ResearchPad - intraocular-pressure https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Hemisphere opposite to vascular trunk deviation is earlier affected by glaucomatous damage in myopic high-tension glaucoma]]> https://www.researchpad.co/article/elastic_article_15760 To investigate whether the position of the central vascular trunk, as a surrogate of lamina cribrosa (LC) shift, is associated with the initial hemisphere of visual field defect in myopic high-tension glaucoma (HTG) eyes.MethodsThe deviation of the central vascular trunk was measured from the center of the Bruch’s membrane opening (BMO), which was delineated by OCT imaging. The angular deviation was measured with the horizontal nasal midline as 0° and the superior location as a positive value. The initial hemisphere developing visual field defect was defined as three connected abnormal points (having a P value with less than 0.5% probability of being normal) appearing in only one hemisphere in pattern deviation plots. If those points were observed in both hemispheres initially, the eye was classified as bi-hemispheric visual field defect.ResultsInitially, 36 eyes (44%) had superior visual field defects, 27 (33%) inferior visual field defects, and 18 (22%) bi-hemispheric visual field defects. After a mean follow-up of 5 years, the number of bi-hemispheric visual field defects had increased to 34 (42%). A logistic regression analysis revealed that inferior deviation of vascular trunk was the only factor associated with initial inferior visual field defect (P = 0.001), while initial bi-hemispheric visual field defects were associated with worse mean deviation at initial visits (P<0.001). A conditional inference tree analysis showed that both the angular deviation (P<0.001) and initial mean deviation (P = 0.025) determined the initial hemispheres developing visual field defect.ConclusionsAlthough both hemispheres were involved as glaucoma progression, the axons on the side counter to the vascular trunk deviation were damaged earlier in HTG. This finding implies the LC shift could add additional stress to axons exposed to high intraocular pressure. ]]> <![CDATA[Axial length and its associations in a Russian population: The Ural Eye and Medical Study]]> https://www.researchpad.co/article/5c5df355d5eed0c484581168

Purpose

To assess the normal distribution of axial length and its associations in a population of Russia.

Methods

The population-based Ural Eye and Medical Study included 5,899 (80.5%) individuals out of 7328 eligible individuals aged 40+ years. The participants underwent an ocular and systemic examination. Axial length was measured sonographically (Ultra-compact A/B/P ultrasound system, Quantel Medical, Cournon d'Auvergne, France).

Results

Biometric data were available for 5707 (96.7%) individuals with a mean age of 58.8±10.6 years (range:40–94 years; 25%, 50%, 75% quartile: 51.0, 58.0, 66.0 years, respectively). Mean axial length was 23.30±1.10 mm (range: 19.02–32.87mm; 95% confidence interval (CI): 21.36–25.89; 25%, 50%, 75% quartile: 22.65mm, 23.23mm, 23.88mm, resp.). Prevalences of moderate myopia (axial length:24.5-<26.5mm) and high myopia (axial length >26.5mm) were 555/5707 (8.7%;95%CI:9.0,10.5) and 78/5707 (1.4%;95%CI:1.1,1.7), respectively. Longer axial length (mean:23.30±1.10mm) was associated (correlation coefficient r2:0.70) with older age (P<0.001;standardized regression coefficient beta:0.14), taller body height (P<0.001;beta:0.07), higher level of education (P<0.001;beta:0.04), higher intraocular pressure (P<0.001;beta:0.03), more myopic spherical refractive error (P<0.001;beta:-0.55), lower corneal refractive power (P<0.001;beta:-0.44), deeper anterior chamber depth (P<0.001;beta:0.20), wider anterior chamber angle (P<0.001;beta:0.05), thinner peripapillary retinal nerve fiber layer thickness (P<0.001;beta:-0.04), higher degree of macular fundus tessellation (P<0.001;beta:0.08), lower prevalence of epiretinal membranes (P = 0.01;beta-0.02) and pseudoexfoliation (P = 0.007;beta:-0.02) and higher prevalence of myopic maculopathy (P<0.001;beta:0.08). In that model, prevalence of age-related macular degeneration (any type: P = 0.84; early type: P = 0.46), diabetic retinopathy (P = 0.16), and region of habitation (P = 0.27) were not significantly associated with axial length.

Conclusions

Mean axial length in this typically multi-ethnic Russian study population was comparable with values from populations in Singapore and Beijing. In contrast to previous studies, axial length was not significantly related with the prevalences of age-related macular degeneration and diabetic retinopathy or region of habitation.

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<![CDATA[Long-term probability of intraocular pressure elevation with the intravitreal dexamethasone implant in the real-world]]> https://www.researchpad.co/article/5c390b97d5eed0c48491d656

Purpose

To evaluate the long-term cumulative probability of intraocular pressure (IOP) elevation with the intravitreal dexamethasone implant (IDI) when used to treat different indications: diabetic macular edema, uveitis, retinal vein occlusion.

Methods

705 IDI injections (429 eyes) were assessed and Kaplan-Meier graphs were generated to assess: the probability of different levels of IOP elevation (IOP≥21, ≥25 or ≥35 mmHg), IOP change ≥10 mmHg, initiation of IOP-lowering treatment, glaucoma surgery, IOP change with repeat injections and IOP elevation in eyes with glaucoma and ocular hypertension (OHT).

Results

The cumulative probability of IOP ≥21, ≥25 and ≥35 mmHg was 50%-60%, 25%-30% and 6%-7% at 12–24 months, respectively. The probability of initiating IOP-lowering medication was 31%-54% at 12–24 months. Glaucoma and OHT eyes had a higher probability of mild IOP elevation (≥21 mmHg, 65.1%, 75% and 57.8%, p = 0.01), yet a similar moderate (≥25 mmHg, 22.3%, 28% and 30.2%, p = 0.91) and severe elevation of IOP (≥35 mmHg, 3.7%, 7.1% and 4%, p = 0.71) as normal eyes. Glaucoma surgery was required in only 0.9% cases (4/429). At baseline, 8.8% of the treated eyes had glaucoma, 6.7% OHT and 16.9% were already on IOP-lowering medication.

Conclusions

In the long-term (24 months), IOP elevation is common, generally mild (30% IOP, ≥25 mmHg) and well-tolerated, resolving with topical treatment (54%) and rarely requiring surgery (0.9%).

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<![CDATA[A Comparison of the Corrected Intraocular Pressure Obtained by the Corvis ST and Reichert 7CR Tonometers in Glaucoma Patients]]> https://www.researchpad.co/article/5989d9f2ab0ee8fa60b6ebd8

The purpose of the study was to investigate the accuracy of two corrected intraocular pressure (IOP) measurements by Corvis Scheimpflug Technology (CST)-IOPpachy and by corneal-compensated IOP (IOPcc) using the Reichert 7CR (7CR) tonometers. We also investigated the effects of corneal anatomical and structural parameters on the IOP measurements. The participants included 90 primary open-angle glaucoma patients. We assessed the IOP measurements, obtained by the CST, 7CR, and Goldmann applanation tonometer (GAT), using a paired t-test with Bonferroni correction, Bland-Altman plots, and multiple regression analyses. The 7CR-IOPcc gave the highest value (15.5 ± 2.7 mmHg), followed by the 7CR-IOPg (13.7 ± 3.1 mmHg), GAT-IOP (13.6 ± 2.2 mmHg), CST-IOP (10.3 ± 2.6 mmHg), and CST-IOPpachy (9.7 ± 2.5 mmHg). The values of CST-IOPpachy were significantly lower than those obtained by the other IOP measurement methods (all, p < 0.01). The values of 7CR-IOPcc were significantly higher than those obtained by the other IOP measurement methods (all, p < 0.01). Bland-Altman plots showed a mean difference between the GAT-IOP and the other IOP measurements (CST-IOP, CST-IOPpachy, 7CR-IOPg, and 7CR-IOPcc), which were −3.20, −3.82, 0.14, and 2.00 mmHg, respectively. The widths of the 95% limits of agreement between all pairs of IOP measurements were greater than 3 mmHg. With the exception of the 7CR-IOPcc, all of the IOP variations were explained by regression coefficients involving gender, average corneal curvature, and central corneal thickness. The IOP values obtained by the GAT, CST, and 7CR were not interchangeable. Each new IOP measurement device that was corrected for ocular structure had its own limitations.

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<![CDATA[The effect of parental factors in children with large cup-to-disc ratios]]> https://www.researchpad.co/article/5989db59ab0ee8fa60bdf0c3

Background

To investigate large cup-to-disc ratios (CDR) in children and to determine the relationship between parental CDR and clinical characteristics associated with glaucoma.

Methods

Two hundred thirty six children aged 6 to 12 years with CDR ≥ 0.6 were enrolled in this study. Subjects were classified into two groups based on parental CDR: disc suspect children with disc suspect (CDR ≥0.6) parents and disc suspect children without disc suspect parents. Ocular variables were compared between the two groups.

Results

Of the 236 disc suspect children, 100 (42.4%) had at least one disc suspect parent. Intraocular pressure (IOP) was higher in disc suspect children with disc suspect parents (16.52±2.66 mmHg) than in disc suspect children without disc suspect parents (14.38±2.30 mmHg, p = 0.023). In the group with disc suspect parents, vertical CDR significantly correlated with IOP (R = -0.325, p = 0.001), average retinal nerve fiber layer (RNFL) thickness (R = -0.319, p = 0.001), rim area (R = -0.740, p = 0.001), and cup volume (R = 0.499, p = 0.001). However, spherical equivalent (R = 0.333, p = 0.001), AL (R = -0.223, p = 0.009), and disc area (R = 0.325, p = 0.001) significantly correlated with vertical CDR in disc suspect children without disc suspect parents, in contrast to those with disc suspect parents. Larger vertical CDR was associated with the presence of disc suspect parents (p = 0.001), larger disc area (p = 0.001), thinner rim area (p = 0.001), larger average CDR (p = 0.001), and larger cup volume (p = 0.021).

Conclusions and relevance

Family history of large CDR was a significant factor associated with large vertical CDR in children. In children with disc suspect parents, there were significant correlations between IOP and average RNFL thickness and vertical CDR.

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<![CDATA[The Effect of Diurnal Fluctuation in Intraocular Pressure on the Evaluation of Risk Factors of Progression in Normal Tension Glaucoma]]> https://www.researchpad.co/article/5989dadaab0ee8fa60bb98ba

Purpose

To investigate whether diurnal fluctuation in intraocular pressure (IOP) can influence the result of the correlations between IOP-related factors and progression of normal tension glaucoma (NTG).

Methods

Glaucoma progression was defined as visual field (VF) progression and changes in the optic disc and/or retinal nerve fiber layer (RNFL). Two different methods were used to evaluate the impact of the diurnal fluctuation in IOP. ‘Conventional method’ used in previous studies included all IOP measurements during the follow up time. ‘Time adjusted method’ was used to adjust diurnal fluctuation in IOP with the preferred time. Mean IOP, long term IOP fluctuation and the difference between the lowest and highest IOP were calculated using both methods. Cox regression analyses were performed to evaluate the association between IOP-related factors and NTG progression.

Results

One hundred and forty eyes of 140 patients with NTG were included in this study. 41% (58 of 140 eyes) of eyes underwent NTG progression. Long term IOP variation calculated by conventional method was not a significant risk factor for NTG progression (hazard ratio[HR], 0.311; 95% confidence interval[CI], 0.056–1.717; P = 0.180). Long term IOP variation calculated by time adjusted method, however, was related to progression, with an HR of 5.260 (95% CI,1.191–23.232; P = 0.029).

Conclusion

Although having the same IOP-related factors, if diurnal fluctuation is included, different results may be found on the relationship between IOP-related factors and NTG progression. Based on our results, diurnal fluctuation in IOP should be considered when IOP-related factors are studied in the future.

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<![CDATA[Comparison of self-measured diurnal intraocular pressure profiles using rebound tonometry between primary angle closure glaucoma and primary open angle glaucoma patients]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbf87

Purpose

To document the diurnal intraocular pressure (IOP) profile with rebound tonometry performed by primary glaucoma patients in non-clinic environment.

Patients and methods

Fifty-three medically-treated eyes of 31 primary angle closure glaucoma (PACG) and 22 primary open angle glaucoma (POAG) patients with no previous eye surgery were recruited. Diurnal IOP was measured 5 times per day at four-hourly intervals from 08:00 to 24:00 for 1 week in patients’ study eye using rebound tonometry in a non-clinic environment. The diurnal IOP profiles were compared between PACG and POAG eyes.

Results

For both PACG and POAG eyes, mean patient-measured IOP was highest in the morning, gradually decreased over the course of a day, and was lowest by midnight (p < 0.001). The diurnal IOP fluctuation ± 1 standard deviation (SD), as documented by SD in daily IOP values, was lower in PACG group (1.6 ± 1.1 mmHg) than in POAG group (2.0 ± 1.2 mmHg; p = 0.049). The mean trough IOP ± 1 SD was higher in PACG group (12.9 ± 2.8 mmHg), compared to POAG group (11.5 ± 3.8 mmHg; p = 0.041). The mean IOP level at midnight ± 1 SD in PACG group (14.0 ± 3.2 mmHg) was higher than that in POAG group (12.1 ± 3.7 mmHg; p = 0.013).

Conclusions

IOP in primary glaucoma patients was highest in the morning, and decreased over the course of a day in non-clinic environment. Treated diurnal IOP fluctuation seemed to be greater in POAG than PACG eyes.

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<![CDATA[Influence of Corneal Opacity on Intraocular Pressure Assessment in Patients with Lysosomal Storage Diseases]]> https://www.researchpad.co/article/5989d9fcab0ee8fa60b7288a

Aims

To investigate an influence of mucopolysaccharidosis (MPS)- and Morbus Fabry-associated corneal opacities on intraocular pressure (IOP) measurements and to evaluate the concordance of the different tonometry methods.

Methods

25 MPS patients with or without corneal clouding, 25 Fabry patients with cornea verticillata ≥ grade 2 and 25 healthy age matched controls were prospectively included into this study. Outcome measures: Goldmann applanation tonometry (GAT); palpatory assessment of IOP; Goldmann-correlated intraocular pressure (IOPg), corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH) assessed by Ocular Response Analyzer (ORA); central corneal thickness (CCT) and density assessed with Pentacam. Statistical analysis was performed using linear mixed effect models and Spearman correlation coefficients. The concordance between tonometry methods was assessed using Bland-Altman analysis.

Results

There was no relevant difference between study groups regarding median GAT, IOPg, IOPcc and CCT measurements. The limits of agreement between GAT and IOPcc/IOPg/palpatory IOP in MPS were: [-11.7 to 12.1mmHg], [-8.6 to 15.5 mmHg] and [- 5.4 to 10.1 mmHg] respectively. Limits of agreement were less wide in healthy subjects and Fabry patients. Palpatory IOP was higher in MPS than in healthy controls and Fabry patients. Corneal opacity correlated more strongly with GAT, IOPg, CH, CRF, CCT and corneal density in MPS (r = 0.4, 0.5, 0.5, 0.7, 0.6, 0.6 respectively) than in Fabry patients (r = 0.3, 0.2, -0.03, 0.1, 0.3, -0.2 respectively). In contrast, IOPcc revealed less correlation with corneal opacity than GAT in MPS (r = 0.2 vs. 0.4).

Conclusions

ORA and GAT render less comparable IOP-values in patients suffering from MPS-associated corneal opacity in comparison to Fabry and healthy controls. The IOP seems to be overestimated in opaque MPS-affected corneas. GAT, IOPg and biomechanical parameters of the cornea correlate more strongly with the corneal clouding than IOPcc in MPS patients.

Trial Registration

ClinicalTrials.gov NCT01695161

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<![CDATA[Coarsened Exact Matching of Phaco-Trabectome to Trabectome in Phakic Patients: Lack of Additional Pressure Reduction from Phacoemulsification]]> https://www.researchpad.co/article/5989dadcab0ee8fa60bba262

Purpose

To compare intraocular pressure (IOP) after trabectome-mediated ab interno trabeculectomy surgery in phakic patients (T) and trabectome with same session phacoemulsification (PT) using Coarsened Exact Matching. Although phacoemulsification is associated with IOP reduction when performed on its own, it is not known how much it contributes in PT.

Methods

Subjects were divided into phakic T and PT. Exclusion criteria were follow-up for <12 months and additional glaucoma surgery. Demographics were compared by the Mann-Whitney U test and chi-squared test for continuous and categorical variables, respectively. Multiple imputation was utilized to avoid eliminating data with missing values. Groups were then matched using Coarsened Exact Matching based on age, race, type of glaucoma, baseline IOP, and number of preoperative glaucoma medications. Univariate linear regression was used to examine IOP reduction after surgery; those variables that were statistically significant were included in the final multivariate regression model.

Results

A total of 753 cases were included (T: 255, PT: 498). When all variables except for age were kept constant, there was an additional IOP reduction of 0.05±0.01 mmHg conferred for every yearly increment in age. Every 1 mmHg increase in baseline IOP correlated to an additional IOP reduction of 0.80±0.02 mmHg. Phacoemulsification was not found to be a statistically significant contributor to IOP when comparing T and PT (p≥0.05). T had a 21% IOP reduction to 15.9±3.5 mmHg (p<0.01) while PT had an 18% reduction to 15.5±3.6 mmHg (p<0.01). Number of medications decreased (p<0.01) in both groups from 2.4±1.2 to 1.9±1.3 and from 2.3±1.1 to 1.7±1.3, respectively.

Conclusion

Phacoemulsification does not make a significant contribution to postoperative IOP or number of medications when combined with trabectome surgery in phakic patients.

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<![CDATA[Estimated Cerebrospina Fluid Pressure and the 5-Year Incidence of Primary Open-Angle Glaucoma in a Chinese Population]]> https://www.researchpad.co/article/5989db39ab0ee8fa60bd436d

Purpose

We aim to assess the longitudinal association between baseline estimated cerebrospinal fluid pressure (CSFP) and 5-year incident primary open angle glaucoma (POAG) in a population-based sample of Bai Chinese living in rural China.

Methods

Among the 2133 Bai Chinese aged 50 years or older who had participated in the baseline examination of the Yunnan Minority Eye Study, 1520 (71.3%) attended the follow-up examination after five years and 1485 were at risk of developing POAG. Participants underwent comprehensive ophthalmic examinations at both baseline and follow-up surveys. CSFP in mmHg was estimated as 0.55 × body mass index (kg/m2) + 0.16 × diastolic blood pressure (mmHg)-0.18 × age (years)-1.91. Glaucoma was defined using the International Society of Geographical and Epidemiological Ophthalmology Classification criteria. Multivariate logistic regression models were established to determine the association between baseline CSFP and incident POAG.

Results

After a mean follow-up time of 5 years, 19 new cases of POAG were detected, with an incidence rate of 1.3% (95% confidence interval, 0.7–1.9%). In multivariate logistic regression analysis, after adjusting for age, gender, education, intraocular pressure, central corneal thickness, hypertension and diabetes, no significant associations, nor any trends, were evident between baseline estimated CSFP and incident POAG. The association between estimated CSFP per mmHg increase in baseline and 5-year incidence of POAG was also non-significant, with adjusted relative risk of 0.96 (P = 0.11) in multivariate analysis.

Conclusions

This longitudinal cohort study does not support previously observed cross-sectional association between estimated CSFP and POAG in population-based studies.

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<![CDATA[Positional and Curvature Difference of Lamina Cribrosa According to the Baseline Intraocular Pressure in Primary Open-Angle Glaucoma: A Swept-Source Optical Coherence Tomography (SS-OCT) Study]]> https://www.researchpad.co/article/5989daeaab0ee8fa60bbebf0

Purpose

To investigate the variation of lamina cribrosa (LC) structure based on the baseline intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG) and healthy individuals using swept-source optical coherence tomography.

Methods

A total of 108 eyes with POAG and 61 healthy eyes were recruited. Based on the baseline IOP, the POAG eyes were divided into higher-baseline IOP (HTG; baseline IOP > 21 mmHg, n = 38 eyes) and lower-baseline IOP (NTG; baseline IOP ≤ 21 mmHg, n = 70 eyes). The anterior laminar insertion depth (ALID), mean LC depth (mLCD), and the LC curvature index (mLCD–ALID) were measured, and compared among the three groups. The regional variation of LC structure was evaluated by vertical-horizontal ALID difference.

Results

The mLCD and LC curvature index were greatest in HTG eyes (520.3 ± 123.0 and 80.9 ± 30.7 μm), followed by NTG (463.2 ± 110.5 and 64.5 ± 30.7 μm) and healthy eyes (382.9 ± 107.6 and 47.6 ± 25.7 μm, all P < 0.001). However, there were no significant difference in ALID between HTG and NTG eyes. The vertical-horizontal ALID difference was larger in NTG eyes (72.8 ± 56.2 μm) than in HTG (32.7 ± 61.4 μm, P = 0.004) and healthy eyes (25.5 ± 34.8 μm, P < 0.001).

Conclusions

Lamina cribrosa position and curvature differed in POAG eyes with low and high IOP. This would support the theory that IOP induced biomechanical effects on the optic play a role on glaucoma.

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<![CDATA[Effects of Exercise on the Structure and Circulation of Choroid in Normal Eyes]]> https://www.researchpad.co/article/5989dadfab0ee8fa60bbb5a9

Aims

To determine the effects of dynamic exercise on the circulation and the luminal and stromal areas of the choroid in normal eyes.

Methods

This was a prospective interventional study of 38 eyes of 38 normal subjects enrolled by invitation. The systolic and diastolic blood pressures, heart rate, intraocularpressure, mean ocular perfusion pressure (MOPP), choroidal blood velocity, and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before, and immediately after mild dynamic exercise. The same measurements were recorded after 10 min of rest. The choroidal blood velocity was measured bylaser speckle flowgraphy, and the mean blur rate was used for the evaluations. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross sectional choroidal area, luminal areas, stromal areas, and the ratio of luminal area to total choroidal area (L/C ratio) were determined from these images.

Results

The systolic and diastolic blood pressures, heart rate, MOPP, and the mean blur rate were significantly increased immediately after the exercise and significantly decreased 10 minutes after the exercise. There wereno significant changes in the mean CCT, the mean total choroidal area, the mean luminal and stromal areas, and the mean L/C ratio after the exercise.

Conclusions

Our results suggest that a rest period is needed before measurements of blood flow velocity but not necessary for the EDI-OCT imaging to determine the choroidal thickness and area.

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<![CDATA[Estimated Trans-Lamina Cribrosa Pressure Differences in Low-Teen and High-Teen Intraocular Pressure Normal Tension Glaucoma: The Korean National Health and Nutrition Examination Survey]]> https://www.researchpad.co/article/5989daffab0ee8fa60bc6143

Background

To investigate the association between estimated trans-lamina cribrosa pressure difference (TLCPD) and prevalence of normal tension glaucoma (NTG) with low-teen and high-teen intraocular pressure (IOP) using a population-based study design.

Methods

A total of 12,743 adults (≥ 40 years of age) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2012 were included. Using a previously developed formula, cerebrospinal fluid pressure (CSFP) in mmHg was estimated as 0.55 × body mass index (kg/m2) + 0.16 × diastolic blood pressure (mmHg)—0.18 × age (years)—1.91. TLCPD was calculated as IOP–CSFP. The NTG subjects were divided into two groups according to IOP level: low-teen NTG (IOP ≤ 15 mmHg) and high-teen NTG (15 mmHg < IOP ≤ 21 mmHg) groups. The association between TLCPD and the prevalence of NTG was assessed in the low- and high-teen IOP groups.

Results

In the normal population (n = 12,069), the weighted mean estimated CSFP was 11.69 ± 0.04 mmHg and the weighted mean TLCPD 2.31 ± 0.06 mmHg. Significantly higher TLCPD (p < 0.001; 6.48 ± 0.27 mmHg) was found in the high-teen NTG compared with the normal group. On the other hand, there was no significant difference in TLCPD between normal and low-teen NTG subjects (p = 0.395; 2.31 ± 0.06 vs. 2.11 ± 0.24 mmHg). Multivariate logistic regression analysis revealed that TLCPD was significantly associated with the prevalence of NTG in the high-teen IOP group (p = 0.006; OR: 1.09; 95% CI: 1.02, 1.15), but not the low-teen IOP group (p = 0.636). Instead, the presence of hypertension was significantly associated with the prevalence of NTG in the low-teen IOP group (p < 0.001; OR: 1.65; 95% CI: 1.26, 2.16).

Conclusions

TLCPD was significantly associated with the prevalence of NTG in high-teen IOP subjects, but not low-teen IOP subjects, in whom hypertension may be more closely associated. This study suggests that the underlying mechanisms may differ between low-teen and high-teen NTG patients.

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<![CDATA[Increased Intraocular Pressure and Hyperglycemic Level in Diabetic Patients]]> https://www.researchpad.co/article/5989daa1ab0ee8fa60ba5cf5

Purpose

To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR).

Methods

A retrospective chart review was performed on subjects with a diagnosis of NPDR and a corresponding HbA1c level measured within 90 days before or after an IOP measurement over a two-year period. Exclusion criteria included a diagnosis of glaucoma or treatment with IOP lowering medications or oral or topical steroids.

Results

Using 14.5mmHg as a baseline mean value for IOP, 42 subjects had an IOP < 14.5mmHg and mean HbA1c of 8.1±1.1, while 72 subjects had an IOP ≥ 14.5mmHg and a mean HbA1c of 9.0±2.1. Although there was an overlap in the confidence intervals, a significant difference (P = 0.01) in the mean HbA1c level was observed in regression analysis between the two groups. Importantly, diabetic subjects with elevated HbA1c levels rarely (<1%) exhibited reduced IOP levels.

Conclusions

Diabetic subjects with elevated HbA1c levels exhibited significantly higher IOPs compared to those with lower HbA1c levels. Findings from this study indicate an association between hyperglycemia and elevated IOP and that poor glycemic control may contribute to increased IOP levels in long-term diabetic patients.

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<![CDATA[Measurement of Outflow Facility Using iPerfusion]]> https://www.researchpad.co/article/5989dac8ab0ee8fa60bb3292

Elevated intraocular pressure (IOP) is the predominant risk factor for glaucoma, and reducing IOP is the only successful strategy to prevent further glaucomatous vision loss. IOP is determined by the balance between the rates of aqueous humour secretion and outflow, and a pathological reduction in the hydraulic conductance of outflow, known as outflow facility, is responsible for IOP elevation in glaucoma. Mouse models are often used to investigate the mechanisms controlling outflow facility, but the diminutive size of the mouse eye makes measurement of outflow technically challenging. In this study, we present a new approach to measure and analyse outflow facility using iPerfusion, which incorporates an actuated pressure reservoir, thermal flow sensor, differential pressure measurement and an automated computerised interface. In enucleated eyes from C57BL/6J mice, the flow-pressure relationship is highly non-linear and is well represented by an empirical power law model that describes the pressure dependence of outflow facility. At zero pressure, the measured flow is indistinguishable from zero, confirming the absence of any significant pressure independent flow in enucleated eyes. Comparison with the commonly used 2-parameter linear outflow model reveals that inappropriate application of a linear fit to a non-linear flow-pressure relationship introduces considerable errors in the estimation of outflow facility and leads to the false impression of pressure-independent outflow. Data from a population of enucleated eyes from C57BL/6J mice show that outflow facility is best described by a lognormal distribution, with 6-fold variability between individuals, but with relatively tight correlation of facility between fellow eyes. iPerfusion represents a platform technology to accurately and robustly characterise the flow-pressure relationship in enucleated mouse eyes for the purpose of glaucoma research and with minor modifications, may be applied in vivo to mice, as well as to eyes from other species or different biofluidic systems.

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<![CDATA[Allometry and Scaling of the Intraocular Pressure and Aqueous Humour Flow Rate in Vertebrate Eyes]]> https://www.researchpad.co/article/5989dac4ab0ee8fa60bb1fce

In vertebrates, intraocular pressure (IOP) is required to maintain the eye into a shape allowing it to function as an optical instrument. It is sustained by the balance between the production of aqueous humour by the ciliary body and the resistance to its outflow from the eye. Dysregulation of the IOP is often pathological to vision. High IOP may lead to glaucoma, which is in man the second most prevalent cause of blindness. Here, we examine the importance of the IOP and rate of formation of aqueous humour in the development of vertebrate eyes by performing allometric and scaling analyses of the forces acting on the eye during head movement and the energy demands of the cornea, and testing the predictions of the models against a list of measurements in vertebrates collated through a systematic review. We show that the IOP has a weak dependence on body mass, and that in order to maintain the focal length of the eye, it needs to be an order of magnitude greater than the pressure drop across the eye resulting from gravity or head movement. This constitutes an evolutionary constraint that is common to all vertebrates. In animals with cornea-based optics, this constraint also represents a condition to maintain visual acuity. Estimated IOPs were found to increase with the evolution of terrestrial animals. The rate of formation of aqueous humour was found to be adjusted to the metabolic requirements of the cornea, scaling as Vac0.67, where Vac is the volume of the anterior chamber. The present work highlights an interdependence between IOP and aqueous flow rate crucial to ocular function that must be considered to understand the evolution of the dioptric apparatus. It should also be taken into consideration in the prevention and treatment of glaucoma.

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<![CDATA[Circadian Patterns of Intraocular Pressure Fluctuation among Normal-Tension Glaucoma Optic Disc Phenotypes]]> https://www.researchpad.co/article/5989da95ab0ee8fa60ba19dd

Objective

To characterize the 24-h habitual-position intraocular pressure (IOP) patterns of optic disc phenotypes (ODPs) in untreated normal-tension glaucoma (NTG) and the relationships between nocturnal IOP elevation and various clinical factors.

Design

Prospective, cross-sectional, observational study.

Methods

Eighty-two NTG patients with focal ischemic (FI) ODP and 82 age- and disease severity-matched NTG patients with myopic glaucomatous (MG) ODP were recruited prospectively over 3 years. The IOP was recorded 11 times over a 24-hour (h) period by a single ophthalmologist using a hand-held tonometer (TonoPen®XL). A cosinor model was used to describe the 24-h IOP rhythm. Associations between nocturnal IOP elevation and both ocular and demographic variables were evaluated using the generalized estimating equation (GEE).

Results

Mean habitual-position IOP was significantly higher during nighttime than daytime in the FI group (16.44 vs. 14.23 mmHg, P < 0.001), but not in the MG group (15.91 vs. 15.70 mmHg, P = 0.82). The FI group also exhibited a significantly higher peak IOP during sleeping hours (P = 0.01) and lower trough IOP during the 24-h period than the MG group (P < 0.01). The MG group showed a significantly higher peak IOP during waking hours than the FI group (P < 0.01). Therefore, 24-h IOP fluctuation range was significantly higher in the FI group than the MG group (P = 0.013). In the FI group, peak habitual-position IOP and the highest frequency of IOP peaks occurred during sleeping hours (12 AM–6 AM). By contrast, IOP peaks in the MG group occurred during morning hours (8 AM–12 PM). The FI group showed an overall nocturnal acrophase in habitual-position IOP, with 45 patients (54.9%) having a nocturnal acrophase; 10 (12.2%), a diurnal acrophase; and 27 (32.9%), no evident acrophase. By contrast, the MG group showed no evident peak in habitual-position IOP, with 9 patients (10.9%) having a nocturnal acrophase; 43 (52.4%), a diurnal acrophase; and 30 (36.6%), no evident acrophase. In multivariate modeling using the GEE, ODP (P < 0.001) and spherical equivalent (SE, P = 0.001) were independently associated with nocturnal IOP elevation.

Conclusions

Based on 24-h habitual-position IOP data, FI is associated with significant nocturnal IOP elevation, while no such nocturnal IOP elevation is observed in MG ODP. In untreated NTG, there are also significant differences in the 24-h IOP pattern between FI and MG ODPs.

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<![CDATA[Astrocyte Structural and Molecular Response to Elevated Intraocular Pressure Occurs Rapidly and Precedes Axonal Tubulin Rearrangement within the Optic Nerve Head in a Rat Model]]> https://www.researchpad.co/article/5989db39ab0ee8fa60bd435b

Glaucomatous axon injury occurs at the level of the optic nerve head (ONH) in response to uncontrolled intraocular pressure (IOP). The temporal response of ONH astrocytes (glial cells responsible for axonal support) to elevated IOP remains unknown. Here, we evaluate the response of actin-based astrocyte extensions and integrin-based signaling within the ONH to 8 hours of IOP elevation in a rat model. IOP elevation of 60 mm Hg was achieved under isoflurane anesthesia using anterior chamber cannulation connected to a saline reservoir. ONH astrocytic extension orientation was significantly and regionally rearranged immediately after IOP elevation (inferior ONH, 43.2° ± 13.3° with respect to the anterior-posterior axis versus 84.1° ± 1.3° in controls, p<0.05), and re-orientated back to baseline orientation 1 day post IOP normalization. ONH axonal microtubule filament label intensity was significantly reduced 1 and 3 days post IOP normalization, and returned to control levels on day 5. Phosphorylated focal adhesion kinase (FAK) levels steadily decreased after IOP normalization, while levels of phosphorylated paxillin (a downstream target of FAK involved in focal adhesion dynamics) were significantly elevated 5 days post IOP normalization. The levels of phosphorylated cortactin (a downstream target of Src kinase involved in actin polymerization) were significantly elevated 1 and 3 days post IOP normalization and returned to control levels by day 5. No significant axon degeneration was noted by morphologic assessment up to 5 days post IOP normalization. Actin-based astrocyte structure and signaling within the ONH are significantly altered within hours after IOP elevation and prior to axonal cytoskeletal rearrangement, producing some responses that recover rapidly and others that persist for days despite IOP normalization.

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<![CDATA[Tonographic Effect of Ocular Response Analyzer in Comparison to Goldmann Applanation Tonometry]]> https://www.researchpad.co/article/5989da1eab0ee8fa60b7de66

Aims

The tonographic effect is a phenomenon of intraocular pressure (IOP) reduction following repeated tonometry. This study examines whether the tonographic effect occurs following IOP measurement performed with Ocular Response Analyzer (ORA).

Methods

Both eyes of 31 glaucoma patients and 35 healthy controls underwent nine IOP-measurements performed with GAT and ORA. The number of GAT and ORA measurements performed on each eye differed depending on the randomly allocated investigation scheme. Central corneal thickness (CCT), anterior chamber volume (ACV) and anterior chamber depth (ACD) were assessed with Pentacam before and after the repeated GAT/ORA measurements.

Results

There was no statistically significant tonographic effect for IOP readings obtained by the ORA: corneal compensated intraocular pressure (IOPcc) (-0.11 ± 3.06 mmHg, p = 0.843 in patients and -0.71 ± 3.28 mmHg, p = 0.208 for controls) and Goldmann-correlated intraocular pressure (IOPg) (-0.31 ± 2.38 mmHg, p = 0.469 in patients and -0.31 ± 2.37 mmHg, p = 0.441 in controls) measured with ORA. There was a significant IOP reduction from the first to the second GAT measurement, i.e. tonographic effect (-0.55 ± 2.00 mmHg, p = 0.138 in patients and -1.15 ± 1.52 mmHg, p < 0.001 in controls). CCT, corneal hysteresis (CH) and corneal resistance factor (CRF) were lower in glaucoma patients. The repeated IOP measurements resulted in an increase of CCT in all subjects (but no change of ACV and ACD). The tonographic effect of GAT correlated with CCT in glaucoma patients (r = 0.37).

Conclusion

In contrast to GAT, repeated ORA measurements do not result in the tonographic effect. Repeated IOP measurements resulted in an increase of central corneal thickness, but did not influence the volume and depth of anterior chamber.

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<![CDATA[ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway]]> https://www.researchpad.co/article/5989db5dab0ee8fa60be0481

Elevated intraocular pressure is the most prevalent and only treatable risk factor for glaucoma, a degenerative disease of the optic nerve. While treatment options to slow disease progression are available, all current therapeutic and surgical treatments have unwanted side effects or limited efficacy, resulting in the need to identify new options. Previous reports from our laboratory have established a novel ocular hypotensive effect of ATP-sensitive potassium channel (KATP) openers including diazoxide (DZ) and nicorandil (NCD). In the current study, we evaluated the role of Erk1/2 signaling pathway in KATP channel opener mediated reduction of intraocular pressure (IOP). Western blot analysis of DZ and NCD treated primary normal trabecular meshwork (NTM) cells, human TM (isolated from perfusion cultures of human anterior segments) and mouse eyes showed increased phosphorylation of Erk1/2 when compared to vehicle treated controls. DZ and NCD mediated pressure reduction (p<0.02) in human anterior segments (n = 7 for DZ, n = 4 for NCD) was abrogated by U0126 (DZ + U0126: -9.7 ± 11.5%, p = 0.11; NCD + U0126: -0.1 ± 11.5%, p = 1.0). In contrast, U0126 had no effect on latanoprostfree acid-induced pressure reduction (-52.5 ± 6.8%, n = 4, p = 0.001). In mice, DZ and NCD reduced IOP (DZ, 14.9 ± 3.8%, NCD, 16.9 ± 2.5%, n = 10, p<0.001), but the pressure reduction was inhibited by U0126 (DZ + U0126, 0.7 ± 3.0%; NCD + U0126, 0.9 ± 2.2%, n = 10, p>0.1). Histologic evaluation of transmission electron micrographs from DZ + U0126 and NCD + U0126 treated eyes revealed no observable morphological changes in the ultrastructure of the conventional outflow pathway. Taken together, the results indicate that the Erk1/2 pathway is necessary for IOP reduction by KATP channel openers DZ and NCD.

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