Elsevier

Ophthalmology

Volume 114, Issue 11, November 2007, Pages 1965-1972
Ophthalmology

Original article
Predictors of Long-term Progression in the Early Manifest Glaucoma Trial

https://doi.org/10.1016/j.ophtha.2007.03.016Get rights and content

Purpose

To determine progression factors at the end of the Early Manifest Glaucoma Trial (EMGT) based on all EMGT patients and evaluate separately patients with higher and lower baseline intraocular pressure (IOP; median split).

Design

Cohort of clinical trial participants.

Participants

Patients with early open-angle glaucoma randomized to argon laser trabeculoplasty plus betaxolol (n = 129) or no immediate treatment (n = 126), examined every 3 months for up to 11 years.

Methods

Cox proportional hazard analyses, expressed by hazard ratios (HRs) and 95% confidence intervals (CIs).

Main Outcome Measure

Time to progression, defined by perimetric and photographic disc criteria.

Results

Overall progression was 67% when follow-up ended (median, 8 years). Treatment approximately halved progression risk (HR, 0.53; 95% CI, 0.39–0.72); results were similar for patients with higher and lower baseline IOP (HRs, 0.41 and 0.55). Baseline progression factors (HRs, 1.51–2.12; P<0.01) were higher IOP, exfoliation, bilateral disease, and older age, as previously reported. New baseline predictors were lower ocular systolic perfusion pressure in all patients (≤160 mmHg; HR, 1.42; 95% CI, 1.04–1.94), cardiovascular disease history (HR, 2.75; 95% CI, 1.44–5.26) in patients with higher baseline IOP, and lower systolic blood pressure (BP) (≤125 mmHg; HR, 0.46; 95% CI, 0.21–1.02) in patients with lower baseline IOP. Postbaseline progression factors were IOP levels at follow-up, with 12% to 13% average increase per millimeter of mercury in all patients (HRs, 1.12–1.13 per mmHg higher) and similar results in patients with higher and lower baseline IOP (HRs, 1.15 and 1.13 per mmHg higher). Disc hemorrhages (HR, 1.02; 95% CI, 1.01–1.03 per percent higher frequency) also predicted progression. Thinner central corneal thickness (CCT) (HR, 1.25; 95% CI, 1.01–1.55 per 40 μm lower) was a new significant factor, a result observed in patients with higher baseline IOP (HR, 1.42; 95% CI, 1.05–1.92 per 40 μm lower) but not lower baseline IOP, with significant IOP–CCT interaction.

Conclusions

Treatment and follow-up IOP continued to have a marked influence on progression, regardless of baseline IOP. Other significant factors were age, bilaterality, exfoliation, and disc hemorrhages, as previously determined. Lower systolic perfusion pressure, lower systolic BP, and cardiovascular disease history emerged as new predictors, suggesting a vascular role in glaucoma progression. Another new factor was thinner CCT, with results possibly indicating a preferential CCT effect with higher IOP.

Section snippets

Materials and Methods

As detailed in previous reports,1, 2, 3 the trial included 255 men and women, 50 to 80 years of age with newly diagnosed and untreated glaucoma with early visual field defects, mainly recruited through population screening. Patients were randomized to treatment with betaxolol plus argon laser trabeculoplasty or no immediate treatment (129 treated and 126 controls) and followed every 3 months. The National Eye Institute and the Swedish Research Council funded the study.

Results

At the close of the study, 67% of the patients had progressed. The median time to progression was 60 months and the median follow-up time was 8 years. Table 1 presents univariate HR and median time to progression for significant factors. Progression was 59% in treated versus 76% in control patients, for an unadjusted HR of 0.60. This HR is of the same magnitude as that previously reported,2 which was based on a shorter follow-up and a lower progression of 53% (45% among treated and 62% among

Discussion

The updated results of EMGT reveal stability of previously reported estimates, confirming the important effect of treatment on progression, as well as of IOP, exfoliation, bilateral disease, and older age.2 The current analyses, based on a longer follow-up period, showed only minor variations in HR for these baseline and follow-up progression factors (Table 2). However, the extended follow-up with additional progressions at the end of the study allowed identifying new significant predictors.

References (36)

  • J.W. Kim et al.

    Central corneal pachymetry and visual field progression in patients with open-angle glaucoma

    Ophthalmology

    (2004)
  • N.G. Congdon et al.

    Central corneal thickness and corneal hysteresis associated with glaucoma damage

    Am J Ophthalmol

    (2006)
  • A. Heijl et al.

    Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial

    Arch Ophthalmol

    (2002)
  • M.C. Leske et al.

    Factors for glaucoma progression and the effect of treatment: the Early Manifest Glaucoma Trial

    Arch Ophthalmol

    (2003)
  • B. Bengtsson et al.

    Perimetric probability maps to separate change caused by glaucoma from that caused by cataract

    Acta Ophthalmol Scand

    (1997)
  • D. Cox

    Regression models and life-tables

    J R Stat Soc Ser B

    (1972)
  • N. Breslow

    Covariance analysis of censored survival data

    Biometrics

    (1974)
  • P.D. Allison

    Survival Analysis Using SAS: A Practical Guide

  • Cited by (1090)

    • Neurovascular dysfunction in glaucoma

      2023, Progress in Retinal and Eye Research
    • Endpoints for clinical trials in ophthalmology

      2023, Progress in Retinal and Eye Research
    • Impact of smoking on glaucoma

      2024, Current Opinion in Ophthalmology
    View all citing articles on Scopus

    Manuscript no. 2006-1164.

    The authors have no commercial or proprietary interest in the products or companies mentioned in the article.

    Members also include the Department of Ophthalmology, Lund University Hospital, Lund, Sweden; Department of Ophthalmology, Helsingborg Hospital, Helsingborg, Sweden; and National Eye Institute, National Institutes of Health, Bethesda, Maryland.

    View full text