Natural history of normal-tension glaucoma

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.

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.

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.

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.

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.

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.