Safety and Efficacy of Three Variants of Canaloplasty with Phacoemulsification to Treat Open-Angle Glaucoma and Cataract: 12-Month Follow-Up.

BACKGROUND: A single-center prospective randomized observational study to compare three types of canaloplasty, i.e., ab externo (ABeC), minicanaloplasty (miniABeC) and ab interno, (ABiC) combined with cataract surgery in primary open-angle glaucoma (POAG) patients over 12 months. METHODS: 48 POAG patients underwent one of three canaloplasty procedures: ABeC (16 eyes), miniABeC (16 eyes) or ABiC (16 eyes) or combined with phacoemulsification. Patients were assessed at baseline, at day 0-1-7 and at month 1-3-6-12. Successful treatment was defined as unmedicated IOP reduction ≥20%. Complete surgical success was defined as an IOP ≤ 15 mmHg without medications, and a qualified surgical success as IOP ≤ 15 mmHg with or without medications. RESULTS: Pre-washout IOP median values (mmHg) were 17 (ABeC), 18 (miniABeC) and 17 (AbiC) and decreased at 12-month follow up postoperatively to 13 (p = 0.005), 13 (p = 0.004) and 14 (p = 0.008), respectively-successful treatment was achieved in approximately 100% of patients for ABeC and in 93.8% for both miniABeC and AbiC groups. Preoperatively, the median number of medications was 2.0 (range 1-3) (ABeC), 2.0 (1-3) (miniABeC) and 2.0 (0-4) (ABiC); 12-month post-operatively, all medications were withdrawn except in two patients (followed miniABeC and AbiC). CONCLUSIONS: The three variants of canaloplasty significantly reduced IOP and the number of medications in patients with mild to moderate POAG and gave no significant complications.

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.

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.

The effect of changes in cardiovascular activity on corneal biomechanics and pulsation in rabbits.

The aim was to assess the relationships between cardiovascular activity, corneal pulse characteristics, and corneal biomechanics in rabbits. Seventeen rabbits were randomly assigned to one of two anesthetic regimens to induce differences in arterial blood pressure and heart rate. Experimental protocol included measuring blood flow parameters in the ophthalmic artery by color Doppler imaging, corneal biomechanical parameters using a non-contact tonometer Corvis ST, and the corneal pulse (CP) signal using a non-contact ultrasonic technique. Statistically significantly lower mean values of normalized amplitudes of higher CP harmonics and changes in eight of the twelve corneal biomechanical parameters were observed in the rabbit group with lower arterial blood pressure and higher heart rate, intraocular pressure, and resistive index. The results of partial correlations showed that the CP signal energy and amplitude of its first harmonic correlate with the resistive index, diastolic and mean arterial pressures, whereas no statistically significant correlation was found between any of the CP parameters and intraocular pressure. Our pilot study indicates, for the first time, that non-contact and continuous measuring of corneal pulse allows indirectly assessing changes in cardiovascular activity when the confounding effect of intraocular pressure is eliminated.

Using the entropy of the corneal pulse signal to distinguish healthy eyes from eyes affected by primary open-angle glaucoma.

OBJECTIVE: The purpose of this study was to evaluate whether the complexity of the corneal pulse (CP) signal can be used to differentiate patients with primary open-angle glaucoma (POAG) from healthy subjects. APPROACH: The study sample consisted of 28 patients with POAG and a control, age-matched group of 30 subjects. After standard ophthalmic examination, the CP signal from a randomly selected eye of each participant was measured using non-contact ultrasonic micro-displacement measurement technology. After pre-processing, the complexity of the CP signal was estimated using refined composite multiscale fuzzy entropy (RCMFE) up to scale factor 50. The average RCMFE values were computed from three repeated measurements of the CP signals for each participant and each scale factor. MAIN RESULTS: The complexity of the CP signal in glaucomatous eyes was higher than that observed in healthy ones. Also, RCMFE of the CP signal was found to differentiate (statistically significantly) between the two groups for scales in the range from 26 to 43. For these scales, the one for which the lowest p-value (t-test, p = 0.017) was obtained when comparing RCMFE between the two groups was selected as the optimal scale. Next, a receiver operating characteristic analysis for the optimal scale showed that the proposed approach of calculating the multiscale entropy of the CP signal has some potential to discriminate between patients with POAG and healthy controls (sensitivity, specificity and accuracy of 0.643, 0.700 and 0.672, respectively). SIGNIFICANCE: In conclusion, RCMFE, as a complexity measure, may be considered an auxiliary indicator to support glaucoma diagnostics.

Corneal pulsation and biomechanics during induced ocular pulse. An ex-vivo pilot study.

The purpose of this study was to ascertain the relationships between the amplitude of the corneal pulse (CP) signal and the parameters of corneal biomechanics during ex-vivo intraocular pressure (IOP) elevation experiments on porcine eyes with artificially induced ocular pulse cycles. Two experiments were carried out using porcine eyes. In the first one, a selected eye globe was subjected to three IOP levels (15, 30 and 45 mmHg), where changes in physical ocular pulse amplitude were controlled by infusion/withdrawal volumes (ΔV). In the second experiment, six eyes were subjected to IOP from 15 mmHg to 45 mmHg in steps of 5 mmHg with a constant ΔV, where corneal deformation parameters were measured using Corvis ST. In both experiments, at each IOP, the CP and IOP signals were acquired synchronically using a non-contact ultrasonic distance sensor and a pressure transmitter, respectively. Based on the amplitudes of the CP and IOP signals ocular pulse based corneal rigidity index (OPCRI) was calculated. Results indicate positive correlations between ΔV and the physical ocular pulse amplitude, and between ΔV and the corneal pulse amplitude (both p < 0.001). OPCRI was found to increase with elevated IOP. Furthermore, IOP statistically significantly differentiated changes in OPCRI, the amplitudes of CP and IOP signals and in most of the corneal deformation parameters (p < 0.05). The partial correlation analysis, with IOP as a control variable, revealed a significant correlation between the length of the flattened cornea during the first applanation (A1L) and the corneal pulse amplitude (p = 0.002), and between A1L and OPCRI (p = 0.003). In conclusion, this study proved that natural corneal pulsations, detected with a non-contact ultrasonic technique, reflect pressure-volume dynamics and can potentially be utilized to assess stiffness of the cornea. The proposed new rigidity index could be a simple approach to estimating corneal rigidity.

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.

Relationship Between the Parameters of Corneal and Fundus Pulse Signals Acquired With a Combined Ultrasound and Laser Interferometry Technique.

PURPOSE: To estimate the relationship between the characteristics of the corneal pulse (CP) signal and those of the fundus pulse (FP) signal measured with a combined noncontact ultrasonic and laser interferometry technique in healthy subjects. METHODS: Twenty-two healthy subjects participated in experiments that included measurements of intraocular pressure, ocular pulse amplitude, ocular biometry, blood pressure, and heart rate. Additionally, simultaneous recordings of CP and FP signals were acquired with a noncontact ultrasonic device combined with laser interferometry. Subsequently, ocular perfusion pressure (OPP) and the time and spectral parameters of CP and FP signals were computed. A system model was proposed to relate the FP signal to the CP signal. RESULTS: The system model revealed that the eye globe transfers information between signals of the posterior and anterior eye, relatively amplifying higher spectral harmonics. The amplitude of the second CP harmonic is predicted by FPRMS and OPP (R 2 = 0.468, P = 0.002). Partial correlation analysis showed that the CP signal parameters are statistically significantly correlated with those of the FP signal and OPP, after correcting for age and sex. CONCLUSIONS: The eye globe can be viewed as a high pass filter, in which the CP characteristic changes in relation to the fundus pulsation. The FP signal and OPP have an impact on the variations of the CP signal morphology. TRANSLATIONAL RELEVANCE: Investigation of differences between the characteristics of the anterior and posterior tissue movements is a promising method for evaluating the role of circulatory and biomechanical components in the pathophysiology of ocular diseases.

Changes in spectral parameters of corneal pulse following canaloplasty.

PURPOSE: To ascertain whether changes in the spectral content of the corneal pulse (CP) signal, measured in vivo in primary open-angle glaucoma (POAG) patients, indirectly reflect changes in corneal biomechanics after canaloplasty. METHODS: Fifteen eyes of 15 POAG patients who underwent canaloplasty combined with phacoemulsification were enrolled. Standard ophthalmic examinations were conducted before washout, pre-operatively, at days 1, 7, and 1, 3, 6, and 12 months after surgery. Non-contact measurements of the CP signal were performed at pre-washout, pre-operatively, and at 3, 6, and 12 months post-operatively. Then, amplitudes of the CP first five harmonics associated with the heart rate were estimated. Temporal changes of all considered parameters were tested at a Bonferroni-adjusted significance level set to 0.005. RESULTS: A decrease in the amplitude of the first harmonic and an increase in the normalized amplitude of the third harmonic (ACP3n) of the CP signal were noticed between the pre-washout and the pre-operative stages (p = 0.003 and p = 0.004, respectively). This corresponds to an increase in median intraocular pressure (IOP) values by 6.0 mmHg (p = 0.0045). After surgery, ACP3n reached the highest value at 3 months post-operatively, compared with pre-washout level (p = 0.0045). CONCLUSIONS: Alterations in corneoscleral stiffness caused by surgery are reflected in changes in the ACP3n value. Hence, post-operative corneal biomechanics could be monitored indirectly by this supporting indicator that can be used to estimate the time at which measures of IOP are no longer biased by the changed cornea boundary conditions caused by canaloplasty. CLINICAL TRIALS REGISTRATION: NCT02908633.

In-vivo corneal pulsation in relation to in-vivo intraocular pressure and corneal biomechanics assessed in-vitro. An animal pilot study.

The aim was to ascertain whether the characteristics of the corneal pulse (CP) measured in-vivo in a rabbit eye change after short-term artificial increase of intraocular pressure (IOP) and whether they correlate with corneal biomechanics assessed in-vitro. Eight New Zealand white rabbits were included in this study and were anesthetized. In-vivo experiments included simultaneous measurements of the CP signal, registered with a non-contact method, IOP, intra-arterial blood pressure, and blood pulse (BPL), at the baseline and short-term elevated IOP. Afterwards, thickness of post-mortem corneas was determined and then uniaxial tensile tests were conducted leading to estimates of their Young's modulus (E). At the baseline IOP, backward stepwise regression analyses were performed in which successively the ocular biomechanical, biometric and cardiovascular predictors were separately taken into account. Results of the analysis revealed that the 3rd CP harmonic can be statistically significantly predicted by E and central corneal thickness (Models: R2 = 0.662, p < 0.005 and R2 = 0.832, p < 0.001 for the signal amplitude and power, respectively). The 1st CP harmonic can be statistically significantly predicted by the amplitude and power of the 1st BPL harmonic (Models: R2 = 0.534, p = 0.015 and R2 = 0.509, p < 0.018, respectively). For elevated IOP, non-parametric analysis indicated significant differences for the power of the 1st CP harmonic (Kruskal-Wallis test; p = 0.031) and for the mean, systolic and diastolic blood pressures (p = 0.025, p = 0.019, p = 0.033, respectively). In conclusion, for the first time, the association between parameters of the CP signal in-vivo and corneal biomechanics in-vitro was confirmed. In particular, spectral analysis revealed that higher amplitude and power of the 3rd CP harmonic indicates higher corneal stiffness, while the 1st CP harmonic correlates positively with the corresponding harmonic of the BPL signal.

Assessing Efficacy of Canaloplasty Using Continuous 24-Hour Monitoring of Ocular Dimensional Changes.

PURPOSE: We investigated whether 24-hour monitoring of corneoscleral limbus area (CSLA) with the Sensimed Triggerfish contact lens sensor (CLS) can be used clinically to assess midterm efficacy of canaloplasty and to assess the relationships of CSLA changes with the heart rhythm. METHODS: Ten eyes of 10 patients, with POAG, which were qualified either to canaloplasty or canaloplasty and phacoemulsification, were included in this study. Eyes were washed out before the surgery and control visits were done at days 1, 7, and 3, 6, 12 months postoperatively, at which subjects were examined. We performed 24-hour monitoring of CSLA changes and Holter ECG at washout, and at 3- and 12-month postop visits. Raw CLS signals were processed to lead two parameters describing short-term 24-hour variability of CSLA (VAR, â). Heart activity parameters from CLS were compared to those acquired from Holter ECG. RESULTS: Mean post washout IOP was 20.6 ± 4.7 and decreased to 14.2 ± 3.0 mm Hg 1 year after surgery (P < 0.01). A decreasing trend in VAR and â parameters were noted. Statistically significant differences were found between the washout and 3-month postop visit for VAR and â (P = 0.014 and P = 0.027, respectively) as well as between the washout and 12-month postop result for the parameter â (P = 0.031). No statistically significant differences were found between the 3- and 12-month postop results for both considered parameters. CONCLUSIONS: Canaloplasty alone or combined with cataract surgery is a successful surgical method of lowering IOP in glaucoma patients. Canaloplasty decreases 24-hour CSLA fluctuation pattern measured with CLS.

Wavelet representation of the corneal pulse for detecting ocular dicrotism.

PURPOSE: To develop a reliable and powerful method for detecting the ocular dicrotism from non-invasively acquired signals of corneal pulse without the knowledge of the underlying cardiopulmonary information present in signals of ocular blood pulse and the electrical heart activity. METHODS: Retrospective data from a study on glaucomatous and age-related changes in corneal pulsation [PLOS ONE 9(7),(2014):e102814] involving 261 subjects was used. Continuous wavelet representation of the signal derivative of the corneal pulse was considered with a complex Gaussian derivative function chosen as mother wavelet. Gray-level Co-occurrence Matrix has been applied to the image (heat-maps) of CWT to yield a set of parameters that can be used to devise the ocular dicrotic pulse detection schemes based on the Conditional Inference Tree and the Random Forest models. The detection scheme was first tested on synthetic signals resembling those of a dicrotic and a non-dicrotic ocular pulse before being used on all 261 real recordings. RESULTS: A detection scheme based on a single feature of the Continuous Wavelet Transform of the corneal pulse signal resulted in a low detection rate. Conglomeration of a set of features based on measures of texture (homogeneity, correlation, energy, and contrast) resulted in a high detection rate reaching 93%. CONCLUSION: It is possible to reliably detect a dicrotic ocular pulse from the signals of corneal pulsation without the need of acquiring additional signals related to heart activity, which was the previous state-of-the-art. The proposed scheme can be applied to other non-stationary biomedical signals related to ocular dynamics.

Glaucomatous and age-related changes in corneal pulsation shape. The ocular dicrotism.

PURPOSE: To ascertain whether the incidence of ocular dicrotic pulse (ODP) increases with age, it is more pronounced in glaucomatous than in normal eyes and whether it is related to cardiovascular activity. METHODS: 261 subjects aged 47 to 78 years were included in the study and classified into four groups: primary open angle glaucoma (POAG), primary angle-closure glaucoma (PACG), glaucoma suspects with glaucomatous optic disc appearance (GODA) and the controls (CG). Additionally, in each group, subjects with ODP were divided into two age subgroups around the median age. A non-contact ultrasonic method was used to measure corneal indentation pulse (CIP) synchronically with the acquisition of electrocardiography (ECG) and blood pulse signals. ODP was assessed from the acquired signals that were numerically processed in a custom written program. RESULTS: ODP incidence was about 78%, 66%, 66% and 84% for CG, GODA, POAG, and PACG group, respectively. With advancing age, the ODP incidence increased for all subjects (Δ = 12%), the highest being for the PACG and POAG groups (Δ = 30%). GODA group did not show an age-related increase in the incidence of ODP. CONCLUSIONS: The ocular dicrotism, measured with non-contact ultrasonic method, was found to be a common phenomenon in elderly subjects. The increased ODP incidence in PACG and POAG group may correspond to either higher stiffness of glaucoma eyes, biochemical abnormalities in eye tissues, changes in ocular hemodynamics, may reflect the effect of medications or be a combination of all those factors. The results of GODA group suggest different mechanisms governing their ocular pulse that makes them less susceptible to generating ODP and having decreased predisposition to glaucoma.

Age-related changes in corneal pulsation: ocular dicrotism.

PURPOSE: To evaluate age-related changes in the shape of corneal indentation pulse (CIP) in relation to simultaneously registered blood pulsation (BPL) and electrocardiogram (ECG) signals in healthy subjects. METHODS: Seventy-seven subjects were recruited for the study, including 36 young subjects (aged 23 to 32 years) and 41 older subjects (aged 44 to 72 years) with no reported ocular and cardiovascular abnormalities and free of any systemic diseases. Corneal indentation pulse was measured with a noninvasive ultrasonic distance sensor. Simultaneously, BPL and ECG were acquired with a pulse oximeter placed on the earlobe and Eindhoven triangle setup, respectively. Correlation analysis was applied to identify the interactions between the parameters of the averaged signals, estimated with dedicated signal processing algorithms, for all subject measurements and separately for both considered groups. RESULTS: Twenty-nine out of 41 older subjects showed evidence of a double peak-shaped CIP waveform that could be interpreted as ocular pulse dicrotism. None of the young subjects exhibited this phenomenon. For the young group, significant correlations (p < 0.05) were found between the CIP crest time of a single peak-shaped CIP waveform and the other shape parameters of the CIP, BPL, and ECG signals. Similarly, for the older group of subjects, significant corresponding correlations were only found between the preliminary crest time of a double peak-shaped CIP waveform. CONCLUSIONS: Using noninvasive corneal indentation pulse measurement revealed, for the first time, an ocular pulse dicrotism. This might be a natural sign of aging or an early indication of hemodynamic aspects of cardiovascular diseases.

Phase dependencies between longitudinal corneal apex displacement and cardiovascular signals: is the ocular pulse influenced by the electrical activity of the heart?

BACKGROUND: The aim was to establish phase relationships between the principal harmonic, related to the heart rate, of synchronically registered longitudinal corneal apex displacement (LCAD), blood pulsation (BP) and electrical heart activity signals in a group of healthy subjects. METHODS: Longitudinal corneal apex displacement was non-invasively measured using an ultrasonic distance sensor. Synchronously, electrocardiographic (ECG) and blood pulsation signals were acquired. As all considered signals are non-stationary (that is, their spectral characteristics vary in time), a reliable and repeatable phase estimation method was sought. For this, a range of phase estimators were tested in the windowed regime of simulated non-stationary signals. Two robust estimators that showed minimum mean square error performance, were selected for further analysis of real signals registered for seven subjects participating in the study. RESULTS: The windowed cross-correlation and the windowed minimum sum of squared error method achieved the best results among the estimators considered and their outputs were averaged to arrive at a robust phase estimator. Across the subjects, it was found that an increase in the time delay between the principal harmonic of BP and ECG signals, θ(BP,ECG), corresponds to a slight time delay increase between the corresponding harmonics of longitudinal corneal apex displacement and blood pulsation signals, θ(LCAD,BP) and a decrease in the time delay between those of longitudinal corneal apex displacement and ECG signals, θ(LCAD,ECG). Significant correlation (paired t-test, p < 0.05) were found between θ(BP,ECG) and θ(LCAD,BP) as well as between θ(BP,ECG) and θ(LCAD,ECG). There was no significant correlation found between θ(LCAD,BP) and θ(LCAD,ECG). CONCLUSION: The results indicate that longitudinal corneal apex displacement and correspondingly the ocular pulse phenomenon have not only a vascular origin but could also be influenced by the electrical activity of the heart.