Elsevier

Ophthalmology

Volume 108, Issue 2, February 2001, Pages 247-253
Ophthalmology

Natural history of normal-tension glaucoma

https://doi.org/10.1016/S0161-6420(00)00518-2Get rights and content

Abstract

Objective

A recently reported randomized study described the role of intraocular pressure (IOP) in normal-tension glaucoma (NTG) pathogenesis and the effect of therapeutic lowering of IOP. This is a report of an analysis of the natural course of NTG during the time eyes were not receiving therapy, either in the time interval awaiting randomization or after being randomly assigned not to receive treatment to lower the IOP.

Design

Analysis of prospectively collected data on the long-term course of a cohort of untreated subjects with normal-tension glaucoma, a subset of subjects enrolled in a randomized controlled clinical trial.

Randomization and subject selection

If the field defect in the study eye threatened the point of fixation, the subject was randomly assigned to start on treatment immediately or to be observed without treatment until progression was documented. Otherwise, an eye was randomly assigned only when and if, subsequent to enrollment, it showed visual field progression, progression of optic disc cupping, or a new disc hemorrhage.

Participants

Data were collected for this report on 160 subjects observed without treatment among a total enrollment of 260. They consist of 49 subjects who were randomly assigned on enrollment not to receive therapy, 24 followed without treatment for a time until later being randomly assigned to treatment, 31 similarly followed without treatment and who were later randomly assigned to be followed for an additional time without treatment, and 56 who enrolled but were never randomly assigned.

Main outcome measures

Visual field data were used in this report only from the interval during which the eye had not been assigned to receive therapy and were analyzed by two measures of progression: the “survival” time to meeting a criterion of confirmed localized progression and the rate of change in the mean deviation (MD) index over time.

Results

The four subgroups just described were similar at baseline, except that the average MD index was slightly better for the 56 eyes that never progressed during the period of follow-up. By Kaplan-Meier analysis of all untreated subjects combined, approximately one third showed localized progression within 3 years and about half within 5 to 7 years. Of subjects followed for 3 years or more, 62 of 109 did not show a statistically significant negative slope of MD regressed over time, whereas the others showed a statistically significant MD decline, mainly between −0.2 and −2 db per year.

Conclusions

Some cases of NTG progress more rapidly than others. Although approximately half of cases showed a confirmed localized visual field deterioration by 7 years, the change is typically small and slow, often insufficient to measurably affect the MD index.

Section snippets

Methods

Details of the study protocol were documented earlier.3, 4, 7 Pertinent here is that 260 subjects were enrolled from 24 collaborating centers, each with Institutional Review Board approval. To be considered eligible, the protocol called for the inclusion of subjects who had unilateral or bilateral NTG evidenced by glaucomatous cupping of the disc and field loss (as defined) with a median IOP of 20 mmHg or less in 10 baseline measurements. One reading of 23 or 24 mmHg was allowed by the

Characterization of subjects

Sixty-one of the 160 subjects were men and 99 were women. Their mean age and standard deviation were 63.6 ± 9.8 years. The eyes analyzed had a mean IOP at baseline of 16.1 ± 2.1 mmHg, and their baseline mean MD was −5.9 ± 4.2. Baseline data (Table 1) reveal no significant differences among the four subgroups in the distribution of gender, in mean age, or in mean IOP at entry. The MD index at entry was slightly less abnormal in those never randomized (P < 0.001).

The mean duration of the

Analysis of the natural course

In the total group of 160 eyes, 52 end points (four-of-five criteria) occurred. The Kaplan-Meier analysis (Fig 1A) estimated the mean time to end point and standard error (SE) at 2046 ±103 days. As illustrated in Figure 1B, there is no apparent or statistical difference (P = 0.778) between those immediately randomly assigned (group IRC) and the others (group NIR). The estimated mean survival for the IRC group is 1795 days (SE ± 169), for the NIR group 2070 days (SE ± 121), with 15 of 49 end

Discussion

In this multicenter clinical study of NTG, we collected data that made it possible to examine the natural history of the untreated disease in a large group of subjects. We believe that such an analysis has not been done previously.

If the subjects with NTG in some clinical practices differ from those we studied, our results may not apply fully. However, our study was conducted at a large number of centers, we have no reason to suspect that particular types of subjects were selectively included

Collaborating centers

Wallace L. M. Alward, MD, University of Iowa Hospital, Iowa City, Iowa

Frederick Feldman, MD, FRCS (C), Graham Trope, MD, University of Toronto, Ontario, Canada

L. Frank Cashwell, MD, Wake Forest University Medical Center, Winston-Salem, North Carolina

Jacob Wilensky, MD,UIC Eye Center, Chicago, Illinois

H. Caroline Geijssen, MD, Erik Greeve, MD, University of Amsterdam, The Netherlands

Harry Quigley, MD, Henry Jampel, MD, Johns Hopkins Hospital, Baltimore, Maryland

Greg Skuta, MD, Paul R. Lichter,

Data and coordinating center

Tara Steele Glaucoma Research Foundation, San Francisco, California

Statistical center

Michael Schulzer, MD, PhD, Departments of Medicine and Biostatistics, University of British Columbia, Vancouver, British Columbia, Canada

Reading committee

Douglas R. Anderson, MD, Stephen M. Drance, OC, MD

Data and safety monitoring committee

John Clarkson, MD (Chairman, 1989–1995), Steven Litinsky, MD (Chairman, 1995–), Robert Hardy, PhD (1993–1996) Joyce Schiffman, MS, Alvin Rose, PhD, James Neaton, PhD (1996–), Stephen M. Drance, OC, MD, Michael Schulzer, MD, PhD, Douglas R. Anderson, MD, Tara Steele

Steering & writing committee

Douglas R Anderson, MD, Stephen M Drance, OC, MD, Michael Schulzer, MD, PhD

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Funded by the Glaucoma Research Foundation, San Francisco, California, with special grants from the Oxnard Foundation and the Edward J. Daly Foundation, San Francisco, California.

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