Assessing Corneal Speckle in Optical Coherence Tomography: A New Look at Glaucomatous Eyes.

SIGNIFICANCE: Optical coherence tomography speckle is used here in an unconventional way as the indirect source of information on tissue microstructure. The study reveals that the corneal speckle of glaucoma suspects has a similar relationship between the parameters of scattering exhibited in glaucoma patients. PURPOSE: The purpose of this study was to evaluate the potential of optical coherence tomography imaging of the cornea in early diagnosis of glaucoma. METHODS: Corneas of 64 subjects of three groups, including 18 primary open-angle glaucoma patients, 24 glaucoma suspects with normal levels of IOP and uncompromised visual field, and 22 age-matched controls, were imaged with spectral optical coherence tomography. A central region of interest in each optical coherence tomography image visualizing the stroma was automatically extracted, and the intensity data within that region were fit with the generalized gamma distribution. Its parameters describe the scatterer cross section and scatterer density and indirectly assess corneal microstructure. In addition, subjects underwent measurements of IOP, visual field, Heidelberg Retinal Tomography, retinal nerve fiber layer thickness, and biometry. Group means of all parameters were tested for equality. Within each group of subjects, correlation was evaluated between the statistical parameters of the corneal speckle. RESULTS: Glaucoma suspects had statistically significantly different IOP, visual field parameters, mean retinal fiber layer thickness, and central corneal thickness from those of glaucoma patients but not from those of the control group. The parameters of the corneal speckle were not significantly different between the groups, but they showed a markedly higher and statistically significant coefficient of determination for glaucoma patients and suspects than that for the control group (0.927 and 0.707 vs. 0.336). CONCLUSIONS: The results indicate that glaucoma suspects have similar relationship between the corneal scatterer cross section and scatterer density to that exhibited in the glaucoma patients but markedly different from that of healthy controls.

Quantitative automated circumpapillary microvascular density measurements: a new angioOCT-based methodology.

PURPOSE: To develop a new methodology to detect glaucoma damage based on circumpapillary microvascular density (cpmVD) as measured by optical coherence tomography angiography (angioOCT). METHODS: AngioOCT scans from a random eye of 40 healthy subjects (aged 63 ± 14 years) and 82 glaucoma patients (aged 66 ± 9 years with an average visual field loss of -7.8 ± 6.5 dB) were used to develop a new angioOCT evaluation methodology. Optic disc-centred 3 × 3 mm images were collected (Angioplex®, Zeiss Cirrus 5000 HD-OCT). An annular area with an inner radius of 1.16 mm and outer radius of 1.44 mm was chosen as the region of interest (ROI), with cpmVD calculated through lower envelope modulation avoiding the influence of the major retinal vessels. Additionally, the cpmVD and the microvascular density (mVD), stratified by sectors, were compared with the respective retinal nerve fibre layer (RNFL) thickness. RESULTS: A significantly lower cpmVD was observed in the glaucoma group, for all visual field sectors (p < 0.001), when comparing to the healthy group. The inferior and superior mVD sectors showed the largest differences between groups. Moreover, glaucoma was linked to a reduction of cpmVD variation when compared to the healthy group. Lastly, a comparison between two healthy subgroups showed that the method is not biased by the presence of slight movement artefacts, optic disc dimensions and vessel crowding (p > 0.05). CONCLUSIONS: The presented open-source methodology provides a robust quantitative analysis of the 360˚ mVD. It shows that cpmVD, and mVD sectors measured by angioOCT, can be used in everyday glaucoma practice.

Heterogeneity in arterial hypertension and ocular perfusion pressure definitions: Towards a consensus on blood pressure-related parameters for glaucoma studies.

PURPOSE: Glaucoma studies have long taken into account the blood pressure (BP) status of patients. This study summarizes and evaluates the impact of the different criteria that have been used for BP-related variables in glaucoma research. METHODS: Studies included in two meta-analyses that reviewed the role of BP in glaucoma were analyzed. Additional studies published after the search periods of the meta-analyses were also included. Criteria for the definition of arterial hypertension and other BP-related variables, such as mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP), were retrieved. RESULTS: Sixty-four studies were evaluated. One-third used 140 mmHg as a systolic BP cut-off to define hypertension, 20% used 160 mmHg and the remaining half used various other criteria. Less than 20% of studies reported MAP and/or MOPP. While eight of the ten studies reporting MAP used a correct formula that only happened for five of the eleven studies reporting MOPP. Using as an example average blood pressure values, incorrectly used formulas could have led to an overestimation of more than 100% of the expected values. CONCLUSION: Considerable heterogeneity exists in BP-related variables in glaucoma research and different definitions can lead to large disparities. Glaucoma research would benefit from a consensus regarding blood pressure parameters.

The utility of measuring tear film break-up time for prescribing contact lenses.

PURPOSE: To evaluate the clinical value of non-invasive keratograph tear film breakup time (NIKBUT) in the assessment of pre-corneal and pre-lens tear film quality for prescribing contact lenses (CLs). METHODS: Forty-six subjects aged 25.5±4.3 (mean±standard deviation) years were recruited. Visual acuity (VA), anterior eye health checks and NIKBUT were evaluated. On the following day, subjects were fitted with a daily Silicon Hydrogel (SiHy) CL in one eye and a Hydrogel (Hy) CL in the other. After four hours one material for both eyes was chosen based on a qualitative analysis which included VA, CL fitting and comfort. Information about the first and the mean NIKBUT was then contrasted against the prescription decision. RESULTS: Thirty-four subjects were fitted with SiHy and twelve with Hy CL. No statistically significant differences were found for both NIKBUT parameters between left and right eye at baseline (p=0.38 and p=0.50, respectively) and post four hours of CL wear (p=0.61 and p=0.06). The chosen lens did not always correspond to longer NIKBUT. In 39.1% and 34.8% of cases (i.e., 18 and 16 out of 46), there was a match between prescription decision and the first and the mean NIKBUT results, respectively. CONCLUSIONS: Although there is no evidence whether tear film surface quality measurement has a superior diagnostic values compared to other traditional clinical measures used in practice, NIKBUT measurements have provided additional information that could be of interest during CL fit.

Influence of eye biometrics and corneal micro-structure on noncontact tonometry.

PURPOSE: Tonometry is widely used as the main screening tool supporting glaucoma diagnosis. Still, its accuracy could be improved if full knowledge about the variation of the corneal biomechanical properties was available. In this study, Optical Coherence Tomography (OCT) speckle statistics are used to infer the organisation of the corneal micro-structure and hence, to analyse its influence on intraocular pressure (IOP) measurements. METHODS: Fifty-six subjects were recruited for this prospective study. Macro and micro-structural corneal parameters as well as subject age were considered. Macro-structural analysis included the parameters that are associated with the ocular anatomy, such as central corneal thickness (CCT), corneal radius, axial length, anterior chamber depth and white-to-white corneal diameter. Micro-structural parameters which included OCT speckle statistics were related to the internal organisation of the corneal tissue and its physiological changes during lifetime. The corneal speckle obtained from OCT was modelled with the Generalised Gamma (GG) distribution that is characterised with a scale parameter and two shape parameters. RESULTS: In macro-structure analysis, only CCT showed a statistically significant correlation with IOP (R2 = 0.25, p<0.001). The scale parameter and the ratio of the shape parameters of GG distribution showed statistically significant correlation with IOP (R2 = 0.19, p<0.001 and R2 = 0.17, p<0.001, respectively). For the studied group, a weak, although significant correlation was found between age and IOP (R2 = 0.053, p = 0.04). Forward stepwise regression showed that CCT and the scale parameter of the Generalised Gamma distribution can be combined in a regression model (R2 = 0.39, p<0.001) to study the role of the corneal structure on IOP. CONCLUSIONS: We show, for the first time, that corneal micro-structure influences the IOP measurements obtained from noncontact tonometry. OCT speckle statistics can be employed to learn about the corneal micro-structure and hence, to further calibrate the IOP measurements.

Assessment of corneal properties based on statistical modeling of OCT speckle.

A new approach to assess the properties of the corneal micro-structure in vivo based on the statistical modeling of speckle obtained from Optical Coherence Tomography (OCT) is presented. A number of statistical models were proposed to fit the corneal speckle data obtained from OCT raw image. Short-term changes in corneal properties were studied by inducing corneal swelling whereas age-related changes were observed analyzing data of sixty-five subjects aged between twenty-four and seventy-three years. Generalized Gamma distribution has shown to be the best model, in terms of the Akaike's Information Criterion, to fit the OCT corneal speckle. Its parameters have shown statistically significant differences (Kruskal-Wallis, p < 0.001) for short and age-related corneal changes. In addition, it was observed that age-related changes influence the corneal biomechanical behaviour when corneal swelling is induced. This study shows that Generalized Gamma distribution can be utilized to modeling corneal speckle in OCT in vivo providing complementary quantified information where micro-structure of corneal tissue is of essence.

Precise measurement of scleral radius using anterior eye profilometry.

PURPOSE: To develop a new and precise methodology to measure the scleral radius based on anterior eye surface. METHODS: Eye Surface Profiler (ESP, Eaglet-Eye, Netherlands) was used to acquire the anterior eye surface of 23 emmetropic subjects aged 28.1±6.6years (mean±standard deviation) ranging from 20 to 45. Scleral radius was obtained based on the approximation of the topographical scleral data to a sphere using least squares fitting and considering the axial length as a reference point. To better understand the role of scleral radius in ocular biometry, measurements of corneal radius, central corneal thickness, anterior chamber depth and white-to-white corneal diameter were acquired with IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany). RESULTS: The estimated scleral radius (11.2±0.3mm) was shown to be highly precise with a coefficient of variation of 0.4%. A statistically significant correlation between axial length and scleral radius (R2=0.957, p<0.001) was observed. Moreover, corneal radius (R2=0.420, p<0.001), anterior chamber depth (R2=0.141, p=0.039) and white-to-white corneal diameter (R2=0.146, p=0.036) have also shown statistically significant correlations with the scleral radius. Lastly, no correlation was observed comparing scleral radius to the central corneal thickness (R2=0.047, p=0.161). CONCLUSIONS: Three-dimensional topography of anterior eye acquired with Eye Surface Profiler together with a given estimate of the axial length, can be used to calculate the scleral radius with high precision.

On the Methods for Estimating the Corneoscleral Limbus.

OBJECTIVE: The aim of this study was to develop computational methods for estimating limbus position based on the measurements of three-dimensional (3-D) corneoscleral topography and ascertain whether corneoscleral limbus routinely estimated from the frontal image corresponds to that derived from topographical information. METHODS: Two new computational methods for estimating the limbus position are proposed: One based on approximating the raw anterior eye height data by series of Zernike polynomials and one that combines the 3-D corneoscleral topography with the frontal grayscale image acquired with the digital camera in-built in the profilometer. The proposed methods are contrasted against a previously described image-only-based procedure and to a technique of manual image annotation. RESULTS: The estimates of corneoscleral limbus radius were characterized with a high precision. The group average (mean ± standard deviation) of the maximum difference between estimates derived from all considered methods was 0.27 ± 0.14 mm and reached up to 0.55 mm. The four estimating methods lead to statistically significant differences (nonparametric ANOVA (the Analysis of Variance) test, p 0.05). CONCLUSION: Precise topographical limbus demarcation is possible either from the frontal digital images of the eye or from the 3-D topographical information of corneoscleral region. However, the results demonstrated that the corneoscleral limbus estimated from the anterior eye topography does not always correspond to that obtained through image-only based techniques. SIGNIFICANCE: The experimental findings have shown that 3-D topography of anterior eye, in the absence of a gold standard, has the potential to become a new computational methodology for estimating the corneoscleral limbus.

Principles of operation, accuracy and precision of an Eye Surface Profiler.

PURPOSE: To introduce a newly developed instrument for measuring the topography of the anterior eye, provide principles of its operation and to assess its accuracy and precision. METHODS: The Eye Surface Profiler is a new technology based on Fourier transform profilometry for measuring the anterior eye surface encompassing the corneo-scleral area. Details of technical principles of operation are provided for the particular case of sequential double fringe projection. Technical limits of accuracy have been assessed for several key parameters such as the carrier frequency, image quantisation level, sensor size, carrier frequency inaccuracy, and level and type of noise. Further, results from both artificial test surfaces as well as real eyes are used to assess precision and accuracy of the device (here benchmarked against one of popular Placido disk videokeratoscopes). RESULTS: Technically, the Eye Surface Profiler accuracy can reach levels below 1 µm for a range of considered key parameters. For the unit tested and using calibrated artificial surfaces, the accuracy of measurement (in terms of RMS error) was below 10 µm for a central measurement area of 8 mm diameter and below 40 µm for an extended measurement area of 16 mm. In some cases, the error reached levels of up to 200 µm at the very periphery of the measured surface (up to 20 mm). The SimK estimates of the test surfaces from the Eye Surface Profiler were in close agreement with those from a Placido disk videokeratoscope with differences no greater than ±0.1 D. For real eyes, the benchmarked accuracy was within ±0.5D for both the spherical and cylindrical SimK components. CONCLUSIONS: The Eye Surface Profiler can successfully measure the topography of the entire anterior eye including the cornea, limbus and sclera. It has a great potential to become an optometry clinical tool that could substitute the currently used videokeratoscopes and provide a high quality corneo-scleral topography.

Age-related changes of the corneal speckle by Optical Coherence Tomography.

Ageing of the population has several consequences for the human visual system. The corneal tissue which is responsible for two thirds of the total optical power is not an exception, suffering structural and anatomical changes with the age. In this study, we have explored the usefulness of Optical Coherence Tomography (OCT) speckle to study the age-related changes in corneal stroma. The Generalized Gamma distribution has been suggested as a model for OCT corneal speckle and was used here to investigate OCT envelope statistics in three different age groups (65 subjects in total). The scaling and the two shape parameters have shown significant statistical differences (p <; 0.05) among the age groups, showing the possibility to track the corneal changes using envelope statistics. This study shows that Generalized Gamma distribution has a great potential to fit the corneal speckle and could be a helpful complement to evaluate the structure and elastic properties of the cornea in vivo.

Simplifying numerical ray tracing for two-dimensional non circularly symmetric models of the human eye.

Ray tracing is a powerful technique to understand the light behavior through an intricate optical system such as that of a human eye. The prediction of visual acuity can be achieved through characteristics of an optical system such as the geometrical point spread function. In general, its precision depends on the number of discrete rays and the accurate surface representation of each eye's components. Recently, a method that simplifies calculation of the geometrical point spread function has been proposed for circularly symmetric systems [Appl. Opt.53, 4784 (2014)]. An extension of this method to 2D noncircularly symmetric systems is proposed. In this method, a two-dimensional ray tracing procedure for an arbitrary number of surfaces and arbitrary surface shapes has been developed where surfaces, rays, and refractive indices are all represented in functional forms being approximated by Chebyshev polynomials. The Liou and Brennan anatomically accurate eye model has been adapted and used for evaluating the method. Further, real measurements of the anterior corneal surface of normal, astigmatic, and keratoconic eyes were substituted for the first surface in the model. The results have shown that performing ray tracing, utilizing the two-dimensional Chebyshev function approximation, is possible for noncircularly symmetric models, and that such calculation can be performed with a newly created Chebfun toolbox.

Using ultrasound backscattering signals and Nakagami statistical distribution to assess regional cataract hardness.

This study aims to analyze the protein aggregates spatial distribution for different cataract degrees, and correlate this information with the lens acoustical parameters and by this way, assess the cataract regional hardness. Different cataract degrees were induced ex vivo in porcine lenses. A 25 MHz ultrasonic transducer was used to obtain the acoustical parameters (velocity, attenuation, and backscattering signals). B-scan and Nakagami images were constructed. Also, lenses with different cataract degrees were sliced in two regions (nucleus and cortex), for fibers and collagen detection. A significant increase with cataract formation was found for the velocity, attenuation, and brightness intensity of the B-scan images and Nakagami m parameter ( ). The acoustical parameters showed a good to moderate correlation with the m parameter for the different stages of cataract formation. A strong correlation was found between the protein aggregates in the cortex and the m parameter. Lenses without cataract are characterized using a classification and regression tree, by a mean brightness intensity ≤0.351, a variance of the B-scan brightness intensity ≤0.070, a velocity ≤1625 m/s, and an attenuation ≤0.415 dB/mm·MHz (sensitivity: 100% and specificity: 72.6%). To characterize different cataract degrees, the m parameter should be considered. Initial stages of cataract are characterized by a mean brightness intensity >0.351 and a variance of the m parameter >0.110. Advanced stages of cataract are characterized by a mean brightness intensity >0.351, a variance of the m parameter ≤0.110, and a mean m parameter >0.374. For initial and advanced stages of cataract, a sensitivity of 78.4% and a specificity of 86.5% are obtained.