Trans-lamina Pressure Difference Research Articles

Is Glaucoma a Two-Pressure-Related Optic Neuropathy? A Systematic Review and Meta-Analysis.

To review the current literature related to the correlation between translaminar pressure difference (TLPD) and glaucoma. In this article, we conducted a literature review using MEDLINE via PubMed, Cochrane Eyes and Vision, and Google Scholar from 01/01/2010 to 31/12/2022. Search terms included "glaucoma", "intraocular pressure", "translaminar cribrosa pressure gradient/difference", "intracranial pressure", and "cerebrospinal fluid pressure". Of 471 results, 8 articles were selected for the meta-analysis. Our meta-analysis demonstrated significantly higher intraocular pressure, lower cerebrospinal fluid pressure (CSFp), and greater TLPD in high-tension and normal-tension glaucoma groups compared to healthy groups. The differences in CSFp and TLPD between glaucoma and healthy people detected in current studies suggests a potential relationship between TLPD and glaucoma.

“Dual‐pressure theory” in pathogenesis of glaucomatous optic neuropathy from the Beijing intracranial and intraocular pressure study

AbstractThe mechanical theory of glaucoma indicates that high intraocular pressure (IOP) leads to glaucomatous optic nerve damage. However, nearly half of primary open‐angle glaucoma patients with normal intraocular pressure also exhibit progression of what appears to be glaucomatous optic nerve damage. Our earlier prospective study identified for the first time that the relatively low intracranial pressure (ICP) is also an important risk factor for progressive glaucomatous injury of normal‐tension glaucoma. When considering the results of studies in nonhuman primates, clinical research, large‐scale natural‐population studies, and basic laboratory investigations, a new understanding of the pathophysiology of glaucoma, the “Dual‐Pressure Theory”, has been proposed. This theory states that “either high IOP or low ICP contributes to increasing the translaminar cribrosa pressure difference; it is the pressure difference rather than the IOP alone that results in the glaucomatous optic neuropathy”. Here, we provide a systematic introduction to Dual‐Pressure Theory relating to glaucoma, the form of a research map, an outline of basic laboratory investigations, the main methodology, and research updates.

The mechanical theory of glaucoma in terms of prelaminar, laminar, and postlaminar factors

Abstract The mechanical theory is one of the oldest concepts regarding the development of glaucomatous neural degeneration. However, after a prolonged period of relative monopoly among the various theories explaining the pathogenesis of glaucoma, this concept gradually faded away from discourse. Several developments in the recent past have rekindled interest in the mechanical theory of glaucoma. Now we know a lot more about the biomechanics of the eye, prelaminar changes, mechanisms of retinal ganglion cell death, biomechanical features of the optic nerve head and sclera, extracellular matrix composition and its role, astrocytic changes, axoplasmic flow, and postlaminar factors such as translaminar pressure difference. These factors and others can be categorized into prelaminar, laminar, and postlaminar elements. The objective of this review was to present a concise analysis of these recent developments. The literature search for this narrative review was performed through databases, such as PubMed, Google Scholar, and Clinical Key.

The Relationship between Intraocular Pressure and Estimated Intracranial Pressure in Patients with Normal Tension Glaucoma

This study aims to determine the relationship between intracranial pressure (ICP) and intraocular pressure (IOP) in patients with normal-tension glaucoma (NTG) who were already on anti-glaucoma treatment using an estimated ICP (estICP) and translaminar pressure difference (estTPD) formula. A cross-sectional comparative study consisted of 66 subjects (66 eyes) who were divided into NTG (n=33) and normal (n=33) group was conducted from 1st November 2017 until 31st May 2020 at a tertiary hospital in Malaysia. After obtaining consent from subjects, ocular and systemic data including IOP, visual field testing, axial length, central corneal thickness (CCT), peripapillary and macular retinal nerve fibre layer evaluation as well as blood pressure (BP) and body mass index (BMI) were collected. The estICP (mm Hg) was calculated as 0.44 x BMI (kg/m2) + 0.16 x diastolic blood pressure (mmHg) – 0.18 x age (years) – 1.91. The estTPD was derived from this calculated value, where estTPD (mm Hg) = IOP – estICP. Analysis showed there was no significant difference in estimated ICP between NTG and normal subjects [mean difference (95% CI): 0.37 (-1.39, 2.12), p=0.679]. The difference in estTPD between NTG and normal subjects were found to be statistically insignificant too [mean difference (95% CI): -1.24 (-2.95, 0.47), p=0.149]. The variables significant in multivariate model included best corrected visual acuity (p=0.028), retinal nerve fiber layer (RNFL) (p=0.003), average macular (p=0.002) and estTPD (p=0.008). The EstTPD was found to be protective towards NTG, which the unit increased in estTPD will decreased the odds of having NTG by 26.5% [Adj. OR (95% CI): 0.735 (0.586, 0.922), p=0.008]. In conclusion, ICP was correlated in increased in IOP. A higher TPD may be associated with a lower chance of developing NTG.

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 < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (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 < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management.

Reference values for trans-laminar cribrosa pressure difference and its association with systemic biometric factors.

To provide reference values of trans-laminar cribrosa pressure difference (TLCPD) and reveal the association of TLCPD with systemic biometric factors. In this cross-sectional study, 526 quasi-healthy subjects (including 776 eyes) who required lumbar puncture for medical reasons were selected from 4915 neurology inpatients from 2019 to 2022. Patients with any diseases affecting intraocular pressure (IOP) or intracranial pressure (ICP) were excluded. The ICPs of all subjects were obtained by lumbar puncture in the left lateral decubitus position. IOP was measured in the seated position by a handheld iCare tonometer prior to lumbar puncture. TLCPD was calculated by subtracting ICP from IOP. Systemic biometric factors were assessed within 1 h prior to TLCPD measurement. The TLCPD (mean ± standard deviation) was 4.4 ± 3.6 mmHg, and the 95% reference interval (defined as the 2.5th-97.5th percentiles) of TLCPD was -2.27 to 11.94 mmHg. The 95% reference intervals for IOP and ICP were 10-21 and 6.25-15.44 mmHg, respectively. IOP was correlated with ICP (r = 0.126, p < 0.001). TLCPD was significantly negatively correlated with body mass index (r = -0.086, p = 0.049), whereas it was not associated with age, gender, height, weight, blood pressure, pulse, or waist and hip circumference. This study provides reference values of TLCPD and establishes clinically applicable reference intervals for normal TLCPD. Based on association analysis, TLCPD is higher in people with lower BMI.

Correlation between systemic and ocular pressure‐related factors with anatomic parameters in patients with diabetes

AbstractPurpose: Previous studies suggested pressure‐related factors to be involved in the pathogenesis of diabetic retinopathy. In this study, we aim to correlate systemic and ocular pressure‐related factors with anatomic parameters in control subjects and in patients with and without diabetic retinopathy (DR).Methods: We included 31 control subjects, 32 patients with diabetes mellitus (DM) without DR and 37 patients with DR. The following parameters were evaluated: best corrected visual acuity, intraocular pressure (IOP) (mmHg), body mass index (BMI), mean blood pressure (MBP) (mmHg), HbA1c (%), estimated cerebrospinal fluid pressure (CSFP) (mmHg), trans‐laminar pressure difference (TLPD) (mmHg), ocular perfusion pressure (OPP) (mmHg), axial length (AL) (mm), spherical equivalence (SE) (D) and OCT parameters (optic disk area (mm2), optic cup/disk (C/D) ratio, retinal nerve fibre layer thickness (NFLT) (μm), foveal thickness (μm), average macular thickness (AMT) (μm)). We used either Pearson's or Spearman' coefficient of correlation depending on data distribution. Results were considered statistically significant with p value &lt; 0.05.Results: Presence of DM had a significant low association with CSFP (Rs = 0.28, p = 0.006), BMI (Rs = 0.24, p = 0.019) and with AL (Rs = −0.27, p = 0.011). CSFP had a significant low association with SE (R = −0.38, p = 0.002) and with NFLT (R = 0.27, p = 0.046) only in patients with DM. TLPD had a significant low association with optic C/D ratio in control subjects (R = 0.45, p = 0.014) and a significant low association with NFLT in patients with DM (R = −0.35, p = 0.007). In patients with DM, IOP had a significant low association with MBP (R = 0.26, p = 0.032), BMI (R = 0.29, p = 0.017) and CSFP (R = 0.29, p = 0.017), whereas in control subjects IOP had a significant moderate association with optic C/D ratio (R = 0.57, p = 0.001) and a significant low association with AMT (R = −0.43, p = 0.016).Conclusions: Systemic and ocular pressure related factors have different correlation patterns in patients with DM than in control subjects.

Lamina cribrosa curvature index: A reliable parameter to screen diabetic patients for glaucoma.

To compare the translaminar pressure difference (TLPD), anterior lamina cribrosa surface depth (ALCSD), lamina cribrosa thickness (LCT), lamina cribrosa curvature index (LCCI) and peripapillary vascular density (pVD) in diabetic and healthy subjects. Two hundred and eighty eyes of 140 patients (79 patients with diabetes mellitus (DM) without diabetic retinopathy (DR) and 61 healthy subjects) were enrolled in this study. Full ophthalmological examination, as well as optical coherence tomography (OCT) and OCT angiography (OCT-A) images, were analyzed. The ALCSD, LCT, LCCI were measured by enhanced depth imaging (EDI) OCT and the pVD by OCT-A. The TLPD values and relationships between TLPD and lamina cribrosa features and pVD were investigated in all subjects. The ALCSD and LCT were significantly shallower and thinner in diabetic patients when compared to healthy subjects (p <0.001). There was no significant difference in the LCCI in diabetics 13.717 (5.74-33.91) vs healthy subjects 13.118 (5.53-27.05) (p = 0.181). OCT-A revealed that the pVD in the diabetic group was significantly lower than in the non-diabetic group (p <0.001). TLPD was significantly lower in diabetic patients compared to healthy controls. There are early changes in pVD and peripapillary vessel morphology in patients with DM. ALCSD and LCT were shallower and thinner in diabetic patients whereas the LCCI did not differ significantly. LCCI may be more valuable in assessing the lamina cribrosa (LC) of diabetic patients. The TLPD was found to be lower in diabetic patients compared to normal controls.

Approach to glaucoma diagnosis and prediction based on multiparameter neural network.

To investigate the effect of comprehensive factor analysis on the relationship between glaucoma assessment and combined parameters including trans-laminar cribrosa pressure difference (TLCPD) and fractional pressure reserve (FPR). The clinical data of 1029 patients with 15 indicators from the medical records of Beijing Tongren Hospital and 600 cases with 1322 indicators from Beijing Eye Research were collected. The doc2vec method was used to vectorize. The multivariate imputation by chained equations (MICE) method was used to interpolate. The original data combined with TLCPD, combined with FPR, and not combined parameters were respectively applied to train the neural network based on VGG16 and autoencoder to predict glaucoma and to evaluate the effect of combined parameters. The accuracy rates used to classify the glaucoma of the two sets reach over 0.90, and the precision rates reach 0.70 and 0.80 respectively. After using TLCPD and FPR for the autoencoder method, the accuracy rates are both close to 1.0, and the precision rates are 0.90 and 0.70 respectively. Using the combined parameters of FPR and TLCPD can effectively improve the diagnosis and prediction of glaucoma. Compared with TLCPD, FPR is more suitable for improving the effect of neural network for glaucoma classification.

Mathematical modelling of the CSF system: effects of microstructures and posture on optic nerve subarachnoid space dynamics

BackgroundThe pressure difference between the eye and brain in upright postures may be affected by compartmentalization of the optic nerve subarachnoid space (ONSAS). Both pressure and deformation will depend on the microstructures of the ONSAS, and most likely also on ocular glymphatic clearance. Studying these factors could yield important knowledge regarding the translaminar pressure difference, which is suspected to play a role in normal-tension glaucoma.MethodsA compartment model coupling the ONSAS with the craniospinal CSF system was used to investigate the effects of microstructures on the pressure transfer through the ONSAS during a posture change from supine to upright body postures. ONSAS distensibility was based on MRI measurements. We also included ocular glymphatic flow to investigate how local pressure gradients alter this flow with changes in posture.ResultsA compartmentalization of the ONSAS occurred in the upright posture, with ONSAS porosity (degree of microstructural content) affecting the ONSAS pressure (varying the supine/baseline porosity from 1.0 to 0.75 yielded pressures between − 5.3 and − 2 mmHg). Restricting the minimum computed porosity (occurring in upright postures) to 0.3 prevented compartmentalization, and the ONSAS pressure could equilibrate with subarachnoid space pressure (− 6.5 mmHg) in le 1 h. The ocular glymphatics analysis predicted that substantial intraocular-CSF flows could occur without substantial changes in the ONSAS pressure. The flow entering the ONSAS in supine position (both from the intraocular system and from the cranial subarachnoid space) exited the ONSAS through the optic nerve sheath, while in upright postures the flow through the ONSAS was redirected towards the cranial subarachnoid space.ConclusionsMicrostructures affect pressure transmission along the ONSAS, potentially contributing to ONSAS compartmentalization in upright postures. Different pathways for ocular glymphatic flow were predicted for different postures.

Estimated intracranial pressure in glaucoma patients and its correlation with disease severity

Purpose To compare the intracranial pressure (ICP) and the translaminar pressure difference (TLPD) between primary open-angle glaucoma (POAG) patients and non-glaucoma subjects and to assess the correlation between the ICP (and TLPD) and glaucoma severity. Methods This was a cross-sectional study. Patients with POAG and age-matched controls were included. ICP was calculated using proxy algorithm to attain indirect surrogate parameter values. Differences were compared between groups. The correlation between ICP (and TLPD) and both structural and functional variables was evaluated using linear and non-linear regression analysis and estimated with Pearson’s correlation coefficient. Results Fifty patients with POAG and 25 normal controls were included. The mean estimated ICP was lower in POAG (10.9 ± 3.2 mmHg) as compared to controls (15.0 ± 3.7 mmHg, p < 0.001). The TLPD was higher in POAG (2.6 ± 4.1 mmHg) when compared to non-glaucoma (−0.3 ± 3.6 mmHg, p = 0.002). ICP displayed a negative correlation with cup-to-disk ratio (r = −0.566; 95% CI, −0.699 to −0.369, p’0.000) and a positive correlation with retinal nerve fiber layer thickness (r = 0.441; 95% CI, 0.230 to 0.612; p’0.000). There was a positive correlation between ICP and mean deviation (r = 0.280; 95% CI, 0.05 to 0.482, p = 0.017). Conclusion Glaucoma patients presented lower ICP values; lower ICP values were associated with more advanced disease. These observations strengthen the role of ICP as a potential player on the glaucoma pathogeny.

Dual Orexin Receptor Antagonist Attenuates Increases in IOP, ICP, and Translaminar Pressure Difference After Stimulation of the Hypothalamus in Rats.

PurposeIntraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures.MethodsSprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI).ResultsAdministration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8–40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R2 = 0.18, P = 0.04). The ICP responses during the peak response period (4–16 minutes) versus DORA dose were also linear (R2 = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015).ConclusionsDORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.

Cerebrospinal fluid and ophthalmic disease.

The purpose of this review is to discuss the contemporary body of literature examining the relationship between cerebrospinal fluid (CSF) and ophthalmic disease. This review focuses on diseases that have a pathogenesis related to the translaminar pressure difference, defined as the pressure difference between the orbital subarachnoid space (OSAS) and the intraocular pressure. The diseases discussed include glaucoma, idiopathic intracranial hypertension, and spaceflight associated neuro-ocular syndrome. The relationship between cerebrospinal and ophthalmic disease has been investigated for over 100 years. Recent research provides insight into the mechanisms that dictate CSF circulation in the OSAS and how alterations in these mechanism lead to disease. This review discusses these recent findings and their relationship to major ophthalmic diseases. The recent findings provide insight into diseases that have pathogenic mechanisms that are not fully understood. This information will help physicians gain a clearer understanding of the relationship between CSF and ophthalmic disease and guide future research.

Translaminar Pressure Difference and Ocular Perfusion Pressure in Glaucomatous Eyes with Different Optic Disc Sizes.

Purpose Intracranial pressure (ICP) and ocular perfusion pressure (OPP) are both involved with the pathogenesis of glaucoma. The orbital ICP determines a retrolaminar counter pressure that is antagonistic to the intraocular pressure (IOP). The purpose of this study is to evaluate whether the translaminar pressure difference (TLPD) and the OPP varies in glaucoma patients with different optic disc sizes.Methods In this university hospital-based, observational, cross-sectional clinical study, all patients underwent an ophthalmic evaluation. Blood pressure, height, weight, and the results of retinal nerve fiber layer examination with optical coherence tomography examination were recorded. TLPD and OPP were calculated for each patient using proxy algorithms to attain indirect surrogate parameter values. Patients' eyes were stratified into three quantiles according to optic disc sizes and the differences compared. Data from both eyes were used after using the appropriate correction for inter-eye dependency.ResultsThe sample consisted of 140 eyes of 73 patients with primary open-angle glaucoma and suspects. Patients with large disc size presented with higher TLPD as compared to those with average and small-sized discs (2.4 4.5, 2.8 3.8, and 3.7 4.7 mmHg for first, second, and third tertile, respectively (P 0.000). OPP did not vary according to the optic disc size.ConclusionGlaucoma patients with larger optic discs have higher TLPD. The pathological significance of this finding warrants further investigation.

Optic Nerve Head Morphological Changes Over 12 Hours in Seated and Head-Down Tilt Postures.

PurposeThe purpose of this study was to determine changes in optic nerve head (ONH) morphology in seated and 6° head-down tilt (HDT) postures over a 12-hour period.MethodsThirty eyes of 30 healthy human subjects (15 females) were included. Composite radial and circular optical coherence tomography (OCT) scans centered on the ONH, intraocular pressure (IOP), and optic nerve sheath diameter (ONSD) were acquired every two hours from 7 a.m. to 7 p.m. for both seated (n = 30) and HDT (n = 10) sessions. Global minimum rim width (BMO-MRW), total retinal thickness (TRT), retinal nerve fiber layer thickness (RNFLT), and Bruch's membrane opening (BMO) height were quantified.ResultsBMO-MRW decreased an average of 9.55 ± 8.03 µm (P < 0.01) over 12 hours in a seated position (range, −26.64 to +3.36 µm), and thinning was greater in females (−13.56 vs. −5.55 µm, P = 0.004). Modest decreases in TRT from the BMO to 500 µm (P < 0.04) and RNFLT for the 2.7, 3.5, and 4.2 mm circular scans (P < 0.02) were also observed. BMO-MRW thinning was not related to changes in IOP or ONSD (P = 0.34). In HDT, IOP and ONSD increased, BMO height moved anteriorly, and BMO-MRW thinning did not occur (P > 0.1).ConclusionsThe neuroretinal rim thins throughout the day in healthy individuals, and this change cannot be explained by changes in IOP or ONSD during the same time period. A HDT posture blunts the neuroretinal rim thinning observed in a seated position, suggesting a role of the translaminar pressure difference.

Three-Decade Evaluation of Cerebrospinal Fluid Pressure in Open-Angle Glaucoma at a Tertiary Care Center.

Elevated intraocular pressure (IOP) is the most prevalent risk factor for primary open-angle glaucoma. However, IOP alone does not fully describe a mechanical basis for disease in patients with normal tension glaucoma or primary open-angle glaucoma. The translaminar pressure difference (TLPD) theory proposes that the pressure gradient generated by the difference of IOP and cerebrospinal fluid pressure (CSFp) acting at the level of the optic nerve can lead to cupping and glaucoma when IOP is higher than normal and/or CSFp is lower than normal. The study results to date have generally supported the TLPD theory; however, varying methods, populations, and sample sizes make it difficult to compare results. To further assess whether there is an association between low CSFp and open-angle glaucoma, 30 years of clinical data that assess 96,543 lumbar punctures were analyzed. Patients with open-angle glaucoma showed a significantly lower CSFp than randomly selected normal control patients (9.9 ± 3 mm·Hg (n = 86) versus 12.1 ± 3.6 mm·Hg (n = 114), p < 0.001) following adjustment for age and sex. This retrospective study provides strong evidence for an association between open-angle glaucoma and low CSFp.

Correlation between ocular perfusion pressure and translaminar pressure difference in glaucoma: Evidence for a three-pressure disease?

To evaluate the correlation between the translaminar pressure difference (TLPD) and the ocular perfusion pressure (OPP) in glaucoma patients. This was a cross-sectional study. Primary open-angle glaucoma (POAG) patients and normal individuals underwent an ophthalmic evaluation as well as blood pressure, height, and weight measurements. Intracranial pressure (ICP) and OPP were calculated using proxy mathematical formulas to attain indirect surrogate parameter values. The TLPD was calculated as intraocular pressure minus ICP. The association between the variables was evaluated using linear and non-linear regression analysis and the correlation estimated with Pearson's correlation coefficient. The sample included 50 POAG patients and 25 normal subjects. The mean OPP for all 75 subjects (75 eyes) was 53.1 ± 9.3 mmHg and the calculated TLPG was 3.1 ± 4.2 mmHg. TLPG showed a negative correlation with OPP (r = -0.580; 95% CI, -0.690 to -0.366; p < 0.0001). The negative correlation between OPP and TLPD observed in the study substantiates the concept of glaucoma as a three-pressure disease.

Modeling a potential SANS countermeasure by experimental manipulation of the translaminar pressure difference in mice

The spaceflight-associated neuro-ocular syndrome (SANS), which may present after prolonged exposure to microgravity, is thought to occur due to elevated intracranial pressure (ICP). Intracranial pressure interacts with intraocular pressure (IOP) to define the translaminar pressure difference (TLPD; IOP−ICP). We combined inducible models of ICP and IOP elevation in mice to interrogate the relationships among ICP, IOP, and TLPD, and to determine if IOP elevation could mitigate the phenotypes typically caused by elevated ICP and thereby serve as a countermeasure for SANS. Ten C57BL6J mice of both genders underwent experimental elevation of ICP via infusion of artificial cerebrospinal fluid into the subarachnoid space. One eye also underwent experimental elevation of IOP using the bead injection model. Intraocular pressure and ICP were monitored for 2 weeks. Optokinetic-based contrast sensitivity was measured at baseline and after 2 weeks, and post-mortem studies of optic nerve and retina anatomy were performed. Photopic contrast sensitivity was reduced more in IOP elevated than control eyes. Scotopic contrast sensitivity was reduced similarly in IOP elevated and control eyes. However, the pattern of scotopic vision loss was not uniform in IOP elevated eyes; there was minimal loss in eyes that most closely approximated the normal TLPD. Optic nerve axon loss, increased optic nerve disorganization, and retinal ganglion cell loss all occurred similarly between IOP elevated and control eyes. Elevation of IOP in eyes with elevated ICP may counterbalance some effects on vision loss but exacerbate others, suggesting complex relationships among IOP, ICP, and TLPD.

Modern view on normal-tension glaucoma

Glaucoma is a chronic progressive optic neuropathy that causes irreversible loss of visual functions. From the clinical point of view, normal-tension glaucoma (NTG) is regarded in Russian taxonomy as a clinical form of standard primary open-angle glaucoma in which the IOP values stay within the normal range, but the typical progressive visual functions loss is still present. The results of the latest studies put in question the traditional views of NTG pathophysiology that are based solely on intraocular pressure values. New capabilities of diagnostic visualization of central nervous system have considerably broadened our knowledge of the NTG development mechanisms. This article reviews current understanding of the pathogenesis of NTG and its connection to vascular and immune factors, translaminar pressure difference etc. The review also considers the relationship between glaucoma and cognitive defects associated with Alzheimer's and Parkinson's diseases.Глаукома представляет собой хроническую прогрессирующую оптическую нейропатию, характеризующуюся необратимой потерей зрительных функций. С клинической точки зрения в российской классификации нормотензивная глаукома рассматривается как клиническая разновидность обычной первичной открытоугольной (ПОУГ) глаукомы, при которой внутриглазное давление остается внутри условно нормального диапазона, но с прогрессией типичных глаукомных изменений зрительных функций. Результаты последних исследований ставят под сомнение традиционную патофизиологическую картину нормотензивной глаукомы, базирующуюся исключительно на показателях офтальмотонуса. Новые возможности диагностической визуализации центральной нервной системы значительно расширили наши знания о механизмах развития глаукомы нормального давления. В обзоре обсуждаются современные представления о патогенезе нормотензивной глаукомы, связанные с такими факторами, как сосудистые, иммунные, разница трансламинарного давления и т.д. Также рассмотрена взаимосвязь между глаукомой и когнитивными нарушениями, возникающими при болезнях Альцгеймера и Паркинсона.

Selective Early Glial Reactivity in the Visual Pathway Precedes Axonal Loss, Following Short-Term Cerebrospinal Fluid Pressure Reduction.

To examine the early glial reactivity and neuron damage in response to short-term cerebrospinal fluid pressure (CSFp) reduction, as compared with intraocular pressure (IOP) elevation. The experiment included 54 male Sprague-Dawley rats with elevated translaminar cribrosa pressure difference (TLPD), defined as IOP minus CSFp. These rats underwent either continuous CSF drainage for 6 hours (n = 18), or unilateral IOP elevation to 40 mm Hg for 6 hours (n = 18). For control, 18 normal rats were anesthetized for 6 hours. Orthograde axonal transport was examined by intravitreal injection of 3% rhodamine-β-isothiocyanate. We also used transmission electron microscopy to display the ultrastructural features of retinal ganglion cell axons in the optic nerve head. Early glial reactivity in the retina, lateral geniculate nucleus (LGN), and superior colliculus (SC) was detected by immunostaining and Western blot for the glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). We also observed the glial reactivity in the inferior colliculus and hippocampus to rule out possible influences of CSF dynamics and composition. Anterograde staining with 3% rhodamine-β-isothiocyanate revealed decreased fluorescence intensity of the SC and LGN projected from both lower CSFp and higher IOP eyes. Transmission electron microscopy showed loss of axons from the optic nerve head in the high-IOP group, but not in the low-CSFp group. Compared with the anesthesia control group, GFAP expression was significantly increased in the retina, LGN, and SC, whereas GS expression was only increased in the retina following CSFp reduction. However, their expressions were not significantly elevated in the inferior colliculus and hippocampus. In the high-IOP group, expressions of GFAP and GS were significantly increased in the retina, LGN, and SC. Visual system neurons may be much more sensitive than other nervous tissues. Following short-term CSFp reduction, early glial reactivity may precede axonal loss. Changes of translaminar cribrosa pressure difference in both experimental low-CSFp and high-IOP groups induce selective early glial reactivity. The neuron damage from abnormally low CSFp may be pathogenetically similar to high IOP.