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Editors Selection IGR 14-4

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Comment by Alon Harris on:

20036 Predictors of long-term progression in the Early Manifest Glaucoma Trial, Leske MC; Heijl A; Hyman L et al., Ophthalmology, 2007; 114: 1965-1972

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Leske and colleagues identified 125 cases of incident glaucoma (about 0.5% per year for persons 40‐84 years of age) in a cohort of 3,222 Afro-Caribbean persons in Barbados followed for nine years. Risk factors for incident glaucoma in a multivariate analysis included older age, family history, and higher IOP, all of which have been identified consistently as risk factors for glaucoma both in prevalence and incidence studies. In addition, lower perfusion pressure was found to be a risk factor as was a thinner central cornea (CCT was measured at nine years, not at baseline, and only on 1,023 subjects). This is the first time that thin CCT has been found as a risk factor in a population-based cohort study.

Age was clearly an important risk factor with persons over 60 having nearly twice the incidence of glaucoma as those 40‐49 years. This has clear policy implications, as has been seen in the United States where Medicare covers screening of older African-American beneficiaries due to their high incidence of disease. As has been shown in many reports, IOP ≥ 21 mmHg was a risk factor for POAG (RR > 5), but over half the incident cases occurred in individuals with IOP < 21 mmHg at baseline, once again highlighting how limited IOP is as a screening modality.

Leske and colleagues also looked at risk factors for progression in a clinical trial for the treatment of glaucoma, the EMGT (using time to progression as the main outcome). In addition older age and baseline IOP, this study found that exfoliation, worse baseline mean defect on perimetry, bilateral disease, disc hemorrhages and lower systolic perfusion pressure all increased the risk of progression. Thin CCT was a risk factor, but only in patients with higher baseline IOP. When assessing the role of systolic perfusion pressure on progression, the authors found that it was not a risk factor in those with lower baseline IOP (defined as IOP < 21 mmHg), but was a risk factor in those with higher IOP. In addition, cardiovascular disease was a risk factor, once again, only for those with higher IOP. These findings indicate that vascular factors may be an important determinant of glaucoma progression at high IOP, whereas structural factors of the optic nerve likely are more important predictors of who gets worse at lower IOP. The solution to the vascular versus mechanical argument for glaucoma pathogenesis is likely 'both'.

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