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Editors Selection IGR 11-1

Medical treatment: Treatment and bloodflow

Alon Harris

Comment by Alon Harris on:

12398 Intravenous administration of L-arginine increases retinal and choroidal blood flow, Garhöfer G; Resch H; Lung S et al., American Journal of Ophthalmology, 2005; 140: 69-76


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While lowering IOP remains the sine qua non of treating glaucoma, it is now well established that Primary Open Angle Glaucoma (POAG) is a multi-factorial disease. There is increasing evidence that ischemia, secondary to altered vascular autoregulation, also contributes to glaucomatous optic neuropathy. In fact many studies have reported decreased ocular blood flow in the retina, choroid, retrobulbar vessels and optic nerve head in POAG patients. It is believed, though not yet proven, that decreased ocular perfusion is also associated with retinal ganglion cell ischemia and apoptosis in POAG. At this stage it is unclear whether abnormal vascular autoregulation is due to a deficiency of vasodilatory substances such as NO or the inability of retinal vessels to respond to humoral factors. Garhöfer et al. (638) report a very interesting study in which they examine the effects of L-arginine on OBF (Ocular Blood Flow) in healthy subjects. Extensive work has previously demonstrated L-arginine's role as a substrate of nitric oxide (NO) synthesis, which in turn plays a role in systemic vasodilation. However, little has been published regarding the effects of L-arginine on OBF, particularly the retina. In order to determine such effects, this study examined ocular hemodynamics before, during, and after intravenous administration of L-arginine, compared to placebo. The authors found that subjects with exposure to IV L-arginine had significantly lowered mean arterial pressure (MAP) and increased choroidal blood flow.Retinal vein blood flow was calculated to increase by 21% &plm; 18% after 20 minutes of L-arginine infusion, and 21% &plm; 19% (mean &plm; SD, p < 0.01) thirty minutes L-arginine administration. Additionally, red blood cell velocity was significantly higher when patients received L-arginine, 22% &plm; 23% higher during infusion and 20% &plm; 19% higher afterwards (p < 0.01). This is a very important study, since it attempts to uncover the metabolic basis of vascular autoregulation in comparison to clinical OBF observations. However, the vasculature of young healthy individuals likely reacts differently to vasodilators than the elderly glaucomatous population. The relatively low statistical power of the study, as well as the lack of documentation of the specificity and reproducibility of the flicker fundus pulsation, and laser Doppler velocimetry imaging techniques, requires consideration.

Interestingly, L-arginine was not found to increase the flicker-induced vasodilation in retinal vessels, contrary to what would be expected from the results of studies that have shown L-NMMA (a NO synthase inhibitor) to blunt the vasodilatory response to flicker stimulation in the retina (Buerk et al., Dorner et al.). These findings may be more consistent with a larger sample size (the L-arginine study had only twelve subjects), or may suggest the possibility of saturation of the retinal microcirculation endothelial NO receptors preventing further flicker-induced vasodilation.

The ability of L-arginine to increase retrobulbar blood flow reveals clinical potential for the use of NO precursors in the treatment of ocular conditions of a vascular nature. A larger study that quantifies the oxygenation of the retinal tissues is needed. Examining an older population may also contribute to the understanding of the effects of the aging per say on ocular vaso-reactivity to vasodilatory substances such as NO. It would be very interesting to expand on this study and perform a comprehensive blood flow analysis using color Doppler imaging, scanning laser Doppler flowmetry and oximetry in glaucoma patients who have been receiving L-arginine (Rechtman et al.)

References

  • Buerk DG, Riva CE, Cransoun SD. Nitric oxide has a vasodilatory role in cat optic nerve head during flicker stimuli. Microvasc Res 1996;52:13-26.
  • Dorner GT, Garhofer G, Kiss B, et al. Nitric oxide regulates retinal vascular tone in man. Am J Physiol Heart Circ Physio 2003; 285:631-636.
  • Rechtman, E., Harris, A., Kumar, R., Cantor, L.B., Ventrapragada, S., Desai, M., Friedman, S., Kagemann, L., Garzozi, H.J. An Update on Retinal Circulation Assessment Technologies. Curr Eye Res. 2003 Dec; 27(6): 329-43.


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