Does phacoemulsification under topical anesthesia affect retrobulbar blood flow?

PURPOSE: To investigate with color Doppler imaging the effects of phacoemulsification surgery under topical anesthesia on retrobulbar vessels hemodynamics. METHODS: In this prospective study, color Doppler imaging was used to measure the maximum (Vmax) and minimum flow velocity (Vmin) of the central retinal vein, and the Vmax and Vmin, pulsatility index and resistance index of the central retinal artery, nasal, and temporal posterior ciliary arteries, and ophthalmic artery blood flow before and 1 day after phacoemulsification surgery under topical anesthesia. RESULTS: After phacoemulsification surgery under topical anesthesia, Vmin of the central retinal artery increased (p ≤ 0.05), whereas the other variables showed no significant change. CONCLUSIONS: Phacoemulsification surgery under topical anesthesia has a minor effect on retrobulbar blood flow. Therefore topical anesthesia should be suitable for patients with ocular perfusion disorders (eg, glaucoma).

Preclinical pharmacology of AL-12182, a new ocular hypotensive 11-oxa prostaglandin analog.

PURPOSE: The aim of this study was to determine selected in vivo ocular properties of AL-12182 (5,6-dihydro-4,5-didehydro-11-deoxy-11-oxa-16-(3-chlorophenoxy)-omega-tetranor-PGF(2alpha) isopropyl ester) and the in vitro profile of its free acid, AL-12180. METHODS: Previously documented radioligand binding and functional assays involving human ciliary muscle cells (h-CM), human trabecular meshwork (h-TM) and other cells, and porcine ocular arteries were utilized. For in vivo procedures, we utilized rabbits, cats, and nonhuman primates to measure hyperemia, pupil diameter, and intraocular pressure (IOP), respectively. RESULTS: AL-12180 exhibited the highest affinity for the FP-receptor (K(i) = 143 +/- 36 nM) and much lower affinity for DP-, EP(3)-, IP-, and TP-receptors, and for several nonprostanoid receptors, enzymes, neurotransmitter uptake sites, ion channels, and other regulatory sites. AL-12180 activated phospholipase C-mediated phosphoinositide hydrolysis (potency, EC(50) = 13.7-42.7 nM) through the FP-receptor in a variety of cells, such as h-CM, h-TM cells, human embryonic kidney cells expressing the cloned human ciliary body FP-receptor (HEK-FP), mouse 3T3 cells, and rat vascular smooth muscle cells. AL-8810, an FP-antagonist, blocked the effects of AL-12180 in h-CM cells (IC(50) = 8.7 microM). AL-12180 also stimulated the mobilization of intracellular Ca(2+) ([Ca(2+)](i)) in h-TM cells (EC(50) = 111 +/- 36 nM), h-CM cells (EC(50) = 11 nM), and in host cells expressing the cloned human ciliary body FP-receptor (EC(50) = 5.9 +/- 3.1 nM). AL-12180 lacked significant agonist activity at DP-, EP(2)-, EP(4)-, IP-, and TP-receptors in cell-based assays. However, AL-12180 contracted porcine central retinal and short posterior ciliary arteries in vitro with micromolar potencies that appeared to involve TP-receptor activation. in vivo, AL-12182 elicited dose-related hyperemia in the rabbit eye, miosis in the cat eye, and ocular hypotension in the nonhuman primate eye. CONCLUSIONS: AL-12180 is a relatively potent and selective FP-receptor agonist whose isopropyl ester prodrug (AL-12182) lowers IOP by as much as 40% following topical ocular dosing in a laser-induced nonhuman primate model of ocular hypertension.

Effects of hachimi-jio-gan (ba-wei-di-huang-wan) on blood flow in the human central retinal artery.

Hachimi-jio-gan (HJG), a Chinese herbal formula, and a placebo were given to 12 healthy adults, and the changes in blood flow in the central retinal artery were observed with the latest ultrasonic diagnosis device before and after administration. After administration of HJG, the systolic flow velocity, diastolic flow velocity and mean flow velocity in the central retinal artery showed significant increases. No change was observed in vascular resistance. The subjects deemed suitable for use of HJG showed remarkable increases in blood flow. No changes in blood flow velocities and vascular resistance were observed after administration of the placebo. HJG is frequently used in the aged, often with eye diseases such as cataract. It has been reported that a decrease of blood flow in the central retinal artery becomes more marked in proportion to the progress of various eye diseases. As increases in blood flow were obvious in the cases that were treated with HJG, it is suggested that increases in blood flow in the central retinal artery due to HJG give direct evidence supporting the positive effects of HJG on eye diseases.

Ginkgo biloba extract increases ocular blood flow velocity.

We evaluated a possible therapeutic effect of Ginkgo biloba extract (GBE) on glaucoma patients that may benefit from improvements in ocular blood flow. A Phase I cross-over trial of GBE with placebo control in 11 healthy volunteers (8 women, 3 men: Age; 34 +/- 3 years, mean +/- SE) was performed. Patients were treated with either GBE 40 mg or placebo three times daily orally, for 2 days. Color Doppler imaging (Siemens Quantum 2000) was used to measure ocular blood flow before and after treatment. There was a two week washout period between GBE and placebo treatment. Ginkgo biloba extract significantly increased end diastolic velocity (EDV) in the ophthalmic artery (OA) (baseline vs GBE-treatment; 6.5 +/- 0.5 vs 7.7 +/- 0.5 cm/sec, 23% change, p=0.023), with no change seen in placebo (baseline vs GBE-treatment; 7.2 +/- 0.6 vs 7.1 +/- 0.5 cm/sec, 3% change, p=0.892). No side effects related to GBE were found. Ginkgo biloba extract did not alter arterial blood pressure, heart rate, or IOP. Ginkgo biloba extract significantly increased EDV in the OA and deserves further investigation in ocular blood flow and neuroprotection for possible application to the treatment of glaucomatous optic neuropathy as well as other ischemic ocular diseases.

A color Doppler analysis of nifedipine-induced posterior ocular blood flow changes in open-angle glaucoma.

PURPOSE: This pilot study used color Doppler imaging to investigate the effects of nifedipine on the posterior ocular blood flow of patients with glaucoma progression at normal intraocular pressures. PATIENTS AND METHODS: Eighteen patients, 11 men and seven women with a median age of 61.7 years, were imaged before and 6 weeks after the initiation of 30 mg of sustained-release nifedipine (Procardia XL; produced by either Pfizer or Pratt) daily. RESULTS: There was no statistically significant change in the blood velocity of the ophthalmic artery, central retinal artery, and main nasal and temporal short posterior ciliary arteries after treatment with nifedipine. CONCLUSION: The routine use of nifedipine in patients with normal tension glaucoma progression is not supported by this study.

Vascular responses of ophthalmic arteries to exogenous and endogenous norepinephrine.

A participation of neuronal and tissue uptake mechanism in responses to periarterial electrical sympathetic nerve stimulation (ES) and intra-arterial applications of norepinephrine (NE) was investigated in the isolated and perfused canine ophthalmic arteries (OA), using key pharmacological drugs such as imipramine, tyramine, cocaine, cortisol and diltiazem. Results were as follows: (1) NE, KCl and ES induced marked vasoconstrictions in a dose- and frequency-related manner, but tyramine induced only a slight constriction even at large doses; (2) cortisol, an uptake2 blocker, did not significantly modify KCl- and ES-induced vasoconstrictions, but significantly enhanced NE-induced responses; (3) small doses of imipramine, a neuronal uptake1 blocker, did not modify NE-induced vasoconstrictions, but large doses decreased them. On the other hand, the ES-induced response was slightly increased by a relative small dose of imipramine; (4) cocaine, another uptake1 blocker, slightly enhanced NE- and ES-induced responses; (5) ES-induced response was reduced by not only diltiazem, but also Ca2+-free solution with EGTA (1 mM l-1). The NE-induced response was not affected by diltiazem (Ohkubo and Chiba, 1987, Exp. Eye Res. 45, 263-70), and slightly but significantly depressed by Ca2+-free solution with EGTA. These results suggest that tissue and neuronal uptake mechanisms exist in responses to ES and NE1, the response to ES was markedly dependent on Ca2+ influx to the cell membrane2, and exogenous NE may induce Ca2+ movement mainly from the intracellular store site.