Xiaobin Xie

Orbital cerebrospinal fluid space in glaucoma: the Beijing intracranial and intraocular pressure (iCOP) study.

OBJECTIVE Low cerebrospinal fluid pressure (CSF-P) may be involved in the pathogenesis of glaucoma. We measured the optic nerve subarachnoid space width (ONSASW) as a surrogate for orbital CSF-P in patients with primary open-angle glaucoma (POAG) with normal and high pressure and a control group. DESIGN Prospective observational study. PARTICIPANTS The study included 39 patients with POAG; 21 patients had normal pressure (intraocular pressure [IOP] 21 mmHg), and 18 patients had high pressure (IOP >21 mmHg); 21 subjects formed the control group. METHODS By using magnetic resonance imaging (MRI) with fat-suppressed fast recovery fast spin echo (FRFSE) T2-weighted sequence, we determined the ONSASW at 3, 9, and 15 mm posterior to the globe. MAIN OUTCOME MEASURES The ONSASW and optic nerve diameter. RESULTS At all 3 measurement locations of 3, 9, and 15 mm, the ONSASW was significantly (P<0.001, P<0.001, and P = 0.003, respectively) narrower in the normal-pressure group (0.67±0.16, 0.55±0.09, and 0.51±0.12 mm, respectively) than in the high-pressure group (0.93±0.21, 0.70±0.12, and 0.62±0.11 mm, respectively) or the control group (0.87±0.15, 0.67±0.07, and 0.61±0.07 mm, respectively). The high-pressure and control groups did not vary significantly at 3, 9, and 15 mm (P = 0.31, P = 0.39, and P = 0.44, respectively). At all 3 measurement locations, ONSASW was narrower in the normal-pressure group compared with the high-pressure and control groups after adjustment for optic nerve diameter (P<0.01). Correspondingly, the width of the optic nerve subarachnoid space measured at 3, 9, and 15 mm behind the globe, respectively, was significantly (all P<0.05) associated with IOP after adjustment for optic nerve diameter and visual field defect. CONCLUSIONS The narrower orbital optic nerve subarachnoid space in patients with POAG with normal pressure compared with high pressure suggests a lower orbital CSF-P in patients with POAG with normal pressure.

Optic Neuropathy Induced by Experimentally Reduced Cerebrospinal Fluid Pressure in Monkeys

PURPOSE To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve a CSF of approximately 40 mm H2O, while the shunt remained closed in the control group (n = 5 monkeys). At baseline and in monthly intervals thereafter, optical coherence tomographic and photographic images of the optic nerve head and RNFL were taken of all monkeys. RESULTS Two out of four monkeys in the study group showed bilaterally a progressive reduction in RNFL thickness between 12% and 30%, reduction in neuroretinal rim area and volume, and increase in cup-to-disc area ratios. A third monkey developed a splinter-like disc hemorrhage in one eye. The fourth monkey in the study group did not develop morphologic changes during follow-up, nor did any monkey in the control group. CONCLUSIONS Experimental and chronic reduction in CSF in monkeys was associated with the development of an optic neuropathy in some monkeys.

Noninvasive intracranial pressure estimation by orbital subarachnoid space measurement: the Beijing Intracranial and Intraocular Pressure (iCOP) study

IntroductionThe orbital subarachnoid space surrounding the optic nerve is continuous with the circulation system for cerebrospinal fluid (CSF) and can be visualized by using magnetic resonance imaging (MRI). We hypothesized that the orbital subarachnoid space width (OSASW) is correlated with and can serve as a surrogate for intracranial pressure (ICP). Our aim was to develop a method for a noninvasive measurement of the intracranial CSF-pressure (CSF-P) based on MRI-assisted OSASW.MethodsThe prospective observational comparative study included neurology patients who underwent lumbar CSF-P measurement and 3.0-Tesla orbital magnetic resonance imaging (MRI) for other clinical reasons. The width of the orbital subarachnoid space (OSASW) around the optic nerve was measured with MRI at 3, 9, and 15 mm behind the globe. The study population was randomly divided into a training group and a test group. After adjusting for body mass index (BMI) and mean arterial blood pressure (MABP), algorithms for the associations between CSF-P and OSASW were calculated in the training group. The algorithms were subsequently verified in the test group. Main outcome measures were the width of the orbital subarachnoid space (OSASW) and the lumbar cerebrospinal fluid pressure (CSF-P).ResultsSeventy-two patients were included in the study. In the training group, the algorithms for the associations between CSF-P and OSASW were as follows: (a) CSF-P = 9.31 × OSASW (at 3 mm) + 0.48 × BMI + 0.14 × MABP-19.94; (b) CSF-P = 16.95 × OSASW (at 9 mm) + 0.39 × BMI + 0.14 × MABP-20.90; and (c) CSF-P = 17.54 × OSASW (at 15 mm) + 0.47 × BMI + 0.13 × MABP-21.52. Applying these algorithms in the independent test group, the measured lumbar CSF-P (13.6 ± 5.1 mm Hg) did not differ significantly from the calculated MRI-derived CSF-P (OSASW at 3 mm: 12.7 ± 4.2 mm Hg (P = 0.07); at 9 mm: 13.4 ± 5.1 mm Hg (P = 0.35); and at 15 mm: 14.0 ± 4.9 mm Hg (P = 0.87)). Intraclass correlation coefficients (ICCs) were higher for the CSF-P assessment based on OSASW at 9 mm and at 15 mm behind the globe (all ICCs, 0.87) than for OSASW measurements at 3 mm (ICC, 0.80).ConclusionsIn patients with normal, moderately decreased or elevated ICP, MRI-assisted measurement of the OSASW appears to be useful for the noninvasive quantitative estimation of ICP, if BMI and MABP as contributing parameters are taken into account.Trial registrationClinical trial registered with the Chinese Clinical Trial Registry: ChiCTR-OCC-11001271

Trans-Lamina Cribrosa Pressure Difference and Open-Angle Glaucoma. The Central India Eye and Medical Study

PURPOSE To assess associations of the trans-lamina cribrosa pressure difference (TLCPD) with glaucomatous optic neuropathy. METHODS The population-based Central India Eye and Medical Study included 4711 subjects. 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] -1.91. TLCPD was IOP-CSFP. RESULTS Mean TLCPD was 3.64±4.25 mm Hg in the non-glaucomatous population and 9.65±8.17 mmHg in the glaucomatous group. In multivariate analysis, TLCPD was associated with older age (P<0.001; standardized coefficient beta:0.53; regression coefficient B:0.18; 95% confidence interval (CI):0.17, 0.18), lower body mass index (P<0.001; beta: -0.28; B: -0.36; 95%CI: -0.38, -0.31), lower diastolic blood pressure (P<0.001; beta: -0.31; B: -0.12; 95%CI: -0.13, -0.11), higher pulse (P<0.001; beta:0.05; B:0.02; 95%CI:0.01,0.2), lower body height (P = 0.02; beta: -0.02; B: -0.01; 95%CI: -0.02,0.00), higher educational level (P<0.001; beta:0.04; B:0.15; 95%CI:0.09,0.22), higher cholesterol blood concentrations (P<0.001; beta:0.04; B:0.01; 95%CI:0.01,0.01), longer axial length (P = 0.006; beta:0.03; B:0.14; 95%CI:0.04,0.24), thicker central cornea (P<0.001; beta:0.15; B:0.02; 95%CI:0.02,0.02), higher corneal refractive power (P<0.001; beta:0.07; B:0.18; 95%CI:0.13,0.23) and presence of glaucomatous optic neuropathy (P<0.001; beta:0.11; B:3.43; 95%CI:2.96,3.99). Differences between glaucomatous subjects and non-glaucomatous subjects in CSFP were more pronounced for open-angle glaucoma (OAG) than for angle-closure glaucoma (ACG) (3.0 mmHg versus 1.8 mmHg), while differences between glaucomatous subjects and non-glaucomatous subjects in IOP were higher for ACG than for OAG (8.5 mmHg versus 3.0 mmHg). Presence of OAG was significantly associated with TLCPD (P<0.001; OR:1.24; 95%CI:1.19,1.29) but not with IOP (P = 0.08; OR:0.96; 95%CI:0.91,1.00). Prevalence of ACG was significantly associated with IOP (P = 0.04; OR:1.19; 95%CI:1.01,1.40) but not with TLCPD (P = 0.92). CONCLUSIONS 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 open-angle glaucoma.

Subfoveal choroidal thickness and cerebrospinal fluid pressure: the Beijing Eye Study 2011.

PURPOSE The venous choroidal blood drains through the superior orbital vein into the intracranial cavernous sinus. The cerebrospinal fluid pressure (CSFP) may thus influence the choroidal venous blood pressure. Since volume and thickness of the choroid depend on its pressure, we tested the hypothesis whether the subfoveal choroidal thickness (SFCT) is associated with CSFP. METHODS The population-based Beijing Eye Study 2011 included 3468 individuals. A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of SFCT. The CSFP was calculated as CSFP (mm Hg) = 0.44 × Body Mass Index (kg/m(2)) + 0.16 × Diastolic Blood Pressure (mm Hg) - 0.18 × Age (years) - 1.91. RESULTS Mean calculated CSFP was 8.8 ± 3.7 mm Hg and mean SFCT was 254 ± 107 μm. In multivariate analysis, SFCT was significantly associated with higher CSFP (P = 0.009; standardized coefficient β: 0.08; regression coefficient B: 2.27) after adjusting for lower age (P < 0.001; β: -0.36; B: -3.99), shorter axial length (P < 0.001; β: -0.37; B: -35.7), lower body mass index (P = 0.02; β: -0.05; B: -1.51), and higher corneal curvature radius (P < 0.001; β: 0.10; B: 41.1). In univariate analysis, SFCT increased by 9.2 μm (95% confidence interval: 8.3, 10.1) for each mm Hg increase in CSFP. In a reverse manner, CSFP was significantly associated with thicker SFCT (P < 0.001; B: 0.007; β: 0.21), after adjusting for region of habitation (P < 0.001; B: -0.31; β: -2.32), higher levels of glucose (P = 0.02; B: 0.10; β: 0.04) and triglycerides (P < 0.001; B: 0.13; β: 0.09), higher intraocular pressure (P < 0.001; B: 0.17; β: 0.12), and thinner lens (P < 0.001; B: -2.39; β: -0.22). CONCLUSIONS Thicker subfoveal choroid was associated with higher CSFP after adjustment for age, axial length, body mass index, and corneal curvature radius. This association may explain thicker SFCT measurements in the morning than evening. It shows the importance of the CSFP for the physiology of the eye.

Body height, estimated cerebrospinal fluid pressure and open-angle glaucoma. The Beijing Eye Study 2011.

Purpose To 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. Methods The 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]-1.91 Results Data 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. Conclusions Taller 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.

Ocular and systemic factors associated with diabetes mellitus in the adult population in rural and urban China. The Beijing Eye Study

PurposeTo assess ocular and systemic factors associated with diabetes mellitus in the adult population in rural and urban China.MethodsThe Beijing Eye Study 2006, a population-based, cross-sectional cohort study, included 3251 subjects aged 45 years and more (participation rate: 73.2%). Blood samples were available for 2960 (91.0%) subjects. Diabetes mellitus was defined by a fasting plasma glucose concentration ≥7.0 mmol/l or by a self-reported history diagnosis of diabetes.ResultsDiabetes mellitus was found in 381 (12.9%) subjects. In binary regression analysis, the presence of diabetes mellitus was significantly associated with body mass index, systolic blood pressure, triglyceride concentrations, intraocular pressure, cylindrical refractive dioptre, presence of arteriolar sheathing, rural vsurban region, lower best-corrected visual acuity, lower high-density lipoprotein level, and lower diastolic blood pressure. It was not statistically associated with age, presence of cataract (nuclear, cortical, or subcapsular), size of the optic disc, neuroretinal rim, αzone and βzone of peripapillary atrophy, retinal artery and vein diameters, arteriovenous nicking, focal or general narrowing, refractive error, prevalence of glaucoma, and early or late stage of age-related macular degeneration.ConclusionsIn a population-based setting, diabetes mellitus was not associated with optic disc, rim and peripapillary atrophy measurements, retinal vessel diameters, arteriovenous nicking, focal or general retinal artery narrowing, and prevalence of age-related macular degeneration. Although diabetes mellitus was significantly correlated with higher intraocular pressure, it was not associated with glaucoma.

Structural brain alterations in primary open angle glaucoma: a 3T MRI study

Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield, and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma.

Incident retinal vein occlusions and estimated cerebrospinal fluid pressure. The Beijing Eye Study

To examine whether the incidence of retinal vein occlusions (RVOs) is associated with estimated cerebrospinal fluid pressure (CSFP).

Altered Amplitude of Low-Frequency Fluctuation in Primary Open-Angle Glaucoma: A Resting-State fMRI Study

PURPOSE To analyze the altered amplitude of low-frequency fluctuation (ALFF) of the brain using resting-state functional magnetic resonance imaging (fMRI) in patients with primary open-angle glaucoma (POAG). METHODS Resting-state fMRI was conducted in 21 POAG patients and 22 age-matched healthy control subjects. After the ALFF and fractional amplitude of low-frequency fluctuation (fALFF) for slow 4 and slow 5 bands were calculated, the results between POAG patients and healthy controls were compared. Then the correlations between ALFF/fALFF values and the disease stage of POAG were analyzed. RESULTS Compared with controls, POAG patients showed significantly decreased ALFF/fALFF values in the visual cortices, posterior regions of the default-mode network (DMN), and motor and sensory cortices. Meanwhile, ALFF/fALFF values in the prefrontal cortex, left superior temporal gyrus (STG), right middle cingulate cortex (MCC), and left inferior parietal lobule (IPL) significantly increased in POAG patients. Hodapp-Anderson-Parrish (HAP) score for POAG was positively correlated with ALFF values of the right superior frontal gyrus (SFG) and negatively correlated with that of the left cuneus. For the slow 5 band, the fALFF values of the bilateral middle temporal gyri (MTG) of POAG patients were negatively correlated with HAP score. CONCLUSIONS Primary open-angle glaucoma is a neurodegenerative disease involving multiple brain regions, including the visual cortices, DMN, limbic system, and motor and sensory networks. Moreover, the alterations in some of these networks are correlated with the progression of POAG; for the abnormal spontaneous neural activities in the left cuneus, bilateral MTG and right prefrontal cortex are correlated with glaucoma severity.