High Trans-lamina Cribrosa Pressure Difference Research Articles

Latest Developments in Normal-Pressure Glaucoma: Diagnosis, Epidemiology, Genetics, Etiology, Causes and Mechanisms to Management.

Normal-pressure glaucoma (NPG) is part of the spectrum of the open-angle glaucomas and morphologically characterized, as any glaucoma, by a loss of neuroretinal rim parallel to an enlargement and deepening of the optic cup, and development or enlargement of parapapillary beta zone. These morphological characteristics, in addition to the therapeutic benefit of lowering the intraocular pressure (IOP), make NPG differ from vascular-induced optic neuropathy. Based on the anatomy of the optic nerve as a cerebral fascicle, the physiological counter-pressure against the IOP is the orbital cerebrospinal fluid pressure (CSFP), with both pressures forming the trans-lamina cribrosa pressure difference (TLCPD). In contrast to the IOP, the TLCPD is the true pressure exerting force on the optic nerve fibers when passing through the lamina cribrosa. As a theoretical notion, an abnormally high TLCPD due to a low CSFP, in association with a low arterial blood pressure, could therefore be involved in the pathogenesis of NPG. It fits with the finding that the reduction of the IOP (and thus indirectly of the TLCPD) is (the only proven) procedure for NPG therapy. This review additionally highlights the genetic background, diagnostic methods, and therapeutic modalities of NPG.

Noninvasive evaluation of cerebrospinal fluid pressure in ocular hypertension: a preliminary study

To compare the orbital cerebral spinal fluid pressure (CSFP) and trans-lamina cribrosa pressure difference (TLCPD) determined noninvasively in ocular hypertensive (OH) subjects and controls. Cross-sectional observational study. Magnetic resonance imaging was used to measure orbital subarachnoid space width (OSASW). The CSFP (mmHg) was estimated from a published formula as 17.54×MRI derived OSASW at 15mm behind the globe+0.47×body mass index+0.13×mean arterial blood pressure -21.52. Estimated TLCPD was calculated as IOP- CSFP. The orbital subarachnoid space width was significantly wider (p=0.01) in the OH group than in the control group at all three measurement locations. The MRI derived CSFP value in OH (14.9±2.9mmHg) was significantly higher than in the normal group (12.0±2.8mmHg; p<0.01). The estimated TLCPD value in OH (9.0±4.2mmHg) was significantly higher than in controls (3.6±3.0mmHg; p<0.01). The wider OSASW and higher estimated CSFP in OH subjects suggest a higher orbital CSFP. Despite a higher orbital CSFP that could be protective, the higher TLCPD in OH may play a significant role in the risk of developing glaucoma.

Association of intraocular pressure-related factors and retinal vessel diameter with optic disc rim area in subjects with and without primary open angle glaucoma.

The data may support the notion that the intra-ocular pressure (IOP)-related factors and vascular factors were implicated concurrently in glaucomatous optic nerve damage. To study the association of intraocular pressure (IOP)-related factors, IOP, trans-lamina cribrosa pressure difference (TLCPD), cerebrospinal fluid pressure (CSFP) and retinal vessel diameters (RVD), central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) with neuro-retinal rim area (RA). A population-based, cross-sectional study. A total of 6830 people aged 30 years and over. All participants underwent a comprehensive eye examination, fundus photograph-based measurements of RVD and Heidelberg retinal tomogram (HRT) measurement of optic disc. RA, CRAE, CRVE, IOP, body mass index (BMI), CSFP and TLCPD. Primary open-angle glaucoma (POAG) was diagnosed using two separate methods: 67 from expert consensus, and 125 from the International Society of Geographical and Epidemiologic Ophthalmology (ISGEO) classification. After excluding of those with high myopia or without gradable HRT images, 4194 non-glaucoma and 40 POAG were analysed for determinants of RA. On multivariable analysis determinants of reduced RA were POAG (P < 0.001), higher IOP (P = 0.03), higher refractive error (P < 0.01), longer axial length (P = 0.01), CRVE (P < 0.001), lower BMI (P = 0.015), older age (P < 0.001) smaller disc area (P < 0.001) and higher TLCPD (P = 0.03). When age and/or BMI were omitted from the model, reduced RA was also associated with lower CSFP (P < 0.001). Reduced RA is associated with narrow CRVE and higher IOP or lower CSFP. The data supports the concurrent role of IOP-related and vascular factors in glaucomatous optic nerve damage.

Glymphatic stasis at the site of the lamina cribrosa as a potential mechanism underlying open-angle glaucoma.

The underlying pathophysiology of primary open-angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans-lamina cribrosa pressure difference, has gained interest as a new risk factor for glaucoma. New research now lends support to the hypothesis that a paravascular transport system is present in the eye analogous to the recently discovered 'glymphatic system' in the brain, which is a functional waste clearance pathway that promotes elimination of interstitial solutes, including β-amyloid, from the brain along paravascular channels. Given that β-amyloid has been reported to increase by chronic elevation of intraocular pressure in glaucomatous animal models and to cause retinal ganglion cell death, the discovery of a paravascular clearance system in the eye may provide powerful new insights into the pathophysiology of primary open-angle glaucoma. In this review, we provide a new conceptual framework for understanding the pathogenesis of primary open-angle glaucoma, present supporting preliminary data from our own post-mortem study and hypothesize that the disease may result from restriction of normal glymphatic flow at the level of the lamina cribrosa owing to a low intracranial pressure and/or a high trans-lamina cribrosa pressure gradient. If confirmed, this viewpoint could offer new perspectives for the development of novel diagnostic and therapeutic strategies for this devastating disorder.

Non-invasive Evaluation of Cerebrospinal Fluid Pressure in Ocular Hypertension: The Beijing Intracranial and Intraocular Pressure Study

Objective: To compare the orbital CSFP and trans-lamina cribrosa pressure difference (TLCPD) determined noninvasively in Ocular Hypertension (OH) and controls, and study its association with the estimated risk of conversion to glaucoma. Design: Cross-sectional observational study. Participants: 19 subjects with OH recruited from the Tongren Eye Center and 23 controls enrolled in the Beijing Intracranial and Intraocular Pressure Study between June 2010 to December 2013. Methods: Magnetic resonance imaging was used to measure orbital subarachnoid space width (OSASW) at 3, 9 and 15 mm posterior to the globe. The CSFP (mmHg) was estimated from a published formula as 17.54 × MRI derived OSASW at 15 mm behind the globe +0.47 × body mass index +0.13 × mean arterial blood pressure -21.52. Estimated TLCPD was calculated as IOP- CSFP. The values of CSFP and TLCPD were compared between OH and controls. The estimated risk of progression to glaucoma in OH was calculated and its correlation with CSFP determined. Main outcome measures: Orbital subarachnoid space width; MRI derived CSFP value; TLCPD value. Association of risk of progression with CSFP. Results: The orbital subarachnoid space width was significantly wider (P=0.01) in the OH group than in the control groups at all three measurement locations. The MRI derived CSFP value in OH (14.9 ± 2.9 mmHg) was significantly higher than in the normal group (12.0 ± 2.8 mmHg; P<0.01). The estimated TLCPD value in OH (9.0 ± 4.2 mmHg) was significantly higher than in controls (3.6 ± 3.0 mmHg; P<0.01). The estimated risk of conversion to glaucoma in OH (15.2 ± 8.7%) was negatively correlated with the MRI derived CSFP value (r=-0.51, r2=-0.26, P<0.01). Conclusions: The wider OSASW and higher estimated CSFP in OH subjects suggest a higher orbital CSFP. Despite a higher orbital CSFP that could be protective, the higher TLCPD in OH may play a significant role in the risk of developing glaucoma.

Estimated trans-lamina cribrosa pressure difference versus intraocular pressure as biomarker for open-angle glaucoma. The Beijing Eye Study 2011.

To examine whether an estimated trans-lamina cribrosa pressure difference (TLCPD) better than intraocular pressure (IOP) correlated with markers for glaucoma. The population-based Beijing Eye Study 2011 included 3468 individuals. Cerebrospinal fluid pressure (CSFP) was calculated as CSFP [mmHg] = 0.44 × Body Mass Index [kg/m(2) ] + 0.16 × Diastolic Blood Pressure [mmHg] - 0.18 × Age [Years] - 1.91. TLCPD was IOP-CSFP. In the non-glaucomatous population, mean TLCPD was 5.8 ± 4.1 mmHg and mean estimated CSFP was 8.9 ± 3.7 mmHg. IOP was higher (p = 0.008), CSFP was lower (p < 0.001), and TLCPD was (p < 0.001) higher in the glaucoma group than in the non-glaucomatous group. The intergroup difference was highest for TLCPD (2.1 mmHg) followed by CSFP (1.7 mmHg) and IOP (0.4 mmHg). Open-angle glaucoma (OAG) was associated with higher TLCPD [p < 0.001; odds ratio (OR): 1.14; 95% confidence intervals (CI): 1.08, 1.19] but not with IOP (p = 0.22; OR: 0.96; 95% CI: 0.89, 1.03). In contrast, angle-closure glaucoma (ACG) was associated with higher IOP (p = 0.03; B: 0.14; OR: 1.15; 95% CI: 1.01, 1.30) but not with TLCPD (p = 0.98), after adjustment for age and anterior chamber depth. Retinal nerve fibre layer thickness was associated with lower TLCPD (p = 0.036) but not with IOP (p = 0.96), after adjusting for gender, age, region of habitation, optic disc area and refractive error. Neuroretinal area and volume were associated with smaller TLCPD (p = 0.002, and p < 0.001, respectively), after adjusting for gender, optic disc area and refractive error, but not with IOP (p = 0.43 and p = 0.25, resp.). In OAG, but not in ACG, calculated TLCPD versus IOP showed a better association with glaucoma presence and amount of glaucomatous optic neuropathy. It supports the notion of a potential role of low CSFP in the pathogenesis of OAG.

The role of low intracranial pressure in the development of glaucoma in patients with Alzheimer's disease

October 22, 2013Dear Editor,We read with great interest the paper by Janssen et al. (2013)entitled ‘The vast complexityof primaryopen angle glaucoma: Dis-ease genes, risks, molecular mechanisms and pathobiology.’ Theauthors deserve appreciation for their very informative reviewarticle.However,wewishtomakeacommentconcerningtheirdis-cussion of the potential role of intracranial pressure (ICP) in Alz-heimer’s disease (AD) and glaucoma.In the last section of their paper, Janssen and colleaguesdiscuss the potential relation between primary open angle glau-coma (POAG) and AD. As the authors mention, several studieshave found an increase in the occurrence of glaucoma in AD pa-tients. The authors state: “In our view, POAG damage could becaused by the net pressure over the optic disk, involving boththe aqueous humor pressure of the eye and cerebrospinal fluid(CSF) pressure of the brain, as described above. Also, CSF pressurechanges have been described in AD (Silverberg et al., 2006).Could these pressure changes underlie a relationship betweenPOAG and AD, and at the same time explain the apparently con-flicting association studies?” Further, the authors state: “We hy-pothesize that there is a strong association between normalpressure glaucoma and late AD, since both disease stages,following the ‘net pressure on the optic disk hypothesis’,arecharacterized by one single disease mechanism: an abnormallylow ICP.”Janssen et al. (2013) thus hypothesize that low ICP may play arole in the association between glaucoma and AD. We fully agreewith the authors since our group has previously presented this hy-pothesisforthefirsttime(Wostynetal.,2008,2009a).Intwoofourearlier manuscripts published in 2008 (Wostyn et al., 2008) and2009 (Wostyn et al., 2009a), we proposed low ICP occurring inAD as a factor leading to increased risk of glaucoma. Evidence forthishypothesiswasgainedfromCSFpressuremeasurementstudiesin AD patients and patients with glaucoma. The finding of a highoccurrence of reduced CSF pressure among patients with AD(Silverberg et al., 2006; Wostyn et al., 2009b) could be linked tothe high rate of reported comorbidity between AD and glaucoma(Bayer et al., 2002; Tamura et al., 2006), since it has been shownthat CSF pressure is lower in patients with glaucoma (Berdahlet al., 2008a, 2008b; Ren et al., 2010). This could result in anabnormally high trans-lamina cribrosa pressure difference andlead to glaucomatous damage. Given this previously advanced hy-pothesis, it was a great surprise when Janssen et al. (2013) recentlyhypothesized about the potential role of low ICP in glaucoma andAD without citing our earlier work (Wostyn et al., 2008, 2009a)or making clear the relevant precedents. The authors did cite oneof our papers, one largely focused on the high occurrence rate ofglaucoma among patients with normal pressure hydrocephalus(Wostyn et al., 2010), but this paper has no direct relevance tothe above hypothesis.Sincerely yours,Peter Wostyn, MDVeva De Groot, MD, PhDDebby Van Dam, PhDKurt Audenaert, MD, PhDPeter Paul De Deyn, MD, PhDReferences

Effect of intraocular pressure on glaucomatous damage to the optic nerve

Eyes with normal pressure glaucoma and eyes with high pressure glaucoma show a similar optic disc appearance with marked differences to eyes with vascular optic neuropathy. Non-vascular, potentially barotraumatic factors in addition to intraocular pressure (IOP) may thus play a role in glaucoma. Recent studies have shown that cerebrospinal fluid pressure (CSFP), arterial blood pressure and IOP are correlated with each other, higher CSFP is associated with younger age, higher blood pressure and higher body mass index, some patients with normal (IOP) pressure glaucoma have abnormally low CSFP and thus an abnormally high trans-lamina cribrosa pressure difference and a small orbital CSF space, the orbital CSF space width is associated with CSFP and the estimated CSFP correlated better with open-angle glaucoma-related parameters than IOP. The orbital CSFP as counter-pressure against IOP may play a role in the pathogenesis of glaucoma.

Body Height, Estimated Cerebrospinal Fluid Pressure and Open-Angle Glaucoma. The Beijing Eye Study 2011

PurposeTo examine potential associations between body height, cerebrospinal fluid pressure (CSFP), trans-lamina cribrosa pressure difference (TLCPD) and prevalence of open-angle glaucoma (OAG) in a population-based setting.MethodsThe population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range:50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44×Body Mass Index[kg/m2]+0.16×Diastolic Blood Pressure[mmHg]-0.18×Age[Years]-1.91ResultsData of IOP and CSFP were available for 3353 (96.7%) subjects. Taller body height was associated with higher CSFP (P<0.001; standardized correlation coefficient beta:0.13; regression coefficient B:0.29; 95% confidence interval (CI):0.25,0.33) after adjusting for male gender, urban region of habitation, higher educational level, and pulse rate. If TLCPD instead of CSFP was added, taller body height was associated with lower TLCPD (P<0.001;beta:−0.10;B:−0.20;95%CI:−0.25,−0.15). Correspondingly, higher CSFP was associated with taller body height (P = 0.003;beta:0.02;B:0.01;95%CI:0.00,0.02), after adjusting for age, gender, body mass index, pulse, systolic blood pressure, and blood concentration of cholesterol. If IOP was added to the model, higher CSFP was associated with higher IOP (P<0.001;beta:0.02;B:0.02;95%CI:0.01,0.03). TLCPD was associated with lower body height (P = 0.003;beta:−0.04;B −0.02,95%CI:−0.04,−0.01) after adjusting for age, body mass index, systolic blood pressure, pulse, blood concentrations of triglycerides, axial length, central corneal thickness, corneal curvature radius, and anterior chamber depth. Adding the prevalence of OAG to the multivariate analysis revealed, that taller body height was associated with a lower OAG prevalence (P = 0.03;beta:−0.03;B:−1.20;95%CI:−2.28,−0.12) after adjusting for educational level and gender.ConclusionsTaller body height was associated with higher CSFP and lower TLCPD (and vice versa), after adjusting for systemic and ocular parameters. Parallel to the associations between a higher prevalence of glaucoma with a lower CSFP or higher TLCPD, taller body height was associated with a lower prevalence of OAG.

Senescent Changes in Cerebrospinal Fluid Circulatory Physiology and Their Role in the Pathogenesis of Normal-tension Glaucoma

To evaluate the evidence supporting a role for senescent changes in cerebrospinal fluid (CSF) circulatory physiology in the pathogenesis of normal-tension glaucoma (NTG). Literature review and personal perspective of the authors. Analysis of selected articles in the peer-reviewed literature with interpretation and perspective. Recent studies have reported that intracranial pressure is lower in patients with NTG when compared with patients with primary open-angle glaucoma and nonglaucomatous control subjects. It has been suggested that a low intracranial pressure in patients with normal intraocular pressure could lead to glaucomatous damage. This low intracranial pressure, leading to an abnormally high trans-lamina cribrosa pressure difference, could result in barotraumatically induced optic nerve damage at the lamina cribrosa. However, several experimental studies do not support the speculation that low intracranial pressure and the resulting pressure-dependent effects cause bowing back of the lamina cribrosa and optic disc cupping. On the other hand, CSF production and turnover have been shown to be decreased in aging and in pathologic conditions, such as Alzheimer disease and normal pressure hydrocephalus. Interestingly, recent studies have revealed that both Alzheimer disease patients and patients with normal pressure hydrocephalus may have a higher risk of developing glaucoma. Therefore, we believe that CSF circulatory failure, ultimately resulting in reduced neurotoxin clearance along the optic nerves, could be an alternative explanation as to why glaucoma develops in patients with low intracranial pressure. On the basis of the evidence available from the peer-reviewed literature, our tentative conclusion is that age-related changes in CSF circulatory physiology and the subsequent decrease in CSF turnover, with diminished clearance of toxic substances, can account for, at least in part, the pathogenesis of NTG. It should be stressed that for the moment at least, the present hypothesis remains unproven. Further research will be necessary to determine the possible role of CSF circulatory dysfunction in NTG. If confirmed, this hypothesis could providenew, important insights into the pathogenesis of NTG.

Intracranial Pressure and Glaucoma

Eyes with normal-tension and high-tension glaucoma can have a similar optic nerve head appearance, which differs markedly from the optic disc appearance in vascular optic neuropathies. Factors in addition to intraocular pressure (IOP) may play a role in the pathogenesis of glaucomatous optic neuropathy. Clinical and experimental studies have shown (1) physiologic associations between cerebrospinal fluid pressure (CSFP), systemic arterial blood pressure, IOP, and body mass index; (2) that a low CSFP was associated with the development of glaucomatous optic nerve damage in cats; and (3) that patients with normal-tension glaucoma had significantly lower CSFP and a higher trans-lamina cribrosa pressure difference when compared to normal subjects. Due to anatomic reasons, the orbital CSFP and the optic nerve tissue pressure (and not the atmospheric pressure) form the retro-laminar counter-pressure against the IOP and are thus part of the trans-lamina cribrosa pressure difference and gradient. Assuming that an elevated trans-lamina cribrosa pressure difference and a steeper trans-lamina cribrosa pressure gradient are important for glaucomatous optic nerve damage, a low orbital CSFP would therefore play a role in the pathogenesis of normal-tension glaucoma. Due to the association between CSFP and blood pressure, a low blood pressure would also be indirectly involved.

Aspects of the Pathogenesis of Glaucomatous Optic Neuropathy

Purpose: To discuss aspects of the pathogenesis of glaucomatous optic neuropathy based on morphologic findings of the glaucomatous optic nerve head and examinations of the cerebrospinal fluid pressure. Methods and results: Findings were: normal pressure and high intraocular pressure glaucoma eyes can show a similar appearance of the optic nerve head. These features are not found in any (other) vascular optic neuropathy (except for arteritic anterior ischemic optic neuropathy). The translamina cribrosa pressure difference is of importance for the physiology of the optic nerve head. A physiologic association exists between arterial blood pressure, cerebrospinal fluid pressure and intraocular pressure. Patients with normal (intraocular) pressure glaucoma had significantly lower cerebrospinal fluid pressure and a higher translamina cribrosa pressure difference when compared to normal subjects. Conclusions: A low (orbital) cerebrospinal fluid pressure may be associated with normal (intraocular) pressure glaucoma. A low systemic blood pressure, particularly at night, could physiologically be associated with a low cerebrospinal fluid pressure, which leads to an abnormally high translamina cribrosa pressure difference and as such to a similar situation as if the cerebrospinal fluid pressure is normal and the intraocular pressure is elevated. This model could explain why patients with normal (intraocular) pressure glaucoma tend to have a low systemic blood pressure, and why eyes with normal (intraocular) pressure glaucoma and eyes with high-pressure glaucoma, in contrast to eyes with a direct vascular optic neuropathy, show profound similarities in the appearance of the optic nerve head.

Role of cerebrospinal fluid pressure in the pathogenesis of glaucoma

The pathogenesis of normal (intraocular) pressure glaucoma has remained unclear so far. As hospital-based studies showed an association of normal-pressure glaucoma with low systemic blood pressure, particularly at night, and with vasospastic symptoms, it has been hypothesized that a vascular factor may play a primary role in the pathogenesis of normal-pressure glaucoma. That assumption may, however, be contradicted by the morphology of the optic nerve head. Eyes with normal-pressure glaucoma and glaucomatous eyes with high-intraocular pressure can show a strikingly similar appearance of the optic nerve head, including a loss of neuroretinal rim, a deepening of the optic cup, and an enlargement of parapapillary atrophy. These features, however, are not found in any (other) vascular optic neuropathy, with the exception of an enlargement and deepening of the optic cup in arteritic anterior ischaemic optic neuropathy. One may additionally take into account (i) that it is the trans-lamina cribrosa pressure difference (and not the trans-corneal pressure difference, i.e. the so-called intraocular pressure) which is of importance for the physiology and pathophysiology of the optic nerve head; (ii) that studies have shown that the anatomy of the optic nerve head including the intraocular pressure, the anatomy and biomechanics of the lamina cribrosa and peripapillary sclera, retrobulbar orbital cerebrospinal fluid pressure and the retrobulbar optic nerve tissue pressure may be of importance for the pathogenesis of the highly myopic type of chronic open-angle glaucoma; (iii) that studies have suggested a physiological association between the pressure in all three fluid filled compartments, i.e. the systemic arterial blood pressure, the cerebrospinal fluid pressure and the intraocular pressure; (iv) that an experimental investigation suggested that a low cerebrospinal fluid pressure may play a role in the pathogenesis of normal (intraocular) pressure glaucoma; and (v) that recent clinical studies reported that patients with normal (intraocular) pressure glaucoma had significantly lower cerebrospinal fluid pressure and a higher trans-lamina cribrosa pressure difference when compared to normal subjects. One may, therefore, postulate that a low cerebrospinal fluid pressure may be associated with normal (intraocular) pressure glaucoma. A low systemic blood pressure, particularly at night, could physiologically be associated with a low cerebrospinal fluid pressure, which leads to an abnormally high trans-lamina cribrosa pressure difference and as such to a similar situation as if the cerebrospinal fluid pressure is normal and the intraocular pressure is elevated. This model could explain why patients with normal (intraocular) pressure glaucoma tend to have a low systemic blood pressure, and why eyes with normal (intraocular) pressure glaucoma and eyes with high-pressure glaucoma, in contrast to eyes with a direct vascular optic neuropathy, show profound similarities in the appearance of the optic nerve head.

Cerebrospinal Fluid Pressure in Glaucoma: A Prospective Study

To assess whether a low cerebrospinal fluid pressure (CSF-P) is associated with open-angle glaucoma in eyes with normal intraocular pressure (IOP). Prospective, interventional study. The study included 43 patients with open-angle glaucoma (14 with a normal IOP, and 29 with an elevated IOP) and 71 subjects without glaucoma. All patients underwent standardized ophthalmologic and neurologic examinations and measurement of lumbar CSF-P. Cerebrospinal fluid pressure and IOP. Lumbar CSF-P was significantly (P<0.001) lower in the normal IOP glaucoma group (9.5+/-2.2 mmHg) than in the high IOP glaucoma group (11.7+/-2.7 mmHg) or the control group (12.9+/-1.9 mmHg). The trans-lamina cribrosa pressure difference (IOP minus CSF-P) was significantly (P<0.001) higher in the normal IOP glaucoma group (6.6+/-3.6 mmHg) and the high-IOP glaucoma group (12.5+/-4.1 mmHg) than in the control group (1.4+/-1.7 mmHg). The extent of glaucomatous visual field loss was negatively correlated with the height of the CSF-P and positively correlated with the trans-lamina cribrosa pressure difference. In the control group, CSF-P was significantly correlated with both systolic blood pressure (P = 0.04) and IOP (P<0.001). The trans-lamina cribrosa pressure difference was not significantly associated with blood pressure (P = 0.97). In open-angle glaucoma with normal IOP, CSF-P is abnormally low, leading to an abnormally high trans-lamina cribrosa pressure difference. Pathogenetically, a low CSF-P in normal-IOP glaucoma may be similar to a high IOP in high-IOP glaucoma. Consequently, the glaucomatous visual field defect is positively correlated with the trans-lamina cribrosa pressure difference and inversely correlated with the CSF-P. In nonglaucomatous subjects, CSF-P, blood pressure, and IOP are significantly associated with each other.

More advanced Alzheimer's disease may be associated with a decrease in cerebrospinal fluid pressure

In a recent article, elevated cerebrospinal fluid pressure (CSFP) consistent with very early normal pressure hydrocephalus (NPH), was found in a small subset of Alzheimer's disease (AD) patients (possible AD-NPH hybrids) enrolled in a clinical trial for chronic low-flow cerebrospinal fluid drainage. Also in the same study, was another interesting finding that merits further discussion: a substantial proportion of AD patients had very low CSFP. Based on the characteristics of these subjects, we hypothesize that more advanced AD may be associated with a decrease in CSFP. Reduced CSFP among a group of AD patients could provide a clue towards a better understanding of the high rate of comorbidity reported between AD and glaucoma since it has been shown that mean CSFP is lower in subjects with primary open-angle glaucoma. This could result in an abnormally high trans-lamina cribrosa pressure difference and lead to glaucomatous damage.