The nitric oxide donating triamcinolone acetonide NCX 434 does not increase intraocular pressure and reduces endothelin-1 induced biochemical and functional changes in the rabbit eye.

BACKGROUND: NCX 434 is a nitric oxide (NO)-donating triamcinolone acetonide (TA), shown to enhance optic nerve head (ONH) oxygen saturation in non-human primate eyes. Here, the effects of a single intravitreal (IVT) injection of TA were compared with those of NCX 434 on intraocular pressure (IOP), retinal function and retrobulbar haemodymamics in endothelin-1 (ET-1) induced ONH ischaemia/reperfusion in rabbits. Biochemical changes were also assessed in the aqueous humour and in retinal biopsies. METHODS: IOP and resistivity index of ophthalmic artery (RI-OA) were recorded using TonoPen and ecocolor Doppler, respectively. Retinal function was assessed using photopic electroretinography. Cytokine expression and oxidative stress markers were evaluated with immunoassay techniques. RESULTS: At 4 weeks post IVT treatment, TA increased IOP and RI-OA while NCX 434 did not (IOP(Vehicle)=13.6±1.3, IOP(NCX 434)=16.9±2.2, IOP(TA)=20.9±1.9 mm Hg; p<0.05 vs vehicle; RI-OA(Vehicle)=0.44±0.03; RI-OA(NCX 434)=0.47±0.02; RI-OA(TA)=0.60±0.04). Both NCX 434 and TA reversed ET-1 induced decrease in electroretinography amplitude to similar extents. NCX 434 attenuated ET-1 induced oxidative stress markers and nitrotyrosine in retinal tissue, and interleukin-6 and tumour necrosis factor-α in aqueous humour more effectively than TA. CONCLUSION: NCX 434 attenuates ET-1 induced ischaemia/reperfusion damage without increasing IOP, probably due to NO release. If data are confirmed in other species and models, this compound could represent an interesting new therapeutic option for retinal and ONH diseases, including diabetic retinopathy.

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.

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 Student's 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.

Deep sclerectomy with SkGel implant: 5-year results.

PURPOSE: To evaluate the results of deep sclerectomy with SkGel at 3 and 5 years. MATERIALS AND METHODS: This 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. RESULTS: Mean 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 (IOP16 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. CONCLUSIONS: Deep sclerectomy with SkGel provides stable control of IOP and VF.

Ocular perfusion pressure and retrobulbar haemodynamics in pseudoexfoliative glaucoma.

BACKGROUND: Previous 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). METHODS: Forty-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. RESULTS: OPP 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). CONCLUSIONS: Ocular 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.

Retrobulbar hemodynamics and corneal surface temperature in glaucoma surgery.

AIM: The purpose of this study was to investigate the effects of glaucoma surgery on retrobulbar hemodynamics and corneal surface temperature (CST). METHODS: A total of 22 primary open-angle glaucoma eyes underwent deep sclerectomy, and 19 trabeculectomy. The follow-up was of 3 months. The peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistivity index (RI) were evaluated in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs) by color Doppler imaging (CDI). CST was measured using infrared thermography. RESULTS: At 3 months, EDV was increased in OA (P<0.001 in deep sclerectomy, P=0.005 in trabeculectomy), CRA (P=0.044 and P<0.001), and SPCAs (P=0.011 and P=0.003), and RI decreased in OA, CRA, and SPCAs (P<0.001 in both groups). CST values were augmented (P<0.001 in both groups). A negative correlation between the postoperative changes in RI-OA and CST was found (P=0.023 and P=0.032, respectively). CONCLUSIONS: Deep sclerectomy and trabeculectomy seem to be equally effective in improving retrobulbar hemodynamics. Color Doppler imaging and infrared thermography might be useful to evaluate the vascular outcome of glaucoma surgery.

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.

Ocular hemodynamics and glaucoma prognosis: a color Doppler imaging study.

OBJECTIVE: To evaluate the effect of optic nerve circulation, using color Doppler imaging (CDI), on the progression of visual field damage in primary open-angle glaucoma. METHODS: The relationship between the results of retrobulbar CDI, performed shortly after the diagnosis of primary open-angle glaucoma, and the progression of visual field loss for 7 years was evaluated in 44 glaucoma patients. Color Doppler imaging variables in patients with a stable and deteriorating clinical course were compared, and the pattern of increasing risk for different CDI values was analyzed using an additive logistic model. Based on this nonparametric analysis, we arrived at a discriminant CDI value identifying glaucoma patients with a poor prognosis. On the basis of the discriminant value, patients were divided into 2 groups, and the odds ratio of visual field loss for each group was then estimated. RESULTS: Patients with a stable visual field had a higher diastolic velocity and a lower resistivity index in the ophthalmic artery (P<.001 for both) compared with those with a deteriorating visual field during the study. The odds of visual field deterioration in patients with an ophthalmic artery resistivity index of 0.78 or higher was about 6 times that of patients with an ophthalmic artery resistivity index lower than 0.78. CONCLUSION: Color Doppler imaging variables of the ophthalmic artery correlate with the risk of visual field deterioration in patients with primary open-angle glaucoma.

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.