Lina Siaudvytyte

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.

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.

Ophthalmic Drug Delivery in Glaucoma—A Review

Glaucoma is a progressive optic neuropathy and medical therapy is the initial option for the treatment of this potentially blinding condition. Topical instillation of eye drops from the bottle is the most common glaucoma drug delivery form. Due to limited permeability of anterior ocular surface, natural clearance and drainage, eye drops contain large amounts of inactive ingredients. Effective penetration enhancers are known as irritants causing ocular discomfort. Although drug efficacy is determined by active ingredients, inactive agents can affect tolerance and can result in conjunctival irritation and hyperemia and influence patients’ adherence and quality of life.

Neuroretinal rim area and ocular haemodynamic parameters in patients with normal-tension glaucoma with differing intracranial pressures

Purpose To assess the differences in the neuroretinal rim area (NRA) and ocular haemodynamic parameters in patients with normal-tension glaucoma (NTG) with differing intracranial pressure (ICP) values. Methods 40 patients (11 males) with NTG (age 61.1 (11.5)) were included in the prospective study. Intraocular pressure (IOP), non-invasive ICP, retrobulbar blood flow (RBF) and confocal laser scanning tomography for optic nerve disc (OND) structural parameters were assessed. Non-invasive ICP was measured using a novel two-depth Transcranial Doppler device. RBF was measured using colour Doppler imaging in the ophthalmic artery (OA). The patients were divided into two groups, ICP ≥ and <8.3 mm Hg, based on the statistical median of ICP. p Values <0.05 were considered statistically significant. Results Patients with NTG had mean ICP 8.8 (2.5) mm Hg, IOP 13.6 (2.1) mm Hg, OND size 2.3 (0.6) mm2, NRA 1.2 (0.4) mm2. Lower ICP was correlated with decreased NRA (r=0.51, p=0.001). Patients with NTG having lower ICP (N=20) had significantly lower NRA 1.0 (0.3) mm2, than patients with NTG having higher ICP (N=20) 1.3 (0.3) mm2, p=0.002, although there were no significant differences in OND size (accordingly, 2.2 (0.5) and 2.3 (0.6) mm2, p=0.55) and IOP (accordingly, 13.5 (2.4) and 13.7 (1.8) mm Hg, p=0.58). Patients with NTG having lower ICP had significantly lower OA blood flow velocities (peak systolic volume (PSV) 28.7 (8.0), end-diastolic volume (EDV) 6.9 (3.0) cm/s), compared with patients with NTG having higher ICP (PSV 35.5 (10.2), EDV 9.4 (4.1) cm/s), p<0.04. Conclusions Patients with NTG having lower ICP have decreased neuroretinal rim area and OA blood flow parameters compared with patients having higher ICP. Further longitudinal studies are needed to analyse the involvement of ICP in NTG management.

Effect of Trabeculectomy on Ocular Hemodynamic Parameters in Pseudoexfoliative and Primary Open-angle Glaucoma Patients.

Purpose:To evaluate the effects of trabeculectomy on ocular hemodynamic parameters in pseudoexfoliative glaucoma (PXG) and primary open-angle glaucoma (POAG) patients and to analyze serum antiphospholipid antibody levels (APLAs) in PXG. Methods:Thirty open-angle glaucoma patients were included in the prospective study. Intraocular pressure (IOP), ocular perfusion pressure (OPP), blood pressure, and pulsatile ocular blood flow (POBF) were measured. Retrobulbar blood flow (RBF) was measured using the color Doppler imaging. Venous blood samples were obtained from PXG patients; APLAs IgG levels were assessed. The level of significance was P<0.05. Results:IOP decreased significantly in both groups after trabeculectomy [from 30.1 (7.2) to 15.0 (5.1) in PXG; from 29.1 (7.7) to 13.1 (5.5) in POAG, P<0.05]. OPP increased from 38.9 (10.3) to 55.5 (8.6) in PXG and from 40.9 (11.0) to 56.7 (8.9) in POAG group, P<0.05. Both groups showed significant increase in CRA PSV [from 8.75 (2.27) to 9.79 (2.31) in PXG and from 8.55 (2.59) to 10.11 (2.64) in POAG, P<0.05]. Both groups showed an increase in POBF [from 13.09 (3.41) to 18.81 (5.70) in PXG and from 11.89 (5.79) to 19.29 (9.02) in POAG, P<0.05). Patients with normal APLAs levels showed significant decrease in IOP [from 30.7 (8.1) to 15.2 (5.9)] and increase in POBF [from 13.24 (3.69) to 19.94 (5.03)], CRA PSV [from 8.78 (2.39) to 9.46 (2.17)], and tSPCA PSV [from 7.61 (2.15) to 8.35 (1.98)], P<0.05. Conclusions:Trabeculectomy resulted in a significant decrease in IOP and increase in ocular blood flow. Effects of trabeculectomy in PXG patients were significantly less compared with POAG. Patients with normal APLA levels had a significant increase in ocular hemodynamic parameters compared with patients with higher APLAs levels.

Comparison of Intraocular Pressure, Blood Pressure, Ocular Perfusion Pressure and Blood Flow Fluctuations During Dorzolamide Versus Timolol Add-On Therapy in Prostaglandin Analogue Treated Glaucoma Subjects

Objective: To compare the effects of dorzolamide and timolol add-on therapy in open-angle glaucoma (OAG) patients previously treated with prostaglandin analogue (Pg), by evaluating fluctuations in the intraocular (IOP), blood (BP), ocular perfusion pressures (OPP) and retrobulbar blood flow (RBF) parameters. Methods: 35 OAG patients (35 eyes), 31 women (88.6%) age 63.3 (8.9) years were evaluated in a 3 month randomized, cross-over, single-masked study. During the experiments BP, heart rate, IOP and OPP were assessed 4 times per day (8–12–16–20 h). RBF was measured twice per day (8–20 h) using Color Doppler imaging in the ophthalmic (OA), central retinal (CRA), nasal (nSPCA) and temporal (tSPCA) posterior ciliary arteries. In each vessel, peak systolic velocity (PSV) and end-diastolic velocity (EDV) were assessed and vascular resistance (RI) calculated. Results: Both add-on therapies lowered IOP in a statistically significant manner from 15.7 ± 2.4 mmHg at latanoprost baseline to 14.9 ± 2.2 mmHg using dorzolamide (p < 0.001) and 14.2 ± 1.9 mmHg using timolol (p < 0.001). The IOP lowering effect was statistically significant at 20 h, favoring timolol as compared to dorzolamide (1.4 ± 2.4 vs. 0.2 ± 2.1 mmHg), (p < 0.05). Dorzolamide add-on therapy showed smaller IOP (2.0 ± 1.4), SPP (13.3 ± 7.9), systolic BP (13.5 ± 8.7) and diastolic BP (8.4 ± 5.4) fluctuations as compared to both latanoprost baseline or timolol add-on therapies. Higher difference between morning and evening BP was correlated to decreased evening CRA EDV in the timolol group (c = −0.41; p = 0.01). With increased MAP in the morning or evening hours, we found increased evening OA RI in timolol add-on group (c = 0.400, p = 0.02; c = 0.513, p = 0.002 accordingly). Higher MAP fluctuations were related to impaired RBF parameters during evening hours-decreased CRA EDV (c = −0.408; p = 0.01), increased CRA RI (c = 0.576; p < 0.001) and tSPCA RI (c = 0.356; p = 0.04) in the dorzolamide group and increased nSPCA RI (c = 0.351; p = 0.04) in the timolol add-on group. OPP fluctuations correlated with increased nSPCA RI (c = 0.453; p = 0.006) in the timolol group. OPP fluctuations were not related to IOP fluctuations in both add-on therapies (p < 0.05). Conclusions: Both dorzolamide and timolol add-on therapies lowered IOP in a statistically significant fashion dorzolamide add-on therapy showed lower fluctuations in IOP, SPP and BP. Higher variability of daytime OPP led to impaired RBF parameters in the evening.

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.

Cognitive functions and normal tension glaucoma

Purpose: Only a few studies have analyzed the potential link between glaucoma and cognitive function impairment. They have found controversial results. This study aims to perform quick cognitive function assessment with clock drawing test (CDT) using two different scoring systems and compare between normal tension glaucoma (NTG) and cataract patients. Methods: Totally, 30 NTG and 30 patients with cataracts were included in a prospective, pilot study. The predrawn circle was given, and patients were asked to draw the clock showing a time of 11:10. The test was evaluated using two methods – Freund method using a 7-point scoring scale (optimal cutoff ≤4) and Rakusa using a 4-point scoring scale (optimal cutoff ≤3). The level of significance was set at P < 0.05. Results: CDT result was significantly better in cataract group than in NTG group: 3.5 (2) versus 2 (2) by Freund, (P = 0.003) and 6.5 (1) versus 4.5 (2.75) by Rakusa, respectively (P = 0.004). Sixty percent (n = 18) of NTG group and 10% (n = 3) of cataract group patients completed the CDT in the specific picture manner (the short hand on 11 and the long hand between 11 and 12), (P = 0.001). Conclusions: Lower CDT results were seen in NTG patients according to two different scoring systems. NTG patients showed a specific manner of drawing. Further prospective studies are needed to investigate the CDT reliability as fast screening test of cognitive function impairment in glaucoma patients.