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Glaucoma Dialogue IGR 9-4

Response

Comment by Cristina Leske 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

See also comment(s) by Makoto Araie • Josef Flammer • David Friedman • Alon Harris • Kuldev Singh • Fotis Topouzis •

Find related abstracts

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We appreciate the very positive comments on the strength of the methods and findings of our recent papers from the Barbados Eye Studies (BESs) and the Early Manifest Glaucoma Trial (EMGT). Additional remarks follow regarding our results and their interpretation.

Despite the dissimilarities, the results of both analyses were remarkably consistent

Although both studies included a long follow-up period, they were markedly different in design and composition. Thus, our latest BESs results were based on a large national sample (n = 3222) of a popu-lation of African origin, while the EMGT was a randomized clinical trial conducted among Scandinavian glaucoma patients (n = 255). Their goals also differed, as the BESs analyses aimed to detect risk factors for newly developing, incident open-angle glaucoma, while the EMGT analyses aimed to identifyprogression factors for existing glaucoma. Yet despite these dissimilarities, the results of both analyses were remarkably consistent. In addition to the well-known relationships with age and intraocular pressure, the two studies suggested a role for low ocular perfusion pressure, low blood pressure and thinner central corneal thickness, both as risk factors for glaucoma incidence and as progression factors for established disease. These similarities support the possibility of relevant relationships, particularly since all the BESs participants, and most of the EMG patients, were identified from population-based samples.

Our new results strongly support a multifactorial causality in open-angle glaucoma, which is influenced by the interaction of genetic and non-genetic factors

Our data adds to prior evidence indicating that the associations of open-angle glaucoma to vascular factors are consistent, strong, and biologically plausible. However, both our papers extensively address the caveats in interpreting the findings, which are echoed by our colleagues. For example, a low ocular perfusion pressure could reflect the influence of low blood pressure, high intraocular pressure, treatment to lower blood pressure or intraocular pressure, or some combination. Our analyses attempted to carefully evaluate these issues and controlled for these and other pertinent variables.

The evidence for a role of vascular factors in glaucoma is mounting and is supported further by our new results.

Furthermore, we did conduct analyses according to blood pressure status and systemic antihypertensive treatment, with generally similar and consistent patterns. Of course, these results must be followed up in future studies that focus on vascular factors, perhaps pooling data to increase numbers in subcategories. Similarly, the relation-ships with central corneal thickness await further clarification. As mentioned by our colleagues, the BESs provide the first such as-sociation found in a population-based study, lending further credence to the relationship.

What are some general conclusions?

• Our new results strongly support a multifactorial causality in open-angle glaucoma, which is influenced by the inter-action of genetic and non-genetic factors.
• Ocular perfusion pressure and vascular factors are a like-ly component of this interaction by affecting glaucoma in-cidence and/or progression. The importance and magnitude of their role should be delineated by further studies, include-ing those of ocular blood fl ow.
• The relationships of open-angle glaucoma to blood pressure/ hypertension remain unclear. Most population studies had modest, non-statistically signifi cant findings (e. g., Baltimore Eye Survey, Rotterdam Eye Study) and others provide incon-sistent data. These discrepancies are not surprising, as bra-chial blood pressure is affected by many factors and does not necessarily reflect vascular status at the optic disc. In contrast, associations with low ocular perfusion pressure are consistent; this variable also seems more relevant to glaucoma than blood pressure alone.
• Vascular factors have potential implications for patient man-agement. If maintaining perfusion pressure is pertinent in glaucoma, should we avoid excessive lowering of blood pres-sure in some patients? This is a concern in clinical prac-tice, as high blood pressure and high intraocular pressure often coexist. Furthermore, not all patients presenting for eye care have careful assessments of blood pressure and its treatment.
• While a clarification of these issues remains pending, the ev-idence for a role of vascular factors in glaucoma is mounting and is supported further by our new results.

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