Measuring intraocular pressure with OCT: the first approach.

The variability of corneal OCT speckle statistics is indirectly related to changes in corneal microstructure, which may be induced by intraocular pressure (IOP). A new approach is considered, which attempts to estimate IOP based on corneal speckle statistics in OCT images. An area (A) under trajectories of contrast ratio with respect to stromal depth was calculated. The proposed method was evaluated on OCT images from the ex-vivo study on porcine eyeballs and in-vivo study on human corneas. A statistically significant multivariate linear regression model was obtained from the ex-vivo study: IOP = 0.70 · A - 6.11, in which IOP was precisely controlled in the anterior chamber. The ex-vivo study showed good correlation between A and IOP (R = 0.628, at the least) whereas the in-vivo study showed poor correlation between A and clinical air-puff tonometry based estimates of IOP (R = 0.351, at the most), indicating substantial differences between the two studies. The results of the ex-vivo study show the potential for OCT speckle statistics to be utilized for measuring IOP using static corneal imaging that does not require corneal deformation. Nevertheless, further work is needed to validate this approach in living human corneas.

OCT based corneal densitometry: the confounding effect of epithelial speckle.

Corneal densitometry is a clinically validated method for objectively assessing the transparency of stroma. The technique is currently dominated by Scheimpflug technology. Still, optical coherence tomography (OCT), in which examination of the statistical properties of corneal speckle is undertaken, has also been considered to assess corneal densitometry. In-vivo, the stroma is observed via the epithelium. However, the effect of this external layer on stromal densitometry has not been considered as yet. This study aims to quantify the influence of epithelium integrity on corneal OCT densitometry. OCT images from eleven freshly enucleated porcine eyes before and after epithelial debridement were used. OCT densitometry was investigated at different stromal depths using four metrics of speckle statistics. Results indicate that there exist statistically significant differences in speckle statistics for a given stromal depth depending on the presence or absence of the epithelium. The estimation error in speckle statistics can reach over 20% depending on the stromal depth. The anterior stroma densitometry values are the ones most affected by epithelial integrity. In conclusion, if OCT densitometry stromal parameters are to be considered in absolute terms, it is essential to consider the confounding effect of the epithelial layer in the analysis.

Assessing Age-Related Changes in Corneal Densitometry Parameters With Anterior Segment OCT Speckle.

Purpose: The purpose of this study was to assess in vivo regional variability in the densitometry parameters of corneal stroma and the modulating effect of age on those parameters using statistical characterization of optical coherence tomography (OCT) speckle. Methods: OCT imaging of central and peripheral cornea was performed in a group of 20 younger (24 to 30 years old) and 19 older (50 to 87 years old) subjects. The sample size was estimated using normal assumptions and previously reported data on speckle parameter variability. Statistical parameters of corneal OCT speckle were calculated in the regions of interest (ROI) encompassing central and peripheral stroma as well as taking into account their anterior and posterior subregions. Both parametric (Burr-2 parameters: α and k) and a nonparametric approach (contrast ratio [CR]) were considered. Two-way analysis of variance was used to test for differences in densitometry parameters with respect to ROI position and age. Results: Both approaches showed statistically significant differences within the ROI positions (all P < 0.001 for α, k, and CR) and age (P < 0.001, P = 0.002, and P = 0.003, for α, k, and CR, respectively) indicating substantial stromal asymmetry. Additionally, CR showed statistically significant differences between anterior and posterior subregions (P < 0.001). Conclusions: Corneal OCT-based densitometry is inherently asymmetrical and are influenced by age. The results indicate that regional variability of stromal structure is not limited to the central and peripheral regions but that differences exist also between the nasal and temporal parts of the cornea. Translational Relevance: The in vivo acquired parameters of corneal OCT speckle can be used to indirectly assess corneal structure.

Indirectly assessing changes in corneal properties with OCT speckle after crosslinking in porcine eyes.

The aim of this study was to assess the effect of the standard crosslinking (CXL) procedure on corneal properties and subsequent changes in collagen bonds formation using optical coherence tomography (OCT) corneal speckle statistics and vibrational spectroscopy. Porcine eyes with intact corneal epithelium were randomly selected to one of the four study groups: (1) untreated eyes moistened with phosphate-buffered saline (PBS); (2) eyes after the epithelial debridement and riboflavin application; (3) eyes after CXL procedure according to the Dresden protocol; and (4) eyes after corneal epithelial debridement, regularly moistened with PBS. Before and after this selection, each eyeball was subjected to the constant intraocular pressure of 20 mmHg. Then, ocular biometry was performed and the central cornea was imaged using spectral-domain OCT. Following this, a nonparametric approach to speckle modeling (the Contrast Ratio (CR)) was utilized within the region of interest for each B-scan covering the central corneal stroma. To verify whether the CXL performed ex-vivo results in formation of new bonds in the cornea, Fourier Transform Infrared Attenuated Total Reflectance (ATR-FTIR) spectra of dried corneas, dissected from examined eyeballs, were collected and analyzed. Corneal epithelium removal alone or with the riboflavin application leads to a statistically significant decrease in the CR median value (the Wilcoxon signed-rank test, p < 0.05). However, the most pronounced change in CR median value, which decreases with the increased number of scatterers, was shown after the complete CXL procedure including riboflavin soaking and UVA irradiation (the Wilcoxon signed-rank test, p = 0.004). Analysis of ATR-FTIR spectra revealed influence of UVA irradiation on collagen matrix. The study has shown the increased dehydration accompanied by almost no alteration of collagen native triple-helical structure. Significant changes have been observed for bands related to collagen crosslinks. Specifically, the predominant changes occurred in the sugar region from 1150 to 975 cm-1, as well as in the absorbance of carbonyl groups. Furthermore, the ratio of two Amide I components at approximately 1660 cm-1 and 1675 cm-1 decreased after UVA irradiation. Together, these results provided the evidence for the creation of new corneal crosslinks. In conclusion, this study clearly indicates that the UVA exposure causes the substantial difference in optical scattering occurring in corneal stroma as a result of the induced biochemical changes at the molecular level in this tissue assessed with ATR-FTIR. The proposed speckle-based methodology brings a new insight into the development of OCT technology useful in an indirect assessment of some collagen changes.

Assessing and compensating for the confounding factors in Scheimpflug-based corneal densitometry.

Scheimpflug-based corneal densitometry is a clinically verified method for assessing corneal transparency. Nevertheless, the estimates of corneal densitometry appear to be correlated with age and eye biometry parameters, such as the anterior chamber depth or the pupil size, and that ensues a convoluted conditional estimation problem, where it is difficult to interpret the results. This study aims at devising a methodology for compensating for such confounding factors by using, as a research platform, a commercially available Scheimpflug camera that allows exporting images in a dynamic fashion, allowing averaging the results from multiple acquisitions. Two approaches are considered, one based on appropriately normalizing the line densitometry signal and one based on image histogram equalization. Then, three parameters for describing corneal densitometry are derived including the mean value of backscatter and the scale and shape parameters of the Weibull distribution estimated in regions of interest encompassing parts of corneal stroma. The results show that, unlike the non-normalized measures, the proposed approaches lead to parameters that are not correlated with age nor the eye biometry.

Tear Film Surface Quality in Modern Daily Disposable Contact Lens Wear.

OBJECTIVES: As reported previously, tear film surface quality (TFSQ) should be considered in contact lens (CL) fitting. This study followed noninvasive keratograph tear film break-up time (NIKBUT) in CL wearers for 12 months to validate its clinical utility in predicting CL performance. METHODS: Fifty-five subjects (M/F=17/38) aged 26±4 years were prescribed silicone hydrogel or hydrogel CLs. The study included baseline measurements without CLs; 2 visits for CL fitting and control; follow-up after 3, 6, and 12 months of CL wear; and postwear visit without CLs. Ocular Surface Disease Index (OSDI), 8-Item Contact Lens Dry Eye Questionnaire (CLDEQ-8), first and mean NIKBUT (F/M-NIKBUT), fluorescein tear film break-up time (FBUT), and ocular surface staining were evaluated. RESULTS: Post hoc analysis of each pair of visits showed differences between baseline and all CL visits for F-NIKBUT, M-NIKBUT, FBUT, and corneal staining. No difference was reported in symptoms. In addition, differences between baseline and postwear visits were noted in OSDI, M-NIKBUT, FBUT, and corneal staining, with three of the latter parameters showing a downward trend. CONCLUSIONS: No changes in TFSQ and symptoms were reported over 12 months. Introducing NIKBUT as part of routine CL fitting is advised to improve CL fit and predict success.

Statistical analysis of corneal OCT speckle: a non-parametric approach.

In biomedical optics, it is often of interest to statistically model the amplitude of the speckle using some distributional approximations with their parameters acting as biomarkers. In this paper, a paradigm shift is being advocated in which non-parametric approaches are used. Specifically, a range of distances, evaluated in different domains, between an empirical non-parametric distribution of the normalized speckle amplitude sample and the benchmark Rayleigh distribution, is considered. Using OCT images from phantoms, two ex-vivo experiments with porcine corneas and an in-vivo experiment with human corneas, an evidence is provided that the non-parametric approach, despite its simplicity, could lead to equivalent or better results than the parametric approaches with distributional approximations. Concluding, in practice, the non-parametric approach should be considered as the first choice to speckle modeling before a particular distributional approximation is utilized.

Glaucoma classification based on scanning laser ophthalmoscopic images using a deep learning ensemble method.

This study aimed to assess the utility of optic nerve head (onh) en-face images, captured with scanning laser ophthalmoscopy (slo) during standard optical coherence tomography (oct) imaging of the posterior segment, and demonstrate the potential of deep learning (dl) ensemble method that operates in a low data regime to differentiate glaucoma patients from healthy controls. The two groups of subjects were initially categorized based on a range of clinical tests including measurements of intraocular pressure, visual fields, oct derived retinal nerve fiber layer (rnfl) thickness and dilated stereoscopic examination of onh. 227 slo images of 227 subjects (105 glaucoma patients and 122 controls) were used. A new task-specific convolutional neural network architecture was developed for slo image-based classification. To benchmark the results of the proposed method, a range of classifiers were tested including five machine learning methods to classify glaucoma based on rnfl thickness-a well-known biomarker in glaucoma diagnostics, ensemble classifier based on inception v3 architecture, and classifiers based on features extracted from the image. The study shows that cross-validation dl ensemble based on slo images achieved a good discrimination performance with up to 0.962 of balanced accuracy, outperforming all of the other tested classifiers.

Corneal Optical Coherence Tomography Speckle in Crosslinked and Untreated Rabbit Eyes in Response to Elevated Intraocular Pressure.

Purpose: To ascertain the influence of intraocular pressure (IOP) on corneal optical coherence tomography (OCT) speckle in untreated and ultraviolet A-riboflavin induced corneal collagen crosslinked rabbit eyes. Methods: Left corneas of eight rabbits were de-epithelialized and crosslinked by applying riboflavin and 30-minute ultraviolet A light exposure. After enucleation (6 months after treatment), each eyeball (treated and untreated) was mounted in a measurement setup, in which IOP was increased from 15 to 45 mm Hg in steps of 5 mm Hg. At each IOP value, single B-scans of the central cornea were acquired three times with the spectral-domain OCT Copernicus-HR. Then, three regions of interest, including the anterior, posterior, and entire corneal stroma, were automatically extracted. Five different probability distributions were used as a model for the corneal speckle and the one with the best goodness of fit was chosen for further analysis. Results: The generalized gamma distribution achieved the best goodness of fit and its scale (a) and shape (v) parameters statistically significantly changed with increasing IOP in the three regions of analysis (two-way repeated measures analysis of variance, all P < 0.05). The statistically significant difference between untreated and crosslinked eyes was observed for the shape parameters of the posterior and entire corneal stroma. Conclusions: Corneal OCT speckle is influenced by IOP and shows to be significantly different in untreated and crosslinked eyes. Corneal OCT speckle analysis has the potential to be indirectly used for assessing changes in corneal stroma in ex vivo and in vivo studies. Translational Relevance: Investigation of corneal OCT speckle statistics can offer additional diagnostic biomarkers related to changes in the corneal stroma after ocular surgeries.

The effect of intraocular pressure elevation and related ocular biometry changes on corneal OCT speckle distribution in porcine eyes.

The aim of this study was to evaluate the influence of increase in intraocular pressure (IOP) and cooccurring changes in ocular biometry parameters on the corneal optical coherence tomography (OCT) speckle distribution in ex-vivo experiments on porcine intact eyes. Twenty-three eyeballs were used in the inflation test where IOP in the anterior chamber was precisely set from 10 mmHg to 40 mmHg in steps of 5 mmHg and where eye biometry was utilized (IOL Master 700). To assess the influence of the duration of the experiment on the OCT speckle statistics, the second experiment was performed with 10 eyeballs at the constant IOP of 15 mmHg. Based on the OCT scans of central cornea (Copernicus REVO), spatial maps of the scale parameter (a) and the shape parameter (v) of the gamma distribution speckle model were estimated. The means of both parameters for each spatial map were computed within the 2 mm of the central stroma. Both distributional parameters statistically significantly varied with IOP and time (one way repeated measures ANOVA, all p-values < 0.001). The a parameter revealed a faster statistically significant increase in IOP up to 25 mmHg, regardless of time. Central corneal thickness (CCT), the anterior chamber depth, and the mean equivalent spherical power varied significantly with IOP, whereas CCT and axial length changed statistically significantly with time. Statistically significant correlation was found between CCT and the a parameter, after removing IOP as a confounding factor (r = -0.576, p < 0.001). The parameters of the gamma distribution can be used not only for identifying IOP induced changes in the optical scattering within the corneal stroma, but also in corneal geometry. The approach of corneal speckle analysis could be potentially utilized for an indirect and noninvasive assessment of some properties of corneal stroma.

Associating the biomarkers of ocular blood flow with lamina cribrosa parameters in normotensive glaucoma suspects. Comparison to glaucoma patients and healthy controls.

PURPOSE: To evaluate association between ocular blood flow biomarkers and lamina cribrosa parameters in normotensive glaucoma suspects compared to glaucoma patients and healthy controls. METHODS: A total of 211 subjects (72 normotensive glaucoma suspects, 70 with primary open-angle glaucoma and 69 controls) were included. Ocular blood flow biomarkers in ophthalmic artery, central retinal artery, as well as in nasal and temporal short posterior ciliary arteries were measured using colour Doppler imaging. Lamina cribrosa position was assessed by measuring its depth, deflection depth, lamina cribrosa shape index and its horizontal equivalent (LCSIH) on B-scan images obtained using optical coherence tomography. RESULTS: Ocular blood flow biomarkers in glaucoma patients were statistically significantly reduced when compared to healthy controls in peak systolic velocity (PSV) (P = 0.001 in ophthalmic artery and P<0.001 in central retinal artery) and mean flow velocity (Vm) (P = 0.008 in ophthalmic artery and P = 0.008 in central retinal artery), but not statistically significantly different to that of glaucoma suspects except for PSV in central retinal artery (P = 0.011). Statistically significant correlations corrected for age, central corneal thickness and intraocular pressure were found in glaucoma patients between LCSIH and end diastolic velocity of central retinal artery (P = 0.011), and of nasal short posterior ciliary artery (P = 0.028), and between LCSIH and Vm of central retinal artery (P = 0.011) and of nasal short posterior ciliary artery (P = 0.007). No significant correlations were observed between these parameters in glaucoma suspects and healthy controls. CONCLUSIONS: Impaired ocular blood flow associated with the deformation of lamina cribrosa was found in glaucoma patients, whereas glaucoma suspects had similar lamina cribrosa shape to glaucoma patients but that deformation was not associated with ocular blood flow biomarkers.

Reducing the Number of MEG/EEG Trials Needed for the Estimation of Brain Evoked Responses: A Bootstrap Approach.

OBJECTIVE: A common problem in magnetoencephalographic (MEG) and electroencephalographic (EEG) experimental paradigms relying on the estimation of brain evoked responses is the lengthy time of the experiment, which stems from the need to acquire a large number of repeated recordings. Using a bootstrap approach, we aim at reliably reducing the number of these repeated trials. METHODS: To this end, we assessed five variants of non-parametric bootstrapping based on the classical signal-plus-noise model constituting the foundation of signal averaging in MEG/EEG. We explain which of these approaches should and which should not be used for the aforementioned purpose, and why. RESULTS: We present results for two advocated bootstrap variants applied to auditory MEG data. The ensuing trial-averaged magnetic fields served as input to the estimation of cortical source generators, with spatio-temporal matching pursuit as an example of an inverse solution technique. We propose, for a wide range of trial numbers, a general framework to evaluate the statistical properties of the parameter estimates for source locations and related time courses. CONCLUSION: The proposed bootstrap framework offers a systematic approach to reduce the number of trials required to estimate the evoked response. The general validity of our findings is neither bound to any particular type of MEG/EEG data nor to any specific source localization method. SIGNIFICANCE: Practical implications of this work relate to the optimization of acquisition time of MEG/EEG experiments, thus reducing stress for the subjects (especially for patients) and minimizing related artifacts.

Keratoconus Detection Based on a Single Scheimpflug Image.

Purpose: To introduce a new approach for keratoconus detection based on corneal microstructure observed in vivo derived from a single Scheimpflug image. Methods: Scheimpflug single-image snapshots from 25 control subjects and 25 keratoconus eyes were analyzed; from each group, five subjects were randomly selected to provide out-of-sample data. Each corneal image was segmented, after which the stromal pixel intensities were statistically modeled with a Weibull distribution. Distribution estimated parameters α and ß, characterizing corneal microstructure, were used in combination with a macrostructure parameter, central corneal thickness (CCT), for the detection of keratoconus. In addition, receiver operating characteristic curves were used to determine the sensitivity and specificity of each parameter for keratoconus detection. Results: The combination of CCT (sensitivity = 88%; specificity = 84%) with microscopic parameters extracted from statistical modeling of light intensity distribution, α (sensitivity = 76%; specificity = 76%) and ß (sensitivity = 96%; specificity = 88%), from a single Scheimpflug image was found to be a successful tool to differentiate between keratoconus and control eyes with no misclassifications (sensitivity = 100%; specificity = 100%) with coefficients of variation up to 2.5%. Conclusions: The combination of microscopic and macroscopic corneal parameters extracted from a static Scheimpflug image is a promising, non-invasive tool to differentiate corneal diseases without the need to perform measurements based on induced deformation of the corneal structure. Translational Relevance: The proposed methodology has the potential to support clinicians in the detection of keratoconus, without compromising patient comfort.

Omnibus test for normality based on the Edgeworth expansion.

Statistical inference in the form of hypothesis tests and confidence intervals often assumes that the underlying distribution is normal. Similarly, many signal processing techniques rely on the assumption that a stationary time series is normal. As a result, a number of tests have been proposed in the literature for detecting departures from normality. In this article we develop a novel approach to the problem of testing normality by constructing a statistical test based on the Edgeworth expansion, which approximates a probability distribution in terms of its cumulants. By modifying one term of the expansion, we define a test statistic which includes information on the first four moments. We perform a comparison of the proposed test with existing tests for normality by analyzing different platykurtic and leptokurtic distributions including generalized Gaussian, mixed Gaussian, α-stable and Student's t distributions. We show for some considered sample sizes that the proposed test is superior in terms of power for the platykurtic distributions whereas for the leptokurtic ones it is close to the best tests like those of D'Agostino-Pearson, Jarque-Bera and Shapiro-Wilk. Finally, we study two real data examples which illustrate the efficacy of the proposed test.

Mixed polar-nonpolar lipid films as minimalistic models of Tear Film Lipid Layer: A Langmuir trough and fluorescence microscopy study.

The Tear Film Lipid Layer (TFLL) covering the surface of the aqueous film at human cornea forms a first barrier between the eye and environment. Its alterations are related to dry eye disease. TFLL is formed by a complex mixture of lipids, with an excess of nonpolar components and a minor fraction of polar molecules. Its thickness is up to 160 nm, hence a multilayer-like structure of TFLL is assumed. However, details of TFLL organization are mostly unavailable in vivo due to the dynamic nature of the human tear film. To overcome this issue, we employ a minimalistic in vitro lipid model of TFLL. We study its biophysical characteristics by using a combination of the Langmuir trough with fluorescence microscopy. The model consists of two-component polar-nonpolar lipid films with a varying component ratio spread on the aqueous subphase at physiologically relevant temperature. We demonstrate that the model lipid mixture undergoes substantial structural reorganization as a function of lateral pressure and polar to nonpolar lipid ratio. In particular, the film is one-molecule-thick and homogenous under low lateral pressure. Upon compression, it transforms into a multilayer structure with inhomogeneities in the form of polar-nonpolar lipid assemblies. Based on this model, we hypothesize that TFLL in vivo has a duplex polar-nonpolar structure and it contains numerous mixed lipid aggregates formed because of film restructuring. These findings, despite the simplified character of the model, seem relevant for TFLL physiology as well as for understanding pathological conditions related to the lipids of the tear film.

A 12-month Prospective Study of Tear Osmolarity in Contact Lens Wearers Refitted with Daily Disposable Soft Contact Lenses.

SIGNIFICANCE: Tear osmolarity has been reported as one of the best diagnostic tests for dry eye disease and its management. Contact lens wear is thought to influence tear homeostasis. Understanding how regular wear of contact lenses and their type affect tear osmolarity is important. PURPOSE: The purpose of this study was to assess changes in tear osmolarity and ocular symptoms over a period of 12 months following refitting contact lens wearers with daily disposable contact lenses. METHODS: Fifty subjects aged (mean ± SD) 26 ± 4 years were refitted with either silicone-hydrogel (delefilcon A, SiHy, n = 34) or hydrogel (omafilcon A, Hy, n = 16) daily disposable soft contact lenses. Study included seven visits: baseline measurements without contact lenses; two visits for contact lens fit and selection; follow-up measurements after 3, 6, and 12 months of contact lens wear; and a post-study visit without contact lenses. Lens type selection was based on a set of objective measurements. Subjects were instructed to follow strict wearing rules. Impedance-based osmometer was used to collect samples from the lower tear meniscuses. The Ocular Surface Disease Index (OSDI) and the eight-item Contact Lens Dry Eye Questionnaire were used to assess subject-reported ocular symptoms and contact lens discomfort, respectively. RESULTS: Downward trend of tear osmolarity was noted over the time course of study. Statistically significant differences were noted in tear osmolarity (Friedman test, χ = 21.91 [P < .001], and χ = 13.89 [P = .003]) for the right and left eyes, respectively. A statistically significant decrease in tear osmolarity was apparent only for initially symptomatic subjects (for OSDI ≥13: χ = 26.25, P < .001; for OSDI <13: χ = 5.65, P = .13). Statistically significant differences were not noted in OSDI and the eight-item Contact Lens Dry Eye Questionnaire between the baseline and 12-month visit (χ = 5.92 [P = .12] and R = 0.015 [P = .87], respectively). There was a difference between baseline and post-study visits (P = .002) in OSDI, showing lower score at the latter visit. CONCLUSIONS: Refitting with daily disposable contact lenses was demonstrated to lower tear osmolarity.

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.

Factors Influencing Pseudo-Accommodation-The Difference between Subjectively Reported Range of Clear Focus and Objectively Measured Accommodation Range.

The key determinants of the range of clear focus in pre-presbyopes and their relative contributions to the difference between subjective range of focus and objective accommodation assessments have not been previously quantified. Fifty participants (aged 33.0 ± 6.4 years) underwent simultaneous monocular subjective (visual acuity measured with an electronic test-chart) and objective (dynamic accommodation measured with an Aston open-field aberrometer) defocus curve testing for lenses between +2.00 to -10.00 DS in +0.50 DS steps in a randomized order. Pupil diameter and ocular aberrations (converted to visual metrics normalized for pupil size) at each level of blur were measured. The difference between objective range over which the power of the crystalline lens changes and the subjective range of clear focus was quantified and the results modelled using pupil size, refractive error, tolerance to blur, and ocular aberrations. The subjective range of clear focus was principally accounted for by age (46.4%) and pupil size (19.3%). The objectively assessed accommodative range was also principally accounted for by age (27.6%) and pupil size (15.4%). Over one-quarter (26.0%) of the difference between objective accommodation and subjective range of clear focus was accounted for by age (14.0%) and spherical aberration at maximum accommodation (12.0%). There was no significant change in the objective accommodative response (F = 1.426, p = 0.229) or pupil size (F = 0.799, p = 0.554) of participants for levels of defocus above their amplitude of accommodation. Pre-presbyopes benefit from an increased subjective range of clear vision beyond their objective accommodation due in part to neural factors, resulting in a measured depth-of-focus of, on average, 1.0 D.

Meibomian Gland Morphology: The Influence of Structural Variations on Gland Function and Ocular Surface Parameters.

PURPOSE: To objectively and quantitatively characterize meibomian gland morphology and to investigate the influence of morphological variations on gland function and ocular surface and tear film parameters. METHODS: One hundred fifty subjects were enrolled. The examinations included tear osmolarity, tear meniscus height, bulbar conjunctival hyperemia, noninvasive tear film breakup time, lid margin thickness, foam secretion, meibomian gland expressibility, count of functioning glands, corneal and conjunctival staining, fluorescein breakup time, lid wiper epitheliopathy, and Schirmer test. Patient symptoms were assessed using the Ocular Surface Disease Index questionnaire. Images from noncontact meibography were analyzed using an automated method that objectively estimates dropout area, number of glands, gland length and width, and gland irregularity. RESULTS: Gland irregularity highly correlated with dropout area (r = -0.4, P < 0.001) and showed significant partial correlations with fluorescein breakup time (r = 0.162, P = 0.049) and the Ocular Surface Disease Index questionnaire (r = -0.250, P = 0.002) Subjects with dropout area <32% were divided into 2 groups: high and low irregularity. Gland expressibility was statistically significantly different between the 2 groups (U = 319.5, P = 0.006). In the high irregularity group, gland irregularity correlated with the Schirmer test (r = 0.530, P = 0.001) and corneal fluorescein staining (r = -0.377, P = 0.021). CONCLUSIONS: Automated morphological analysis of meibomian gland structure provides additional quantitative and objective information regarding gland morphology. The link between dropout area and gland function is not clear. Assessment of gland irregularity might better predict gland function and its effects on ocular surface and tear film parameters.

A Novel Automated Approach for Infrared-Based Assessment of Meibomian Gland Morphology.

PURPOSE: We present and validate a new methodology for analyzing, in an automated and objective fashion, infrared images of the meibomian glands (MG). METHODS: The developed algorithm consists of three main steps: selection of the region of interest, detection of MG, and analysis of MG morphometric parameters and dropout area (DOA). Additionally, a new approach to quantify the irregularity of MG is introduced. We recruited 149 adults from a general population. Infrared meibography, using Keratograph 5M, was performed. Images were assessed and graded subjectively (Meiboscore) by two experienced clinicians and objectively with the proposed automated method. RESULTS: The correlation of subjective DOA assessment between the two clinicians was poor and the average percentage of DOA estimated objectively for each Meiboscore group did not lie within their limits. The objective assessment showed lower variability of meibography grading than that obtained subjectively. Additionally, a new grading scale of MG DOA that reduces intraclass variation is proposed. Reported values of MG length and width were inversely proportional to the DOA. Gland irregularity was objectively quantified. CONCLUSIONS: The proposed automatic and objective method provides accurate estimates of the DOA as well as additional morphologic parameters that could add valuable information in MG dysfunction understanding and diagnosis. TRANSLATIONAL RELEVANCE: This approach highlights the shortcomings of currently used subjective methods, and provides the clinicians with an objective, quantitative and less variable alternative for assessing MG in a noninvasive and automated fashion. It provides a viable alternative to more time-consuming subjective methods.