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

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

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Relationship between intracranial pressure and visual field clusters in normal-tension glaucoma patients

Purpose: To assess relationship between intracranial pressure (ICP) and visual field (VF) clusters in normal-tension glaucoma (NTG) patients. Methods: 80 NTG patients [age 59.5(11.6) years] with minimal VF defects (according to Hodapp-Parrish-Anderson glaucoma grading scale) were included in the prospective study. During the study intraocular pressure (IOP), non-invasive ICP and perimetry were assessed. Non-invasive ICP was measured using two-depth Transcranial Doppler device (Vittamed UAB, Kaunas, Lithuania). VF tests were conducted using the Humphrey 24-2 Swedish interactive thresholding algorithm (SITA) perimeter. The VFs of each patient were divided into five clusters: nasal, temporal, peripheral, central and paracentral. The score for each cluster was the averaged pattern deviation scores of all tested points within the cluster. The level of significance p 0.05). NTG patients with deeper nasal VF defects had statistically significantly lower ICP 7.3 (2.1) mmHg, compared to NTG patients with other deeper VF clusters [temporal 9.3 (2.5) mmHg, p = 0.02; peripheral 9.2 (2.7) mmHg, p = 0.02; central 9.9 (2.0) mmHg, p = 0.01; paracentral 9.2 (2.0) mmHg, p = 0.02]. There were no statistically significant differences in IOP between NTG patients with different deeper VF clusters, p = 0.36. Conclusions: NTG patients with deeper nasal VF defects had lower ICP compared to NTG patients with other deeper VF clusters. ICP was positively correlated with nasal VF cluster defects. Further studies are needed to analyze the involvement of ICP in norm [...]

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 &lt; 0.001) and 14.2 ± 1.9 mmHg using timolol (p &lt; 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 &lt; 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 &lt; 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 &lt; 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

The Relationship between Intracranial Pressure and Visual Field Zones in Normal-Tension Glaucoma Patients

Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP’s relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management

Can the treatment of normal-pressure hydrocephalus induce normal-tension glaucoma? A narrative review of a current knowledge

Ventriculoperitoneal shunt placement is the most commonly used treatment of normal-pressure hydrocephalus (NPH). It has been hypothesized that normal-tension glaucoma (NTG) is caused by the treatment of NPH by using the shunt to reduce intracranial pressure (ICP). The aim of this study is to review the literature published regarding this hypothesis and to emphasize the need for neuro-ophthalmic follow-up for the concerned patients. The source literature was selected from the results of an online PubMed search, using the keywords “hydrocephalus glaucoma” and “normal-tension glaucoma shunt”. One prospective study on adults, one prospective study on children, two retrospective studies on adults and children, two case reports, three review papers including medical hypotheses, and one prospective study on monkeys were identified. Hypothesis about the association between the treatment of NPH using the shunt to reduce ICP and the development of NTG were supported in all reviewed papers. This suggests that a safe lower limit of ICP for neurological patients, especially shunt‑treated NPH patients, should be kept. Thus, we proposed to modify the paradigm of safe upper ICP threshold recommended in neurosurgery and neurology into the paradigm of safe ICP corridor applicable in neurology and ophthalmology, especially for shunt-treated hydrocephalic and glaucoma patients

The Effect of Diluted Penetration Enhancer in Nebulized Mist &lt;em&gt;versus&lt;/em&gt; Liquid Drop Preparation Forms on Retrobulbar Blood Flow in Healthy Human Subjects

The aim of this study was to compare the effects of nebulized mist and liquid drop applications on retrobulbar blood flow. A prospective, non-randomized clinical trial was used to collect data from 40 healthy human eyes. Color Doppler Imaging determined peak systolic (PSV) and end diastolic (EDV) blood flow velocities and resistance index (RI) in the ophthalmic artery after both applications. Measurements were taken at baseline and at 1 min post-treatment in both eyes with 5 min measurements in the treatment eye only. &lt;em&gt;p&lt;/em&gt; values ≤ 0.05 were considered statistically significant. Mist application to treatment eye produced an increase in 1 min and 5 min PSV and EDV (0.001 &lt; &lt;em&gt;p &lt;/em&gt;&lt; 0.03) and a decrease in 5 min RI (&lt;em&gt;p&lt;/em&gt;&lt;em&gt; &lt;/em&gt;= 0.01), with no significant changes in PSV, EDV or RI of control eye or in treatment eye 1 min RI (&lt;em&gt;p&lt;/em&gt; &gt; 0.05). Drop application to treatment eye produced an increase in PSV (&lt;em&gt;p&lt;/em&gt; &lt; 0.001) and EDV (&lt;em&gt;p&lt;/em&gt; = 0.01) at 1 min, with an increase in control eye 1 min PSV and EDV (&lt;em&gt;p&lt;/em&gt; = 0.03). There were no statistically significant changes in treatment eye PSV, EDV and RI after 5 min (&lt;em&gt;p&lt;/em&gt; &gt; 0.05). The use of nebulized mist may provide an effective alternative to liquid drop medication application