Intraocular pressure control and long-term visual field loss in the Collaborative Initial Glaucoma Treatment Study

Abstract

Objective: To evaluate the impact of measures of intraocular pressure (IOP) control on progression of visual field (VF) loss during long-term treatment for open-angle glaucoma (OAG).

Design: Longitudinal, randomized clinical trial.

Participants: We included 607 participants with newly diagnosed OAG.

Methods: Study participants were randomly assigned to initial treatment with medications or trabeculectomy, and underwent examination at 6-month intervals. Standardized testing included Goldmann applanation tonometry and Humphrey 24-2 full threshold VFs. Summary measures of IOP control during follow-up included the maximum, mean, standard deviation (SD), range, proportion less than 16, 18, 20, or 22 mmHg, and whether all IOP values were less than each of these 4 cutpoints. Predictive models for VF outcomes were based on the mean deviation (MD) from VF testing, and were adjusted for age, gender, race, baseline VF loss, treatment, and time. Each summary IOP measure was included as a cumulative, time-dependent variable, and its association with subsequent VF loss was assessed from 3 to 9 years postrandomization. Both linear mixed models, to detect shifts in MD levels, and logistic models, to detect elevated odds of substantial worsening (≥3 dB), were used.

Main outcome measures: We measured the MD from Humphrey 24-2 full threshold VF tests.

Results: The effect of the summary IOP measures differed between the medicine and surgery groups in models that addressed the continuous MD outcome. After adjustment for baseline risk factors, in the medicine group larger values of 3 IOP control measures-maximum IOP (P = 0.0003), SD of IOP (P = 0.0056), and range of IOP (P<0.0001)-were significantly associated with lower (worse) MD over the 3- to 9-year period. No IOP summary measure was significantly associated with MD over time in the surgery group. The same 3 IOP summary measures were also significantly associated with substantial worsening of MD; however, the effects were similar in both treatment groups. In models predicting inadequate IOP control, consistently significant predictors of higher maximum, SD, and range of IOP included black race, higher baseline IOP, and clinical center.

Conclusions: These results support considering more aggressive treatment when undue elevation or variation in IOP measures is observed.

Figure 1

Model-based estimates of the mean deviation over follow-up for low and high values of two cumulative IOP summary measures (maximum IOP and proportion <20 mmHg), by initial treatment. Results are presented for the 25^th and 75^th percentile values of each IOP summary measure: (a) maximum IOP: 17.5 & 24.0 mmHg, respectively; (b) proportion of IOP values that were < 20 mmHg: 80% & 100%, respectively. IOP: intraocular pressure; mmHg: millimeters of mercury; dB: decibels

Figure 2

Forest plot of the difference in MD associated with substantial changes in individual IOP summary measures. Panel (a) presents the difference in MD (estimate, 95% CI) resulting from a 1 SD increase in the IOP summary measure for measures that showed differences by initial treatment; Panel (b) presents the difference in MD (estimate, 95% CI) resulting from a 1 SD increase in the IOP summary measure for measures that had no significant treatment effect; for the percent-based measures (e.g, percent of IOP measurements that were <18 mmHg), differences are presented in terms of a 20% increase (e.g., difference in MD between having 60% vs. 80% of IOP measurements <18 mmHg). Note: all estimates are adjusted for baseline MD, age at baseline, cataract, diabetes, age, and interactions. Estimates in Panel (b) are also adjusted for initial treatment. MD: mean deviation; IOP: intraocular pressure; CI: confidence interval; mmHg: millimeters of mercury; dB: decibels

Figure 3

Forest plot of ORs and 95% CIs for the association of individual IOP summary measures with a worsening of mean deviation (3 dB or more decrease) from baseline. ORs are shown for a one SD increase in the mean, maximum, SD, and range summary measures. For measures of percent IOP < 16, 18, 20, 22 mmHg, or percent of baseline IOP, ORs are shown for a 20% increase (e.g., OR for having 80% vs. 60% of IOP measurements <18 mmHg). Note: all ORs are adjusted for baseline MD, initial treatment, age at baseline, cataract, diabetes, age, and interactions. OR: odds ratio; CI: confidence interval; IOP: intraocular pressure; dB: decibels; SD: standard deviation; mmHg: millimeters of mercury; MD: mean deviation