Evaluation of optic nerve head blood flow in response to increase of intraocular pressure.
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ABSTRACT:
SUBMITTER: Iwase T
PROVIDER: S-EPMC6250699 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Evaluation of optic nerve head blood flow in response to increase of intraocular pressure.
Iwase Takeshi T Akahori Tomohiko T Yamamoto Kentaro K Ra Eimei E Terasaki Hiroko H
Scientific reports 20181122 1
The time course of the changes in the optic nerve head (ONH) blood flow in response to changes in the ocular perfusion pressure (OPP) induced by an artificial elevation of the intraocular pressure (IOP) has not been determined. We measured the blood flow, represented by the mean blur rate (MBR), on the ONH determined by laser speckle flowgraphy. The MBR was determined before, during, and after the IOP was elevated by 20 or 30 mmHg by pressure applied on the eye by an ophthalmodynamometer in a to ...[more]
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Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury. Six- to eight-week old C57Bl/6 male mice were used in this experiment. One eye underwent an elevation in intraocular pressure to 30 mmHg for 1 hour and then allowed to recover for 3 days. The contralateral eye served as a control. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. We used 10 mice to generate five biological replicates for each condition.
2013-05-17 | E-GEOD-40009 | biostudies-arrayexpress
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Project description:AimIn the present study the response of optic nerve head blood flow to an increase in ocular perfusion pressure during isometric exercise was studied. Based on our previous studies we hypothesized that subjects with an abnormal blood flow response, defined as a decrease in blood flow of more than 10% during or after isometric exercise, could be identified.MethodsA total of 40 healthy subjects were included in this study. Three periods of isometric exercise were scheduled, each consisting of 2 minutes of handgripping. Optic nerve head blood flow was measured continuously before, during and after handgripping using laser Doppler flowmetry. Blood pressure was measured non-invasively in one-minute intervals. Intraocular pressure was measured at the beginning and the end of the measurements and ocular perfusion pressure was calculated as 2/3*mean arterial pressure -intraocular pressure.ResultsIsometric exercise was associated with an increase in ocular perfusion pressure during all handgripping periods (p < 0.001). By contrast no change in optic nerve head blood flow was seen. However, in a subgroup of three subjects blood flow showed a consistent decrease of more than 10% during isometric exercise although their blood pressure values increased. In addition, three other subjects showed a consistent decline of blood flow of more than 10% during the recovery periods.ConclusionOur data confirm previous results indicating that optic nerve head blood flow is autoregulated during an increase in perfusion pressure. In addition, we observed a subgroup of 6 subjects (15%) that showed an abnormal response, which is in keeping with our previous data. The mechanisms underlying this abnormal response remain to be shown.
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Project description:Intraocular pressure (IOP) is an important risk factor for glaucoma, and the response of the ONH and surrounding tissues to elevated IOP are often investigated to better understand pathophysiology. In vivo structure including that of the optic nerve head (ONH) and surrounding tissue of the eye are often assessed using optical coherence tomography (OCT). With advances in OCT technology, both large vessels and capillaries can be imaged non-invasively (OCT Angiography). Because a significant portion of retinal thickness is comprised of vasculature, the purpose of the current study was to investigate OCT structural and vascular changes in healthy non-human primate eyes with systematic graded increases and decreases in IOP. Six healthy animals with no previous experimental intervention were used. The pressure in the anterior chamber was adjusted from 10?mmHg to 60?mmHg and back to 10?mmHg in 10?mmHg steps every 10?min. Using optical coherence tomography (OCT), retinal nerve fiber layer (RNFL) thickness, minimum rim width (MRW), Bruch's membrane opening (BMO) size and relative height, anterior lamina cribrosa surface (ALCS) depth, choroidal thickness, and angiography (OCTA) were quantified. With IOP challenge there were significant changes in all morphological measures quantified (p?<?0.01) other than BMO size (p?=?0.30) and RNFL thickness (p?=?0.29). Specifically, the position of the BMO was sensitive to both an increase and decease in IOP. The inner retinal capillary density gradually decreased with increasing IOP, reaching statistical significance when pressure exceeded 50?mmHg, but returned when IOP was reduced. The average choroidal thickness around the ONH decreased for elliptical annuli 500-1000??m and 1000-1500??m, from the BMO, with increasing IOP (p?<?0.01). For the 1000-1500??m annulus, choroid thickness did not return to baseline with IOP reduction. Similarly, the MRW decreased with increase in IOP, but with pressure reduction did not return, and at the final 10?mmHg time point was thinner than at baseline (p?<?0.01). The results from this experiment illustrate differences in ONH neural rim tissue, RNFL and vessel density changes with acute IOP challenge. Overall, vessel collapse could not completely account for changes in RNFL or ONH MRW thickness. The study supports the hypothesis neural rim compression may be an important part of IOP-induced damage.
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Project description:Purpose:Optic nerve head (ONH) astrocytes provide support for axons, but exhibit structural and functional changes (termed reactivity) in a number of glaucoma models. The purpose of this study was to determine if ONH astrocyte structural reactivity is axon-dependent. Methods:Using rats, we combine retrobulbar optic nerve transection (ONT) with acute controlled elevation of intraocular pressure (CEI), to induce total optic nerve axon loss and ONH astrocyte reactivity, respectively. Animals were euthanized immediately or 1 day post CEI, in the presence or absence of ONT. ONH sections were labeled with fluorescent-tagged phalloidin and antibodies against ?3 tubulin, phosphorylated cortactin, phosphorylated paxillin, or complement C3. ONH label intensities were quantified after confocal microscopy. Retrobulbar nerves were assessed for axon injury by light microscopy. Results:While ONT alone had no effect on ONH astrocyte structural orientation, astrocytes demonstrated significant reorganization of cellular extensions within hours after CEI, even when combined with ONT. However, ONH astrocytes displayed differential intensities of actin (phosphorylated cortactin) and focal adhesion (phosphorylated paxillin) mediators in response to CEI alone, ONT alone, or the combination of CEI and ONT. Lastly, label intensities of complement C3 within the ONH were unchanged in eyes subjected to CEI alone, ONT alone, or the combination of CEI and ONT, relative to controls. Conclusions:Early ONH astrocyte structural reactivity to elevated IOP is multifaceted, displaying both axon dependent and independent responses. These findings have important implications for pursuing astrocytes as diagnostic and therapeutic targets in neurodegenerative disorders with fluctuating levels of axon injury.
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Project description:This study presents a quantification method for the assessment of the optic nerve head (ONH) deformations of the living human eye under acute intraocular pressure (IOP) elevation and change of cerebrospinal fluid pressure (CSFP) with body position. One eye from a brain-dead organ donor with open-angle glaucoma was imaged by optical coherence tomography angiography during an acute IOP and CSFP elevation test. Volumetric 3D strain was computed by digital volume correlation. With increase in IOP the shear strain consistently increased in both sitting and supine position (p < 0.001). When CSFP was increased at constant IOP by changing body position, a global reduction in the ONH strain was observed (-0.14% p = 0.0264). Strain in the vasculature was significantly higher than in the structural tissue (+0.90%, p = 0.0002). Retinal nerve fiber layer (RNFL) thickness strongly associated (ρ = -0.847, p = 0.008) with strain in the peripapillary sclera (ppScl) but not in the retina (p = 0.433) and lamina (p = 0.611). These initial results show that: CSFP independently to IOP modulates strain in the human ONH; ppScl strains are greater than strains in lamina and retina; strain in the retinal vasculature was higher than in the structural tissue; In this glaucoma eye, higher ppScl strain associated with lower RNFL thickness.
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Project description:PurposeIn this study, we aimed to compare blood flow changes in the optic nerve head (ONH) during horizontal ocular duction among normal, primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG) eyes.MethodsIn this cross-sectional study, we included 90 eyes from 90 participants (30 control eyes, 30 POAG eyes, and 30 NTG eyes). ONH blood flow was measured with laser speckle flowgraphy using an external fixation light to induce central gaze, abduction, and adduction at 30 degrees for each eye. The mean blur rate (MBR) of the entire ONH area (MA), vascular region (MV), and tissue region (MT), and the change ratio were analyzed. The change ratio was defined as abduction or adduction value/central gaze value.ResultsIn the control group, MA significantly decreased during adduction (22.9 ± 3.7) compared with that during central gaze (23.6 ± 3.9, P < 0.05). In the POAG group, MA (adduction = 17.4 ± 3.8 and abduction = 17.3 ± 3.6) and MV (adduction = 37.9 ± 5.6 and abduction = 38.0 ± 5.6) significantly decreased during adduction and abduction compared with those during central gaze (18.0 ± 4.1 and 39.5 ± 6.3, respectively, P < 0.05). In the NTG group, MA significantly decreased during adduction (17.4 ± 4.2) compared with that during central gaze (18.1 ± 4.6) and abduction (18.1 ± 4.8, P < 0.05). The change ratio did not differ between the glaucoma and control groups.ConclusionsONH blood flow decreased during horizontal ocular duction regardless of normal or glaucoma states; however, the change ratio was comparable between the normal and glaucoma groups.
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Project description:ImportanceThe acute biomechanical response of the optic nerve head (ONH) to intraocular pressure (IOP) elevations may serve as a biomarker for the development and progression of glaucoma.ObjectiveTo evaluate the association between visual field loss and the biomechanical response of the ONH to acute transient IOP elevations.Design, setting, and participantsIn this observational study, 91 Chinese patients (23 with primary open-angle glaucoma [POAG], 45 with primary angle-closure glaucoma, and 23 without glaucoma) were recruited from September 3, 2014, through February 2, 2017. Optical coherence tomography scans of the ONH were acquired at baseline and at 2 sequential IOP elevations (0.64 N and then 0.90 N, by applying forces to the anterior sclera using an ophthalmodynamometer). In each optical coherence tomography volume, lamina cribrosa depth (LCD) and minimum rim width (MRW) were calculated. The mean deviation (MD) and the visual field index (VFI), as assessed by automated perimetry, were correlated with IOP-induced changes of LCD and MRW globally and sectorially.Main outcomes and measuresThe LCD, MRW, MD, and VFI.ResultsAmong the 91 patients, 39 (42.9%) were women; the mean (SD) age was 65.48 (7.23) years. In POAG eyes, a greater change in LCD (anterior displacement) was associated with worse MD and VFI (R = -0.64; 95% CI, -0.97 to -0.31; P = .001; and R = -0.57; 95% CI, -0.94 to -0.19; P = .005, respectively) at the first IOP elevation, and a greater reduction in MRW was also associated with worse MD and VFI (first IOP elevation: R = -0.48; 95% CI, -0.86 to -0.09; P = .02; and R = -0.57; 95% CI, -0.94 to -0.20; P = .004, respectively; second IOP elevation: R = -0.56; 95% CI, -0.98 to -0.13; P = .01; and R = -0.60; 95% CI, -1.03 to -0.17; P = .008, respectively), after adjusting for age, sex, and baseline IOP. A correlation was found between the reduction in MRW in the inferior-temporal sector and the corresponding visual field cluster in POAG eyes at the second elevation (? = -0.55; 95% CI, -0.78 to -0.18; P = .006).Conclusions and relevanceThe biomechanical response of the ONH to acute IOP elevations was associated with established visual field loss in POAG eyes, but not in primary angle-closure glaucoma eyes. This suggests that ONH biomechanics may be related to glaucoma severity in POAG and that the 2 glaucoma subgroups exhibit inherently different biomechanical properties.
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Project description:PurposeOptic nerve head (ONH) blood flow decrease without changes in intraocular pressure in a possible rat model of retinal ganglion cell loss by systemic administration of aldosterone. To compare the blood flow in the ONH, using laser speckle flowgraphy (LSFG), in healthy eyes and in eyes with primary aldosteronism (PA).MethodsThe ONH tissue area mean blur rate (MT) was evaluated in this single center, retrospective, cross-sectional study using LSFG. In order to compare the MT between PA patients and normal subjects, mixed-effects models were used, with adjustments made for the mean arterial pressure, disc area, and β-peripapillary atrophy (β-PPA) area. Mixed-effects models were also used to analyze the risk factors affecting the MT.ResultsThis study evaluated a total of 29 eyes of 17 PA patients and 61 eyes of 61 normal subjects. There was a significantly lower MT in PA patients (10.8 ± 0.4) as compared to the normal subjects (12.3 ± 0.3) (P = 0.004). The MT was significantly lower in PA patients (10.8 ± 0.6) even after adjusting for the potential confounding factors when compared to normal subjects (12.3 ± 0.3) (P = 0.046). Multivariate mixed-effects model analysis demonstrated that the MT was significantly associated with the PA and β-PPA.ConclusionsThere was a significantly lower ONH blood flow in PA patients as compared to normal subjects.
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Project description:IntroductionTo evaluate the characteristics of optic nerve head (ONH) in highly myopic eyes and its role in predicting intraocular pressure (IOP) spikes after cataract surgery.MethodsPatients who are highly myopic and were scheduled for cataract surgery were enrolled in this prospective case series study. IOP was measured preoperatively and at 1 day and 3 days postoperatively. ONH characteristics including area, tilt ratio, lamina cribrosa (LC) thickness, and depth, and the presence of LC defects were evaluated with enhanced depth imaging optical coherence tomography. Factors influencing LC defects and early IOP spike were investigated using multivariate stepwise logistic regression.ResultsIn total, 200 highly myopic eyes of 200 patients were analyzed: 35.00% had small ONH, 53.00% had ONH tilt, and 14.00% had LC defects. Multivariate analysis demonstrated female patients with larger ONH area and deeper LC tended to have LC defects (all P < 0.05). As to postoperative IOP, IOP change, and incidence of IOP spikes, eyes with small ONH, ONH tilt, and LC defects had similar (all P > 0.05), higher (all P < 0.05), and lower (all P < 0.05) outcomes compared with those without the corresponding characteristic, respectively. Multivariate analysis showed that presence of LC defects and thicker LC were protective factors for early IOP spikes, and axial length > 28 mm was a risk factor (all P < 0.05).ConclusionFemale patients with larger ONH area and deeper LC tend to have LC defects, which, together with thicker LC, was correlated with less IOP spikes in highly myopic eyes.Trial registrationThis study was conducted as part of a larger project, the Shanghai High Myopia Study, registered at www.Clinicaltrialsgov (accession number NCT03062085).
| S-EPMC10287873 | biostudies-literature