In this paper we demonstrate the integration of two technologies, Line-Scanning Laser Ophthalmoscopy (LSLO) and Spectral Domain Optical Coherence Tomography (SDOCT) into a single compact instrument that shares the same imaging optics and line scan camera for both LSLO and OCT imaging. Co-registered high contrast wide-field en face retinal LSLO and SDOCT images are obtained non-mydriatically with less than 600 microwatts of broadband illumination at 15 frames/sec. The hybrid instrument can work in three different modes: LSLO mode, SDOCT mode, and LSLO/SDOCT interleaved mode. This instrument could be useful in clinical ophthalmic diagnostics and emergency medicine.

Ophthalmic OCT was performed using a novel, compact external cavity semiconductor laser at ~850 nm. Retinal imaging was demonstrated with a resolution of <7 microns in tissue at a speed of 16,000 axial scans per second. The coherence length of the laser is >10 mm, enabling an axial measurement range of ~2.5 mm. Real-time display and data streaming capabilities enable video-rate imaging of the retina at >30 frames per second. High-definition and three-dimensional imaging were demonstrated on normal retinas. The resolution of <7 microns in the retina is, to our knowledge, the highest resolution achieved in the retina with swept source OCT to date. The long coherence length of the laser enables high-sensitivity measurements over a large axial measurement range. The speed of 16,000 axial scans per second is comparable to current spectrometer-based spectral/Fourier domain OCT systems. The low cost and small footprint of our laser (~10 cm x 20 cm) may enable the development of OCT for novel applications. Further improvements in speed will be possible by using alternative scanning methods.

The ability to obtain true three-dimensional (3D) morphology of the retinal structures is essential for future clinical and experimental studies. It becomes especially critical if the measurements acquired with different instruments need to be compared, or precise volumetric data are needed for monitoring and treatment of retinal disease. On the other hand, it is well understood that optical coherence tomography (OCT) images are distorted by several factors. Only limited work has been performed to eliminate these problems in ophthalmic retinal imaging, perhaps because they are less evident in the more common 2D representation mode of time-domain OCT. With recent progress in imaging speed of Fourier domain - OCT (Fd-OCT) techniques, however, 3D OCT imaging is more frequently being used, thereby exposing problems that have been ignored previously. In this paper we propose possible solutions to minimize and compensate for artifacts caused by subject eye and head motion, and distortions caused by the geometry of the scanning optics. The first is corrected by cross-correlation based B-scan registration techniques; the second is corrected by incorporating the geometry of the scanning beam into custom volume rendering software. Retinal volumes of optical nerve head (ONH) and foveal regions of healthy volunteer, with and without corrections, are presented. Finally, some common factors that may lead to increased distortions of the ophthalmic OCT image such as refractive error or position of the subject's head are discussed.

For daily practice, in particular clinical studies using optical coherence tomography, the commercial OCT3/Stratus scanner has until now been the prevalent instrument of choice. Whereas the ongoing development of OCT-systems will permit evaluation of pathology on a cellular scale, this is a goal which is not within the limit of the present generation of clinical OCT. On the other hand it is possible to get improved retinal information from clinical equipment like the OCT3 system by registering and combining a series of scans. Due to the widespread clinical use of OCT3 this paper explores the potential improvement for a number of clinical cases using such a technique. The basic idea of composite image enhancement might also be useful for image-enhancement with the new generations of OCT equipment.

Fourier Domain OCT proved to be an outstanding tool for measuring 3D retinal structures with high sensitivity, resolution, and speed. We extended the FDOCT concept towards functional imaging by analyzing the spectroscopic tissue properties, polarization contrast and Doppler velocity imaging. Differential spectral contrast FDOCT allows optical staining of retinal tomograms and to contrast tissue of high pigmentation such as the retinal pigment epithelium (RPE). The latter shows strong correlation if compared to polarization sensitive OCT images. First implementations of Doppler FDOCT systems demonstrated the capability of measuring in-vivo retinal blood flow profiles and pulsatility. We developed a new concept of Doppler FDOCT that allows measuring also large flow velocities typically close to the optic nerve head. Studies of retinal perfusion based on Laser Doppler Flowmetry (LDF) demonstrated the high sensitivity of blood flow to external stimuli. We performed first experiments of studying retinal perfusion in response to flicker stimulation. An increase in vessel diameter by 11% and of flow velocity by 49% was measured. We believe that a multi-modal functional imaging concept is of high value for an accurate and early diagnosis and understanding of retinal pathologies and pathogenesis.

A non-invasive, phase-insensitive optical coherence angiography method has been demonstrated for in vivo human retinal imaging based on high-speed spectral-domain optical coherence tomography with a center wavelength of 840nm. Three-dimensional view of the choroidal vasculature was obtained by segmenting choroidal vessels using threshold values from the intensity distribution at each depth plane relative to the retinal pigment epithelium layer. A vascular projection image was obtained by integrating the segmented choroidal vasculature.

We used optical coherence tomography (OCT) for non-invasive imaging of the anterior segment of the eye for investigating partial-thickness scleral channels created with a femtosecond laser. Glaucoma is associated with elevated intraocular pressure (IOP) due to reduced outflow facility in the eye. A partial-thickness aqueous humor (AH) drainage channel in the sclera was created with 1.7-&mgr;m wavelength femtosecond laser pulses to reduce IOP by increasing the outflow facility, as a solution to retard the progression of glaucoma. It is hypothesized that the precise dimensions and predetermined location of the channel would provide a controlled increase of the outflow rate resulting in IOP reduction. Therefore, it is significant to create the channel at the exact location with predefined dimensions. The aim of this research has two aspects. First, as the drainage channel is subsurface, it is a challenging task to determine its precise location, shape and dimensions, and it becomes very important to investigate the channel attributes after the laser treatment without disturbing the internal anterior structures. Second, to provide a non-invasive, image-based verification that extremely accurate and non-scarring AH drainage channel can be created with femtosecond laser. Partial-thickness scleral channels created in five human cadaver eyes were investigated non-invasively with a 1310-nm time-domain OCT imaging system. Three-dimensional (3D) OCT image stacks of the triangular cornea-sclera junction, also known as anterior chamber angle, were acquired for image-based analysis and visualization. The volumetric cutting-plane approach allowed reconstruction of images at any cross-sectional position in the entire 3D volume of tissue, making it a valuable tool for exploring and evaluating the location, shape and dimension of the channel from all directions. As a two-dimensional image-based methodology, an image-processing pipeline was implemented to enhance the channel features to augment the analysis. In conclusion, we successfully demonstrate that our image-based visualization tool is appropriate for effective investigation and evaluation of femtosecond laser-created, partial-thickness aqueous humor drainage channels in the sclera.

Noninvasive in vivo examination of the rodent retina without sacrificing the animal is the key to being able to perform longitudinal studies. This allows the monitoring of disease progression and the response to therapies through its entire course in individual animal. A high-speed high resolution three-dimensional spectral-domain OCT is built for non-contact in vivo imaging of rodent retina. The system is able to acquire high quality 3D images of the rodent retina in 2.7 seconds (total imaging time is ~5 minutes). The system was tested on mice with normal retina (B6/SJLF2), mouse model for photoreceptor degeneration (Rho^-/-), and mouse model for retinoblastoma (LH_BETAT_AG). For the first time to our knowledge, 3D image of the tumor in retinoblastoma mouse model was successfully imaged in vivo. By segmenting the tumor boundaries in each frame of the OCT image the volume of the tumor was successfully calculated.

Cataract surgery is considered to be the most successful surgery worldwide. However, new developments are ongoing either to improve the surgical stress or to improve the surgical outcome. While restoration of the transparency and optical parameters of the eye were initially the first goals, the need to improve the quality of sight (QOS) and to restore accommodation became evident during the last decades. By introducing the bag-in-the-lens (BIL) intraocular lens (IOL) and technique of implantation (US Patent 6,027,531) in 2000, PCO was no longer a matter of concern. Clinical studies conducted between 2000 and 2004 proved the efficacy of this new IOL with respect to PCO control, but showed additional advantages like surgeon-controlled centration and rotational stability. Surgeon-controlled IOL centration based on the alignment of the first and third Purkinje reflexes is one method to promote IOL centration but future tracking devices will probably enhance the precision by which IOL centration along the line of sight can be achieved. Optimal alignment is a major issue if toric correction and compensation of the spherical aberrations is intended to be incorporated into the IOL optic. IOL optics with toric correction to compensate for regular astigmatism are in development now, but toric correction for irregular astigmatism remains extremely challenging for the manufacturers. Improving the quality of the image by compensating for the spherical aberrations is the next step on our research programme. The BIL offers some opportunities to optimize postoperative accommodation by introducing the capsular accommodation ring.

The relationship between retinal nerve fiber layer (RNFL) birefringence (&Dgr;n) and neurotubule density (NTD, retinal ganglion cell (RGC) neurotubules per unit RNFL area) was investigated by correlating measurements of these two parameters in 1 eye of a healthy cynomolgus monkey. Phase retardation per unit depth (PR/UD, proportional to &Dgr;n) was measured at 5.6-15^o intervals around the optic nerve head (ONH) with an enhanced polarization-sensitive optical coherence tomography (EPS-OCT) instrument. Transverse tissue sections containing 3 RGC nerve fiber bundles from each peripapillary RNFL octant were imaged with a transmission electron microscope (TEM). Morphological measurements taken in TEM images were used by a novel algorithm to estimate NTD. Registered PR/UD and NTD data were then correlated using single- and multi-level models, yielding correlation coefficients in the range 0.49 ⩽ r ⩽ 0.61 (0.06 ⩽ P ⩽ 0.11). It was found that in order for the single-level correlation coefficient (r = 0.61) to be statistically significant (P ⩽ 0.05) and powerful (Power ⩾ 80%), NTD measurements in at least 16, rather than 8, RNFL sectors were needed. Interestingly, a single-level correlation coefficient of r = 0.81 (P = 0.01) was calculated between octant-averaged PR/UD and RGC axoplasmic area (A_x, axon area less non-cytoskeletal organelle area) mode. A_x represents a RGC axon's neurotubule-inhabitable area. Intuitively, a strong relationship should exist between A_x and neurotubule number if neurotubules provide the primary structural support for RGC axons and structural requirements are the same in all RGC axons. If this relationship exists, error resulting from NTD estimation methods or preservation artifacts may have caused lower observed correlations of PR/UD with NTD than with A_x mode, and more accurate methods of measuring in vivo NTD may be required to determine an accurate relationship between RNFL birefringence and NTD.

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^1-6. Recently, scanning laser polarimetry was used to selectively emphasize the different layers of the retina^1-3. Birefringence and depolarization were observed in the area with deep retinal lesions in macular disease^1-3. To confirm the origin of these polarization changes, layer by layer analysis is required. Optical coherence tomography (OCT) has been developed to measure the depth-resolved image of the retina, and polarization-sensitive OCT (PS-OCT) could visualize the polarization properties of various retinal layers^5-7. With combination of scanning laser polarimetry and PS-OCT, we can obtain more information about polarization properties of the macular disease. In this study, we compared scanning laser polarimetry image and PS-OCT image to evaluate the polarization properties of the deep retinal lesion in macular disease.

We developed a high-speed polarization sensitive optical coherence tomography (PS-OCT) system for retinal imaging based on spectral domain OCT. The system uses two spectrometers, one for each polarization channel, that operate in parallel at 20000 A-lines/s each. It provides reflectivity, retardation, and cumulative optic axis orientation simultaneously. With this setup we measured the three dimensional polarization properties of human retinas in vivo and compared them with results obtained from a commercially available scanning laser polarimetry system.

We present a system for high and isotropic resolution imaging of the retina. A polarization sensitive optical coherence tomography (PS-OCT) instrument with a depth resolution of ~4.5&mgr;m within the retina was used and adapted to achieve a high transverse resolution. The realized transverse resolution was sufficient to resolve the human cone mosaic in vivo without the use of adaptive optics. Since the technique is based on a fast transversal scanning of the retina, scanning laser ophthalmoscope (SLO) images can be acquired simultaneously to OCT images which allows a direct comparison of the two techniques. Furthermore, the system incorporates the possibility of a dynamic shift of focus within the retina which is essential to maintain the high transverse resolution over the whole imaging depth. Using a resonant scanner operated at 4kHz the system is capable to record 8000 transversal lines per second. Backscattered intensity, retardation and fast axis orientation of the human retina are presented with this high isotropic resolution.

Purpose: To study correlation among corneal asphericity, higher-order aberrations and visual performance for eyes of virgin myopia and postoperative laser in situ keratomileusis (LASIK). Methods: There were 320 candidates 590 eyes for LASIK treatment included in this study. The mean preoperative spherical equivalence was -4.35±1.51D (-1.25 to -9.75), with astigmatism less than 2.5 D. Corneal topography maps and contrast sensitivity were measured and analyzed for every eye before and one year after LASIK for the analysis of corneal asphericity and wavefront aberrations. Results: Preoperatively, only 4th and 6th order aberration had significant correlation with corneal asphericity and apical radius of curvature (p<0.001). Postoperatively, all 3th to 6th order aberrations had statistically significant correlation with corneal asphericity (p<0.01), but only 4th and 6th order aberration had significant correlation with apical radius of curvature (p<0.05). The asymmetrical aberration like coma had significant correlation with vertical offset of pupil center (p<0.01). Preoperatively, corneal aberrations had no significant correlation with visual acuity and area under the log contrast sensitivity (AULCSF) (P>0.05). Postoperatively, corneal aberrations still didn't have significant correlation with visual acuity (P>0.05), but had significantly negative correlation with AULCSF (P<0.01). Corneal asphericity had no significant correlation with AULCSF before and after the treatment (P>0.05). Conclusions: Corneal aberrations had different correlation with corneal profile and visual performance for eyes of virgin myopia and postoperative LASIK, which may be due to changed corneal profile and limitation of metrics of corneal aberrations.

Comprehensive evaluation of retinal image quality requires that light scatter as well as optical aberrations be considered. In investigating how retinal image degradation affects eye growth in the chick model of myopia, we developed a simple method based on Shack-Hartmann images for evaluating the effects of both monochromatic aberrations and light scatter on retinal image quality. We further evaluated our method in the current study by applying it to data collected from both normal chick eyes and albino eyes that were expected to show increased intraocular light scatter. To analyze light scatter in our method, each Shack-Hartmann dot is treated as a local point spread function (PSF) that is the convolution of a local scatter PSF and a lenslet diffraction PSF. The local scatter PSF is obtained by de-convolution, and is fitted with a circularly symmetric Gaussian function using nonlinear regressions. A whole-eye scatter PSF also can be derived from the local scatter PSFs for the analyzed pupil. Aberrations are analyzed using OSA standard Zernike polynomials, and aberration-related PSF calculated from reconstructed wavefront using fast Fourier transform. Modulation transfer functions (MTFs) are computed separately for aberration and scatter PSFs, and a whole-eye MTF is derived as the product of the two. This method was applied to 4 normal and 4 albino eyes. Compared to normal eyes, albino eyes were more aberrated and showed greater light scatter. As a result, overall retinal image degradation was much greater in albino eyes than in normal eyes, with the relative contribution to retinal image degradation of light scatter compared to aberrations also being greater for albino eyes.

Artal and co-researchers are primarily credited with formulating the principle of the double-pass method for obtaining the ocular point spread function (PSF) in 1998. This method requires a long time to calculate the partial phase-retrieval algorithm based on the iteration method. The purpose of this study was to develop a new and rapid phase retrieval algorithm. We developed a new algorithm that extrapolates the value of the real and imaginary parts of the optical transfer function (OTF). This algorithm was obtained from the characteristics of the continuous changes of the OTF value. In this article, we describe the new algorithm and its effectiveness by simulating and reconstructing ocular PSFs using double-pass PSFs with the same and different pupil sizes.

A new type of spectacle lens was developed incorporating a thin layer of a novel polymer with a light-programmable refractive index. The refractive index change can be used to change the optical power of the lens. One of the applications of this new lens is the correction of high-order aberrations of the human eye. A feasibility study was conducted to determine whether such wavefront-guided high-order correcting spectacle lenses can be 1) accurately manufactured, and 2) improve vision of human subjects. The ocular wavefront of 30 subjects was measured with a Z-View^TM diffractive aberrometer. A vision correcting high-order zone canceling the subjects' ocular wavefront was "programmed" directly into pairs of wavefront-guided spectacle lenses (WFGSL). The lenses could be successfully manufactured to an average Zernike rms accuracy of 81% (range 70% to 90%). Comparison was made against identical spectacles without the high-order zone. Double-masked vision tests included high and low-contrast visual acuity, and contrast sensitivity. The subject was allowed only a few minutes of adaptation time to the spectacles. While some experienced a dramatic improvement in vision, this was not observed for all subjects, in particular for subjects with small amounts of high-order aberrations. We speculate that more consistent vision improvement can be achieved by 1) determining a subject's candidacy for WFGSL based on the subject's ocular aberrations, 2) correcting only selected aberrations, 3) manufacture with higher purity and accuracy, and 4) lengthening the adaptation period before testing each lens.

Electronic retinal prostheses represent a potentially effective approach for restoring some degree of sight in blind patients with retinal degeneration. Functional restoration of sight would require hundreds to thousands of electrodes effectively stimulating remaining neurons in the retina. We present a design of an optoelectronic retinal prosthetic system having 3mm diameter retinal implant with pixel sizes down to 25 micrometers, which allows for natural eye scanning for observing a large field of view, as well as spatial and temporal processing of the visual scene to optimize the patient experience. Information from a head mounted video camera is processed in a portable computer and delivered to the implanted photodiode array by projection from the LCD goggles using pulsed IR (810 nm) light. Each photodiode converts pulsed light (0.5 ms in duration) into electric current with efficiency of 0.3 A/W using common bi-phasic power line. Power is provided by the inductively-coupled RF link from the coil on the goggles into a miniature power supply implanted between the sclera and the conjuctiva, and connected to subretinal implant with a thin 2-wire trans-scleral cable. 3-dimensional structures in the subretinal prosthesis induce retinal migration and thus ensure close proximity between stimulating electrodes and the target retinal neurons. Subretinal implantations of the 3-dimentional pillar and chamber arrays in RCS rats with 2 and 6 week follow-up demonstrate achievement of intimate proximity between the stimulation cites and the inner nuclear layer. In some instances formation of a fibrotic seal has been observed.

Purpose: To show potential of Spectral Optical Coherence Tomography system for high resolution, cross-sectional and three-dimensional imaging of eye surface pathologies. Methods: High-speed spectral OCT prototype instrument with 4.5 &mgr;m axial resolution was designed and constructed for clinical use. Measurements of anterior segment of human eye have been performed in ophthalmology clinic on 86 patients suffering various eye surface disorders including corneal dystrophies, corneal scars, conjunctival folds, keratoconus, bullus keratopathy, filtration blebs and other post-operative changes. Additionally, examinations of contact lens fit on 97 healthy corneas have been performed up to date. Results: High quality, high resolution cross-sectional images and three-dimensional reconstructions of cornea, conjunctiva and sclera of pathologic eyes together with examples of numerical analysis including segmentation of fluid in filtration blebs, scars and deposits are shown. Quantitative analysis of contact lens fit is demonstrated.

A two- and three- dimensional swept source optical coherence tomography (SS-OCT) system is demonstrated. This system uses 1.3 &mgr;m probe band, posesses a depth resolution of 14 &mgr;m, and operated at a sensitivity of 100 dB. This SS-OCT is capable of realtime display of two-dimensional OCT, and can take three-dimensional OCT with the measurement time of 2 s. 28 cases of 25 patients including 6 types of corneal diseases, 4 types of uveal diseases, 1 type of scleral disease and 3 types of glaucoma surgery are examined by this SS-OCT.

We report on the development of quantitative, reproducible diagnostic observables for age-related macular degeneration (AMD) based on high speed spectral domain optical coherence tomography (SDOCT). 3D SDOCT volumetric data sets (512 x 1000 x 100 voxels) were collected (5.7 seconds acquisition time) in over 50 patients with age-related macular degeneration and geographic atrophy using a state-of-the-art SDOCT scanner. Commercial and custom software utilities were used for manual and semi-automated segmentation of photoreceptor layer thickness, total drusen volume, and geographic atrophy cross-sectional area. In a preliminary test of reproducibility in segmentation of total drusen volume and geographic atrophy surface area, inter-observer error was less than 5%. Extracted volume and surface area of AMD-related drusen and geographic atrophy, respectively, may serve as useful observables for tracking disease state that were not accessible without the rapid 3D volumetric imaging capability unique to retinal SDOCT.

The aim of this study is to assess the application of multiphoton autofluorescence and second harmonic generation (SHG) microscopy for investigating the structural alterations and the pattern of microbial spreading during corneal infectious process in an in vitro organ culture model. The autofluorescence spectrum derived from pathogens allows us to monitoring the pattern of microbial spreading within corneal lamellae. In addition, the destruction and regeneration of second harmonic generating collagen during infectious process can also be monitored in a non-invasive fashion. Therefore we propose that multiphoton microscopy may potentially be applied as an effective monitoring tool for corneal infection studies.

As a part of an ongoing research project on morphometrical diagnosis of the corneal endothelium, an experimental optical setup has been created. The structure of the corneal endothelial cells could be considered a reflecting periodical aperture. Hence, the diffraction pattern reflected from the endothelium contains valuable morphometrical information. In the present work, focus has been on sampling the posterior surface of explanted corneas. Methods: An optical setup was created, using a 632.8 nm He-Ne laser as the light source. The desired diffraction pattern was produced as a collimated reflection. Hence, because the posterior surface of the cornea is concave, lenses were used to attain the right divergence of the light impingent on the corneal endothelium. These lenses also made it possible to adjust the sampling spot size. A beam splitter (BS) was used to provide an optical path for both the impinging laser beam as well as the reflected diffracted beam. The lens acting as a Fourier lens was then placed after the BS. At the back focal plane of the Fourier lens, a CCD detector was used for recording in the Fourier plane. In the process of creating the setup, explanted corneas were emulated using grated contact lenses. Results: The current optical set up allows identification of a diffraction pattern from a concave spherical surface with a radius of curvature of the same order as a human cornea.

A Doppler velocimeter exploiting a self-mixing laser diode is proposed. The system has been design to evaluate the retinal blood flow velocity. The central frequency of the Doppler band obtained from the self-mixing laser diode measurement is related to the blood flow velocity in the vessel under test. The measurement can be done under the light-intensity feedback ratio below -100 dB without using highly sensitive electronics since the laser acts as a high-efficiency mixer oscillator and a shot-noise-limited quantum detector. The advantages in adopting such technique consist in its low cost, easiness of implementation and small size. Moreover, the self-mixing laser diode method offers the advantage to have the excitation and measurement beams spatially overlapped overcoming the alignment difficulty due to limited optical accessibility imposed by the finite aperture of the pupil.

Neurovascular coupling in the optic nerve is the physiological mechanism that adjusts the blood perfusion in the microcirculation of the optic nerve to support the neural activity induced by vision. The resulting variations in blood flow and thus in neural tissue oxygenation induce changes in the optical properties of the tissues. These variations can be detected optically as reflectivity changes in the neural tissues, i.e. the retina and optic nerve disk. To achieve a better understanding of the mechanisms underlying the neurovascular coupling, our study is aimed at the evaluation of reflectance changes of the optic nerve induced by visual stimulation. For this purpose, an ocular fundus reflectometer has been developed.

Laser-induced thermal changes in the cornea have been used clinically for refractive surgery. This study describes the creation of variable depth thermal lesions in the cornea using a tunable Thulium fiber laser. Thermal lesions were created in fresh rabbit corneas, ex vivo, at three different wavelengths (1873 nm, 1890 nm, and 1904 nm) (n=6 corneas each). All other laser parameters were kept fixed with power of 5.5 W, 25-ms exposure time, and 650-&mgr;m diameter spot, yielding a single pulse exposure of 138 mJ, and a fluence of 42 J/cm². Optical coherence tomography (OCT) and histology were used to measure pre- and post-operative corneal thickness and lesion dimensions. OCT measurements of pre and post-operative corneal thickness and lesion depth (in microns) were: (1873 nm: 450±30, 801±95, 655±51), (1890 nm: 460±27, 618±70, 332±56), (1904 nm: 448+20, 550±42, 245+36), respectively. By comparison, histologic measurements were: (1873 nm: 470+25, 828+21, 540±31), (1890 nm: 457±13, 625±17, 350±43), (1904 nm: 465±40, 627±35, 239±23), respectively. OCT lesion depth measured 82%, 54%, and 45% of corneal thickness, compared to histologic analysis of 65%, 56%, and 38%. This is the first preliminary test of a compact and tunable Thulium fiber laser for creating variable depth thermal lesions in the cornea. The Thulium fiber laser may have potential use as a replacement for the Ho:YAG and diode lasers for thermal keratoplasty.

Diode laser welding of the cornea is a technique used to provide immediate sealing of corneal wounds: the cut is stained with a water solution of Indocyanine Green and is then irradiated with an 810 nm laser at low power densities (12-16 W/cm²), which induces a localized heating of the stroma in the range 55-66 °C range. In this study, we present a microscopic analysis aimed at evaluating the structural modifications induced in the stromal collagen of pig eyes during the laser welding of corneal wounds. Cornea samples obtained from twenty freshly-enucleated eyes were cut with a pre-calibrated knife and subjected to the laser welding procedure. Histological slices of the laser-welded stroma were examined by means of optical and transmission electron microscopy. These analyses indicated that bridges of lamellar structures crossed the wound edges with no presence of a coagulation effect. After laser welding, collagen fibrils appeared differently oriented among themselves in comparison with those of the control samples, but with similar mean fibril diameters. The laser-induced effect appeared to be confined to the ICG stained area of the cut walls, and no heat damage was observed at the operative power levels of laser corneal welding.

Femtosecond lasers start to be routinely used in refractive eye surgery. Current research focuses on their application to glaucoma and cataract surgery as well as cornea transplant procedures. To avoid unwanted tissue damage during the surgical intervention it is of utmost importance to maintain a working energy just above the ablation threshold and maintain the laser energy at this working point independently of the local and global tissue properties. To quantify the attenuation of the laser power density in the tissue by absorption, scattering and modification of the point spread function we monitor the second harmonic radiation generated in the collagen matrix of the cornea when exposed to ultrashort laser pulses. We use a CPA system with a regenerative amplifier delivering pulses at a wavelength of 1.06 &mgr;m, pulse durations of 400 fs and a maximum energy of 60 &mgr;J. The repetition rate is adjustable from single shot up to 10 kHz. The experiments are performed on human corneas provided by the French Eye bank. To capture the SHG radiation we use a photomultiplier tube connected to a lockin amplifier tuned to the laser repetition rate. The measured data indicates an exponential decay of the laser beam intensity in the volume of the sample and allows for the quantification of the attenuation coefficient and its correlation with the optical properties of the cornea. Complementary analyses were performed on the samples by ultrastructural histology.

The aim of this work is to image the wound healing process of cornea in an in vitro organ culture model with noninvasive multiphoton imaging modality. Autofluorescence and second harmonic generation (SHG) were respectively used to monitor the alterations of cellular and collagenous components during wound healing processes. Within additional developments, this approach may be applied to in vivo visualization of corneal structural destruction and the subsequent regeneration.

As a consequence of pigmentation inhomogeneities and/or different vascularizations of the retinal tissue, retinal laser thermo-treatments are often over- or under-exposed. Our study is focused on the determination of suitable parameters to identify a convenient end-point of the laser treatment. The proposed method is based on the analysis of the temporal fluctuations of the scattered light intensity from the spot area. Motion of molecules and thus frequency of the scattered light fluctuations changes during the laser exposure due to variations of temperature, blood flow and optical parameters, i.e. absorption and scattering coefficient.

In selective retina treatment (SRT) spatial confined tissue damage in the absorbing retinal pigment epithelium (RPE) is obtained by applying microsecond laser pulses. The damage in the RPE is caused by transient microbubbles forming around the laser heated melanin granules inside the cells. For treatment of RPE related diseases, SRT is thought to share the therapeutic benefits of conventional photocoagulation but without affecting the photoreceptors. A drawback for effective clinical SRT is that the laser-induced lesions are ophthalmoscopically invisible. Therefore, a real-time feedback system for dosimetry is demanded in order to avoid undertreatment or unwanted collateral damage to the adjacent tissue. We develop a dosimetry system which uses optical interferometry for the detection of the transient microbubbles. The system is based on an optical fiber interferometer which is operated with a laser diode at 830nm. We present current results obtained with porcine RPE explants in vitro and complete porcine eye globes ex vivo.

To become highly proficient at a given surgical procedure and to reduce risk to patients, physicians must gain experience through a number means. Today optical training devices based on the actual surgical device coupled with computer models can provide the required realism to provide highly effective training. This paper presents a optical system that will be used for training residents to perform panretinal photocoagulation (PRP), a laser surgical procedure for treating the retina. The system will naturally evolve into a computer-assisted device for performing PRP. With the system described herein, simulations are created in the Umbra modeling and simulation framework. The simulation is composed of four building blocks: Pre-operation planning, multi-modality image registration, tracking the patient's eye movement, and positioning the laser according to the pre-planned aim points. A prototype simulation was developed to demonstrate a realistic depiction of the PRP the procedure. The ultimate goal of this project is to integrate the software into an existing ophthalmic device to increase the accuracy of the laser application procedure by providing computer-assisted surgery.

We have developed a virtual reality (VR) simulator for phacoemulsification (phaco) surgery. The current work aimed at developing a performance index that characterizes the performance of an individual trainee. We recorded measurements of 28 response variables during three iterated surgical sessions in 9 subjects naive to cataract surgery and 6 experienced cataract surgeons, separately for the sculpting phase and the evacuation phase of phacoemulsification surgery. We further defined a specific performance index for a specific measurement variable and a total performance index for a specific trainee. The distribution function for the total performance index was relatively evenly distributed both for the sculpting and the evacuation phase indicating that parametric statistics can be used for comparison of total average performance indices for different groups in the future. The current total performance index for an individual considers all measurement variables included with the same weight. It is possible that a future development of the system will indicate that a better characterization of a trainee can be obtained if the various measurements variables are given specific weights. The currently developed total performance index for a trainee is statistically an independent observation of that particular trainee.

Presbyopia is one age related effect every human is suffering beginning at the age of about 45 years. Reading glasses are the conventional treatment so far. According to the Helmholtz theory the loss of accommodation in age is due to the hardening and the resulting loss of elasticity of the crystalline lens. However the ciliary muscle and the lens capsule stay active, respectively. Therefore a possible treatment concept is to regain the flexibility by inducing gliding planes in form of microcuts inside the lens. The increase of flexibility in young porcine lenses by different cutting patterns was shown by Ripken et al.^{1, 2} who verified the increase in flexibility by the spinning test introduced by Fisher.³ We will present our first measurements of flexibility increase of human donor lenses. Furthermore the influence of the laser cuts into the lens on the accommodation amplitude will be shown in a three dimensional finite-element simulation.

Purpose: Orbital tumors and pseudotumor cerebri are sometimes treated with surgical approaches. Our previous studies suggest that potentially endoscopy may be useful for minimally invasive orbital surgery. This study proposed to improve the approach technique for accessing the posterior orbital space via endoscopy, as well as assess visibility improvements with CO₂ insufflation to posterior orbital tissues. Methods: An inferior transconjunctival approach accessed the posterior orbital space in non-survival pigs. Various guidance tubes were compared to assess ability to guide the endoscope to the posterior orbit with the greatest ease and visibility. FEL energy application (6.1 &mgr;m, 2.7 ± 0.5 mJ, 30 Hz, delivered via glass-hollow waveguide) was attempted via endoscopy. The effect of CO₂ gas insufflation was assessed by analyzing visibility of the stuctures before and after CO₂ application. Results: The posterior orbit was accessed via endoscopy in all except the first attempted eye. A beveled transparent butyrate tube provided the best guidance for the endoscope and an opaque metal tube provided the worst guidance. The optic nerve was encountered and FEL energy was applied with the butyrate tube in 8 orbits. Visibility was adequate without CO₂ insufflation, and did not improve with CO₂. Conclusions: The posterior orbit was successfully accessed using endoscopy. The optic nerve was exposed and treated with FEL energy. CO₂ insufflation did not further enhance visibility in this study. Application of endoscopy for posterior orbital procedures is feasible, but extreme surgical care is required and further study with human cadaveric eyes is needed.

Pan-retinal photocoagulation in patients with diabetic retinopathy typically involves application of more than 1000 laser spots; often resulting in physician fatigue and patient discomfort. We present a semi-automated patterned scanning laser photocoagulator that rapidly applies predetermined patterns of lesions; thus, greatly improving the comfort, efficiency and precision of the treatment. Patterns selected from a graphical user interface are displayed on the retina with an aiming beam, and treatment can be initiated and interrupted by depressing a foot pedal. To deliver a significant number of burns during the eye's fixation time, each pulse should be considerably shorter than conventional 100ms pulse duration. We measured coagulation thresholds and studied clinical and histological outcomes of the application of laser pulses in the range of 1-200ms in pigmented rabbits. Laser power required for producing ophthalmoscopically visible lesions with a laser spot of 132&mgr;m decreased from 360 to 37mW with pulse durations increasing from 1 to 100ms. In the range of 10-100ms clinically and histologically equivalent light burns could be produced. The safe therapeutic range of coagulation (ratio of the laser power required to produce a rupture to that for a light burn) decreased with decreasing pulse duration: from 3.8 at 100ms, to 3.0 at 20ms, to 2.5 at 10ms, and to 1.1 at 1ms. Histology demonstrated increased confinement of the thermal damage with shorter pulses, with coagulation zone limited to the photoreceptor layer at pulses shorter than 10ms. Durations of 10-20ms appear to be a good compromise between the speed and safety of retinal coagulation. Rapid application of multiple lesions greatly improves the speed, precision, and reduces pain in retinal photocoagulation.

The purpose of this study is to show that there exists a spectral characteristic that differentiates normal macular tissue from various types of genetic-based macular diseases. This paper demonstrates statistically that hyperspectral images of macular and other retinal tissue can be used to spectrally differentiate different forms of age-related macular degeneration. A hyperspectral fundus imaging device has been developed and tested for the purpose of collecting hyperspectral images of the human retina. A methodology based on partial least squares and ANOVA has been applied to determine the hyperspectral representation of individual spectral characteristics of retinal features. Each discrete tissue type in the retina has an identifiable spectral shape or signature which, when combined with spatial context, aids in detection of pathological features. Variations in the amount and distribution of various ocular pigments or the inclusion of additional biochemical substances will allow detection of pathological conditions prior to traditional histological presentation. Fundus imaging cameras are ubiquitous and are one of the most common imaging modalities used in documenting a patient's retinal state for diagnosis, e.g. remotely, or for monitoring the progression of an ocular disease. The added diagnostic information obtained with only a minor retro-fit of a specialized spectral camera will lead to new diagnostic information to the clinical ophthalmologist or eye-care specialist.

Diabetic retinopathy (DR) is a complication of diabetes affecting up to 80% of all diabetic patients. DR can lead to blindness and reduced quality of life. Some authors have hypothesized that changes in the flow dynamics associated with DR as well as changes in retinal oxygenation can lead to macular edema. Measurements of oxygen saturation in the retina could help understand the real mechanisms behind this condition. We present a novel spectroscopic imaging device to measure oxygen saturation in the retina. Our system uses a lenslet array to spatially and spectrocopically divide a fundus image. A three wavelengths algorithm is used to calculate oxygen saturation in small vessels. Only wavelengths in the 500 - 580 nm range are considered in order to minimize the wavelength dependence of the scattering from erythrocytes. Preliminary testing on healthy subjects showed values of oxygen saturation comparable to the one reported in the literature.

To overcome the difficulty in detection of loss of retinal activity, a functional-Retinal Imaging Device (f-RID) was developed. The device, which is based on a modified fundus camera, seeks to detect changes in optical signals that reflect functional changes in the retina. Measured changes in reflectance in response to the visual stimulus are on the order of 0.1% to 1% of the total reflected intensity level, which makes the functional signal difficult to detect by standard methods because it is masked by other physiological signals and by noise. In this paper, we present a new Independent Component Analysis (ICA) algorithm used to analyze the video sequences from a set of experiments with different patterned stimuli from cats and humans. The ICA algorithm with priors (ICA-P) uses information about the stimulation paradigms to increase the signal detection thresholds when compared to traditional ICA algorithms. The results of the analysis show that we can detect signal levels as low as 0.01% of the total reflected intensity. Also, improvement of up to 30dB in signal detection over traditional ICA algorithms is achieved. The study found that in more than 80% of the in-vivo experiments the patterned stimuli effects on the retina can be detected and extracted.

Scanning laser ophthalmoscopes with adaptive optics (AOSLO) have been shown previously to provide a noninvasive, cellular-scale view of the living human retina. However, the clinical utility of these systems has been limited by the available deformable mirror technology. In this paper, we demonstrate that the use of dual deformable mirrors can effectively compensate large aberrations in the human retina, making the AOSLO system a viable, non-invasive, high-resolution imaging tool for clinical diagnostics. We used a bimorph deformable mirror to correct low-order aberrations with relatively large amplitudes. The bimorph mirror is manufactured by Aoptix, Inc. with 37 elements and 18 &mgr;m stroke in a 10 mm aperture. We used a MEMS deformable mirror to correct high-order aberrations with lower amplitudes. The MEMS mirror is manufactured by Boston Micromachine, Inc with 144 elements and 1.5 &mgr;m stroke in a 3 mm aperture. We have achieved near diffraction-limited retina images using the dual deformable mirrors to correct large aberrations up to ±3D of defocus and ±3D of cylindrical aberrations with test subjects. This increases the range of spectacle corrections by the AO systems by a factor of 10, which is crucial for use in the clinical environment. This ability for large phase compensation can eliminate accurate refractive error fitting for the patients, which greatly improves the system ease of use and efficiency in the clinical environment.

The adaptive optics scanning laser ophthalmoscope may be used in multi-wavelength mode to allow simultaneous imaging and retinal stimulation and so probe retinal function. The wavelengths available are 532 nm, 658 nm and 840 nm. Typically the imaging is performed at 840 nm and precisely coincident retinal stimulation occurs in one of the visible wavelengths. Simultaneous multi-wavelength imaging in the living human retina is demonstrated, and experiments to test retinal function that may be carried out using this instrument are presented.

We evaluate a novel non-invasive technique for observing fast physiological processes, such as phototransduction, in single photoreceptor cells in the living human eye. The method takes advantage of the interference of multiple reflections within the outer segments of cones. This self-interference phenomenon is highly sensitive to phase changes such as those caused by variations in refractive index and scatter within the photoreceptor cell. A high-speed flood-illumination retina camera equipped with adaptive optics (AO) is used to observe this interference pattern, and to monitor the changes in those patterns in response to visible stimuli. AO and high frame rates are necessary for resolving individual cones and their fast temporal dynamics, respectively. Preliminary results suggest that a frame rate of 192 fps, corresponding to a full field 1024x512 pixel rate of 100 MHz, may be sufficient for observing these early stages of phototransduction. This pixel rate is at least 80 and 10 times faster than current flood-illumination and SLO pixel rates, respectively. To our knowledge this is the first demonstration of in vivo single photoreceptor functional imaging, and the first demonstration of in vivo optical detection of phototransduction.

Two deformable mirrors (2DM) were used in an adaptive optics - optical coherence tomography (AO-OCT) system to image in vivo microscopic retinal structures of healthy and diseased retinas. As a result, multiple morphological structures not previously seen in vivo have been visualized. Among those presented are three-dimensional representations of the fovea and optic nerve head (ONH), revealing cellular structures and micro-vasculature. Drusen in macular degeneration and photoreceptor dystrophies are also presented. Different methods for displaying volumetric AO-OCT data to facilitate visualization of certain morphological details are compared.

Adaptive optics (AO) coupled with ultra-fast spectral-domain optical coherence tomography (SD-OCT) has achieved the necessary 3D resolution, sensitivity, and speed for imaging the microscopic retina at the cellular level. While this technology has been rigorously applied to evaluating the 3D morphology of cone photoreceptors, similar detailed studies of cell-sized structures in the inner retina have yet to be undertaken. In this paper, we improve the technical performance of our AO ultrafast SD-OCT and investigate its use for imaging the microscopic inner retina, in particular the nerve fiber layer (NFL) and retinal capillary network. To maximize lateral resolution within the inner retina, focus was controlled with a high stroke, 37-actuator bimorph mirror (AOptix) that also served as the wavefront corrector of the AO. The AO system operated at a closed-loop rate of 25 Hz. The SD-OCT sub-system consisted of a superluminescent diode (&lgr;= 842 nm, &Dgr;&lgr;= 50 nm) and a 512 pixel line scan charge-coupled device (CCD) that acquired 72,000 A-scans/sec. Three different B-scan lengths (36, 60, and 120 A-scans/B-scan), which correspond to B-scan exposure durations of 0.5, 0.83, and 1.67 ms, were evaluated to determine the maximum B-scan length that could be tolerated without noticeable loss in image quality due to eye motion in the well fixated eye. Additional technical improvements included sub-pixel registration to remove instrument error and axial registration of the volume images. Small volume images were acquired at 2 and 7 degrees retinal eccentricity with focus systematically shifted through the retina. Small capillaries, some approaching the smallest in the human eye, were readily detected with AO SD-OCT. Appearance of the nerve fiber layer varied noticeably with depth. The most inner portion (presumably the inner limiting membrane) appeared as a thin irregular surface with little characteristic speckle noise. Within the NFL, complex striation patterns (presumably NFL bundles) were observed throughout the entire thickness with pattern density highest in the inner portion (~15 &mgr;m) and large corrugations (~35 &mgr;m) at the interface with the ganglion cell layer below. Speckle noise was significant throughout the NFL.

Adaptive optics (AO) is used to correct ocular aberrations primarily in the cornea, lens, and tear film of every eye. Among other applications, AO allows high lateral resolution images to be acquired with scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). Spectral domain optical coherence tomography (SDOCT) is a high-speed imaging technique that can acquire cross-sectional scans with micron-scale axial resolution at tens to hundreds of kHz line rates. We present a compact clinical AO-SDOCT system that achieves micron-scale axial and lateral resolution of retinal structures. The system includes a line scanning laser ophthalmscope (LSLO) for simultaneous wide-field retinal viewing and selection of regions-of-interest. OCT and LSLO imaging and AO correction performance are characterized. We present a case study of a single subject with hyper-reflective lesions associated with stable, resolved central serous retinopathy to compare and contrast AO as applied to scanning laser ophthalmoscopy and optical coherence tomography. The two imaging modes are found to be complementary in terms of information on structure morphology. Both provide additional information lacking in the other. This preliminary finding points to the power of combining SLO and SDOCT in a single research instrument for exploration of disease mechanisms, retinal cellular architecture, and visual psychophysics.

We have developed an automatic keratometer module for slit lamp that provides automatic measurements of the radii of the corneal curvature. The system projects 72 light spots displayed in a precise circle at the examined cornea. The displacement and deformation of the reflected image of these light spots are analyzed providing the keratometry. Measurements in the range of 26,8D - 75D can be obtained and a self-calibration system has been specially designed in order to keep the system calibrated. Infrared leds indicate automatically which eye is being examined. Volunteer patients (492) have been submitted to the system and the results show that our system has a high correlation factor with the commercially available manual keratometers and the keratometry measurements from a topographer. Our developed system is 95% in agreement with the corneal topographer (Humphrey - Atlas 995 CZM) and the manual keratometer (Topcon OM-4). The system's nominal precision is 0,05mm for the radii of curvature and 1^o for the associated axis.

We have developed a near-infrared hyperspectral imaging system that can acquire both spectral and spatial data covering a 50-degree field at the fundus surface within 5 seconds. Single wavelength band reflectance images with bandwidth of 20 nm have demonstrated that choroidal vascular patterns can be clearly observed as bright images for the central wavelength ranging from 740 to 860 nm, while retinal blood vessels are seen as dark images for that ranging from 740 to 920 nm. It is desirable for clinical use to separate the choroidal vascular patterns image from the retinal blood vessels image. To this end, we have applied the decorrelation stretch to processing of spectral images. We have found the following. Original fundus spectral images have stripes noise. The decorrelation stretch emphasizes the noise and, thus, the noise has to be removed by, for example, DCT (Discrete Cosine Transform) filter beforehand. The choroidal vascular image can be successfully separated from the retinal vascular image. Furthermore, the macular is superimposed on the latter as it should be so from the viewpoint of anatomy. The result suggests that useful information may be extracted by combining hyperspectral images with the decorrelation stretch.

The neurological control of the visual process is extremely complex and the pupil movement plays an important role. It controls the intensity of light entering the eye, is responsible for focusing depth and avoiding undesired paracentral rays. As such factors vary along the day for each patient individually, allied to the individual answer to determined light stimulation, it is not possible to predict the pupilar size change along the day, leading to undetermined image quality of the patient for a pre-existent condition. Among the clinical and surgical procedures in order to enhance the quality of the visual system of the patient, wave-front based surgeries are performed and its efficiency is strongly dependent on the pupilar position as well as the area to be ablated. In order to predict the individual behavior of the pupil change during an ordinary routine of the patient we have been developing a system to provide means for the personal refractive surgery to be the most efficient as possible. This work presents a method for monitoring the dynamics of the pupil. The methodology presented in this work provides measurements of the patient's pupil sizes along an entire day with light intensity conditioned to the one that the patient is exposed. A prototype has been developed using an eyeglass frame, where a dichroic mirror (70% transmittance) is attached to the frame, as well as a CMOS camera and an infrared illumination system. The image of the pupil is acquired every 4 minutes, its transferring is done by wireless serial communication (RS-232) and saved in a flash memory. Image processing and pupil size determination are done later separately from monitoring. The system is under preliminary tests.

Corneal opacity is main pathological condition in many corneal diseases which cause to loss of Visual acuity. In ocular surface clinics, it is important to assess the relationship between corneal opacity and visual acuity because of patients Quality of Vision. In this study, swept-source-OCT (SS-OCT) system was employed for imaging of the corneal opacity disorder. The purpose of this study is to assess the SS-OCT system for the corneal opacities as quantitative examination and to evaluate the algorithm of keratectomy simulation. This algorithm provides the entire corneal opacity map and demonstrated virtual PTK image with ablation profile.

The computational modeling of the human eye has been wide studied for different sectors of the scientific and technological community. One of the main reasons for this increasing interest is the possibility to reproduce eye optic properties by means of computational simulations, becoming possible the development of efficient devices to treat and to correct the problems of the vision. This work explores this aspect still little investigated of the modeling of the visual system, considering a computational sketch that make possible the use of real data in the modeling and simulation of the human visual system. This new approach makes possible the individual inquiry of the optic system, assisting in the construction of new techniques used to infer vital data in medical investigations. Using corneal topography to collect real data from patients, a computational model of cornea is constructed and a set of simulations were build to ensure the correctness of the system and to investigate the effect of corneal abnormalities in retinal image formation, such as Plcido Discs, Point Spread Function, Wave front and the projection of a real image and it's visualization on retina.

The vision science experiment and optical setup mentioned in this paper are employed in order to develop a compact retinal imager with an adaptive optics system (AOS). The AOS dynamically detects the wavefront and then compensates for the distortion caused by internal and external disturbances. The wavefront sensing of this AOS based on a Michelson interferometer with liquid crystal device (LCD) phase-shift interferometry (PSI). Using accurate phase calibration and transient nematic driving of the LCD, the developed three-step PSI procedure can be achieved in a time of 5 ms. The three fringe patterns associated to the wavefront information are detected by a 16x16 photodiode array and converted to a digital two-dimensional phase image. The PC based controller, xPC Target from the Matlab, then computes appropriate multichannel control signals based on the reconstructed phase image to drive a 127-element transmittance spatial light modulator in such a way as to eliminate the aberration of the eye. The current AOS is expected to be capable of suppressing low-frequency disturbances with a signal-to-noise ratio improvement of more than 20dB and a steady-state phase error of less than 0.02 &pgr; root mean square when the control loop is operated at a frequency of 30 Hz.

Based on the experimental data obtained in vivo from digital analysis of color images of human irises, the mean melanin content in human eye irises has been estimated. For registration of the color images a digital camera Olympus C-5060 has been used. The images have been obtained from irises of healthy volunteers as well as from irises of patients with open-angle glaucoma. The computer program has been developed for digital analysis of the images. The result has been useful for development of novel and optimization of already existing methods of non-invasive glaucoma diagnostics.

Purpose: Patients with tunnel vision have great difficulties in mobility. We have developed an augmented vision head mounted device, which can provide patients 5x expanded field by superimposing minified edge images of a wider field captured by a miniature video camera over the natural view seen through the display. In the minified display, objects appear closer to the heading direction than they really are. This might cause users to overestimate collision risks, and therefore to perform unnecessary obstacle-avoidance maneuvers. A study was conducted in a virtual environment to test the impact of minified view on collision judgment. Methods: Simulated scenes were presented to subjects as if they were walking in a shopping mall corridor. Subjects reported whether they would make any contact with stationary obstacles that appeared at variable distances from their walking path. Perceived safe passing distance (PSPD) was calculated by finding the transition point from reports of yes to no. Decision uncertainty was quantified by the sharpness of the transition. Collision envelope (CE) size was calculated by summing up PSPD for left and right sides. Ten normally sighted subjects were tested (1) when not using the device and with one eye patched, and (2) when the see-through view of device was blocked and only minified images were visible. Results: The use of the 5x minification device caused only an 18% increase of CE (13cm, p=0.048). Significant impact of the device on judgment uncertainty was not found (p=0.089). Conclusion: Minification had only a small impact on collision judgment. This supports the use of such a minifying device as an effective field expander for patients with tunnel vision.

It has recently been shown that bone marrow cells can differentiate into various lineage cells including neural cells in vitro and in vivo. Therefore it is an attractive therapeutic intervention to apply autologous bone marrow-derived stem cells that may offer neuroprotection to laser-induced retinal injuries. The purpose of this study is to develop a method with which to visualize bone marrow stem cells dynamics in mouse retinal circulation. We have used a physiological method, confocal scanning laser ophthalmoscope (SLO), to track the highly enriched stem/progenitor cells circulating in the retina. Stem cells were enriched by immunomagnetic depletion of cells committed to the T- and B lymphocytic, myeloid and erythorid lineages. CellTracker^TM Green-labeled stem cells were injected into the tail veins of mice with laser-induced focal retinal injuries. Bone marrow stem cells labeled with CellTracker^TM Green were visible in the retinal circulation for as long as 1 hour and 30 minutes. These studies suggest that stem cell-enriched bone marrow cells may have the ability to mobilize into laser-induced retinal injuries and possibly further proliferate, differentiate and functionally integrate into the retina.

The severity and characteristics of retinal injury following laser radiation derived from laser and tissue related factors. We have previously shown that retinal damage following Nd:YAG Q-switched laser radiation in rabbits was related to physical parameters, i.e. energy levels and number of pulses. Yet, an extremely large variability in the severity of the damage was found under similar exposure paradigms, even within the same retina. This emphasizes the role of the biological variables in the pathological mechanism of laser-induced retinal damage. The aim of the present study was to further study histological parameters of the injury in relation to retinal site and to elucidate their role in the initiation and characteristics of the damage, following various energy levels (10-50 &mgr;J) and number of pulses (1-4). Pigmented rabbits were exposed to Nd:YAG laser radiation (532nm, pulse duration: 20ns). Exposures were conducted in retina tissue, adjacent to the optic nerve, with a total of 20 exposures per retina. Animals were sacrificed 15 min or 24 hours post exposure, eyes enucleated and processed for paraffin embedding. 4&mgr;m thick serial sections, stained with hematoxylin and eosin, were examined under light microscopy. Two major types of retinal damage were observed: focal edema confined to the pigmented epithelium and the photoreceptor cells, and hemorrhages, associated with destruction of retinal tissue. While focal edema associated with slight elevation of the photoreceptor layer seems to depend on the pigmented epithelium, hemorrhages were related also to the choroid vasculature at the site of radiation. It is suggested that a thermo-mechanical mechanism is involved in laser induced retinal hemorrhages at energies above 10-30&mgr;J (2-1 pulses, respectively).

The emergence of high resolution optical coherence tomography (OCT) along with evidence showing beneficial effects of anti-inflammatory drugs for retinal edema and neovascularization suggests a rational plan for the diagnosis and management of patients with acute laser eye injury. We review the results of recent experiments we conducted to evaluate treatment of laser lesions followed by reports of two cases of acute laser eye injury with foveal involvement. The initial presentation of these cases was notable for the lack of significant abnormalities on fluorescein angiography whereas OCT readily disclosed the size and extent of retinal involvement from exposure to laser energy. Prompt referral of these cases resulted in rapid initiation of medical therapy which included a 10-14 day combined course of steroid and non-steroidal anti-inflammatory medication. An initial decrease in Snellen visual acuity of approximately two lines (20/25- to 20/30) was noted on presentation. In both cases, a measurable improvement of visual acuity was noted by two weeks post injury. The use of anti-inflammatory medication may enhance the initial recovery of vision and reduce the likelihood of longer term retinal complications from scarring and neovascularization.

In previous investigations of minimal spot, q-switched laser visible (532 nm) on-line pulsed laser exposure, non-human primate (NHPs) required up to 13 times the retinal damage threshold for the emergence of permanent visual acuity dysfunction. In the present experiment, a Landolt ring contrast sensitivity task, employing 4 NHPs trained on a Landolt ring contrast sensitivity task, was employed to determine the effect of threshold retinal damage (532 nm, 3 microjoules, 20 Hz, PRF) on the slope of the NHP Landolt ring contrast sensitivity function measured under repeated threshold exposure conditions. All four animals initially showed uniform deficits in contrast sensitivity requiring about 6 to 16 min post exposure for complete recovery. Over several months of repeated exposures made in 3 NHPs, a steepening of the contrast sensitivity slopes appeared, manifested by an inability to measure sensitivity for the finest Landolt ring spatial frequencies and an associated enhancement in the mid and lower spatial frequencies. In one animal that had undergone a longer period of repeated threshold laser exposure, the slope of its contrast sensitivity function shifted to a uniform deficit relative to pre exposure with an inability to provide sensitivity measurements above 20 Hz/deg, demonstrating an abrupt loss in the ability to measure the higher spatial frequencies associated with maximal optimal visual acuity. Ophthalmic retinal observations demonstrated the presence of punctate lesions induced by minimal spot foveal exposure. These data support measurements of high contrast acuity undergoing repeated q-switched exposure at damaging levels. While the acuity in such exposure situations eventually undergoes a permanent deficits, measurements of the entire contrast sensitivity function, in which acuity function maybe obtained at and above 60 Hz/deg, may reveal enhanced lower spatial frequency sensitivity as well as permanent a permanent deficits in higher spatial frequencies.

Experimental studies with repetitively pulsed lasers show that the ED₅₀, expressed as energy per pulse, varies as the inverse fourth power of the number of pulses in the exposure, relatively independently of the wavelength, pulse duration, or pulse repetition frequency of the laser. Models based on a thermal damage mechanism cannot readily explain this result. Menendez et al. proposed a probability-summation model for predicting the threshold for a train of pulses based on the probit statistics for a single pulse. The model assumed that each pulse is an independent trial, unaffected by any other pulse in the train of pulses and assumes that the probability of damage for a single pulse is adequately described by the logistic curve. The requirement that the effect of each pulse in the pulse train be unaffected by the effects of other pulses in the train is a showstopper when the end effect is viewed as a thermal effect with each pulse in the train contributing to the end temperature of the target tissue. There is evidence that the induction of cell death by microcavitation bubbles around melanin granules heated by incident laser irradiation can satisfy the condition of pulse independence as required by the probability summation model. This paper will summarize the experimental data and discuss the relevance of the probability summation model given microcavitation as a damage mechanism.

Excised bovine retinas were used as an explant model for threshold determination of laser induced thermal damage for multiple pulse exposures for the laser wavelength of 532 nm. The thresholds as determined by fluorescence viability staining compare very well with the prediction of thermal damage computer model that is based on the Arrhenius damage integral. Comparison of the experimental data with the thermal damage computer model that additivity of multiple pulses can be understood on the basis of partial thermal damage induced by the individual pulses. Both models were previously (BIOS 2006) validated against non-human primate threshold data. The multiple pulse thresholds for a given series of pulses were compared against the MPE evaluation method for multiple pulses, referred to as N^-1/4 or Total on Time (TOT) rule. Variation of the pulse duration, retinal spot size and the spacing between pulses shows that the TOT rule either reflects the damage threshold trend for multiple pulses very well or errs on the conservative side.

The ability of a laser beam to damage the retina of the eye depends on the accuracy to which the optics of the eye focuses the beam onto the retina. Data acquired through retinal injury threshold studies indicate that the focus achieved by the eye of an anesthetized non-human primate (NHP) is worse than theoretical predictions, and therefore the measured injury threshold will decrease with decreasing retinal irradiance area until the beam diameter at the retina is less than 10 &mgr;m. However, a number of investigations over a range of wavelengths and exposure durations show that the incident energy required to produce a retinal injury in a NHP eye does not decrease for retinal irradiance diameters smaller than ~100 &mgr;m, but reaches a minimum at that diameter and remains nearly constant for smaller diameters. A possible explanation is that uncompensated aberrations of the eye of the anesthetized NHP are larger than predicted. Focus is a dynamic process which is purposely defeated while performing measurements of retinal injury thresholds. Optical wavefront correction systems have become available which have the capability to compensate for ocular aberrations. This paper will report on an injury threshold experiment which incorporates an adaptive optics system to compensate for the aberrations of a NHP eye during exposure to a collimated laser beam, therefore producing a near diffraction limited beam spot on the retina.

Carbon dioxide lasers are used in numerous applications that involve human exposure to the radiation that can produce ocular injury. The objective of this study is to show that the thermal gradient produced in the eye by the radiation from an 80 ns CO₂ laser pulse can generate a thermoacoustical tensile pressure wave with large enough magnitude to rupture the epithelial layer of the cornea. A Gaussian-shaped temperature distribution will be employed. It is assumed that the corneal tissue is inhomogeneous, with the density and wave velocity varying slowly in space. Under these conditions, the acoustical wave equation is decoupled into two first-order partial differential equations, one that propagates energy into the eye from the point of thermoacoustical wave generation, and the other toward the front of the eye. These equations are solved numerically using the Lax-Wendroff numerical method. A compressional wave generated in the epithelial tissue of the cornea due to the thermal gradient of the laser arrives at the air-tear layer interface with a pressure amplitude of ~6600 Pa. When this wave is reflected back into the eye, the resulting tensile pressure wave has a tensile strength of approximately 4.6 x 10⁸ Pa/m just inside of the epithelial layer of the cornea. This is an order of magnitude larger than what is necessary to produce cellular damage to the cornea.

According to the new European Directive on Artificial Optical Radiation (2006/25/EC) the employer has to determine the exposure and the assessment of risks, i.e. workers shall not be exposed above the exposure limit values, which are based on various ICNIRP guidelines. In addition, the employer shall give particular attention, when carrying out the risk assessment, to any indirect effects amongst others such as temporary blinding. Since up to now no quantitative values exist in order to rank or classify artificial optical sources and its associated capability of temporary blinding, we have investigated some aspects of glare and dazzling from a high-brightness LED (HB-LED). With such a single device and an array consisting of 80 HB-LEDs we have found in a previous investigation that the frequency of the blink reflex exceeds the one achieved with laser belonging to class 2 according to the international standard IEC 60825-1, however is less than about 50 %. The size of an after-image as a function of time and the visual acuity after an exposure from a white high-brightness LED has been investigated in detail with 3 test persons. The results have shown that the size of an after-image on the human retina remains nearly constant with a slight decrease over a time duration of about 12 minutes, whereas the initial visual acuity is recovered within 30 up to 60 seconds. Linear and exponential regression descriptions are given for both characteristics.

Intact retinal function provides the visual guidance component for visual motor performance tasks. Laser induced damage to the retina can degrade visual motor performance by limiting the normal retinal input to the motor system for visual motor guidance. Unlike tasks that are based strictly on the availability of normal visual function, visual motor performance may provide a lesser degree of diagnostic evidence of laser induced visual dysfunction in the presence of significant retinal damage. In order to more exactly track the extent of laser induced retinal damage, we have incorporated measurements of spectral sensitivity derived from a Non-Human Primate (NHP) visual pursuit motor tracking task and derived cone spectral sensitivity functions with peaks consistent with NHP cone photoreceptor spectral sensitivity functions. The reciprocal threshold energy levels for each of nine spectral points in the visible spectrum were determined and energy normalized with respect to the maximum energy. Pre-exposure spectral sensitivity functions revealed spectral peaks in regions comparable to the trichromatic cone photoreceptor system peaks. Post exposure spectral sensitivity measurements at exposure levels 2 log units below the retinal damage threshold revealed transient changes in the shape of the peaks in the post exposure spectral sensitivity that persisted up to 4 weeks post exposure. These effects are linked with transient retinal cone dysfunction and possibly with long term neural adaptive mechanisms.

The need for tools that can assist in evaluating visual function is an essential and a growing requirement as lasers on the modern battlefield mature and proliferate. The requirement for rapid and sensitive vision assessment under field conditions produced the USAMRD Aidman Vision Screener (AVS), designed to be used as a field diagnostic tool for assessing laser induced retinal damage. In this paper, we describe additions to the AVS designed to provide a more sensitive assessment of laser induced retinal dysfunction. The AVS incorporates spectral LogMar Acuity targets without and with neural opponent chromatic backgrounds. Thus, it provides the capability of detecting selective photoreceptor damage and its functional consequences at the level of both the outer and inner retina. Modifications to the original achromatic AVS have been implemented to detect selective cone system dysfunction by providing LogMar acuity Landolt rings associated with the peak spectral absorption regions of the S (short), M (middle), and L (long) wavelength cone photoreceptor systems. Evaluation of inner retinal dysfunction associated with selective outer cone damage employs LogMar spectral acuity charts with backgrounds that are neurally opponent. Thus, the AVS provides the capability to assess the effect of selective cone dysfunction on the normal neural balance at the level of the inner retinal interactions. Test and opponent background spectra have been optimized by using color space metrics. A minimal number of three AVS evaluations will be utilized to provide an estimate of false alarm level.

Recent advancements in Light-Emitting Diode (LED) technology have led to significant proliferation of solid-state lighting in our every-day life. White light and monochrome LED-based solid-state sources provide a small size, lower power consumption, and longer life alternative to several types of traditional light sources, such as incandescent lights. However, the spectral characteristics of LEDs are significantly different from the spectra of self-luminous objects that human eyes are adapted to through evolution and, therefore, may pose a real threat of photic-induced eye injury. In this paper the spectral characteristics of individual sources are considered from a photobiological safety perspective, and are used to estimate the retinal hazard potential of LEDs relative to that for daylight and blackbody radiators. The presented LED source retinal hazard exposure ranking considerations could be accounted for during illumination system design to minimize photic-induced eye injury risk. The importance of the material presented herein can not be underestimated since high power LED sources are found in a variety of high volume lighting applications and systems including automotive lamps, signal lighting, flash lights and other illumination devices.

Calculations of retinal illuminance from are used to show that combining a blue-green flood light with a red-orange spot light creates a flashlight ten times brighter both on-axis and in peripheral vision than an equivalent dark-adaptation preserving white light.

A concept for laser safety glasses is demonstrated where the laser intensity itself introduces phase distortion on the transmitted laser beam and is therefore self-limiting. The absorbed light in the polycarbonate glass heats it and changes its index of refraction. A coating on the surface produces a non-uniform intensity pattern on the transmitted laser beam. This non-uniform intensity results in a non-uniform phase distortion which destroys the coherence of the laser and does not allow the cornea to focus the laser strongly on the retina. The absorption in the glass is the same for all laser wavelengths (the glass is sometimes referred to as a neutral density filter) and therefore the safety glasses are good for all laser wavelengths. The amount of laser absorption required to meet the ANSI standard for max allowable exposure is a transmission of 0.1% and this is experimentally verified by the data obtained. This attenuation is sufficient to protect the eye from damage until the heating and phase distortion kicks in. Once this happens, the protection is better - the higher the incident intensity. Experimental demonstration of the effectiveness of the prototype has been obtained at 488 mm (blue light) and 514 mm (green light) from an argon ion laser with laser duration from 0.04 seconds to 0.25 seconds. The data shows that as you increase the laser intensity beyond a certain value the intensity at the focus of a lens actually decreases, and further increases in intensity lowers the focal plane intensity even further. For the phase distortion safety glasses, we can calculate the transmission which meets the ANSI standard where the phase distortion is optimum. Thus our glasses not only meet the ANSI standard but provide protection for any higher laser intensity. The optical quality of the prototype was very good with no fogging, or optical distortion of transmitted laser, and after the experiment, the prototype returned to the identical optical quality with no permanent optical distortion.