Elsevier

Ophthalmology

Volume 114, Issue 1, January 2007, Pages 10-19.e2
Ophthalmology

Original Article
Validated Prediction Model for the Development of Primary Open-Angle Glaucoma in Individuals with Ocular Hypertension

Presented at: American Academy of Ophthalmology Annual Meeting, November 2006, Las Vegas, Nevada.
https://doi.org/10.1016/j.ophtha.2006.08.031Get rights and content

Objective

To test the validity and generalizability of the Ocular Hypertension Treatment Study (OHTS) prediction model for the development of primary open-angle glaucoma (POAG) in a large independent sample of untreated ocular hypertensive individuals and to develop a quantitative calculator to estimate the 5-year risk that an individual with ocular hypertension will develop POAG.

Design

A prediction model was developed from the observation group of the OHTS and then tested on the placebo group of the European Glaucoma Prevention Study (EGPS) using a z statistic to compare hazard ratios, a c statistic for discrimination, and a calibration χ2 for systematic overestimation/underestimation of predicted risk. The 2 study samples were pooled to increase precision and generalizability of a 5-year predictive model for developing POAG.

Participants

The OHTS observation group (n = 819; 6.6 years’ median follow-up) and EGPS placebo group (n = 500; 4.8 years’ median follow-up).

Testing

Data were collected on demographic characteristics, medical history, ocular examination visual fields (VFs), and optic disc photographs.

Main Outcome Measure

Development of reproducible VF abnormality or optic disc progression as determined by masked readers and attributed to POAG by a masked end point committee.

Results

The same predictors for the development of POAG were identified independently in both the OHTS observation group and the EGPS placebo group—baseline age, intraocular pressure, central corneal thickness, vertical cup-to-disc ratio, and Humphrey VF pattern standard deviation. The pooled multivariate model for the development of POAG had good discrimination (c statistic, 0.74) and accurate estimation of POAG risk (calibration χ2, 7.05).

Conclusions

The OHTS prediction model was validated in the EGPS placebo group. A calculator to estimate the 5-year risk of developing POAG, based on the pooled OHTS–EGPS predictive model, has high precision and will be useful for clinicians and patients in deciding the frequency of tests and examinations during follow-up and advisability of initiating preventive treatment.

Section snippets

Materials and Methods

The OHTS11 and EGPS14 are both randomized clinical trials that tested the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the development of POAG in individuals with ocular hypertension. The OHTS and EGPS protocols are described in their respective baseline design articles.15, 16 The OHTS protocol is also available at https://vrcc.wustl.edu. The protocol of each study was approved by the institutional review boards of all participating clinics and resource

Results

Baseline demographic and clinical features of participants who did or did not develop POAG in the OHTS observation group and EGPS placebo group are reported in Table 3, Table 4. The percentages of participants developing POAG in Table 4 were not adjusted for duration of follow-up.

In the OHTS observation group, the Kaplan–Meier estimate of the 5-year cumulative probability of developing POAG was 9.3% (104/819; median follow-up of 6.6 years). In the EGPS placebo group, the Kaplan–Meier estimate

Discussion

Using data from the OHTS observation group, we developed a multivariate model that identified baseline older age, higher IOP, larger vertical C/D ratio, thinner central corneal measurement, and greater PSD as predictive factors for the development of POAG in ocular hypertensive individuals. When the generalizability of the OHTS model was tested by applying it to data from the placebo group of the EGPS, the same predictive factors were identified. The hazard ratios for the predictive factors

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    Manuscript no. 2006-545.

    Supported by grants from the National Eye Institute, Bethesda, Maryland, and National Center for Minority Health and Health Disparities, Bethesda, Maryland (nos. EY09341, EY09307); European Commission, Brussels, Belgium (no. BMH4-CT-96-1598); Merck Research Laboratories, White House Station, New Jersey; Pfizer, Inc., New York, New York; and Research to Prevent Blindness, New York, New York (unrestricted).

    See “Appendix” for writing committee membership and the full membership of each study group.

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