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Editors Selection IGR 9-4

Therapeutic Prognosis and Outcome: Anticardiolipin antibody and rate of progression

Comment by Felipe Medeiros on:

27093 Canadian glaucoma study: 3. Impact of risk factors and intraocular pressure reduction on the rates of visual field change, Chauhan BC; Mikelberg FS; Artes PH et al., Archives of Ophthalmology, 2010; 128: 1249-1255

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The Canadian Glaucoma Study was a prospective multi-center cohort study enrolling 258 glaucoma patients and designed to evaluate whether peripheral vasospasm plays a role in the risk of disease progression. In 2008, the authors published their first results and were unable to find any statistically significant difference in progression rates between patients with and without vasospastic responses. However, secondary analyses showed that abnormal baseline anticardiolipin antibody (ACA) levels, higher mean follow-up intraocular pressure, older age and female sex were risk factors for progression in patients under ocular hypotensive treatment. In their most recent publication, Chauhan et al. (2046) conducted further analyses on these previously identified risk factors and their relationship with the rates of glaucoma progression, as measured by the mean deviation of standard automated perimetry. They found that patients with abnormal ACA levels had faster rates of change compared to those with normal levels, which could suggest that these antibodies could be a marker for patients at risk for fast glaucoma deterioration. However, it is important to note that only ten of the 258 patients (5.5%) had abnormal ACA levels. Such a small sample resulted in imprecise estimates of the predictive effect of ACA levels for glaucoma progression, with very large confidence intervals as reported in their first study. Additionally, their analysis of the effect of ACA levels on rates of change in their recent publication did not adjust for potentially important confounding factors, such as age, IOP, disease severity at baseline or presence of pseudo-exfoliation. Although the authors performed some multivariable analyses in their first publication, the small sample size clearly limited their ability to evaluate the predictive strength of some important factors.

Small sample size limited the ability to evaluate the predictive strength of some important factors

For example, although patients with progressive glaucoma were twice as likely to have pseudo-exfoliation than those with stable disease, the study failed to confirm pseudo-exfoliation as a risk factor for progression as previously well-demonstrated in the literature. It is interesting to speculate whether patients with pseudo-exfoliation could actually be those with the higher levels of ACA and this could be an important confounding factor in the study.

Their evaluation of the relationship between IOP and progression showed apparently contradictory results. In the event-based analysis of progression, mean IOP during follow-up was a significant risk factor for progression. However, higher mean IOP during follow-up was not associated with faster rates of progression in the trendbased analyses. Although reductions of IOP during follow-up were associated with apparent slowing of glaucoma progression in a subgroup of 49 patients, there was no relationship between change in MD rate and the magnitude or percentage of IOP reduction, which again could be due to the relatively small sample size available to evaluate this issue.

Despite its limitations, the CGS should be seen as an important study that has raised our awareness to other potentially important risk factors for glaucoma progression which deserve further study.

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