Retinal blood flow

Cardioembolism Cardioembolism accounts for approximately 30% of all stroke and 25-30% of strokes in the young (age <45 years)." AF accounts for a large proportion of these strokes (15-25%). Symptoms may be suggestive, but they are not diagnostic. Repetitive, stereotyped, transient ischemic attacks (TIAs) are unusual in embolic stroke. The classic presentation for cardioembolism is the sudden onset of maximal symptoms. The size of the embolic material determines, in part, the course of the embolic material. Small emboli can cause retinal ischemic or lacunar symptoms. Posterior cerebral artery territory infarcts, in particular, are often due to cardiac embolism. This predilection is not completely consistent across the various cardiac structural abnormalities that predispose to stroke, and may be due to patterns of blood flow associated with specific cardiac pathologies. 

Improving giycaemic control may not only reduce the rate of non-enzymatic glycosyiation and monosaccharide autooxidation, but lower polyol pathway activity. In addition, it should have a beneficial effect on other haemodynamic and hormonal factors involved in the development of diabetic vascular disease. However, in studies of diabetic retinopathy, rapid control of glucose levels by intensive insulin therapy has been shown to worsen vascular disease initially and it could be postulated that a sudden improvement in retinal blood flow promotes further free-radical damage as part of a reperfusion-ischaemic injury. 

Polymers are also used as sutures. Fighters and other athletes have used poly(alpha-cyanoacrylates), super glues, to quickly stop blood flow in surface cuts. Today, super glue is also used for, in place of or along with, more traditional polymeric suture threads for selected surface wounds, internal surgery, and retinal and corneal surgery. The alpha-cyanoacrylate polymers (structure 19.22) undergo anionic polymerization in the presence of water. More about sutures is explained in Section 19.6. 

In ophthalmological application, this characteristic of the PFCLs is not used yet. In general, the products used are air equilibrated with the consequence that the oxygen partial pressure in the eye is increased from 15 Torr to 160 Torr and the CO2 partial pressure drops down from 50 Torr to 3 Torr initially. These differences are equilibrated intra-ocularly by diffusion processes, but the initial difference to the physiological level of gas concentration activates the constriction of the retinal vessels, resulting in an increase of the blood flow. In rabbit eyes, a damage of the retina could be attributed to this mechanism [38,39], On the other hand, endotamponade media with controlled levels of dissolved gases could not only avoid such a scenario but should also be useable for a therapeutic manipulation of the retinal perfusion. 

N. Izumi, T. Nagaoka, E. Sato, F. Mori, A. Takahashi, A. Yoshida, DE-085 increases retinal blood flow. Invest. Ophthalmol. Vis. Sci. Abst. 45 (2004) 2340. 

The structure of 4-substituted 3,5-bis(2-pyridyl)pyrazoles [245], seventeen C-nitropyrazoles affected ocular blood flow and retinal function recovery after ischemic insult [244], and a large series of nitroazoloanhydrosacchares [295] has been determined by II and 13C NMR method. 

Generator of NO [272], ocular pharmacology and therapeutics (ocular blood flow, recovery of retinal function after ischemic insult) [273]... 

Chemtob, S., Beharry, K., Rex, J., Chatteijee, T. Varma, D.R., Aranda, J.V. (1991). Ibuprofen enhances retinal and choroidal blood flow autoregulation in newborn piglets. Invest. Ophthl-mol. Vis. Set 32 1799-1807. 

Like levobimolol, metipranolol has an active metabo-Ute,des-acetyl-metiptanolol, which is an effective p-blocker. Metipranolol has been used in concentrations ranging from 0.1% to 0.6% and has ocular hypotensive efficacy within the range of other noncardioselective agents. As with other p-adrenoceptor antagonists, metipranolol decreases aqueous humor production. Retinal perfusion pressure and blood flow appear to increase during treatment with topical metipranolol. 

Brimonidine also does not appear to alter retinal capillary blood flow or vasomotor activity of the anterior optic nerve. Measurements of blood flow velocities in central retinal, ophthalmic, nasal, and temporal posterior ciliary arteries do not change when 0.2% brimonidine is administered twice daily. When applied to human eyes, brimonidine appears to have little or no contralateral lowering effect on lOP. 

An additional clinical use of acetazolamide is unrelated to its ocular hypotensive properties.The 500-mg acetazolamide capsule administered daily for 2 weeks may produce either a partial or a complete resolution of macular edema in patients with cystoid macular edema (CME), retinitis pigmentosa, and chronic intermediate uveitis (pars planitis). Macular edema produced by primary retinal vascular diseases (branch and central retinal vein occlusion and macular telangiectasia) did not respond to acetazolamide therapy. It is believed that acetazolamide may improve visual function if the macular edema stems from retinal pigment epithelial dysfunction. Improved macular edema in these conditions may be associated with fluid movement from the retina to the choroid. However, acetazolamide does not appear to alter macular blood flow. 

Topical dorzolamide does not appear to cause a change in retinal circulatory variables, including venous diameter and volumetric blood flow rate, after a single dose in normal subjects. The drug also does not have any apparent effect on retrobulbar hemodynamics as determined by color Doppler imaging. In some studies, however, improvements in retinal, choroidal, and retrobulbar blood flow as determined by various assessment methods and hemodynamic markers demonstrate that dorzolamide alone or in combination therapy may improve ocular blood flow in patients with glaucoma and ocular... 

A therapeutic strategy could encompass the suppression of protein kinase C activity, thus short-circuiting at least part of the pathway driving VEGF activity in the retina. The initial chemical studied as a protein kinase C inhibitor was known as LY333531 and was found to have very selective inhibition of both [31 and [311 isoforms of protein kinase C. This drug was studied in animal models and was found to reduce VEGF-mediated retinal vascular permeability, increase retinal blood flow, and inhibit retinal neovascularization. 

Blood is supplied to the retina by the central retinal artery and choroidal blood vessels (Oyster, 1999). The central retinal artery arises from the ophthalmic artery, w hich in turn branches off the internal carotid artery. Upon entering the retina, the central retinal artery branches into deep capillary beds in the INL and superficial capillary beds in the GCL. Endothelial cells of retinal capillaries are joined by tight junctions, contributing to the blood/retinal barrier. There is litde or no autonomic regulation of the retinal circulation blood flow through these capillaries is instead primarily controlled by autoregulation (Wangsa-Wirawan and Linsenmeier, 2003). Retinal capillaries drain into the central retinal vein. 

Tafluprost significantly increases retinal blood flow and blood velocity in animal models. The improvement of ocular blood flow is thought to be relevant in glaucoma therapy, especially for normal-tension glaucoma patients since it is assumed that optic nerve damage is involved not only in mechanical compression caused by IOPbut also in impairment of ocular blood flow. 

The effects of tafluprost on IOP and retinal blood flow (RBF) were studied in adult cats [41]. A single drop of tafluprost was placed in one eye and IOP, vessel diameter, blood velocity, and RBF were measured simultaneously by laser Doppler velocimetry. Measurements carried out at 30 and 60min after dosing showed 16.1% and 21.0% IOP reduction, respectively, as well as 1% and 2.4% reduction in mean vessel diameter, respectively. The mean blood velocity increases were 17.4% and 13.7%, respectively, and the mean RBF increases were 20.7% and 18.8%, respectively, 30 and 60min after dosing. 

Izumi, N., Nagaoka, T., Sato, E., et al. (2004) DE-085 increases retinal blood flow. Investigative Ophthalmology Visual Science. 45, Abst. 2340. 

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