Study Identifies Glaucoma Progression Risk Factors

Norra MacReady

May 10, 2011

May 10, 2011 — Peak intraocular pressure, corneal thinning, and retinal atrophy are among the significant risk factors for visual field deterioration in patients with glaucoma, according to a new study published in the May issue of the Archives of Ophthalmology.

These findings add a "real-world" dimension to the information obtained from randomized clinical trials (RCTs), the authors say. "Our results add to and complement the high level of evidence generated by these RCTs, provide information about the behavior of glaucoma patients receiving therapy, and may help clinicians decide how aggressively to treat specific patients to slow the rate of glaucoma progression," they write.

Patient populations and treatments in RCTs do not always resemble those of a typical clinical practice, explain the authors, led by Carlos Gustavo V. De Moraes, MD, from the New York Eye and Ear Infirmary, New York City.

Retrospective studies have drawbacks, such as lack of standardized therapy, the inclusion of various types of glaucoma, and less statistical rigor than RCTs, but they "have the potential of providing clinicians with information on the extent to which these prospective, well-designed trials can be applied to a real-world population," the authors say. They conducted a retrospective study to determine whether risk factors identified in patients enrolled in RCTs can be applied to populations more similar to those seen in everyday practice.

The patients were participants in the New York Glaucoma Progression Study who were evaluated in the glaucoma referral practice of 3 of the study authors between January 1999 and September 2009. Each patient underwent a complete ophthalmologic examination, standard achromatic perimetry testing, and optic disc stereographs. They were then followed-up at 3- to 6-month intervals, with testing repeated at 6- to 12-month intervals. All eligible eyes had a best corrected visual acuity of 20/40 or better at baseline and a spherical equivalent of less than 6 diopters. Patients also had to have had at least 8 visual field (VF) examinations. If both of a patient's eyes were eligible, the eye with the greater number of VF examinations was included in the study.

The authors analyzed data from 587 eyes in 587 patients. At baseline, the patients' mean age was 64.9 years, with a mean number of 11.1 VFs spanning a mean of 6.4 years. Women outnumbered men (58% and 42%, respectively), and 90% of the patients were of European ancestry.

The entire patient cohort had a mean global VF change of −.45 dB/y. "Progressing eyes and stable eyes had a mean (SD) global rate of VF change of −1.0 (0.8) dB/y and −.20 (0.4) dB/y, respectively (P < .01)," the authors report.

They found that peak and mean intraocular pressure (IOP) showed the strongest correlation with progression end points (Pearson r = .74; P < .01). "Using a predefined cutoff value, eyes with a peak IOP higher than 18 mm Hg had an odds ratio (OR) of 1.81 (95% confidence interval, 1.22-2.68; P < .01) associated with a progression outcome," the investigators said. In general, each millimeter of mercury increase in IOP was associated with a significant increase in the risk for disease progression among treated glaucoma patients.

On univariate analysis, factors significantly correlating with increased risk for VF deterioration were older age, baseline diagnosis of exfoliation syndrome, decreased central corneal thickness, detected disc hemorrhage, presence of beta-zone parapapillary atrophy (βPPA), and all IOP parameters. On multivariate analysis, IOP, thinner central corneal thickness, disc hemorrhage, and βPPA atrophy all remained significant risk factors. Peak IOP was a better predictor of VF progression than mean follow-up IOP, although all IOP parameters showed a significant correlation.

Study limitations include the retrospective nature and the biases inherent among patients at a tertiary-care referral center, the authors write. "These limitations, however, are mitigated by the large sample size, the long follow-up period, the large number of VF tests, and a cohort that closely resembles those seen in clinical practice." Still, the authors warn "Our findings may not be applicable to other clinical settings because they reflect a specific population for which certain risk factors may play a more important role than others."

These data confirm the validity of well-known and reported risk factors in the assessment of glaucoma progression, the authors conclude. "Moreover, additional information provided by simple diagnostic tools (tonometry and ophthalmoscopy) suggest the importance of peak IOP and the presence of βPPA to assess the future risk of glaucomatous vision loss."

The study was supported by the Joseph and Geraldine LaMotta Research Fund of the New York the Glaucoma Research Institute and by the Glaucoma Research and Education Fund of Lenox Hill Hospital. The authors have disclosed no relevant financial relationships.

Arch Ophthalmol. 2011;129:562-568. Abstract