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Editors Selection IGR 9-4

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Comment by Fotis Topouzis 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 • Cristina Leske •

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It would be natural to speculate that circulatory status in a tissue is related with the integrity of the tissue and impaired tissue circulation has unfavorable effects on it. As regards glaucomatous damage in the optic nerve head (ONH) and the ONH circulation, such relationship has been long suspected, but there has been a paucity of stronger evidences obtained from prospective cohort studies. The nine-year follow-up results of the the Barbados Eye Study (BES) and 11-year follow-up results of and Early Manifest Glaucoma Trial (EMGT) populations have provided strong evidence indicating that lower OPP is a risk factor for development and progression of glaucoma and lower systemic blood pressure (BP) may be also a risk factor. Given the same peripheral vascular resistance, higher OPP should result in more peripheral blood flow, ant thus the results of these two studies appear to support involvement of vascular insufficiency in the pathogenesis of glaucoma. At present, however, the exact relationship between the ONH blood flow and OPP calculated from brachial arterial BP is still unclear, since no method can measure the ONH blood flow in absolute units. The result of a study concluding that the ONH blood flow was less in glaucoma patients with normal BP than in those with systemic hypertension (Am J Ophthalmol 1999; 127: 516-522) must be interpreted with great caution, since inter-individual comparison of the results of the laser Doppler flowmetry which only yields blood flow parameter values in arbitrary units is theoretically very difficult. It is well known that higher systemic BP is in general associated with higher peripheral vascular resistance, but not with higher cardiac output, and higher risk for cardiovascular and cerebrovascular ischemic events, especially in cases with primary hypertension (e.g., Kaplan NM. Clinical Hypertension, 6^th ed. Williams & Wilkins, Baltimore, 1994). That is, higher BP is not always associated with higher blood flow rate in peripheral tissues.

The results are also highly relevant not only in the treatment of glaucoma, but also of coexisting systemic hypertension

From this point of view, it may be easier to understand the results of the Blue Mountain Eye Study or Rotterdam Study showing association of systemic hypertension and increased risk of glaucoma than those of the current 2 studies in the Early Manifest Glaucoma Trial (EMGT) populations BES suggesting its association and decreased risk of glaucoma. In population-based studies or RCTs, not only subjects with normal BP, but also those with treated and untreated systemic hypertension are to be included. Treatment of systemic hypertension with Ca-antagonists or inhibitors of renin-angiotensin system reduces peripheral vascular resistance to lower BP and may increase the tissue blood flow despite reduced OPP.

On the other hand, treatment with beta-blockers or diuretics may reduce both BP and peripheral blood flow. These factors might be partly responsible for the apparent discrepancy among previous studies. The association of lower OPP and development and progression of glaucoma evidently demonstrated by the current two studies may imply not only involvement of vascular insufficiency in the pathogenesis of glaucoma, but also association of OPP or systemic BP with other non-IOP factors involved in the pathogenesis of glaucoma such as cerebrospinal fluid pressure. The results are also highly relevant not only in the treatment of glaucoma, but also of coexisting systemic hypertension.

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