Laimonas Bartusis

Update in intracranial pressure evaluation methods and translaminar pressure gradient role in glaucoma

Glaucoma is one of the leading causes of blindness worldwide. Historically, it has been considered an ocular disease primary caused by pathological intraocular pressure (IOP). Recently, researchers have emphasized intracranial pressure (ICP), as translaminar counter pressure against IOP may play a role in glaucoma development and progression. It remains controversial what is the best way to measure ICP in glaucoma. Currently, the ‘gold standard’ for ICP measurement is invasive measurement of the pressure in the cerebrospinal fluid via lumbar puncture or via implantation of the pressure sensor into the brains ventricle. However, the direct measurements of ICP are not without risk due to its invasiveness and potential risk of intracranial haemorrhage and infection. Therefore, invasive ICP measurements are prohibitive due to safety needs, especially in glaucoma patients. Several approaches have been proposed to estimate ICP non‐invasively, including transcranial Doppler ultrasonography, tympanic membrane displacement, ophthalmodynamometry, measurement of optic nerve sheath diameter and two‐depth transcranial Doppler technology. Special emphasis is put on the two‐depth transcranial Doppler technology, which uses an ophthalmic artery as a natural ICP sensor. It is the only method which accurately and precisely measures absolute ICP values and may provide valuable information in glaucoma.

Improved diagnostic value of a TCD-based non-invasive ICP measurement method compared with the sonographic ONSD method for detecting elevated intracranial pressure

Abstract Objectives: To compare the diagnostic reliability of optic nerve sheath diameter (ONSD) ultrasonography with a transcranial Doppler (TCD)-based absolute intracranial pressure (ICP) value measurement method for detection of elevated ICP in neurological patients. The ONSD method has been only tested previously on neurosurgical patients. Methods: A prospective clinical study of a non-invasive ICP estimation method based on ONSD correlation with ICP and an absolute ICP value measurement method based on a two-depth TCD technology has recruited 108 neurological patients. Ninety-two of these patients have been enrolled in the final analysis of the diagnostic reliability of ONSD ultrasonography and 85 patients using the absolute ICP value measurement method. All non-invasive ICP measurements were compared with ‘Gold Standard’ invasive cerebrospinal fluid (CSF) pressure measurements obtained by lumbar puncture. Receiver-operating characteristic (ROC) analysis has been used to investigate the diagnostic value of these two methods. Results: The diagnostic sensitivity, specificity, and the area under the ROC curve (AUC) of the ONSD method for detecting elevated intracranial pressure (ICP >14·7 mmHg) were calculated using a cutoff point of ONSD at 5·0 mm and found to be 37·0%, 58·5%, and 0·57, respectively. The diagnostic sensitivity, specificity, and AUC for the non-invasive absolute ICP measurement method were calculated at the same ICP cutoff point of 14·7 mmHg and were determined to be 68·0%, 84·3%, and 0·87, respectively. Conclusions: The non-invasive ICP measurement method based on two-depth TCD technology has a better diagnostic reliability on neurological patients than the ONSD method when expressed by the sensitivity and specificity for detecting elevated ICP >14·7 mmHg.

Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma.

There is increasing evidence in the literature regarding translaminar pressure difference’s (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.

The Difference in Translaminar Pressure Gradient and Neuroretinal Rim Area in Glaucoma and Healthy Subjects

Purpose. To assess differences in translaminar pressure gradient (TPG) and neuroretinal rim area (NRA) in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. Methods. 27 patients with NTG, HTG, and healthy controls were included in the prospective pilot study (each group consisted of 9 patients). Intraocular pressure (IOP), intracranial pressure (ICP), and confocal laser scanning tomography were assessed. TPG was calculated as the difference of IOP minus ICP. ICP was measured using noninvasive two-depth transcranial Doppler device. The level of significance P < 0.05 was considered significant. Results. NTG patients had significantly lower IOP (13.7(1.6) mmHg), NRA (0.97(0.36) mm2), comparing with HTG and healthy subjects, P < 0.05. ICP was lower in NTG (7.4(2.7) mmHg), compared with HTG (8.9(1.9) mmHg) and healthy subjects (10.5(3.0) mmHg); however, the difference between groups was not statistically significant (P > 0.05). The difference between TPG for healthy (5.4(7.7) mmHg) and glaucomatous eyes (NTG 6.3(3.1) mmHg, HTG 15.7(7.7) mmHg) was statistically significant (P < 0.001). Higher TPG was correlated with decreased NRA (r = −0.83; P = 0.01) in the NTG group. Conclusion. Translaminar pressure gradient was higher in glaucoma patients. Reduction of NRA was related to higher TPG in NTG patients. Further prospective studies are warranted to investigate the involvement of TPG in glaucoma management.

Novel Technology of Non-invasive Cerebrovascular Autoregulation Monitoring

A novel technology for non - invasive cerebrovascular auto regulation (CA) status monitoring is presented. This fully non-invasive CA monitor is based on ultrasonic time-of-flight (TOF) measurement of cerebral blood volume pulsations within the brain parenchyma, processing of volumetric waves, and calculation of CA estimation indexes without using any additional arterial blood pressure (ABP) measurements. The CA status is estimated by extracting informative and reference slow waves from non-invasively measured TOF signals and by calculating Pearsons correlation coefficient between these waves as a CA index. The analysis of the signal extracted from the envelope of non-invasively measured pulse waves showed good agreement between this signal and ABP waves (r=0.68). Consequently, it shows that this signal might be used instead of ABP waves as a reference signal for calculation of the CA estimation indexes. Comparative invasive versus non-invasive CA monitoring study of 11 traumatic brain injury patients showed that correlation between invasively measured CA index and fully non-invasively measured CA index (no arterial line) was r=0.75. The proposed innovative CA real-time monitoring method gives us new possibilities to perform estimation of the CA status from intracranial waves only as well as to exclude the ABP lines errors and artifacts from the measurement results.

Non-invasive Cerebrovascular Autoregulation Assessment Using the Volumetric Reactivity Index: Prospective Study

BackgroundThis prospective study of an innovative non-invasive ultrasonic cerebrovascular autoregulation (CA) monitoring method is based on real-time measurements of intracranial blood volume (IBV) reactions following changes in arterial blood pressure. In this study, we aimed to determine the clinical applicability of a non-invasive CA monitoring method by performing a prospective comparative clinical study of simultaneous invasive and non-invasive CA monitoring on intensive care patients.MethodsCA was monitored in 61 patients with severe traumatic brain injuries invasively by calculating the pressure reactivity index (PRx) and non-invasively by calculating the volumetric reactivity index (VRx) simultaneously. The PRx was calculated as a moving correlation coefficient between intracranial pressure and arterial blood pressure slow waves. The VRx was calculated as a moving correlation coefficient between arterial blood pressure and non-invasively-measured IBV slow waves.ResultsA linear regression between VRx and PRx averaged per patients’ monitoring session showed a significant correlation (r = 0.843, p < 0.001; 95% confidence interval 0.751 – 0.903). The standard deviation of the difference between VRx and PRx was 0.192; bias was − 0.065.ConclusionsThis prospective clinical study of the non-invasive ultrasonic volumetric reactivity index VRx monitoring, based on ultrasonic time-of-flight measurements of IBV dynamics, showed significant coincidence of non-invasive VRx index with invasive PRx index. The ultrasonic time-of-flight method reflects blood volume changes inside the acoustic path, which crosses both hemispheres of the brain. This method does not reflect locally and invasively-recorded intracranial pressure slow waves, but the autoregulatory reactions of both hemispheres of the brain. Therefore, VRx can be used as a non-invasive cerebrovascular autoregulation index in the same way as PRx and can also provide information about the CA status encompassing all intracranial hemodynamics.

Location of the internal carotid artery and ophthalmic artery segments for non-invasive intracranial pressure measurement by multi-depth TCD

ABSTRACT The aim of the present study was to locate the ophthalmic artery by using the edge of the internal carotid artery (ICA) as the reference depth to perform a reliable non-invasive intracranial pressure measurement via a multi-depth transcranial Doppler device and to then determine the positions and angles of an ultrasonic transducer (UT) on the closed eyelid in the case of located segments. High tension glaucoma (HTG) patients and healthy volunteers (HVs) undergoing non-invasive intracranial pressure measurement were selected for this prospective study. The depth of the edge of the ICA was identified, followed by a selection of the depths of the IOA and EOA segments. The positions and angles of the UT on the closed eyelid were measured. The mean depth of the identified ICA edge for HTG patients was 64.3 mm and was 63.0 mm for HVs (p = 0.21). The mean depth of the selected IOA segment for HTG patients was 59.2 mm and 59.3 mm for HVs (p = 0.91). The mean depth of the selected EOA segment for HTG patients was 48.5 mm and 49.8 mm for HVs (p = 0.14). The difference in the located depths of the segments between groups was not statistically significant. The results showed a significant difference in the measured UT angles in the case of the identified edge of the ICA and selected ophthalmic artery segments (p = 0.0002). We demonstrated that locating the IOA and EOA segments can be achieved using the edge of the ICA as a reference point. Abbreviations: OA: ophthalmic artery; IOA: intracranial segments of the ophthalmic artery; EOA: extracranial segments of the ophthalmic artery; ICA: internal carotid artery; UT: ultrasonic transducer; HTG: high tension glaucoma; SD: standard deviation; ICP: intracranial pressure; TCD: transcranial Doppler

Graphical and statistical analyses of the oculocardiac reflex during a non-invasive intracranial pressure measurement

Purpose This study aimed to examine the incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement when gradual external pressure was applied to the orbital tissues and eye. Methods Patients (n = 101) and healthy volunteers (n = 56) aged 20–75 years who underwent a non-invasive intracranial pressure measurement were included in this retrospective oculocardiac reflex analysis. Prespecified thresholds greater than a 10% or 20% decrease in the heart rate from baseline were used to determine the incidence of the oculocardiac reflex. Results None of the subjects had a greater than 20% decrease in heart rate from baseline. Four subjects had a greater than 10% decrease in heart rate from baseline, representing 0.9% of the total pressure steps. Three of these subjects were healthy volunteers, and one was a glaucoma patient. Conclusion The incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement procedure was very low and not associated with any clinically relevant effects.

Innovative Computerized Non-invasive Intracranial Pressure Measurement Technology and Its Clinical Validation

An innovative non-invasive absolute intracranial pressure (aICP) measurement method has been validated by multicenter comparative clinical studies. The method is based on two-depth transcranial Doppler technology and employs intracranial and extra cranial segments of the ophthalmic artery as a pressure sensor. The ophthalmic artery is used as a natural pair of scales which compares aICP with controlled pressure aPe which is externally applied to the orbit. In the case of scales balance, aICP=aPe. A two-depth transcranial Doppler device is used as a pressure balance indicator. The proposed method is the only non-invasive aICP measurement method which does not need patient-specific calibration.