Fernando Galassi

A new approach to antiglaucoma drugs: carbonic anhydrase inhibitors with or without NO donating moieties. Mechanism of action and preliminary pharmacology

The clinically used sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor dorzolamide (DRZ), a new sulfonamide CA inhibitor also incorporating NO-donating moieties, NCX250, and isosorbide mononitrate (ISMN) (an NO-donating compound with no CA inhibitory properties) were investigated for their intraocular pressure (IOP) lowering effects in rabbits with carbomer-induced glaucoma. NCX250 was more effective than DRZ or ISMN on lowering IOP, increasing ocular hemodynamics, decreasing the inflammatory processes and ocular apoptosis in this animal model of glaucoma. NO participate to the regulation of IOP in glaucoma, having also antiapoptotic and anti-inflammatory effects. The ophthalmic artery, both systolic and diastolic velocities, were significantly reduced in NCX250-treated eyes in comparison to DRZ treated ones, suggesting thus a beneficial effect of NCX250 on the blood supply to the optic nerve. Combining CA inhibition with NO-donating moieties in the same compound offers an excellent approach for the management of glaucoma.

Color Doppler imaging in evaluation of optic nerve blood supply in normal and glaucomatous subjects

The authors evaluate by means of Color Doppler Imaging (CDI) the blood flow in ophthalmic artery, posterior ciliary arteries and central retinal artery in a group of glaucomatous patients. The data obtained in this study show a statistically significant reduction of the mean systolic peak flow velocity in ophthalmic artery in glaucomas in comparison with controls. In Glaucomatous patients with uncontrolled IOP there was a reduction of end-diastolic flow velocities and a rise of resistivity index in ciliary arteries and central retinal artery.

Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma

Background: To investigate the levels of nitric oxide (NO) markers in plasma and aqueous humour of patients with primary open angle glaucoma (POAG) and their relation to ocular perfusion pressure. Methods: Cyclic guanosine monophosphate (cGMP) and nitrite (NO2 −) were determined in plasma and aqueous humour of 38 patients with POAG and 46 controls. Blood pressure and IOP were measured to calculate ocular perfusion pressure (PP). Results: cGMP and NO2 − plasma levels were significantly decreased in glaucoma patients compared with controls (p = 0.001 v p = 0.004). In the aqueous humour of subjects with POAG, cGMP and NO2 − concentrations were also lower than in normal eyes (p = 0.0001 v p = 0.001). There was a linear association between cGMP in plasma and aqueous humour in glaucomas and controls (r = 0.514, p = 0.029 and r = 0.558, p = 0.004) and this relation differed in the two groups (p = 0.003). Considering glaucoma patients with controls, a positive correlation was found between cGMP and PP (r = 0.379, p = 0.01) and between NO2 − and PP (r = 0.339, p = 0.040). The cGMP/PP correlation was of borderline statistical significance in controls (p = 0.050), whereas it did not attain statistical significance in POAG, as well as the association between NO2 − and PP when glaucomas and controls were considered separately. Conclusions: The authors found alterations of NO markers in the plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO balance could alter ocular perfusion pressure.

Possible Correlations of Ocular Blood Flow Parameters with Intraocular Pressure and Visual-Field Alterations in Glaucoma: A Study by Means of Color Doppler Imaging

The authors evaluated, by means of color Doppler imaging, the blood flow of the ophthalmic artery, ciliary arteries and central retinal artery in normal and glaucomatous subjects. In normals they found that flow velocities of all considered vessels progressively decline while resistivity indices increase with advancing age. In glaucomatous subjects there was a statistically significant reduction of the mean systolic peak flow velocity of the ophthalmic artery in comparison with normals. Glaucomatous eyes with uncontrolled IOP and with visual-field worsening showed a statistically significant decrease in the end-diastolic flow velocities and an increase in the resistivity index values in ciliary arteries.

Systemic vascular dysregulation and retrobulbar hemodynamics in normal-tension glaucoma.

PURPOSE To investigate the influence of systemic vascular dysregulation on retrobulbar hemodynamics in normal-tension glaucoma (NTG). METHODS Forty-four untreated patients with NTG and 40 healthy controls matched for age, sex, and intraocular pressure were included. Cold-induced nailfold capillaroscopic features, mean and diastolic ocular perfusion pressures (mOPP, dOPP), endothelin-1 (ET-1) and nitric oxide markers, as nitrates (NO(2)), plasma values were recorded. Peak-systolic velocity, end-diastolic velocity (EDV), and resistivity index (RI) were measured in the ophthalmic artery (OA), short posterior ciliary arteries, and the central retinal artery by color Doppler imaging. Differences between groups were determined by Students t-test. Relationships among ET-1, NO(2), OPPs, and retrobulbar hemodynamics were assessed using correlation and multiple linear regression analyses. RESULTS Altered capillaroscopy was more frequent (72.7% vs. 5.0%, P < 0.001), mOPP and dOPP values were lower (44.54 ± 2.81 vs. 52.18 ± 4.47 mm Hg; 57.89 ± 4.30 vs. 68.28 ± 6.91 mm Hg; P < 0.001), and ET-1 and NO(2) values were respectively higher and lower (1.62 ± 0.22 vs. 1.12 ± 0.20 pg/mL and 142.17 ± 14.34 vs. 231.30 ± 6.16 μmol/mg prot; P < 0.001) in patients than the same values in controls. EDV was lower and RI higher in OA (5.87 ± 1.17 vs. 11.41 ± 2.30 cm/s; 0.76 ± 0.03 vs. 0.64 ± 0.03; P < 0.001) in subjects with NTG than in controls. In patients RI-OA was positively related to ET-1 (t = 2.704, P = 0.010) and negatively related to NO(2) (t = -4.477, P < 0.001). CONCLUSIONS Impaired retrobulbar hemodynamics may proceed from a vascular endotheliopathy in patients with NTG.

Effects of timolol and dorzolamide on retrobulbar hemodynamics in patients with newly diagnosed primary open-angle glaucoma.

The authors considered a group of patients with newly diagnosed primary open-angle glaucoma studying the effects of a 4-week treatment with timolol or dorzolamide on retrobulbar vessels. Ocular hemodynamics were assessed by means of color Doppler imaging of the ophthalmic artery, the temporal short posterior ciliary arteries (SPCAs) and the central retinal artery. For each vessel, systolic and diastolic blood flow velocities were measured, and the resistivity index (RI) was calculated. The only significant result was a reduction of temporal SPCA RI after dorzolamide treatment in comparison with baseline (p = 0.011). In the same group, dorzolamide treatment had a slight and nonsignificant increase in temporal SPCA diastolic velocity. The resistance decrease observed after dorzolamide treatment in the ciliary circulation may be due to the decrease in intraocular pressure or a possible direct vasodilating effect of the drug.

Ocular haemodynamics in glaucoma associated with high myopia.

AbstractThe ocular blood flow of a group of high myopic and glaucomatous eyes has been investigated by means of the Color Doppler Imaging (CDI) technique, comparing the results with those of some very myopic eyes without glaucoma, some non-myopic glaucomatous eyes and with a control group. The Ophthalmic Artery (OA), the Short Posterior Ciliary Arteries (SPCAs) and the Central Retinal Artery (CRA) were considered. For every vessel, peak systolic velocity (SV), end-diastolic velocity (DV) and the Pourcelot Resistivity Index were studied. The statistical analysis was performed by means of t-test according to Bonferroni procedure for multiple comparisons. The authors registered in the group of eyes with glaucoma associated with very severe myopia some abnormalities of the OA blood flow systolic velocity which might be interpreted as a vascular risk factor for the pathogenesis of the glaucomatous opticneuropathy; these abnormalities are more severe in glaucoma patients with high myopia than in anage-matched group of glaucoma patients without myopia.

Evaluation of ocular surface temperature and retrobulbar haemodynamics by infrared thermography and colour Doppler imaging in patients with glaucoma

Background: Ocular surface temperature (OST) could berelated to retrobulbar haemodynamics in patients with glaucoma. Aims: To compare OST measurements in patients with glaucoma and healthy controls, and to investigate the correlation between OST, intraocular pressure (IOP) and retrobulbar haemodynamics in patients with glaucoma. Methods: 32 patients with primary open-angle glaucoma (POAG) and 40 controls were included in the study. The parameters considered both in patients with POAG and in controls were IOP and OST values measured by infrared ocular thermography. Colour Doppler imaging was used to determine haemodynamic parameters in ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs) in patients with POAG. Results: OST values were significantly lower in patients with POAG than in controls (p<0.001). OST was negatively related with resistivity index of OA (p<0.001), CRA (p = 0.001) and SPCAs (p<0.001), and positively related with end-diastolic velocity of OA (p = 0.02) and SPCAs (p = 0.05). Conclusion: This study suggested that OST could be a marker of impaired retrobulbar haemodynamics in patients with glaucoma.

Deep sclerectomy with SkGel implant: 5-year results.

PurposeTo evaluate the results of deep sclerectomy with SkGel at 3 and 5 years. Materials and MethodsThis retrospective trial comprised 200 eyes with open angle glaucoma having a 3-year follow-up, 97 having a 5-year follow-up. Visual acuity, intraocular pressure (IOP), and slit-lamp examination were recorded at baseline and at follow-up visits. Visual field (VF) testing was repeated every 6 months. ResultsMean IOP decreased from 21.01±5.56 mm Hg before surgery to 13.13±2.24 mm Hg at 36 months and from 20.61±5.50 to 12.85±1.84 mm Hg at 60 months (P<0.0005). At 3 and 5 years, complete success rates (IOP ≤16 mm Hg without medications) were 67.50% and 64.95%, partial success rates were (IOP ≤16 mm Hg with medications) 21.50% and 24.74%, and failure rates were (IOP >16 mm Hg) 11% and 10.31%, respectively. VF testing revealed stable mean deviation and corrected pattern standard deviation values at 3 and 5 years (P>0.05). At 3 years, success rate was greater if goniopuncture was performed within 3 months after surgery (P=0.022). Complications of the surgery were not observed after goniopunctures. ConclusionsDeep sclerectomy with SkGel provides stable control of IOP and VF.

Ocular perfusion pressure and retrobulbar haemodynamics in pseudoexfoliative glaucoma.

BackgroundPrevious investigations have shown that vascular factors are involved in pseudoexfoliative glaucoma (XFG). The present study aims at comparing ocular perfusion pressure (OPP), diastolic ocular perfusion pressure (dOPP), and retrobulbar haemodynamics in pseudoexfoliative glaucoma and primary open-angle glaucoma (POAG).MethodsForty-seven XFGs, 41 POAGs, and 38 healthy controls were evaluated. OPP and dOPP were calculated. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistivity index (RI) were recorded in ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs) by color Doppler imaging (CDI). Correlations between OPP and CDI parameters and between dOPP and CDI parameters were determined.ResultsOPP and dOPP were significantly lower in XFGs than in POAGs and controls (p < 0.001). CDI investigation revealed decreased EDV of OA, SPCAs, and CRA (p < 0.001) and increased RI of all the three considered vessels in XFGs compared with POAGs and controls (p < 0.001). A negative correlation between OPP and RI of OA and between dOPP and RI of OA was found in XFGs (p = 0.022 and p = 0.015 respectively).ConclusionsOcular perfusion pressure is decreased and retrobulbar haemodynamics are worse in pseudoexfoliative glaucoma patients than in primary open-angle glaucoma patients and healthy controls. An impaired ocular vascular regulation is suggested in pseudoexfoliative glaucoma.