Advanced Optical Analysis of Divergence Between the Foci of the Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) and Aiming Beam Lasers.

Purpose: To evaluate the divergence between the neodymium-doped yttrium aluminum garnet (Nd:YAG) surgical laser and the aiming diode laser beams foci. Design: Optical analysis and measurements were performed using a Volk Goldmann 3-mirror lens with a Nidek YC-1800 Nd:YAG laser apparatus. Subjects: None. Methods: We used the Zemax OpticStudio program for the model of Nd:YAG treatment in a human eye. Additionally, theoretical calculations were performed. Main Outcome Measures: The divergence between the Nd:YAG laser focus and the intersection of the 2 aiming beams inside the eye. Results: Focal points of the 2 laser beams converge 8 mm behind the cornea. Posterior to this point, the intersection of the diode laser aiming beams lies in front of the focal point of the Nd:YAG treatment laser, with distance between the 2 foci progressively increasing up to 305 microns at 24 mm behind the cornea. Conclusions: We report the degree of divergence between the 2 lasers' focal points due to the difference in refraction between the corresponding wavelengths. These results have high practical relevance, as they provide a starting point for increasing the accuracy of Nd:YAG laser treatment, particularly when applied to the posterior segment, thereby minimizing the risk of complications. Current Nd:YAG laser devices have the built-in ability to modify the focal point of the aiming beam along the z-axis, thus providing possibility for an immediate application of our findings in clinical practice. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Feasibility Study of Scanning Spectral Imaging Based on a Birefringence Flat Plate.

Hyper-spectral imaging (HSI) systems can be divided into two main types as follows: a group of systems that includes a dedicated dispersion/filtering component whose role is to physically separate the different wavelengths and a group of systems that sample all wavelengths in parallel, so that the separation into wavelengths is performed by signal processing (interferometric method). There is a significant advantage to systems of the second type in terms of the integration time required to obtain a signal with a high signal-to-noise ratio since the signal-to-noise ratio of methods based on scanning interferometry (Windowing method) is better compared to methods based on dispersion. The current research deals with the feasibility study of a new concept for an HSI system that is based on scanning interferometry using the "push-broom" method. In this study, we investigated the viability of incorporating a simple birefringent plate into a scanning optical system. By exploiting the motion of the platform on which the system is mounted, we extracted the spectral information of the scanned region. This approach combines the benefits of scanning interferometry with the simplicity of the setup. According to the theory, a chirped cosine-shaped interferogram is obtained for each wavelength due to the nonlinear behavior of the optical path difference of light in the birefringent plate as a function of the angle. An algorithm converts the signal from a superposition of chirped cosine signals to a scaled interferogram such that Fourier transforming (FT) the interferogram retrieves the spectral information. This innovative idea can turn a simple monochrome camera into a hyperspectral camera by adding a relief lens and a birefringent plate.

The Various Oximetric Techniques Used for the Evaluation of Blood Oxygenation.

Adequate oxygen delivery to a tissue depends on sufficient oxygen content in arterial blood and blood flow to the tissue. Oximetry is a technique for the assessment of blood oxygenation by measurements of light transmission through the blood, which is based on the different absorption spectra of oxygenated and deoxygenated hemoglobin. Oxygen saturation in arterial blood provides information on the adequacy of respiration and is routinely measured in clinical settings, utilizing pulse oximetry. Oxygen saturation, in venous blood (SvO2) and in the entire blood in a tissue (StO2), is related to the blood supply to the tissue, and several oximetric techniques have been developed for their assessment. SvO2 can be measured non-invasively in the fingers, making use of modified pulse oximetry, and in the retina, using the modified Beer-Lambert Law. StO2 is measured in peripheral muscle and cerebral tissue by means of various modes of near infrared spectroscopy (NIRS), utilizing the relative transparency of infrared light in muscle and cerebral tissue. The primary problem of oximetry is the discrimination between absorption by hemoglobin and scattering by tissue elements in the attenuation measurement, and the various techniques developed for isolating the absorption effect are presented in the current review, with their limitations.

Enhanced depth imaging in swept-source optical coherence tomography: Improving visibility of choroid and sclera, a masked study.

PURPOSE: To compare enhanced depth imaging in swept-source optical coherence tomography and non-enhanced depth imaging optical coherence tomography in their ability to capture choroidal and scleral details. METHODS: Averaged foveal B-Scans were obtained from 40 eyes of 20 healthy volunteers by swept-source optical coherence tomography with and without enhanced depth imaging. Visibility and contrast of vascular details within the choroid, choroidoscleral junction, and sclera were evaluated by masked readers using an ordinal scoring scale. Outcomes were analyzed using the Wilcoxon signed rank-sum test. RESULTS: Visibility of the choroidal vascular details (Z = 5.94, p < .001), the choroidoscleral junction (Z = 5.85, p < .001), and the sclera (Z = 6.80, p < .001) was significantly higher with enhanced depth imaging than with non-enhanced depth imaging swept-source optical coherence tomography. Similarly, image contrast was significantly higher with enhanced depth imaging than with non-enhanced depth imaging swept-source optical coherence tomography for the choroidal vascular details (Z = 9.47, p < .001), for the choroidoscleral junction (Z = 9.28, p < .001), and for the sclera (Z = 9.42, p < .001). CONCLUSION: Enhanced depth imaging applied to swept-source optical coherence tomography-averaged foveal B-scans enhances visualization of the choroidal details, of the choroidoscleral junction, and of the sclera. This novel modality can easily be implemented in clinics and could improve our understanding of conditions involving the choroid or the sclera.

Dynamic assessment of the tear film muco-aqueous and lipid layers using a novel tear film imager (TFI).

PURPOSE: The objective of the study was to assess a new technology, the tear film imager (TFI), which can dynamically image the muco-aqueous and lipid layers. METHODS: Prospective pilot case series of individuals with and without dry eye (DE). Two sequential images were obtained with the TFI. Measurements were assessed for reproducibility and compared with clinically derived DE metrics. Individuals were grouped into DE categories based on signs of DE. RESULTS: 49 patients participated in the study with a mean age of 58.8 years (SD 15.9) and a female majority (69%). Reproducibility of the muco-aqueous layer thickness (MALT) was excellent (r=0.88). MALT measurements significantly correlated with the Schirmer score (r=0.31). Lipid break up time (LBUT) as measured by the TFI significantly correlated with the clinical measure of tear break up time (TBUT) (r=0.73). MALT and LBUT were significantly thinner and shorter, respectively, in the DE groups (mild-moderate and severe) compared with the control group. When comparing TFI parameters to clinically assessed signs, sensitivity of the device was 87% and specificity was 88%. CONCLUSION: The TFI is the first machine capable of reproducibly measuring muco-aqueous thickness in human subjects which correlates with Schirmer score. In parallel, it assesses other important aspects of tear film function which correlate with clinician assessed DE metrics.

Mapping the Lipid Layer of the Human Tear Film.

PURPOSE: To describe a new method to distinguish between normal versus lipid-deficient dry eye using a Tear Film Imager (TFI). METHODS: Two groups of study subjects, controls versus lipid-deficient dry eye, were tested using the TFI. This instrument provides an accurate measurement of the thickness and spatial distribution of the muco-aqueous and lipid layers of the tear film. The nanometer thickness resolution of the TFI enables the creation of detailed maps of the lipid layer thickness (LLT) across the corneal surface. These maps are captured with a large field of view of 6.5 mm diameter. RESULTS: A LLT map taken at 1 second from a blink end in the controls appears uniform, whereas a nonuniform layer was measured in the lipid-deficient dry eye. Lipid map uniformity can quantify the spatial variation of lipid across the cornea. A case study showed the ability to distinguish between controls [lipid map uniformity (LMU) = 14 nm] and lipid-deficient dry eye (LMU = 125 nm) through characterization of the LLT distribution. CONCLUSIONS: High-resolution lateral LLT maps demonstrate the significance of the lipid layer uniformity, which may play an important role in maintaining tear film health. LLT maps and the quantitative LMU could be used to diagnose and treat patients with dry eye.

Tear film imager for dynamic mapping of the human tear film.

Dry eye (DE) disease is a multifactorial disease of the outer ocular surface characterized by several ocular symptoms and mainly by tear film instability. We have developed an optical imaging system, the tear film imager (TFI), which is the first instrument that can directly image the muco-aqueous tear layer physical dimension in vivo and evaluate its parameters in a noninvasive mode with nanometer axial resolution. This instrument provides quantified information about many attributes of the tear film, including muco-aqueous layer thickness, lipid layer thickness, thickness change rate, and the break-up time. The TFI performances are based on simultaneous acquisition of large field of view (FOV) imagery and fast spectrometric measurement of the interference from the thin tear film sublayers. Herein, after describing the instrument and the methodology of the measurements, we use a tear film mock-up to quantify device accuracy (2.2 nm) and repeatability (0.25 nm standard deviation). In conclusion, we present a new technology for the assessment of the tear film with an unprecedented axial resolution and excellent accuracy and reproducibility.

Manipulations of Wavefront Propagation: Useful Methods and Applications for Interferometric Measurements and Scanning.

Phase measurements obtained by high-coherence interferometry are restricted by the 2π ambiguity, to height differences smaller than λ/2. A further restriction in most interferometric systems is for focusing the system on the measured object. We present two methods that overcome these restrictions. In the first method, different segments of a measured wavefront are digitally propagated and focused locally after measurement. The divergent distances, by which the diverse segments of the wavefront are propagated in order to achieve a focused image, provide enough information so as to resolve the 2π ambiguity. The second method employs an interferogram obtained by a spectrum constituting a small number of wavelengths. The magnitude of the interferogram's modulations is utilized to resolve the 2π ambiguity. Such methods of wavefront propagation enable several applications such as focusing and resolving the 2π ambiguity, as described in the article.

Hyperspectral imaging camera using wavefront division interference.

An approach for performing hyperspectral imaging is introduced. The hyperspectral imaging is based on Fourier transform spectroscopy, where the interference is performed by wavefront division interference rather than amplitude division interference. A variable phase delay between two parts of the wavefront emanating from each point of an object is created by a spatial light modulator (SLM) to obtain variable interference patterns. The SLM is placed in the exit pupil of an imaging system, thus enabling conversion of a general imaging optical system into an imaging hyperspectral optical system. The physical basis of the new approach is introduced, and an optical apparatus is built.

Spatial-phase-shift imaging interferometry using a spectrally modulated white light source.

An extension of the white light spatial-phase-shift (WLSPS) for object surface measurements is described. Using WLSPS, surface measurements can be obtained from any real object image without the need of a reference beam, thus achieving inherent vibration cancellation. The surface topography is obtained by acquiring multiple images of an object illuminated by a spectrally modulated white light source and using an appropriate algorithm. The modulation of the light source obviates the need for the continuous phase delay to obtain the interferograms.

Surface measurements by white light spatial-phase-shift imaging interferometry.

A novel method of common-path imaging interferometry, the White Light Spatial-Phase-Shift (WLSPS) for object surface measurements, is discussed here. Compared to standard White Light Interferometry (WLI), which uses a reference mirror, the interferometry of WLSPS is obtained by creating manipulations to the light wavefront reflected from an object's surface. Using this approach, surface measurements can be obtained from any real object image, and do not need to be taken directly from the object itself. This creates the ability for a surface measurement tool to be attached to any optical system that generates a real image of an object. Further, as this method does not require a reference beam, the surface measurement system contains inherent vibration cancelation.

Effect of intraocular pressure on the hemodynamics of the central retinal artery: a mathematical model.

Retinal hemodynamics plays a crucial role in the pathophysiology of several ocular diseases. There are clear evidences that the hemodynamics of the central retinal artery (CRA) is strongly affected by the level of intraocular pressure (IOP), which is the pressure inside the eye globe. However, the mechanisms through which this occurs are still elusive. The main goal of this paper is to develop a mathematical model that combines the mechanical action of IOP and the blood flow in the CRA to elucidate the mechanisms through which IOP elevation affects the CRA hemodynamics. Our model suggests that the development of radial compressive regions in the lamina cribrosa (a collagen structure in the optic nerve pierced by the CRA approximately in its center) might be responsible for the clinically-observed blood velocity reduction in the CRA following IOP elevation. The predictions of the mathematical model are in very good agreement with experimental and clinical data. Our model also identifies radius and thickness of the lamina cribrosa as major factors affecting the IOP-CRA relationship, suggesting that anatomical differences among individuals might lead to different hemodynamic responses to IOP elevation.

Impaired ocular blood flow regulation in patients with open-angle glaucoma and diabetes.

BACKGROUND: To elucidate the potential impact of diabetes mellitus on primary open-angle glaucoma pathology through vascular deficiency. DESIGN: Cross-section analysis from a longitudinal, prospective study. PARTICIPANTS: Eighty-four open-angle glaucoma patients (20 diabetic open-angle glaucoma patients and 64 non-diabetic open-angle glaucoma patients) METHODS: Patients were analyzed for ocular structure, ocular perfusion pressure (OPP), retrobulbar blood flow and retinal capillary perfusion. Statistical analysis was performed by SPSS version 18.0. Comparisons between groups were made as well as multivariate linear regression analysis. MAIN OUTCOME MEASURE: Retrobulbar blood flow and the retinal microcirculation. RESULTS: Central retinal artery peak systolic velocity was 13.5% lower in diabetic patients (P = 0.007). In diabetic open-angle glaucoma patients, ocular perfusion pressure positively correlated with central retinal artery and temporal posterior ciliary artery peak systolic velocity (R = 0.476, P = 0.039 and R = 0.529, P = 0.02, respectively), and with central retinal artery and nasal posterior ciliary artery resistance index (R = 0.537, P = 0.018 and R = 0.566, P = 0.012 respectively). Average retinal nerve fibre layer positively correlated with central retinal artery peak systolic velocity and temporal posterior ciliary artery end diastolic velocity (R = 0.501, P = 0.029 and R = 0.553, P = 0.019, respectively), and negatively correlated with superior and inferior retinal avascular space in the diabetic group (R = -0.498, P = 0.030 and R = -0.700, P = 0.001, respectively); no correlations were found in the non-diabetic group. Negative correlations between retrobulbar and retinal circulations were only found in the diabetic open-angle glaucoma patients, whereas positive correlations between retinal flow and non-flow were only found in non-diabetic open-angle glaucoma patients. CONCLUSION: Diabetes may interfere with normal vascular regulation and contribute to glaucoma progression.

Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma.

PURPOSE: To review the role of endothelin in intraocular pressure control, its effect on the trabecular meshwork (TM) and the outflow facility, effect on ocular blood flow and vascular regulation and the potential role of endothelin-1 (ET-1) antagonism in the therapeutic paradigm of glaucoma. METHODS: A thorough review of the medical literature and a meta-analysis on the level of ET-1 in OAG patients in an attempt to demonstrate the evolving importance of endothelin in glaucoma. RESULTS: ET-1 has been identified in the plasma in concentrations that are markedly increased in a number of systemic as well as ocular pathologies such as glaucoma where underlying vascular dysfunction and pathology play a role. It has been shown that ET-1 induces human TM cell contraction in culture and that it can affect the outflow facility. Evidence indicates that systemic ET-1 regulatory mechanisms and vascular responses to it are also altered in glaucoma. Recently, several endothelin antagonists have been shown to have a potential role in glaucoma therapy. In our meta-analysis, only patients with normal tension glaucoma (NTG) (as opposed to patients with high tension glaucoma (HTG)) had significantly higher plasma ET-1 levels compared to non-glaucomatous control. High tension glaucomaHTG patients had significant higher levels of ET-1 in the aqueous humor. CONCLUSIONS: The potential role of ET-1 antagonism in the therapeutic paradigm of glaucoma is an exciting possible new approach in the treatment of OAG patients. In NTG, ET-1 may have both a local and systemic component of vascular dysregulation, while whereas in HTG, the role of ET-1 may be dominantly localized to ocular tissue.

Wavefront reconstruction by spatial-phase-shift imaging interferometry.

Common-path imaging interferometers offer some advantages over other interferometers, such as insensitivity to vibrations and the ability to be attached to any optical system to analyze an imaged wavefront. We introduce the spatial-phase-shift imaging interferometry technique for surface measurements and wavefront analysis in which different parts of the wavefront undergo certain manipulations in a certain plane along the optical axis. These manipulations replace the reference-beam phase shifting of existing interferometry methods. We present the mathematical algorithm for reconstructing the wavefront from the interference patterns and detail the optical considerations for implementing the optical system. We implemented the spatial phase shift into a working system and used it to measure a variety of objects. Measurement results and comparison with other measurement methods indicate that this approach improves measurement accuracy with respect to existing quantitative phase-measurement methods.

Spatial phase-shift interferometry--a wavefront analysis technique for three-dimensional topometry.

We describe a new wavefront analysis method, in which certain wavefront manipulations are applied to a spatially defined area in a certain plane along the optical axis. These manipulations replace the reference-beam phase shifting of existing methods, making this method a spatial phase-shift interferometry method. We demonstrate the system's dependence on a defined spatial Airy number, which is the ratio of the characteristic dimension of the manipulated area and the Airy disk diameter of the optical system. We analytically obtain the resulting intensity data of the optical setup and develop various methods to accurately reconstruct the inspected wavefront out of the data. These reconstructions largely involve global techniques, in which the entire wavefront's pattern affects the reconstruction of the wavefront in any given position. The method's noise sensitivity is analyzed, and actual reconstruction results are presented.

Generalized method for wave-front analysis.

We suggest and demonstrate a new method for wave-front analysis based on common-path phase-shift interferometry. We introduce a formalism and an iterative mathematical algorithm in which the wave front is transformed, modified, and inversely transformed. The resulting intensity data are sufficient to reconstruct the entire wave front. In a more restricted case, in which the wave-front modifications are arbitrarily applied over arbitrary spatial regions of the wave front, the wave front is reconstructed semianalytically by use of a model that allows a local solution, followed by an iterative algorithm. Measurement results indicating that the suggested approach has an improved measurement accuracy with respect to existing quantitative phase measurement methods are presented.