Disturbed Correlation Between Arterial Resistance and Pulsatility in Glaucoma Patients

PURPOSE: (i) To investigate whether pulsatility index (PI) and mean flow velocities (MFV) are altered in glaucoma patients. (ii) To evaluate the significance of PI in retrobulbar autoregulation capacity. METHODS: Patients with primary open-angle glaucoma (POAG; n = 49), normal tension glaucoma (NTG; n = 62) and healthy controls (n = 48) underwent colour Doppler imaging measurements of the retrobulbar vasculature. Kruskal-Wallis test was used to compare variables between the three diagnostic groups. Restricted cubic splines were used to determine nonlinearities between the resistive index (RI) and PI correlations. RESULTS: Mean flow velocities (MFV) were lower in both short posterior ciliary arteries (SCPA) and central retinal arteries (CRA) from the two glaucoma groups (p 0.08). In healthy individuals, correlations between RI and PI were linear in all arteries. In both POAG and NTG patients, CRA presented a nonlinear curve with a cutpoint at RI 0.77 (p < 0.001) and 0.61 (p = 0.03), respectively, above which the slope increased nearly five- and tenfold (POAG: 1.96 to 10.06; NTG: -0.46-4.06), respectively. A nonlinear correlation in the ophthalmic artery was only observed in NTG patients, with a cutpoint at RI 0.82 (p < 0.001), above which the slope increased from 3.47 to 14.03. CONCLUSIONS: Glaucoma patients do not present the linear relationships between RI and PI observed in healthy individuals. Their nonlinear relations may be indicative of an altered autoregulation and suggest a possible threshold RI could be determined above which autoregulatory disturbances become more relevant

Intraocular Pressure Correlates with Optic Nerve Sheath Diameter in Patients with Normal Tension Glaucoma

PURPOSE: 1. Identify differences in optic nerve sheath diameter (ONSD) as an indirect measure of intracranial pressure (ICP) in glaucoma patients and a healthy population. 2. Identify variables that may correlate with ONSD in primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. METHODS: Patients with NTG (n = 46) and POAG (n = 61), and healthy controls (n = 42) underwent B-scan ultrasound measurement of ONSD by an observer masked to the patient diagnosis. Intraocular pressure (IOP) was measured in all groups, with additional central corneal thickness (CCT) and visual field defect measurements in glaucomatous patients. Only one eye per patient was selected. Kruskal-Wallis or Mann-Whitney were used to compare the different variables between the diagnostic groups. Spearman correlations were used to explore relationships among these variables. RESULTS: ONSD was not significantly different between healthy, NTG and POAG patients (6.09 ± 0.78, 6.03 ± 0.69, and 5.71 ± 0.83 respectively; p = 0.08). Visual field damage and CCT were not correlated with ONSD in either of the glaucoma groups (POAG, p = 0.31 and 0.44; NTG, p = 0.48 and 0.90 respectively). However, ONSD did correlate with IOP in NTG patients (r = 0.53, p  0.25 in all groups). CONCLUSIONS: Indirect measurements of ICP by ultrasound assessment of the ONSD may provide further insights into the retrolaminar pressure component in glaucoma. The correlation of ONSD with IOP solely in NTG patients suggests that the translaminar pressure gradient may be of particular importance in this type of glaucoma

Ophthalmic Artery Doppler Waveform Changes Associated with Increased Damage in Glaucoma Patients

PURPOSE: To characterize Doppler waveform variables (early systolic acceleration [ESA] and systolic/diastolic mean velocity ratios [Sm/Dm]) of the Ophthalmic Artery (OA) by color Doppler imaging (CDI) in eyes with primary open-angle glaucoma (POAG). METHODS: Analysis of CDI examinations of the retrobulbar circulation of patients with POAG (n = 102), normal tension glaucoma (NTG, n = 89), and healthy controls (n = 59) by a condition-masked investigator. One-way ANOVA, chi-square, and Spearman's rank correlation tests were used to determine differences, establish comparisons, and to explore associations between variables, respectively. RESULTS: The overall Doppler waveform presented a shift to the right in the glaucoma groups, with significantly lower Sm/Dm ratios when compared to the control group (healthy: 2.94 ± 0.86, POAG: 2.60 ± 0.67, NTG: 2.63 ± 0.84; P = 0.01). ESA was significantly lower in the glaucoma groups (healthy: 688.8 ± 484 cm·s(-2), POAG: 548.1 ± 419 cm·s(-2), NTG: 548.5 ± 337 cm·s(-2); P = 0.03). No statistical differences were, however, detected in the OA velocities or resistance index (P ranged between 0.08 and 0.96). In the glaucoma groups, waveform parameters such as ESA, acceleration time, and systolic mean velocities correlated with systemic blood pressure variables (P < 0.05). In these groups, negative correlations were detected between Sm/Dm ratios and the degree of visual field defects (POAG: P = 0.01; r = -0.25) and retinal nerve fiber layer thickness (NTG: P = 0.02; r = -0.25). CONCLUSIONS: The pattern of blood flow velocities in the OA throughout the cardiac cycle seems to be altered in glaucoma patients. Further studies on how systemic blood pressure affects waveform variables in glaucoma patients may provide a better understanding of an underlying vascular dysfunction

Lack of Spontaneous Venous Pulsation: Possible Risk Indicator in Normal Tension Glaucoma?

PURPOSE: Recently, the absence of spontaneous venous pulsation (SVP) has been suggested as a vascular risk factor for primary open-angle glaucoma (POAG). As the mechanism behind this phenomenon is still unknown, the authors have studied this vascular component using colour Doppler imaging (CDI). METHODS: A total of 236 patients were divided into three diagnostic groups: healthy controls (81), POAG (86) and normal tension glaucoma (NTG; 69). All subjects were submitted to CDI studies of the retrobulbar circulation, intraocular pressure measurements and assessment of SVP existence. Mann-Whitney, chi-square contingency tables and Spearman correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: Eighty-two percent of healthy controls had SVP (66/81), while a smaller numbers were registered in both glaucoma groups: POAG - 50% (43/86); NTG - 51% (35/69). In NTG patients, but not in POAG patients, the prevalence of the SVP phenomenon decreases with increased glaucoma damage (p = 0.04; p = 0.55, respectively). Overall glaucoma patients from both groups had lower central retinal vein (CRV) velocities than the healthy controls (p < 0.05). NTG patients with SVP had less severe visual field defects (mean defect -6.92 versus -11.1, p < 0.05), higher [correction added after online publication 21 September 2012; the word 'higher' has been inserted to replace the word 'lower'] peak systolic and mean flow velocities in the central retinal artery (p < 0.01; p < 0.05, respectively) as well as higher [correction added after online publication 21 September 2012; the word higher has been inserted to replace the word lower] maximal velocities and RI of the CRV (p < 0.02; p < 0.05, respectively). CONCLUSIONS: Glaucoma patients have a decrease in CRV velocities. SVP is less prevalent in glaucoma patients than in healthy individuals. This phenomenon apparently reflects different hemodynamic patterns in the central retinal vessels. This variable may be of particular importance in NTG patients, where it may be associated with more advanced functional damage

Ocular Pulse Amplitude and Doppler Waveform Analysis in Glaucoma Patients

PURPOSE: To determine the correlation between ocular blood flow velocities and ocular pulse amplitude (OPA) in glaucoma patients using colour Doppler imaging (CDI) waveform analysis. METHOD: A prospective, observer-masked, case-control study was performed. OPA and blood flow variables from central retinal artery and vein (CRA, CRV), nasal and temporal short posterior ciliary arteries (NPCA, TPCA) and ophthalmic artery (OA) were obtained through dynamic contour tonometry and CDI, respectively. Univariate and multiple regression analyses were performed to explore the correlations between OPA and retrobulbar CDI waveform and systemic cardiovascular parameters (blood pressure, blood pressure amplitude, mean ocular perfusion pressure and peripheral pulse). RESULTS: One hundred and ninety-two patients were included [healthy controls: 55; primary open-angle glaucoma (POAG): 74; normal-tension glaucoma (NTG): 63]. OPA was statistically different between groups (Healthy: 3.17 ± 1.2 mmHg; NTG: 2.58 ± 1.2 mmHg; POAG: 2.60 ± 1.1 mmHg; p < 0.01), but not between the glaucoma groups (p = 0.60). Multiple regression models to explain OPA variance were made for each cohort (healthy: p < 0.001, r = 0.605; NTG: p = 0.003, r = 0.372; POAG: p < 0.001, r = 0.412). OPA was independently associated with retrobulbar CDI parameters in the healthy subjects and POAG patients (healthy CRV resistance index: β = 3.37, CI: 0.16-6.59; healthy NPCA mean systolic/diastolic velocity ratio: β = 1.34, CI: 0.52-2.15; POAG TPCA mean systolic velocity: β = 0.14, CI 0.05-0.23). OPA in the NTG group was associated with diastolic blood pressure and pulse rate (β = -0.04, CI: -0.06 to -0.01; β = -0.04, CI: -0.06 to -0.001, respectively). CONCLUSIONS: Vascular-related models provide a better explanation to OPA variance in healthy individuals than in glaucoma patients. The variables that influence OPA seem to be different in healthy, POAG and NTG patients

Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II

IMPORTANCE: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). BACKGROUND: Different prostaglandin analogues have been commercially approved, with differences in tolerability. DESIGN: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. PARTICIPANTS: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. METHODS: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. MAIN OUTCOME MEASURES: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. RESULTS: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. CONCLUSIONS AND RELEVANCE: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy

Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes

AIM: To evaluate the possibility of translocating autologous peripheral retinal pigment epithelial (RPE) cells and enhance their adhesion to improve functional outcome after choroidal neovascular membrane extracti

Treatment of steroid-induced elevated intraocular pressure with anecortave acetate: a randomized clinical trial.

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy. METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30 mg AA. All patients then received a 0.5 mL AJD of the assigned treatment. Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3, 4, 5, and 6. IOP was measured at each visit as well as best corrected visual acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination, and assessment of any adverse events. In addition, at baseline and at exit, a dilated fundus examination was carried out and the lens was examined using LOCS II criteria. RESULTS: Seventy patients were randomized to treatment. At week 4, eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline. Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg, 16.6%) were not significantly different than for vehicle control. However, IOP for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline, which was statistically significant (P=0.0487). The mean time to treatment failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA, and 30 mg AA groups, respectively. Adverse events were assessed at each post-treatment visit. There were no serious adverse events that were determined to be related to the test article or its administration. CONCLUSIONS: AA can be of benefit to some patients requiring treatment with corticosteroids, but suffering from the side effect of elevated IOP

The relevance of arterial blood pressure in the management of glaucoma progression: a systematic review

Background Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure and ocular perfusion pressure is poorly understood. Objective This systematic review aims to provide clinicians with the latest literature regarding the management of arterial blood pressure in glaucoma patients. Methods A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial blood pressure and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. Results 80 articles were included in this systemic review. A bimodal relation between blood pressure and glaucoma progression was found. Both high and low blood pressure increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the blood pressure over 24-hours. Conclusions We concluded that systemic blood pressure level associates with glaucomatous damage and provided recommendations for the management and study of arterial blood pressure in glaucoma. Prospective clinical trials are needed to further support these recommendations