Ibopamine treatment in chronic hypotony secondary to long-lasting uveitis. A case report.

PURPOSE: To assess the clinical efficacy of ibopamine eye drops in severe hypotony secondary to chronic progressive uveitis. METHODS: Case report. A 47-year-old man with a 37-year history of diffuse uveitis and severe refractory hypotony was treated with topical 2% ibopamine (Trazyl) six times a day. Intraocular pressure, visual acuity, visual field and side effects were recorded during 15 months of follow-up. RESULTS: IOP, visual acuity and visual field increased after four days of therapy and lasted for two months when the drug was suspended because of the onset of filamentous keratopathy. A new course of treatment with 2% ibopamine eye drops in a different solvent (BSS) resulted in a stable increase in IOP, VA and visual field, with no side effects in a follow-up of 13 months. CONCLUSIONS: Ibopamine 2% eye drops in BSS solvent seem effective in the treatment of uveitis-related hypotony.

Correlation between ocular hypertension induced by ibopamine and perimetric defect in primary open-angle glaucoma.

In 35 patients with bilateral primary open-angle glaucoma (POAG), with asymmetrical evolution of the neuropticopathy between the two eyes, we compared within each patient, the response to ibopamine and the perimetric defect. In 88% of cases (31/35 patients) the eye with the most severe perimetric defect had high intraocular pressure or a larger IOP increase after ibopamine. This result was highly significant at the sign test (P < 0.001). IOP and its increase after ibopamine significantly differed in the most and least affected eye, being higher in the eye with the most impaired visual field. Since ibopamine can be used to quantify the hydrodynamic impairment, which is thus presumably correlated to the perimetric defect. This study further confirms its importance in the development of glaucomatous damage.

Ibopamine in glaucoma diagnostics: a new pharmacological provocative test.

PURPOSE: Ibopamine is used when performing provocative tests, thanks to its pharmacological property of increasing ocular pressure in eyes with outflow system impairment. This study summarizes the latest results that we have achieved with reference to its clinical-diagnostic use. METHODS: 175 (250 eyes) POAG patients, 101 (190 eyes) glaucoma suspects with mild ocular hypertension, 39 (64 eyes) NTG patients and 163 (326 eyes) healthy volunteers underwent an ibopamine provocative test. Among the POAG and the glaucoma suspects, 49 (92 eyes) and 20 (38 eyes) patients were selected who, starting from the performing of ibopamine test, had at least one year of perimetric follow-up. These patients have been assessed for the perimetric defect progression in relation to the (negative or positive) response to ibopamine. RESULTS: the ibopamine test was positive for 92% of the glaucomatous patients, 61% of the glaucoma suspects, 52% of the NTG patients and 0% of the healthy volunteers. It was observed that 28% of the ibopamine-positive glaucoma suspects showed a perimetric deterioration during an average 2.5-year follow-up. No perimetric deterioration was found on ibopamine-negative glaucoma suspects (Fisher's exact test: p = 0.038). Among glaucomatous patients, 46% of the test-positive individuals showed a progressive trend of the perimetric defect, as against about 8% of glaucomatous test-negative patients (Fisher's exact test: p = 0.003). CONCLUSIONS: We believe that the ibopamine provocative test can be usefully applied especially to epidemiological screening studies to identify patients who might develop ocular hypertension or glaucoma and in the follow-up of glaucoma suspects, to identify individuals who have a greater risk of developing perimetric defects.

Increase in aqueous humor production following D1 receptors activation by means of ibopamine.

BACKGROUND: Topically administered 2% ibopamine (a dopaminergic agonist) induces a transitory ocular hypertension in 92% of patients with primary open-angle glaucoma and in 52% of patients with normal tension glaucoma. In normal eyes, ibopamine has no effect on IOP. PURPOSE: The aim of the present study was to verify, by means of fluorophotometric techniques, which hydrodynamic changes could be induced in normal and glaucomatous eyes, stimulating the D1 receptor with 2% ibopamine administered topically. In addiction, we wanted to evaluate if ibopamine could modify IOP before and after an experimentally induced outflow system impairment in rabbits. METHODS: In study 1 we performed a measurement of aqueous humor flow in 6 healthy volunteers and in 6 glaucomatous patients, before and after 2% ibopamine administration. In study 2 the alteration of outflow pathways was induced by means of Laminaria Digitata in 10 rabbits. RESULTS: After 2% ibopamine administration we found a significant increase in aqueous humor production, both in glaucomatous (P = 0.035) and normal eyes (P = 0.004). In rabbits, we found no significant change in IOP at basal conditions. After experimentally induced outflow system impairment by laminaria, we observed a marked increase in IOP (+ 13.5 mmHg SD 7.2; P < = 0.001) following ibopamine administration. CONCLUSIONS: These experimental data have a diagnostic value in glaucoma, since they show how an intraocular hypertensive response due to ibopamine in normotensive eyes is a sign of initial outflow impairment. Moreover, the possibility to increase the aqueous humor production sets new trends in the treatment of post surgical ocular hypotony.

Topical ibopamine and corticosteroids in the treatment of post-surgery ocular hypotony.

PURPOSE: The aim of the present preliminary study, performed on post-surgical hypotony, was the evaluation of the effects on ocular hypotony of the concomitant administration of ibopamine and corticosteroids. METHODS: 14 patients (11 males-3 females; mean age 47 years) with ocular hypotony following several vitroretinal surgical intervention in different districts, were enrolled. The inclusion criteria were: mean IOP during tonometric curve equal or lower than 6 mmHg, stable IOP for at least 60 days, ongoing treatment with 0.1% dexamethasone (4 times/day), successful surgical intervention, 2% ibopamine (4 times/day) was added to the corticosteroid therapy for 30-60 days. RESULTS: Before ibopamine administration, mean IOP was 4.07 mmHg SD 1.71. At the end of the treatment period, mean IOP increased by 89% in comparison to baseline values (+ 3.64 mmHg SD 5.57). This difference was statistically significant (paired t = 2.39; P = 0.03). One month after ibopamine-treatment discontinuation, mean IOP decreased to pre-treatment values (4.86 mmHg SD 3.50). CONCLUSIONS: The results of the present study, although preliminary, suggest the possibility of a future pharmacological treatment of ocular hypotony with ibopamine, whose rationale is based on the increase of aqueous humor production by stimulating the D1 dopaminergic receptor.

Ocular pharmacokinetics and pharmacodynamics in rabbits of ibopamine, a new mydriatic agent.

Ibopamine is an original dopamine analogue. The drug, instilled in the conjunctival sac, induces mydriasis and is well-tolerated. In the present study, we have investigated the pharmacokinetic and pharmacodynamic characteristics of ibopamine after ocular application. Ibopamine produces a dose-dependent mydriasis endowed with very interesting characteristics: rapid onset, marked pupil dilation and rapid return to normal pupillary diameter. Ibopamine is well absorbed through the cornea, it is rapidly hydrolysed by esterases to epinine and the mydriatic effect is correlated with the concentration of epinine in the aqueous humor. The results of the experiments with the alpha 1-antagonists bunazosin and thymoxamine, and with reserpine, suggest that the mydriatic effect of ibopamine is obtained by direct stimulation of the alpha 1-adrenergic receptors; pretreatment with bunazosin almost completely inhibits the mydriatic activity of ibopamine; the mydriasis is also antagonized by thymoxamine. Pretreatment with reserpine has no effect on the extent of the mydriasis induced by ibopamine.

Dopamine, dopaminergic drugs and ocular hypertension.

The study refers to the clinical experiences performed with several D1 and D2 dopaminergic receptors agonists in 20 patients with high tension open angle glaucoma. The substances were administered topically as eye drops as well as an ocular eye bath. The parameter examined was intraocular pressure (IOP). The substances taken in consideration were: Dopamine, Ibopamine (dopamine analog), Fenoldopam and 3B90 (D1-receptor agonists) and Bromocriptine (dopaminergic agonist with higher affinity for D2 than for D1-receptors). It has been shown that all selective D1-receptors agonists induce a significant increase in IOP only in eyes with hydrodynamic disorders (p < 0.001). Such hypertensive effects could not be antagonized either by topically administered dopaminergic antagonists (Sulpiride, D2-receptors antagonist, and Haloperidol, non-selective dopaminergic antagonist) or by the pretreatment with the commonly used topical antiglaucomatous drugs. The only substance which proved able to inhibit the IOP increase induced by the D1-receptors agonists was the D1-selective antagonist SCH-23390, suggesting that IOP increase may be a result of a stimulation of the D1-receptors. The authors hypothesize that dopaminergic system may play a role in the regulation of aqueous humor hydrodynamics.

Brain oedema and intracranial hypertension treatment by GLIAS.

The authors present their results regarding the use of a buffered solution of glycerol 30%-sodium ascorbate 20% (GLIAS) for the treatment of brain oedema and intracranial hypertension. GLIAS was perfused intravenously in 80 patients with several types of brain oedema. In every patients serum and urinary osmolarity, diuresis, main blood and urine parameters, and ICP were monitored. Following GLIAS infusion an increase in plasma osmolarity was observed, changing the average basal value plus 13.4% after 15 min., 10.5% after 30'. At the same time there was a reduction of ICP and improvement in cerebral compliance. In each case there was a decrease in intracranial hypertension and brain oedema without significant collateral effects.

[The mechanism of cholinergic effects on lowering intraocular pressure]. / Prilog mehanizmu delovanja holinergika na snizenje intraokularnog pritiska.

The relationship between vasomotoric activity and blood vessel permeability was studied in the course of discovering the ocular hypotonising mechanism of cholinergic drug activity (pilocarpin and carbamylcholin). The authors found, in experimental conditions, that the vasomotoric activity (vasodilatation) of the two cholinergic drugs is expressed in the increased permeability of the blood-aqueour barrier. In the presence of an elevated extracirculatory pressure (IOP), as in glaucoma, vasodilatation under the influence of cholinergic drugs, is converted to passive vasoconstriction which leads to reduced aqueous humor production. Carbamilcholin reduces aqueous humor production in a greater extent than pilocarpin.

Therapeutic value of citicoline in the treatment of glaucoma (computerized and automated perimetric investigation).

The favourable neurotrophic effects obtained by means of the intramuscular administration of citicoline, one of the intermediate compounds of phospholipids, on the visual field of patients suffering from open-angle glaucoma are referred. The drug was administered at the dose of 1 gm for ten consecutive days. Visual field was examined by means of central computerized perimetry and automated perimetry. All patients had well controlled intraocular pressure through beta-blockers, but presented characteristic glaucomatous perimetric defects. It is suggested that citicoline might be administered as a useful complement to conventional hypotensive therapy, since it acts positively on the glaucomatous optic nerve damage.