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Glaucoma Dialogue IGR 9-4

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Comment by Kuldev Singh 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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In a population-based cohort study of African origin participants with over nine years follow-up, Leske et al. evaluate risk factors for open-angle glaucoma (OAG) and report a 4.4% incidence of OAG (125/3222). The large number of incident glaucoma cases identified (125), the long-term follow-up and the population-based incidence design, which is equivalent to OAG risk, are the advantages of this new report of the Barbados Eye Study, making results easier to interpret compared to those derived from cross-sectional studies. Also, in a prospective randomized clinical trial of 255 Caucasian participants with a median follow-up of eight years, Leske et al. evaluate risk factors for progression of manifest OAG and report an overall progression of 67%. In this new Early Manifest Glaucoma Trial (EMGT) report, the long-term risk of progression of manifest OAG is assessed.

Although these studies are conducted in different populations, with the first evaluating risk factors for OAG incidence and the second evaluating risk factors for progression of manifest OAG, risk factors presented in their results are similar. Specifically, older age, higher intraocular pressure (IOP), thinner central corneal thickness (CCT), lower systolic blood pressure (BP) and lower perfusion pressure (PP) were associated with increased risk in both studies. Pseudoexfoliation was also associated with increased risk in the EMGT, but it was not assessed in the Barbados Eye Study. Family history of glaucoma was one of the baseline factors influencing risk in the Barbados Eye Study, but it was not presented in the EMGT report.

PP involves BP level, but does not involve BP status with regards to normal, hypertension, hypertension with anti-hypertensive treatment, lowered BP secondary to antihypertensive treatment or high BP despite the use of antihypertensive treatment

The Barbados Eye Study is the first incidence study to confirm the role of CCT in a population-based cohort study. Interestingly, the odds ratio of 1.41 reported in the Barbados Eye Study is quite similar to the 1.42 hazard ratio observed in patients with baseline IOP ≥ 21mmHg in the EMGT. More importantly, the common finding of low BP and low PP as risk factors for both glaucoma incidence and manifest glaucoma progression strengthens the possibility of a vascular link to glaucoma.

However, there are some issues that deserve cautious interpretation with regards to BP and PP findings. PP involves BP level, but does not involve BP status with regards to normal, hypertension, hypertension with anti-hypertensive treatment, lowered BP secondary to anti-hypertensive treatment or high BP despite the use of anti-hypertensive treatment. For the same BP level we may have different effects on glaucoma risk depending on BP status. In addition, PP can be influenced by high IOP alone or by IOP-lowering treatment. The results in both studies were adjusted for IOP, use of anti-hypertensive treatment and IOP-lowering treatment but residual confounding may still exist. Further the type and duration of anti-hypertensive treat-ment may contribute to glaucoma risk. Interestingly, in the EMGT subgroup analyses with regards to IOP, systolic BP ≤ 160 mmHg was associated with progression in patients with baseline IOP < 21 mmHg, while systolic PP ≤ 125 mmHg, but non-systolic BP ≤160 mmHg was associated with progression in patients with higher baseline IOP. No analyses by BP status were conducted in either study. Further research is needed to elucidate the role of vascular risk factors in glaucoma incidence and progression.

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