Effect of Treatment on the Rate of Visual Field Change in the Ocular Hypertension Treatment Study Observation Group

Moraes, Carlos Gustavo De; Demirel, Shaban; Gardiner, Stuart K.; Liebmann, Jeffrey M.; Cioffi, George A.; Ritch, Robert; Gordon, Mae O.; Kass, Michael A.

doi:10.1167/iovs.11-8186

Cited by 53 publications

(40 citation statements)

References 24 publications

(21 reference statements)

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“…23 It should be noted that the mean follow-up duration (53.8±10.4 in GS and 48.3±11.8 in glaucoma) and the mean time to progression (53.3 ± 10.5 in GS and 47.1 ± 11.9 in glaucoma) were very close. This finding indicates that an average of 4 years of follow-up is required to observe visual-field progression using PLR in a treated glaucoma cohort, and we might have had found higher number of progressing eyes if these eyes were followed up for a longer period of time or if they were 24 Our results agree with a study conducted by Sung et al, 25 who demonstrated that an abnormal inferior optic disc or RNFL sector were associated with future visualfield progression. We found that lower baseline measures in the inferior optic nerve and RNFL are more likely to influence progressive glaucomatous visual-field loss.…”

Section: Discussionsupporting

confidence: 91%

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

Sehi

Bhardwaj

Chung

et al. 2012

Eye

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Purpose The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Methods Participants with Z28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of 41 dB/year at Z2 adjacent test locations in the same hemifield at Po0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Results Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5 ± 11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8 ± 11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR ¼ 3.76, 95% confidence interval (CI): 1.02-6.80, P ¼ 0.04), SLPECC inferior RNFLT (per À 1 lm, HR ¼ 1.38, 95% CI: 1.02-2.2, P ¼ 0.02), and TDOCT inferior RNFLT (per À 1 lm, HR ¼ 1.11, 95% CI: 1.04-1.2, P ¼ 0.001) had significant HRs for SAP progression. Conclusion Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.

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Section: Discussionsupporting

confidence: 91%

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

Sehi

Bhardwaj

Chung

et al. 2012

Eye

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“…25 While the acute response is reasonably well established, it was important to determine whether there was a sustained elevation in extracellular ATP as many forms of glaucoma progresses over a time course of years. [44][45][46] Given that a loss of RGCs and an elevation of IOP were demonstrated in all three models used here, the increases in extracellular ATP likely result from a combination of mechanosensitive release and cell rupture.…”

Section: Discussionmentioning

confidence: 90%

“…Given that pathophysiological changes develop in many forms of glaucoma over the course of several years, [44][45][46] it is important to demonstrate that any putative mechanism linking elevation of IOP to disease also shows a sustained change. This study provides strong support that the changes in purinergic signaling are sustained throughout the period of IOP elevation.…”

Section: Physiological Implicationsmentioning

confidence: 99%

Rat, Mouse, and Primate Models of Chronic Glaucoma Show Sustained Elevation of Extracellular ATP and Altered Purinergic Signaling in the Posterior Eye

Sévigny

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Lu W, Hu H, Sévigny J, et al. Rat, mouse, and primate models of chronic glaucoma show sustained elevation of extracellular ATP and altered purinergic signaling in the posterior eye. Invest Ophthalmol Vis Sci. 2015;56:3075-3083. DOI:10.1167/iovs.14-15891 PURPOSE. The cellular mechanisms linking elevated IOP with glaucomatous damage remain unresolved. Mechanical strains and short-term increases in IOP can trigger ATP release from retinal neurons and astrocytes, but the response to chronic IOP elevation is unknown. As excess extracellular ATP can increase inflammation and damage neurons, we asked if sustained IOP elevation was associated with a sustained increase in extracellular ATP in the posterior eye. METHODS.No ideal animal model of chronic glaucoma exists, so three different models were used. Tg-Myoc Y437H mice were examined at 40 weeks, while IOP was elevated in rats following injection of hypertonic saline into episcleral veins and in cynomolgus monkeys by laser photocoagulation of the trabecular meshwork. The ATP levels were measured using the luciferin-luciferase assay while levels of NTPDase1 were assessed using qPCR, immunoblots, and immunohistochemistry.RESULTS. The ATP levels were elevated in the vitreal humor of rats, mice, and primates after a sustained period of IOP elevation. The ecto-ATPase NTPDase1 was elevated in optic nerve head astrocytes exposed to extracellular ATP for an extended period. NTPDase1 was also elevated in the retinal tissue of rats, mice, and primates, and in the optic nerve of rats, with chronic elevation in IOP. CONCLUSIONS.A sustained elevation in extracellular ATP, and upregulation of NTPDase1, occurs in the posterior eye of rat, mouse, and primate models of chronic glaucoma. This suggests the elevation in extracellular ATP may be sustained in chronic glaucoma, and implies a role for altered purinergic signaling in the disease.Keywords: ATP release, mechanosensitive, retina G laucoma is one of the leading causes of blindness in humans and is characterized by damage to retinal ganglion cells (RGCs) and the optic nerve.1,2 While abnormally high IOP is a widely recognized risk factor, 3,4 the molecular pathways linking elevated IOP and RGC loss are complex. Although several inroads toward understanding the mechanisms have recently been made, 5-13 much remains to be learned, particularly regarding the responses in chronic injury. Extracellular ATP is a likely candidate to link the elevated IOP in glaucoma to perturbed signaling in the retina and optic nerve. Throughout the body, released ATP conveys information about mechanical strain and accompanies shear stress, swelling, and stretch. [14][15][16][17][18] This mechanosensitive release of ATP can initiate a series of physiological and pathological responses including cell death, volume regulation, pain, inflammatory responses, and neuroprotection by activating ionotropic P2X and metabotropic P2Y receptors. 19Evidence is accumulating for an increased release of ATP following IOP elevation in glaucoma. For instance...

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“…Criteria for overall change (i.e., for the entire visual field) have been based, arbitrarily, on fixed numbers of changing test locations, [8][9][10][11][12] and change at individual test locations has been defined with similarly arbitrary criteria of slope and associated P value. [8][9][10][11]13,14 In consequence, criteria for visual field change with PLR are not adapted to an individual patient's data. Rather, their specificity is likely to vary between patients, making results difficult to interpret.…”

Section: Discussionmentioning

confidence: 99%

Visual Field Progression in Glaucoma: Estimating the Overall Significance of Deterioration with Permutation Analyses of Pointwise Linear Regression (PoPLR)

O’Leary¹,

Chauhan²,

Artes³

2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To establish a method for estimating the overall statistical significance of visual field deterioration from an individual patient's data, and to compare its performance to pointwise linear regression.METHODS. The Truncated Product Method was used to calculate a statistic S that combines evidence of deterioration from individual test locations in the visual field. The overall statistical significance (P value) of visual field deterioration was inferred by comparing S with its permutation distribution, derived from repeated reordering of the visual field series. Permutation of pointwise linear regression (PoPLR) and pointwise linear regression were evaluated in data from patients with glaucoma (944 eyes, median mean deviation À2.9 dB, interquartile range: À6.3, À1.2 dB) followed for more than 4 years (median 10 examinations over 8 years). Falsepositive rates were estimated from randomly reordered series of this dataset, and hit rates (proportion of eyes with significant deterioration) were estimated from the original series. RESULTS.The false-positive rates of PoPLR were indistinguishable from the corresponding nominal significance levels and were independent of baseline visual field damage and length of follow-up. At P < 0.05, the hit rates of PoPLR were 12, 29, and 42%, at the fifth, eighth, and final examinations, respectively, and at matching specificities they were consistently higher than those of pointwise linear regression. CONCLUSIONS.In contrast to population-based progression analyses, PoPLR provides a continuous estimate of statistical significance for visual field deterioration individualized to a particular patient's data. This allows close control over specificity, essential for monitoring patients in clinical practice and in clinical trials. (Invest Ophthalmol Vis Sci. 2012; 53:6776-6784)

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Effect of Treatment on the Rate of Visual Field Change in the Ocular Hypertension Treatment Study Observation Group

Cited by 53 publications

References 24 publications

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

Rat, Mouse, and Primate Models of Chronic Glaucoma Show Sustained Elevation of Extracellular ATP and Altered Purinergic Signaling in the Posterior Eye

Visual Field Progression in Glaucoma: Estimating the Overall Significance of Deterioration with Permutation Analyses of Pointwise Linear Regression (PoPLR)

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