Predictive Factors for Open-Angle Glaucoma among Patients with Ocular Hypertension in the European Glaucoma Prevention Study

doi:10.1016/j.ophtha.2006.05.075

Ophthalmology

Volume 114, Issue 1, January 2007, Pages 3-9

https://doi.org/10.1016/j.ophtha.2006.05.075 Get rights and content

Objective

To evaluate the predictive factors of open-angle glaucoma (OAG) in patients affected by ocular hypertension enrolled in the European Glaucoma Prevention Study (EGPS).

Design

Randomized, double-masked, controlled clinical trial.

Participants

One thousand seventy-seven patients, ≥30 years old, were enrolled at 18 European centers. The patients met inclusion criteria: intraocular pressure, 22 to 29 mmHg; 2 normal and reliable visual fields (VFs) (on the basis of mean deviation and corrected pattern standard deviation [PSD]); and a normal optic disc, as determined by an optic disc reading center.

Intervention

Treatment with dorzolamide or a placebo (the vehicle of dorzolamide) in one or both eyes.

Main Outcome Measures

Efficacy end points were VF and/or optic disc changes. Baseline demographic and clinical data were collected before randomization, except for corneal thickness measurements, which were determined during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the EGPS had developed OAG.

Results

In multivariate analyses, factors that predicted the development of OAG included older age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.04–1.69), larger vertical cup-to-disc (C/D) ratio (HR, 1.34; 95% CI, 1.14–1.58), larger vertical C/D ratio asymmetry (HR, 1.46; 95% CI, 1.11–1.93), higher PSD (HR, 1.66; 95% CI, 1.15–2.38), and lesser central corneal thickness (HR, 1.32; 95% CI, 1.05–1.67).

Conclusions

Baseline age, vertical C/D ratio, vertical C/D ratio asymmetry, and PSD were good predictors of the onset of OAG in the EGPS. Central corneal thickness was found to be a powerful predictor of the development of OAG. The EGPS results agree with the findings of the Ocular Hypertension Treatment Study and support the need for a thorough evaluation of patients with ocular hypertension.

Section snippets

Subjects and Methods

The EGPS was a multicenter, randomized, double-masked, placebo-controlled clinical trial. The design and methods of the EGPS have been described12, 13 and are summarized as follows.

The protocol was approved by the ethical review committee of each participating clinic. In brief, 1081 individuals with IOP ≥ 22 mmHg in at least one eye and no evidence of glaucomatous damage were randomized to either dorzolamide or a placebo. Four patients who were already affected by glaucoma at the time of

Results

Baseline demographic and clinical factors of participants who did and did not develop OAG in the EGPS are reported in Table 1, Table 2. The percentages in Table 1 were calculated by dividing the number of participants who developed OAG by the number of randomized participants (1077). These values are not adjusted for duration of follow-up. Central corneal thickness measurements, which began in 2002, were completed in 854 participants.

Given the very high correlation between the vertical and

Discussion

It is deemed important to assess the predictive (prognostic) factors for the development of OAG to identify the ocular hypertension patients at greater risk for future progression to OAG who may benefit from a prompt therapeutic approach.

In the EGPS, after adjusting for the treatment arm, older age, larger vertical C/D ratio, larger vertical C/D ratio asymmetry, higher PSD, and thinner CCT were the statistically significant predictive factors for development of OAG over a 5-year period. Higher

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Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension
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To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results.
Cross-sectional study.
Six hundred eyes of 306 patients with OHT.
All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis.
Prevalence of RNFL defects.
The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 μm and 568.8 ± 31.2 μm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch’s membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03–1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01–3.29), cup volume (mm³) (OR, 1.24; 95% CI, 1.01–1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01–1.07) were associated with RNFL defects.
A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Value of disc topographic measurements for the discrimination of glaucoma suspects from early primary open angle glaucoma cases: A thin discriminative line
2023, Photodiagnosis and Photodynamic Therapy
To determine the diagnostic value of optic nerve head (ONH) topographic parameters measured by swept-source optical coherence tomography (SS-OCT) in differentiating between early glaucoma cases, glaucoma suspects (GSs), and healthy eyes.
The files of GSs, those with an early primary open angle glaucoma (POAG) diagnosis, and healthy eyes were retrospectively screened. Demographic characteristics, retinal nerve fibre measurements, visual field examinations, and ONH topographic parameters, including rim area, disc area, vertical and horizontal cup-to-disc ratios (CDRs), and cup volume, were compared between the groups. A receiver operating characteristic (ROC) curve analysis was performed on the ONH parameters.
A total of 170 eyes from 85 GSs, 114 eyes from 57 patients with a diagnosis of early POAG, and 70 healthy eyes from 48 subjects were included in the study. The median age was 52.1 ± 0.9 years for the POAG group, 60.2 ± 1.1 years for the GS group, and 60.5 ± 1.6 for the controls. In the comparison of the ONH parameters between the groups, only rim area statistically significantly differed between the POAG and GS groups. However, all ONH parameters statistically significantly differed between the GS and control groups (p< 0.05). The mean rim areas of the GS, POAG, and control groups were 1.278 ± 0.055 mm², 1.073 ± 0.065 mm², and 1.446 ± 0.055 mm², respectively, being statistically significantly higher in the controls and lower in the POAG group (p < 0.001). The highest area under the curve (AUC) value belonged to vertical CDR for the discrimination of the eyes with POAG from healthy eyes [0.806 (0.728–0.869, p < 0.001] and rim area for the discrimination of POAG cases and GSs [0.728 (0.650–0.797, p < 0.001].
There are significant differences in all ONH parameters between the eyes of GSs and healthy eyes. For the discrimination of early POAG and GS cases, topographic disc parameters may have value. In this study, rim area significantly differed between the GS and POAG groups, and it had the highest AUC value amongst the evaluated ONH parameters in the discrimination of early POAG cases S GSs.
Comparison of Goldmann and ORA tonometers in newly diagnosed, untreated, POAG and OHT eyes
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Las propiedades biomecánicas corneales en ojos de pacientes recién diagnosticados de glaucoma e hipertensión oculares (HTO) y que no han recibido tratamiento previo son de gran interés, porque pueden suponer una fuente de error en la medida de la presión intraocular (PIO) medida mediante tonometría de aplanación Goldmann (TAG) y Ocular Response Analyzer® (ORA).
El principal objetivo de este estudio es evaluar los valores de la PIO obtenidos con la TAG y el ORA, en pacientes con glaucoma primario de ángulo abierto (GPAA) e HTO que no han recibido tratamiento antiglaucomatoso previo.
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Se incluyeron 51 pacientes con GPAA y 34 pacientes con HTO. Se encontró un valor de la PIO corneo compensada (PIOcc) significativamente mayor que el de la PIO TAG en el grupo de GPAA (p = 0,0002), mientras que no se encontraron diferencias significativas entre ambos tonómetros en el grupo de HTO (p = 0,1).
La TAG parece infraestimar la PIO «real» en pacientes con GPAA sin tratamiento hipotensor previo, mientras que parece ser más exacta en pacientes con HTO.
The corneal biomechanical properties in naïve, untreated glaucoma and ocular hypertension (OHT) eyes is interesting, because it may be a source of error in intraocular pressure (IOP) measurements by Goldmann applanation tonometer (GAT) and ocular response analyzer (ORA).
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Observational, masked, cross sectional observational study. Newly diagnosed, untreated POAG and OHT eyes were included.
Fifty-one POAG and 34 OHT eyes were analyzed. We found that IOPcc (IOP corneal-compensated) was significantly higher than GAT IOP in POAG (P=.0002) while we did not find any significant difference between both tonometers in OHT (P=.1).
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Age and intraocular pressure (IOP) are the two most important risk factors for the development and progression of open-angle glaucoma. While IOP is commonly considered in models of experimental glaucoma (EG), most studies use juvenile or adult animals and seldom older animals which are representative of the human disease. This paper provides a concise review of how retinal ganglion cell (RGC) loss, the hallmark of glaucoma, can be evaluated in EG with a special emphasis on serial in vivo imaging, a parallel approach used in clinical practice. It appraises the suitability of EG models for the purpose of in vivo imaging and argues for the use of models that provide a sustained elevation of IOP, without compromise of the ocular media. In a study with parallel cohorts of adult (3-month-old, equivalent to 20 human years) and old (2-year-old, equivalent to 70 human years) mice, we compare the effects of elevated IOP on serial ganglion cell complex thickness and individual RGC dendritic morphology changes obtained in vivo. We also evaluate how age modulates the impact of elevated IOP on RGC somal and axonal density in histological analysis as well the density of melanopsin RGCs. We discuss the challenges of using old animals and emphasize the potential of single RGC imaging for understanding the pathobiology of RGC loss and evaluating new therapeutic avenues.
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: Manuscript no. 2005-1232.

: Supported by the European Commission, Brussels, Belgium (BIOMED II program, contract no.: BMH4-CT-96-1598), and Merck & Co., Inc., Whitehouse Station, New Jersey.

: Correspondence to Stefano Miglior, MD, Università di Milano Bicocca, Policlinico di Monza, Via Amati 111, 20052, Monza (Mi), Italy. E-mail:[email protected]

^⁎: See “Appendix” for members of the EGPS Group and Writing Committee.

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Original ArticlePredictive Factors for Open-Angle Glaucoma among Patients with Ocular Hypertension in the European Glaucoma Prevention Study

Objective

Design

Participants

Intervention

Main Outcome Measures

Results

Conclusions

Section snippets

Subjects and Methods

Results

Discussion

Am J Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Surv Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Primary Open-Angle Glaucoma

Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans: the Baltimore Eye Survey

Arch Ophthalmol

Hypertension, perfusion pressure, and primary open angle glaucoma: a population-based assessment

Arch Ophthalmol

Risk factors for open-angle glaucoma: the Barbados Eye Study

Arch Ophthalmol

Incidence of open-angle glaucoma: the Barbados Eye Study

Arch Ophthalmol

Family history and risk of primary open angle glaucoma: the Baltimore Eye Survey

Arch Ophthalmol

Incident open-angle glaucoma and blood pressure

Arch Ophthalmol

Original Article
Predictive Factors for Open-Angle Glaucoma among Patients with Ocular Hypertension in the European Glaucoma Prevention Study