ophthalmic Imaging III: Functional Imaging
  • Visual Optics and Biometry
  • Ophthalmic Tissue Optics and Light-Tissue Interactions
  • Ocular Surgery and Therapy
  • Ophthalmic Diagnostics I: Microscopy, Scattering, Spectroscopy
  • Ophthalmic Diagnostics II: Polarization Techniques
  • Optical Coherence Tomography III: Clinical Applications
  • Session 13
  • Poster Session
Ophthalmic Imaging I: Animal Models
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In vivo imaging of raptor retina with ultra high resolution spectral domain optical coherence tomography
Marco Ruggeri, James C. Major Jr., Craig McKeown, et al.
Among birds, raptors are well known for their exceptional eyesight, which is partly due to the unique structure of their retina. Because the raptor retina is the most advanced of any animal species, in vivo examination of its structure would be remarkable. Furthermore, a noticeable percentage of traumatic ocular injuries are identified in birds of prey presented to rehabilitation facilities. Injuries affecting the posterior segment have been considered as a major impact on raptor vision. Hence, in vivo examination of the structure of the posterior segment of the raptors would be helpful for the diagnosis of traumatized birds. The purpose of this study is to demonstrate the application of ultrahigh-resolution Spectral Domain Optical Coherence Tomography (SD-OCT) for non contact in vivo imaging of the retina of birds of prey, which to the best of our knowledge has never been attempted. For the first time we present high quality OCT images of the retina of two species of bird of prey, one diurnal hawk and one nocturnal owl.
Ophthalmic Imaging II: Adaptive Optics
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Methods of isoplanatic patch widening in human eye retina imaging
We discuss possible ways to enlarge the size of high-resolution area (isoplanatic patch) in fundus imagers equipped with adaptive optics. We first developed customized human eye models of several subjects. Then we considered immersion and multiconjugate methods of isoplanatic patch widening. Using immersion method we obtained about twotimes enlargement of isoplanatic patch size for the developed eye models. For optimal configuration of a multiconjugate system with two correctors and five reference sources isoplanatic patch area increased two times if compared with the case of conventional correction. We consider immersion method to be more preferable due to its relative simplicity and low-cost.
Ultra-high resolution adaptive optics: optical coherence tomography for in vivo imaging of healthy and diseased retinal structures
Ultra-high isotropic resolution imaging of retinal structures was made possible with an adaptive optics system using dual deformable mirrors and a Fourier-domain optical coherence tomography (Fd-OCT) system with correction for longitudinal chromatic aberration. This system was used to image microscopic retinal structures of healthy as well as diseased retinas in vivo. The improved resolution and contrast enhanced visualization of morphological structures in the retina can be clearly seen. The benefits of this instrument are apparent from comparison of new images with those acquired using a previous generation AO-OCT instrument. Big change in the appearance of speckle field (reduction in speckle size) can be observed as well. Additionally, further improvements in volumetric data acquisition and image representation will be discussed. This includes creation of large Field of View (FOV) AO-OCT volume from multiple sub-volumes and its visualization. Also techniques and results of reducing speckle contrast by averaging multiple B-scans will be presented.
Optical Coherence Tomography I: Instrumentation and Image Processing
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Improved representation of retinal data acquired with volumetric Fd-OCT: co-registration, visualization, and reconstruction of a large field of view
Robert J. Zawadzki, Alfred R. Fuller, Stacey S. Choi, et al.
Advances in Fourier-domain optical coherence tomography (Fd-OCT) permit visualization of three-dimensional morphology of in-vivo retinal structures in a way that promises to revolutionize clinical and experimental imaging of the retina. The relevance of these advances will be further increased by the recent introduction of several commercial Fd-OCT instruments that can be used in clinical practice. However, due to some inherent limitations of current Fd-OCT technology (e.g., lack of spectroscopic information, inability to measure fluorescent signals), it is important to co-register Fd-OCT data with images obtained by other clinical imaging modalities such as fundus cameras and fluorescence angiography to create a more complete interpretation and representation of structures imaged. The co-registration between different imaging platforms becomes even more important if small retinal changes are monitored for early detection and treatment. Despite advances in volume acquisition speed with FD-OCT, eye/head motion artifacts can be still seen on acquired data. Additionally high-sampling density, large field-of-view (FOV) Fd-OCT volumes may also be needed for comparison with conventional imaging. In standard Fd-OCT systems, higher sampling density and larger imaging FOV (with constant sampling densities) lead to longer acquisition time which further increases eye/head motion artifacts. To overcome those problems, we tested 3D stitching of multiple, smaller retinal volumes which can be acquired in a less time (reduction of motion artifacts) and/or when stitched create a larger FOV representation of the retina. Custom visualization software that makes possible manual co-registration and simultaneous visualization of volumetric Fd-OCT data sets is described. Volumetric visualizations of healthy retinas with corresponding fundus pictures are presented followed by examples of retinal volumes of high sampling density that are created from multiple "standard" Fd-OCT volumes.
Fast detection and segmentation of drusen in retinal optical coherence tomography images
Sina Farsiu, Stephanie J. Chiu, Joseph A. Izatt, et al.
Accurate detection-characterization of drusen is an important imaging biomarker of age-related macular degeneration (AMD) progression. We report on the development of an automatic method for detection and segmentation of drusen in retinal images captured via high speed spectral domain coherence tomography (SDOCT) systems. The proposed algorithm takes advantage of a priori knowledge about the retina shape and structure in the AMD and normal eyes. In the first step, the location of the retinal nerve fiber layer (RNFL) is estimated by searching for the locally connected segments with high radiometric vertical gradients appearing in the upper section of the SDOCT scans. The high reflective and locally connected pixels that are spatially located below the RNFL layer are taken as the initial estimate of the retinal pigment epithelium (RPE) layer location. Such rough estimates are smoothed and improved by using a slightly modified implementation of the Xu-Prince gradient vector flow based deformable snake method. Further steps, including a two-pass scan of the image, remove outliers and improve the accuracy of the estimates. Unlike healthy eyes commonly exhibiting a convex RPE shape, the shape of the RPE layer in AMD eyes might include abnormalities due to the presence of drusen. Therefore by enforcing local convexity condition and fitting second or fourth order polynomials to the possibly unhealthy (abnormal) RPE curve, the health (normal) shape of the RPE layer is estimated. The area between the estimated normal and the segmented RPE outlines is marked as possible drusen location. Moreover, fine-tuning steps are incorporated to improve the accuracy of the proposed technique. All methods are implemented in a graphical user interface (GUI) software package based on MATLAB platform. Minor errors in estimating drusen volume can be easily manually corrected using the user-friendly software interface and the program is constantly refined to correct for the repeating errors. This semi-supervised approach significantly reduces the time and resources needed to conduct a large-scale AMD study. The computational complexity of the core automated segmentation technique is attractive as it only takes about 6.5 seconds on a conventional PC to segment, display, and record drusen locations in an image of size (512 × 1000) pixels. Experimental results on segmenting drusen in SDOCT images of different subjects are included, which attest to the effectiveness of the proposed technique.
Keynote Lecture
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Technology needs for tomorrow's treatment and diagnosis of macular diseases
Retinal imaging is the basis of macular disease's diagnosis. Currently available technologies in clinical practice are fluorescein and indocyanin green (ICG) angiographies, in addition to optical coherence tomography (OCT), which is an in vivo "histology-like" cross-sectional images of the retina. Recent developments in the field of OCT imaging include Spectral-Domain OCT. However OCT remains a static view of the macula with no direct link with dynamic observation obtained by angiographies. Adaptative optics is an encouraging perspective for fundus analysis in the future, and could be linked to OCT or angiographies. Treatments of macular disease have exploded these past few years. Pharmacologic inhibition of angiogenesis represents a novel approach in the treatment of choroidal neovascularization in eyes with age-related macular degeneration. The major action explored is the direct inhibition of the protein VEGF with antibody-like products. New anti-VEGF drugs are in development aiming at the VEGF receptors or synthesis of VEGF. But various components of the neovascular cascade, including growth factor expression, extracellular matrix modulation, integrin inhibition represent potential targets for modulation with drugs. Intra-vitreal injections are nowadays the main route of administration for these new treatments but they are potentially responsible of side effects such as endophtalmitis. Development of other routes of treatment would require new formulation of used drugs. The improvement of retinal imaging leads to a better understanding of macular disease mechanisms and will help to develop new routes and targets of treatment.
Ophthalmic Imaging III: Functional Imaging
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Improved diagnostics by automated matching and enhancement in fluorescein angiography of the ocular fundus
Herke Jan Noordmans, Pieter van den Biesen, Rowland de Roode, et al.
An interactive image matching program has been developed to help ophthalmologists in perceiving subtle differences between sequential images obtained during fluorescein angiography. In a pilot experiment, it appeared that the image matching program could effectively correct camera alignment errors. By offering simple tools like image overlay, blinking and image subtraction, differences between angiograms can be greatly enhanced and interpreted. It appeared that newly formed, leaking blood vessels could be detected at an earlier stage of the disease process using these tools. Treatment can be initiated right away, thereby preventing the patient from having additional visual loss. The matching program seems to improve the quality of fundus diagnostics but needs to be validated in future studies.
Optical imaging of the retina in response to the electrical stimulation
Takashi Fujikado, Yoshitaka Okawa M.D., Tomomitsu Miyoshi M.D., et al.
Purposes: To determine if reflectance changes of the retina can be detected following electrical stimulation to the retina using a newly developed optical-imaging fundus camera. Methods: Eyes of cats were examined after pupil dilation. Retina was stimulated either focally by a ball-type electrode (BE) placed on the fenestrated sclera or diffusely using a ring-type electrode (RE) placed on the corneoscleral limbus. Electrical stimulation by biphasic pulse trains was applied for 4 seconds. Fundus images with near-infrared (800-880 nm) light were obtained between 2 seconds before and 20 seconds after the electrical stimulation (ES). A two-dimensional map of the reflectance changes (RCs) was constructed. The effect of Tetrodotoxin (TTX) was also investigated on RCs by ES using RE. Results: RCs were observed around the retinal locus where the stimulating electrodes were positioned (BE) or in the retina of the posterior pole (RE), in which the latency was about 0.5 to 1.0 sec and the peak time about 2 to 5 sec after the onset of ES. The intensity of the RCs increased with the increase of the stimulus current in both cases. RCs were completely suppressed after the injection of TTX. Conclusions: The functional changes of the retina either by focal or diffuse electrical stimulation were successfully detected by optical imaging of the retina. The contribution of retinal ganglion cells on RCs by ES was confirmed by TTX experiment. This method may be applied to the objective evaluation of the artificial retina.
Frequency encoded assessment of retinal physiology
We demonstrate in-vivo functional imaging of the human retina with Fourier domain optical coherence tomography employing frequency encoding of an excitation pattern. The principle is based on projecting a modulated rectangular pattern across the foveal region and acquiring a time series of B-Scans at the same vertical position across the pattern. The idea is to modulate the excitation with a frequency that is distinct from the heartbeat and irregular motion artifacts. Fourier analysis of the time series at each transverse position in the B-scan series allows assessing the retinal response as change in the FDOCT reflectivity signal exactly at the pattern modulation frequency. We observe a change in retinal reflectivity within the region of the outer segment photoreceptor layer exactly at the pattern modulation frequency.
Mapping of photoreceptor dysfunction using high resolution three-dimensional spectral optical coherence tomography
B. L. Sikorski, M. Szkulmowski, J. J. Kałużny, et al.
The ability to obtain reliable information on functional status of photoreceptor layer is essential for assessing vision impairment in patients with macular diseases. The reconstruction of three-dimensional retinal structure in vivo using Spectral Optical Coherence Tomography (Spectral OCT) became possible with a recent progress of the OCT field. Three-dimensional data collected by Spectral OCT devices comprise information on light intensity back-reflected from the junction between photoreceptor outer and inner segments (IS/OS) and thus can be used for evaluating photoreceptors impairment. In this paper, we introduced so called Spectral OCT reflectivity maps - a new method of selecting and displaying the spatial distribution of reflectivity of individual retinal layers. We analyzed the reflectivity of the IS/OS layer in various macular diseases. We have measured eyes of 49 patients with photoreceptor dysfunction in course of age-related macular degeneration, macular holes, central serous chorioretinopathy, acute zonal occult outer retinopathy, multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, drug-induced retinopathy and congenital disorders.
Retinal blood flow analysis using joint spectral and time domain optical coherence tomography
We propose a new technique of measuring and analysis of OCT signals: joint Spectral and Time domain Optical Coherence Tomography (STdOCT). This technique is based on a multiple spectral interferogram registration in time increments. The analysis of a single spectral interferogram provides an axial structure of a sample. The analysis of signals registered in time enables velocity estimation of moving sample. The method is applied to biomedical imaging, in particular to in vivo measurements of retinal blood circulation. The velocity estimations obtained with joint STdOCT are compared with the ones obtained by known, phase-resolved OCT. In contrast to the phase-resolved technique, STdOCT correctly reproduces parabolic shape of the flow velocity distribution despite decreasing signal-to-noise ratio (SNR).
Visual Optics and Biometry
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Improved sensitivity measurement of the human eye length in vivo with Fourier domain optical coherence tomography
We present a system for intraocular distance measurement of the human eye in vivo with high sensitivity. The instrument is based on Fourier domain low coherence interferometry (FD-LCI). State-of-the-art FD-LCI systems are capable to image a depth range of only a few mm, because the depth range is determined by the spectral resolution of the spectrometer. To measure larger distances (e.g. human eye length) we implemented two separate reference arms with different arm lengths into the interferometer. Each reference arm length corresponds to a different depth position within the sample (e.g. cornea and retina). Therefore two different depth sections, each with a depth range of a few mm can be imaged simultaneously. With the new system axial distances could be measured with a precision of 8&mgr;m. We demonstrate the performance of the instrument by measuring the axial eye length of 9 patients with cataract and compare our results with those obtained using the IOL Master (Carl Zeiss Meditec Inc.).
Mechanical properties of intra-ocular lenses
Cataract surgery usually involves the replacement of the natural crystalline lens with a rigid or foldable intraocular lens to restore clear vision for the patient. While great efforts have been placed on optimising the shape and optical characteristics of IOLs, little is know about the mechanical properties of these devices and how they interact with the capsular bag once implanted. Mechanical properties measurements were performed on 8 of the most commonly implanted IOLs using a custom build micro tensometer. Measurement data will be presented for the stiffness of the haptic elements, the buckling resistance of foldable IOLs, the dynamic behaviour of the different lens materials and the axial compressibility. The biggest difference between the lens types was found between one-piece and 3-piece lenses with respect to the flexibility of the haptic elements
Typical crosscorrelation between two eyes found in fluctuation of accommodation but not in aberrations
T. Mihashi, M. Kobayashi, Y. Hirohara
We investigated time series of measurements of accommodation and monochromatic wave aberrations (WA) for both eyes. We measured WA for both eyes using an open-view binocular Shack Hartmann wavefront sensor. A landscape picture was presented at the far point of each subject. Two normal subjects in their thirties and a presbyopic subject were measured. We didn't find strong crosscorrelations between any two Zernike modes in one eye and in the same Zernike mode between two eyes; however strong crosscorrelations were found in the accommodation of normal subjects.
Ophthalmic Tissue Optics and Light-Tissue Interactions
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Fs-lentotomy: first in vivo studies on rabbit eyes with a 100 kHz laser system
S. Schumacher, U. Oberheide, M. Fromm, et al.
Up to now reading glasses are the conventional treatment of presbyopia, an age related effect for every human. According to the Helmholtz theory the reason for the development of accommodative loss is a decreasing elasticity of the lens due to the increasing sclerosis. Since the ciliary muscle and the lens capsule remain active and elastic the whole life, a possible treatment could be the increase of the flexibility by creating gliding planes with fs-laser pulses. flexibility of ex vivo porcine as well as human donor lenses with a laboratory laser system. We will present new results with a compact 100 kHz repetition rate turn key laser system which speeds up the treatment time by a factor of 10. This will offer the opportunity for future clinical trials. Furthermore first in-vivo results on rabbits are presented.
Laser parameters, focusing optics, and side effects in femtosecond laser corneal surgery
Karsten Plamann, Valeria Nuzzo, Donald A. Peyrot, et al.
Nowadays, femtosecond lasers are routinely used in refractive eye surgery. Until recently, commercialised clinical systems were exclusively based on ytterbium or neodymium-doped solid state lasers emitting sub-picosecond pulses at a wavelength of about 1 μm and repetition rates of a few 10 kHz. These systems use pulse energies in the μJ range and focussing optics of NA = 0.3 to 0.5. Recent developments have provided a variety of alternative and equally viable approaches: systems are now available using nJ pulses at high numerical apertures and MHz repetition rates - an approach so far only used for femtosecond cell surgery - and fibre laser technology is now being used for femtosecond laser corneal surgery. Recent research has also provided more insight in side effects occurring in present systems: self focusing phenomena and so far unexplained periodical structures have been observed even at high numerical apertures (NA >> 0.5) and moderate pulse energies. The interaction of femtosecond laser pulses with strongly scattering tissue has been studied in view of extending the application of femtosecond lasers to keratoplasty for opaque corneas and to glaucoma surgery. The use of new laser wavelengths and adaptive optics has been proposed. Despite the reputation of femtosecond surgical systems for their precision, repeatability and the absence of secondary effects or complications, a closer examination reveals the presence of subtle phenomena which merit further investigation. We present three of these phenomena: the influence of optical aberration on the quality of the incision, the occurrence of filamentation effects, and the deposit of microscopic glass fragments when performing penetrating incisions.
Ocular Surgery and Therapy
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UV collagen cross-linking of the cornea: safety aspects and design of a UV illumination system
M. Bueeler, E. Spoerl, T. Seiler, et al.
Cross-linking of the cornea is a new curative approach to re-increase the mechanical stability of corneal tissue that is progressively decreasing as a result of a corneal disease such as keratoconus or pellucid marginal degeneration. The new procedure might have the potential to reduce the need for invasive corneal transplantation. The aim of the treatment is to create additional chemical bonds inside the corneal stroma by means of a photopolymerizer and UV light at 365 nm. Two different potential damage mechanisms must be considered: the UV-irradiation alone and the action of the photochemically induced free radicals (photochemical damage). In this study damage thresholds from the literature were compared to the treatment parameters currently used in corneal cross-linking and aspects of the design of a UV illumination system for corneal cross-linking were discussed with respect to the safety of the procedure. It was shown that the currently used UVA dose density of 5.4 mJ/cm2 is below the known damage thresholds of UVA for the corneal endothelium, lens, and retina. All these safety considerations assume an optically homogeneous irradiation. Optical inhomogeneities such as hot spots may lead to localized supra-threshold irradiation with consecutive damage to the corneal endothelium which represents the most endangered structure. Some authors have used direct illumination of the cornea by means of UV-LEDs, which bares the risk of creating too high intensities. Therefore, clinically used light sources must guarantee a perfect homogeneity of the irradiance across the beam area. The illumination system presented here provides good homogeneity and shows a very high tolerance towards variations in treatment distance which was shown to cause dangerous hot spots when direct LED illumination is used.
Combining femtosecond laser ablation and diode laser welding in lamellar and endothelial corneal transplants
Based on our previous clinical experiences in minimally invasive diode laser-induced welding of corneal tissue in penetrating keratoplasty (PK), i.e. full-thickness transplant of the cornea, we combined this technique with the use of a femtosecond laser for applications in lamellar (LK) and endothelial (EK) keratoplasty. In LK, the femtosecond laser was used to prepare donor button and recipient corneal bed; the wound edges were stained with a water solution of Indocyanine Green (ICG) and then irradiated with a diode laser emitting in CW mode to induce stromal welding. Intraoperatory observations and follow-up results up to 6 months indicated the formation of a smooth stromal interface, total absence of edema as well as inflammation, and reduction of post-operative astigmatism, as compared with conventional suturing procedures. In EK the femtosecond laser was used for the preparation of a 100 &mgr;m thick, 8.5mm diameter donor corneal endothelium flap. The flap stromal side was stained with ICG. After stripping the recipient Descemet's membrane and endothelium, the donor flap was positioned in the anterior chamber on the inner face of the cornea by an air bubble and secured to the recipient cornea by diode laser pulses delivered by means of a fiberoptic contact probe introduced in the anterior chamber, which produced welding spots of 200 &mgr;m diameter. Femtosecond laser sculpturing of the donor cornea provided lamellar and endothelial flaps of preset and constant thickness. Diode laserinduced welding showed a unique potential to permanently secure the donor flap in place, avoiding postoperative displacement and inflammation reaction.
Measuring performance in virtual reality phacoemulsification surgery
Per Söderberg, Carl-Gustaf Laurell M.D., Wamidh Simawi M.D., et al.
We have developed a virtual reality (VR) simulator for phacoemulsification surgery. The current work aimed at developing a relative performance index that characterizes the performance of an individual trainee. We recorded measurements of 28 response variables during three iterated surgical sessions in 9 experienced cataract surgeons, separately for the sculpting phase and the evacuation phase of phacoemulsification surgery and compared their outcome to that of a reference group of naive trainees. We defined an individual overall performance index, an individual class specific performance index and an individual variable specific performance index. We found that on an average the experienced surgeons performed at a lower level than a reference group of naive trainees but that this was particularly attributed to a few surgeons. When their overall performance index was further analyzed as class specific performance index and variable specific performance index it was found that the low level performance was attributed to a behavior that is acceptable for an experienced surgeon but not for a naive trainee. It was concluded that relative performance indices should use a reference group that corresponds to the measured individual since the definition of optimal surgery may vary among trainee groups depending on their level of experience.
Ophthalmic Diagnostics I: Microscopy, Scattering, Spectroscopy
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The impact of horizontal offset of the cornea during corneal specular microscopy
Curry Bucht, Per Söderberg, Göran Manneberg
We are developing automated morphometric analysis of the corneal endothelium. Here, the general impact of horizontal offset of the cornea on morphometry was examined. Errors due to perspective during imaging with a Clinical Specular Microscope (CSM) were analyzed considering semi automated analysis software and fully automated Fourier analysis software. Methods: A mathematical model of the cornea was created. Trigonometry was applied to find the relationship between the horizontal offset of the cornea relative to the microscope objective, and the consecutive errors from perspective changes in the image. An experimental setup was created using a cornea made of polymethyl methacrylate (PMMA). The posterior surface of the PMMA cornea was horizontally marked. The PMMA cornea was placed in a holder. Difference in refractive index between real endothelium and aqueous humor was emulated using high refractive index liquid. Images with varying horizontal offset on the PMMA corneal posterior surface, along with their relative offset coordinates were captured, using CSM. Results: Experiments using controlled offset of the cornea in relation to its center estimated that analyzable images can be acquired within an interval of 1.26 mm, using central cornea sampling CSM. Because of refractive indices along with light scattering differences between the corneal tissue and PMMA , the 1.26 mm interval should be considered a first estimate for feasible CSM images. The effect of corneal endothelial offset during imaging with CSM or fully automated Fourier analysis should be considered.
Ex-vivo multiphoton analysis of rabbit corneal wound healing following photorefractive keratectomy
The aim of this study is to assess the application of multiphoton autofluorescence and second harmonic generation (SHG) microscopy for investigating corneal wound healing after high myopic (-10.0D) photorefractive keratectomy (PRK) procedures on the rabbit eyes. The effect of PRK on the morphology and distribution of keratocytes were investigated using multiphoton excited autofluorescence imaging, while the effect of PRK on the arrangement of collagen fibers was monitored by second-harmonic generation imaging. Without histological processing, multiphoton microscopy is able to characterize corneal damage and wound healing from PRK. Our results show that this technique has potential application in the clinical evaluation of corneal damage due to refractive surgery, and may be used to study the unwanted side effects of these procedures.
Multiphoton fluorescence and second harmonic generation microscopy for imaging corneal edema
The purpose of this study is to investigate the structural features of corneal edema by multiphoton fluorescence and second harmonic generation (SHG) microscopy and the potential of this technique as a clinical in vivo monitoring technique for cornea disease diagnosis.
Ophthalmic Diagnostics II: Polarization Techniques
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A polarization measurement method for the quantification of retardation in optic nerve fiber layer
Yasufumi Fukuma, Yoshio Okazaki, Takashi Shioiri, et al.
The thickness measurement of the optic nerve fiber layer is one of the most important evaluations for carrying out glaucoma diagnosis. Because the optic nerve fiber layer has birefringence, the thickness can be measured by illuminating eye optics with circular polarized light and analyzing the elliptical rate of the detected polarized light reflected from the optic nerve fiber layer. In this method, the scattering light from the background and the retardation caused by the cornea disturbs the precise measurement. If the Stokes vector expressing the whole state of polarization can be detected, we can eliminate numerically the influence of the background scattering and of the retardation caused by the cornea. Because the retardation process of the eye optics can be represented by a numerical equation using the retardation matrix of each component and also the nonpolarized background scattering light, it can be calculated by using the Stokes vector. We applied a polarization analysis system that can detect the Stokes vector onto the fundus camera. The polarization analysis system is constructed with a CCD area image sensor, a linear polarizing plate, a micro phase plate array, and a circularly polarized light illumination unit. With this simply constructed system, we can calculate the retardation caused only by the optic nerve fiber layer and it can predict the thickness of the optic nerve fiber layer. We report the method and the results graphically showing the retardation of the optic nerve fiber layer without the retardation of the cornea.
Imaging the anterior eye segment by polarization-sensitive spectral-domain and swept-source optical coherence tomography
Polarization-sensitive optical coherence tomography (PS-OCT) has been developed to measure the birefringent properties of the human eye. In the retina, retinal nerve fiber layer and retinal pigment epitherial layer have the characteristic birefringent properties.1.2 In addition to such normal tissue, abnormal fibrous tissue of the retina can be detected by PS-OCT.3 In the anterior segment, the cornea is a birefringent tissue due to the multi-layered fibril structure.4 The sclera and tendon also have the birefringence and the contrast of these structures can be enhanced by PS-OCT.5 These studies have been used time-domain or spectral-domain PS-OCT. Recently, swept-source OCT (SS-OCT) has been applied for anterior eye segment imaging.6 At the 1.3 um wavelength, SS-OCT is more promising than spectral-domain OCT, because the available camera for the spectrometer is limited. Three-dimensional imaging of the anterior segment is possible owing to the high penetration, high acquisition speed and high sensitivity. We have developed a new system of SS-OCT with polarization sensitivity. In this study, we measure the birefringent properties of anterior eye segment by polarization-sensitive spectral-domain OCT (PS-SD-OCT) at 840 nm and polarizationsensitive swept-source OCT (PS-SS-OCT) at 1.3 um, and evaluated the possibilities for clinical application.
Imaging polarimetry of macular disease
Masahiro Miura, Ann E. Elsner, Benno L. Petrig, et al.
Polarization properties of the human eye have long been used to study the tissues of the human retina, as well as to improve retinal imaging, and several new technologies using polarized light are in use or under development.1-8 The most typical polarimetry technique in ophthalmology clinic is a scanning laser polarimetry for the glaucoma diagnosis.1,2 In the original conceptualization, the thickness of the retinal nerve fiber layer is estimated using the birefringent component of light returning from the ocular fundus. More recently, customized software to analyze data from scanning laser polarimetry was developed to investigate the polarization properties of the macular disease.5-8 In this study, we analyzed macular disease with imaging polarimetry, which provides a method for the noninvasive assessment of macular disease.
Optical Coherence Tomography III: Clinical Applications
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Direct visualization of tear film on soft contact lens using ultra-high resolution spectral domain optical coherence tomography
The integrity of the tear film on the surface of contact lenses is essential to maintaining visual clarity and the overall health of the superficial structures of the eye (cornea and conjunctiva) for contact lens wearers. It is very critical to evaluate pre- and post-lens tear films in contact lens practice to make sure the lens is properly fitted. Improper lens fitting may cause ocular discomfort, visual distortion and ocular infection. It is very often for soft contact lens wearers to experience dry eye, especially in the afternoon after wearing the lens for a period of time. Dry eye has been a common cause of contact lens drop-off. There is currently no method available to directly visualize the tears on and underneath the contact lens in situ on human eye, mainly due to the extremely difficulty in imaging the micrometer-thin tear layer. An ultra-high resolution spectral domain optical coherence tomography has been developed with a telecentric light delivery system mounted with a slit-lamp. The system has a 3 micrometer depth resolution with a scan width up to 15 mm. The system was used to image soft contact lenses on the human eye. For the first time to our knowledge, tear films on the center and edge of the soft contact lens were directly visualized in vivo.
High-penetration imaging of retinal and choroidal pathologies by 1 μm swept-source OCT and optical coherence angiography
Yoshiaki Yasuno, Masahiro Miura, Fumiki Okamoto, et al.
Two pathologic cases are evaluated by high-penetration optical coherence tomography (HP-OCT) to demonstrate its clinical significance. The HP-OCT is based on a swept-source OCT (SS-OCT) technology with a probe wavelength of 1.06 μm. The depth resolution is 10.4 μm in tissue, and the measurement speed is 28,000 depth-scans/sec. A single case of age-related macular degeneration and a single case of Vogt-Koyanagi-Harada disease are examined by HP-OCT.
Session 13
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Retinal thermal laser damage thresholds for different beam profiles and scanned exposure
Karl Schulmeister, Reinhard Gilber, Bernhard Seiser, et al.
A computer model was used to predict thresholds for 532 nm scanned retinal exposure and exposure for different retinal beam profile geometries, including rectangles and ring shaped profiles. The image analysis method described in IEC 60825-1 Edition 1.2--maximizing the ratio of power within a rectangle over the value of &agr; for this rectangle--was applied to the different profiles to determine &agr; and the fractional power that would be compared to the MPE value. The predicted thresholds for these special types of retinal exposure were compared with the predicted damage threshold for top hat profiles for the value of &agr; that resulted from the image analysis method. The comparison shows that the most restrictive power/&agr; ratio method produces appropriate results, provided that a time dependent &agr;max is used, as was proposed at BIOS 2006.
Determination of the time dependence of colored afterimages
Investigations have been done with high-brightness LEDs in order to determine the flight of colors for these high-intensity light sources. By simply glancing into such a device for time durations of less than 10 seconds a long-lasting afterimage that slowly changes colors was observed. A computer assisted measuring system was developed in order to determine the dependency on various parameters like color, optical power, exposure duration of the stimulating LED. For that a specially designed color wheel diagram has been designed and used which contains the necessary information on hue, saturation, and brightness. The time-dependent process and changes of the afterimage colors were determined for 4 different dominant wavelengths, i.e. 455 nm, 530 nm, 590 nm and 625 nm, in the optical power range between 0.05 mW and 0.5 mW for exposure durations between 0.5 s and 5 s. The results obtained with 5 test persons will be reported and especially the time course of the color fractions is given in an 8-bit color space with the respective RGB values. The progression of the afterimage colors as a function of the applied optical energy will be shown in the CIE chromaticity diagram together with the respective total afterimage duration.
Role of superoxide dismutase in the photochemical response of cultured RPE cells to laser exposure at 413 nm
Michael L. Denton, Michael S. Foltz, Kurt J. Schuster, et al.
Thresholds for photochemical damage were performed in RPE cell lines (artificially pigmented) taken from either human (hTERT-RPE1), wild type (wt) mouse, or transgenic mice deficient (+/-) in either superoxide dismutase 1 (SOD1) or SOD2. The four cell lines were characterized by immunohistochemical and immunoblot analyses to determine relative abundance of the SOD proteins. There was no difference in sensitivity between the human, murine wt and murine SOD1-deficient cells, whereas there was a dramatic (2 fold) increase in threshold irradiance value for the murine SOD2-deficient cells. Possible explanations for the unexpected result are provided.
Ocular laser bioeffects in Operation Iraqi Freedom
Henry D. Hacker M.D., Jack Lund, Rachel Cheramie, et al.
Laser hazards on the modern battlefield include numerous applications with the potential for eye damage from both pulsed and high luminance continuous energy laser devices. The multitude of laser devices deployed both by friendly and threat forces represent a significant hazard to vision, and consequently duty performance. Increased application of high luminance devices for tactical use may result in accidental exposure and temporary or persistent symptoms. These symptoms may be confounded by ongoing ocular retinal disorders. The management of these patients requires additional laser training to prevent injury as well as more experience and training for first responders in order to triage individuals with vision disturbances thought secondary to ocular laser exposure.
Psychophysical and perceptual performance in a simulated-scotoma model of human eye injury
R. Brandeis, I. Egoz, D. Peri, et al.
Macular scotomas, affecting visual functioning, characterize many eye and neurological diseases like AMD, diabetes mellitus, multiple sclerosis, and macular hole. In this work, foveal visual field defects were modeled, and their effects were evaluated on spatial contrast sensitivity and a task of stimulus detection and aiming. The modeled occluding scotomas, of different size, were superimposed on the stimuli presented on the computer display, and were stabilized on the retina using a mono Purkinje Eye-Tracker. Spatial contrast sensitivity was evaluated using square-wave grating stimuli, whose contrast thresholds were measured using the method of constant stimuli with "catch trials". The detection task consisted of a triple conjunctive visual search display of: size (in visual angle), contrast and background (simple, low-level features vs. complex, high-level features). Search/aiming accuracy as well as R.T. measures used for performance evaluation. Artificially generated scotomas suppressed spatial contrast sensitivity in a size dependent manner, similar to previous studies. Deprivation effect was dependent on spatial frequency, consistent with retinal inhomogeneity models. Stimulus detection time was slowed in complex background search situation more than in simple background. Detection speed was dependent on scotoma size and size of stimulus. In contrast, visually guided aiming was more sensitive to scotoma effect in simple background search situation than in complex background. Both stimulus aiming R.T. and accuracy (precision targeting) were impaired, as a function of scotoma size and size of stimulus. The data can be explained by models distinguishing between saliency-based, parallel and serial search processes, guiding visual attention, which are supported by underlying retinal as well as neural mechanisms.
Color and contrast sensitivity after glare from high-brightness LEDs
The color contrast capability was investigated for 3 volunteers with 7 specially developed test charts in red, green, blue, cyan, magenta, yellow and black as a reference, namely without and after glare from 4 colored high-brightness LEDs. Each subject completed 56 tests in order to check especially the ability to discriminate low contrast. It was found that a contrast decrease of one level is equivalent to an increase of about 4 s in the required identification time and in addition a delay time between about 14 s and 16 s has been measured at the beginning of the respective test as a result of the dazzling glare from an LED. In addition trials have been performed with 4 different pseudoisochromatic color plates designed by Ishihara for color vision. These plates have been used to determine temporary color deficiencies after an exposure from a high-brightness LED. For this purpose 40 volunteers have been included in a laboratory test. Color vision was impaired for periods between 27 s and 186 s depending on the applied color plate and respective LED color.
Poster Session
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Detecting thermal phase transitions in corneal stroma by fluorescence micro-imaging analysis
Thermal modifications induced in corneal stroma were investigated by the use of fluorescence microscopy. Freshly extracted porcine corneas were immersed for 5 minutes in a water bath at temperatures in the 35-90°C range and stored in formalin. The samples were then sliced in 200-μm-thick transversal sections and analyzed under a stereomicroscope to assess corneal shrinkage. Fluorescence images of the thermally treated corneal samples were acquired using a slow-scan cooled CCD camera, after staining the slices with Indocyanine Green (ICG) fluorescent dye which allowed to detect fluorescence signal from the whole tissue. All measurements were performed using an inverted epifluorescence microscope equipped with a mercury lamp. The thermally-induced modifications to the corneal specimens were evaluated by studying the grey level distribution in the fluorescence images. For each acquired image, Discrete Fourier Transform (DFT) and entropy analyses were performed. The spatial distribution of DFT absolute value indicated the spatial orientation of the lamellar planes, while entropy was used to study the image texture, correlated to the stromal structural transitions. As a result, it was possible to indicate a temperature threshold value (62°C) for high thermal damage, resulting in a disorganization of the lamellar planes and in full agreement with the measured temperature for corneal shrinkage onset. Analysis of the image entropy evidenced five strong modifications in stromal architecture at temperatures of ~45°C, 53°C, 57°C, 66°C, 75°C. The proposed procedure proved to be an effective micro-imaging method capable of detecting subtle changes in corneal tissue subjected to thermal treatment.
Gold nanorods as exogenous chromophores in the welding of ocular tissues
In this paper we show for the first time the suitability of gold nanorods as exogenous chromophores to mediate the near infrared laser welding of connective tissues. We used a 810 nm diode laser to simulate hetero-transplantations of patches of porcine lens capsules stained with nanorods with plasmon resonances about that wavelength. In our preliminary tests, successful welding was achieved at fluences in the 80 - 110 J·cm-2 range, which is, at worst, less than half of the threshold for direct damage, although still about a factor of two higher than the state-of-the-art with conventional chromophores such as Indocyanine Green.
High luminance application of orange fiber laser
Koichi Ito, Kazunobu Kojima, Tokio Ueno, et al.
We developed an orange fiber laser as the source for photocoagulation in ophthalmic applications. While the beam quality (M2=1.2) is excellent in comparison with the existing solid state laser (M2=7~8), there is the unfortunate necessity of an additional optical system to make the focusing beam uniform after transmission into the 50μm core diameter multimode fiber used in the existing photocoagulator. The purpose of this paper is to obtain a high luminance spot while maintaining the uniformity of the beam. We used 4.7μm Mode field diameter, single mode fiber (SMF) to focus the laser beam emitted from the developed 580nm orange fiber laser source. A coupling efficiency of 70% was obtained at the input power of 500 mW. Moreover, the beam quality of M2=1.27 was achieved after fiber coupling. No additional optical system was necessary to make the beam uniform owing to the SMF characteristics. As a result, the beam diameter at the irradiation point became 12.2μm, and the power density was calculated to be about 25 times higher than that of the existing photocoagulator. Significantly high luminance beams were obtained in the method described above. If the laser spot can be focused near the diffraction limit using adaptive optics in the future, it can be used in new operative procedures such as microsurgery in the macular region. When this method is used in photocoagulation, improvement in the quality of vision of patients is expected due to minimizing any damage to the retina. The effects of high luminance laser irradiation on pseudobiological tissue will be examined in a future paper.