New study provides further evidence of risk factors for visual field decline progression

Abnormal anticardiolipin antibody levels and increasing age are found in patients with faster visual field change.

Balwantray C. Chauhan

Patients with abnormal anticardiolipin antibody levels and increasing age had faster visual field change compared with patients with normal levels of the antibody, a study showed.

The Canadian Glaucoma Study (CGS) also reported that a modest IOP reduction in patients with glaucomatous visual field progression significantly improved the rate of visual field decline.

“We attempted to minimize the influence of IOP to find additional risk factors for [visual field] progression. However, as reported in an earlier publication from the study, we showed that the level of IOP was linked to progression. Now we found that IOP reduction in those patients with progression had a significant influence on the subsequent rate of visual field change,” study author Balwantray C. Chauhan, PhD, told Ocular Surgery News.

This prospective multicenter interventional cohort study was designed to provide the rates of visual field change associated with known risk factors and to determine the effect of additional IOP reduction on subsequent rates of visual field change in progressing patients, the study authors said.

Four independent risk factors for progression were identified by an earlier CGS report: abnormal baseline anticardiolipin antibody (ACA) level, higher baseline age, female sex and higher mean follow-up IOP.

Study endpoints

Event-based standard automated perimetry progression criteria based on the glaucoma change probability analyses were used to define an endpoint. Progression was suspected when eight or more locations in the total deviation change probability map, with four or more clustered locations in a single hemifield, were flagged. If progression was not confirmed at a second examination within 7 to 10 days, a third confirmation examination was conducted. Hence, two of three examinations had to demonstrate visual field progression.

In addition to having newly or previously diagnosed open-angle glaucoma, inclusion criteria for enrollment included best corrected visual acuity of 6/10 or better on the ETDRS chart; photographically documented glaucomatous optic disc changes; glaucomatous visual field changes including localized visual field defects, mean deviation better than –10 dB and a positive glaucoma hemifield test; and non-occludable anterior chamber angles.

All 216 patients were followed up at 4-month intervals with perimetry and were monitored for progression. Patients who reached an endpoint based on total deviation analysis underwent 20% or greater reduction in IOP. Rates of mean deviation change were calculated.

“This study was planned in 1992,” Dr. Chauhan said. “The level of IOP reduction was based on the drugs available at the time. However, with the drugs available today, we could have set greater reductions in IOP after progression.”

“Patients with 0, 1 and 2 endpoints had a median of 18, 23 and 25 examinations, respectively. The median [mean deviation] rate in progressing patients prior to the first endpoint was significantly worse compared with those with no progression (–0.35 and 0.05 dB/y, respectively). An abnormal ACA level was associated with a significantly worse [mean deviation] rate compared with a normal ACA level (–0.57 and –0.03 dB/y, respectively). Increasing age was associated with a worse [mean deviation] rate, but female sex and mean follow-up IOP were not,” the authors said in study results published in Archives of Ophthalmology.

“A significant finding in this study was the effect of additional IOP reduction on [mean deviation] rate in patients with one endpoint. In these patients, a median reduction of 3.1 mm Hg (or 20%) resulted in the median slope changing significantly from –0.36 dB/y to –0.11 dB/y. In some patients, this amelioration may not be clinically meaningful; however, over 20 years, the difference in total [mean deviation] change resulting from these two rates is 5 dB. In younger patients with more advanced damage, this difference is likely to be important,” the authors said.

No differences were noted in the sex ratio among patients with zero, one or two endpoints. Baseline age was statistically different among these three groups, with higher age associated with one or two endpoints (P = .01).

Clinical significance

The results of this study have some practical implications. Patients with early to moderate visual field damage are considered to have stable visual fields if they do not reach a visual field endpoint based on localized visual field change and they also maintain an average IOP of approximately 16 mm Hg. A modest additional IOP reduction in patients with an endpoint has a significant effect on the subsequent mean deviation rate, the authors said.

A previous CGS report showed that glaucoma patients with abnormal baseline ACA levels were four times more likely to have visual field progression compared with those with normal ACA levels. These analyses indicate that they have a more rapid rate of visual field deterioration compared with patients with normal ACA levels. While this finding is significant, its practical implications are unclear because only 5.5% of the tested patients had abnormal ACA levels, the authors said.

Additional studies

The benefit of greater IOP reduction in these patients needs further investigation. Several studies have shown that incidence of glaucomatous progression increases with age and the association between the rate of visual field change and age. Female sex and mean IOP during the follow-up were independent risk factors for progression, but there was no association with mean deviation rates, the authors said.

The investigators said that they cannot speculate whether a greater IOP reduction would have had an even more beneficial effect on the visual field or if these findings can be extended to patients with more visual field damage at baseline.

Although the study results showed a positive effect of additional IOP reduction on the rate of visual field change in patients reaching an endpoint, the CGS did not have a control group of patients who did not receive additional treatment after an endpoint. Therefore, other factors may have had an effect on the mean deviation rates.

However, Dr. Chauhan said, well-done randomized clinical trials with untreated arms have been published, showing the benefits of IOP reduction on visual field change. – by Cassandra Richards

References:

• Chauhan BC, Mikelberg FS, Artes PH, et al; Canadian Glaucoma Study Group. Canadian Glaucoma Study: 3. Impact of risk factors and intraocular pressure reduction on the rates of visual field change [published online ahead of print Aug. 9, 2010]. Arch Ophthalmol. doi:10.1001/archophthalmol.2010.196.
• Chauhan BC, Mikelberg FS, Balaszi AG, LeBlanc RP, Lesk MR, Trope GE; Canadian Glaucoma Study Group. Canadian Glaucoma Study: 2. risk factors for the progression of open-angle glaucoma. Arch Ophthalmol. 2008:126(8):1030-1036.
• Canadian Glaucoma Study Group. Canadian Glaucoma Study: 1. Study design, baseline characteristics, and preliminary analyses. Can J Ophthalmol. 2006;41(5):566-575.

• Balwantray C. Chauhan, PhD, can be reached at Department of Ophthalmology and Visual Sciences, Dalhousie University, Room 2035, 2W Victoria Building, 1278 Tower Road, Halifax, Nova Scotia, Canada B3H 2Y9; 902-473-3202; fax: 902-473-2839; e-mail: bal@dal.ca.