Elsevier

Ophthalmology

Volume 116, Issue 12, December 2009, Pages 2271-2276
Ophthalmology

Original article
Natural History of Open-Angle Glaucoma

https://doi.org/10.1016/j.ophtha.2009.06.042Get rights and content

Objective

This article, based on the Early Manifest Glaucoma Trial (EMGT), provides prospective natural history data on progression of glaucomatous field defects in 3 of the most common glaucoma types.

Design

Cohort of EMGT patients randomized to the untreated control group and followed up to the time of progression, when treatment could be initiated.

Participants

We evaluated 118 control patients: 46 with high-tension glaucoma (HTG), 57 with normal-tension glaucoma (NTG), and 15 with pseudoexfoliation glaucoma (PEXG).

Methods

Visual fields were tested every 3 months with the Humphrey 30-2 Full Threshold test program.

Main Outcome Measures

Linear regression analyses of the perimetric mean deviation (MD) values were performed, and the rate of progression was defined as the regression coefficient in decibels per year. Percentages of progressed eyes and time to progression were determined using EMGT event-based predetermined progression criteria derived from Glaucoma Change Probability Maps.

Results

The median and interquartile rates of visual function loss were −0.40 (1.05) dB/year overall and −0.46 (1.61) in HTG, −0.22 (0.65) in NTG, and −1.13 (6.13) in PEXG. Thus, interpatient variability was large. Mean rates were considerably higher than medians: −1.08 dB/year overall, −1.31 in HTG, −0.36 in NTG, and −3.13 in PEXG. Differences in median visual function progression rates among groups were statistically significant (NTG vs. HTG, P = 0.003; PEXG vs. non-PEXG, P<0.001). Progression was considerably and significantly faster in older than in younger patients (P = 0.002). By 6 years, 68% of patients had progressed overall, 74% of those with HTG, 56% of those with NTG, and 93% of those with PEXG (P = 0.012). Median time to progression also differed considerably among groups: 19.5 months in PEXG, 44.8 months in HTG, and particularly 61.1 months in NTG (P<0.0001).

Conclusions

In this 6-year follow-up study, the median untreated rate of progression corresponded to advancing from normal visual function to blindness in approximately 70 years, whereas on the basis of the mean rate, visual function would show the same deterioration in approximately 25 years. Large differences existed among patients and different glaucoma types, with PEXG progressing considerably faster than HTG, and NTG progressing at the lowest rate.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Design Overview

The study design of EMGT (National Institutes of Health ClinicalTrials.gov identifier NCT00000132. Date of registration: September 23, 1999) has been described in detail.2 Briefly, EMGT included patients with newly diagnosed and untreated glaucoma with early to moderate damage. Most patients were identified in a large population-based screening of 44,000 citizens in Malmö and Helsingborg, Sweden, aged 50 to 80 years. The study was approved by the Ethics Committee of the University of Lund,

Results

Baseline characteristics of all study patients and of those in each category are shown in Table 1. Intraocular pressure was naturally higher in patients with HTG than in those with NTG, whereas IOP of patients with PEXG was slightly lower than in those with HTG. Patient age was similar among the 3 diagnostic groups. Attrition was minimal; only 4 patients were lost to follow-up, except for deaths.

  • 1

    Rate of progression

Table 2 presents both median and mean rates of progression, which followed the

Discussion

We studied the natural history of glaucomatous visual field progression in a large group of patients with open-angle glaucoma who had been randomized to no initial treatment in EMGT. After a follow-up time of 6 years, 80 of 118 patients (68%) had shown definite visual field progression. Progression rate and thus time to progression varied considerably among HTG, NTG, and PEXG groups, and among patients within each group. Rates of progression were considerably higher in patients with HTG than

References (38)

  • I. Dielemans et al.

    The prevalence of primary open-angle glaucoma in a population-based study in The Netherlands, the Rotterdam Study

    Ophthalmology

    (1994)
  • P. Mitchell et al.

    Prevalence of open-angle glaucoma in Australia, the Blue Mountains Eye Study

    Ophthalmology

    (1996)
  • L. Bonomi et al.

    Prevalence of glaucoma and intraocular pressure distribution in a defined population, the Egna-Neumarkt Study

    Ophthalmology

    (1998)
  • L.M. Weih et al.

    Prevalence and predictors of open-angle glaucoma: results from the visual impairment project

    Ophthalmology

    (2001)
  • Natural history of normal-tension glaucoma

    Ophthalmology

    (2001)
  • American Academy of Ophthalmology: Preferred Practice PatternPrimary Open-Angle Glaucoma

  • R. Ritch

    Exfoliation syndrome

    Curr Opin Ophthalmol

    (2001)
  • A. Heijl et al.

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

    Arch Ophthalmol

    (2002)
  • M.A. Kass et al.

    The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma

    Arch Ophthalmol

    (2002)
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    Manuscript no. 2008-1396.

    Financial Disclosure(s): The author(s) have made the following disclosure(s): The National Eye Institute and the Swedish Research Council participated in the design of the Early Manifest Glaucoma Trial. The other sponsors had no role in the design or conduct of this research.

    Supported by the Swedish Research Council K2005-74X-10426-13A, National Eye Institute, Bethesda, Maryland, grants no U10EY10260 and U10EY10261, the Järnhardt Foundation, and unrestricted grants from Alcon Research Ltd., Fort Worth, Texas, Allergan Inc., Irvine, California, and Santen Oy, Tampere, Finland. Zhongming Yang, PhD, provided statistical assistance.

    Available online: October 26, 2009.

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