Michele Virno

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 Dl 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.

Acetazolamide, Metabolic Acidosis, and Intraocular Pressure

In order to investigate whether or not there is a causal relationship between the metabolic acidosis and the ocular hypotension induced by acetazolamide, we undertook to correlate over a period of time the blood-acidifying and ocular-hypotonizing effects of administering the lowest intravenous effective dose of acetazolamide; to treat the metabolic acidosis induced by acetazolamide by means of the intravenous introduction of bases, and pulmonary hyperventilation (respiratory alkalosis); to evaluate the effects on the intraocular pressure (IOP) by neutralizing the acetazolamide-induced metabolic acidosis by means of a continuous infusion of sodium bicarbonate; to determine the relationship between the metabolic acidosis induced by blood-acidifying agents, which do not inhibit carbonic anhydrase, and the IOP; and to determine the changes in the acid-base status of the aqueous humor induced by acetazolamide and other blood-acidifying drugs. We found that the hypertonic buffering solution of sodium bicarbonate could reduce the IOP by itself through an osmotic mechanism. On the basis of our results, we believe that a causal relationship exists between the metabolic acidosis induced by acetazolamide, and by other drugs that have a blood-acidifying effect as the result of other mechanisms, and ocular hypotension, bothin the animal and in the glaucomatous patient.

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.

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.

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 (Fishers 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 (Fishers 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.

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.

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 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.

Bluthyperosmolarität durch Azetazolamid und Augeninnendrucksenkung

In dieser Untersuchung haben wir unsere Studien uber die therapeutischen Eigenschaften und uber den Mechanismus der augen-drucksenkenden Wirkung des Azetazol-amids fortsetzen wollen. Insbesondere wollten wir feststellen, ob ein osmotischer Mechanismus eintreten konnte, auch wenn fruhere Autoren keine bedeutenden Veranderungen der osmolaren Spiegel des Plasmas und des Kammerwassers nach Verabreichung von Azetazolamid hervorgehoben haben (Akagi et al. 1959; Auricchio u. Wistrand 1958; Becker 1955; Bill 1974; Levene 1958; Nakamura 1961).