A Comparison of Bimatoprost 0.03% Versus the Fixed-Combination of Latanotoprost 0.005% and Timolol 0.5% in Adult Patients With Elevated Intraocular Pressure: An Eight-Week, Randomized, Open-Label Trial

Introduction and Purpose: Bimatoprost and the fixed combination of latanoprost with timolol maleate are 2 medications widely used to treat glaucoma and ocular hypertension (OHT). The aim of the study is to compare the efficacy of these 2 drugs in reducing intraocular pressure (IOP) after 8 weeks of treatment in patients with primary open angle glaucoma (POAG) or OHT. Methods: In this randomized, open-label trial, 44 patients with POAG or OHT were allocated to receive either bimatoprost (1 drop QD) or latanoprost/timolol (1 drop QD). Primary outcome was the mean diurnal IOP measurement at the 8th week, calculated as the mean IOP measurements taken at 8:00 AM, 10: 00 AM, and 12: 00 PM Secondary outcomes included the baseline change in IOP measured 3 times a day, after the water-drinking test (performed after the last IOP measurement), and the assessment of side effects of each therapy. Results: The mean IOP levels of latanoprost/timolol (13.83, SD = 2.54) was significantly lower than of bimatoprost (16.16, SD = 3.28; P < 0.0001) at week 8. Also, the change in mean IOP values was significantly higher in the latanoprost/timolol group at 10:00 AM (P = 0.013) and 12:00 PM (P = 0.01), but not at 8: 00 AM (P = ns). During the water-drinking test, there was no signifi cant difference in IOP increase (absolute and percentage) between groups; however, there was a signifi cant decrease in mean heart rate in the latanoprost/timolol group. Finally, no signifi cant changes in blood pressure and lung spirometry were observed in either groups. Conclusions: The fixed combination of latanoprost/timolol was significantly superior to bimatoprost alone in reducing IOP in patients with POAG or OHT. Further studies with large sample sizes should be taken to support the superior efficacy of latanoprost/timolol, as well as to better assess its profile of side effects.

Avaliação da tonopaquimetria como exame de rastreio de glaucoma primário de ângulo aberto

Mestrado em Gestão e Avaliação de Tecnologias em Saúde

Estudo comparativo entre o tonómetro de aplanação de Goldmann e o tonómetro de não contacto em pacientes com glaucoma primário de ângulo aberto

Mestrado em Gestão e Avaliação de Tecnologias em Saúde

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 < 0.001), while it did not in POAG patients and healthy controls (p = 0.86, p = 0.46 respectively). Patient's age did not relate to ONSD in any of the groups (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.

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 < 0.04 versus healthy controls). No differences were detected in RI or PI in any arteries of the three diagnostic 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.

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 the efficacy and longevity of nonpenetrating glaucoma surgery with and without a new, nonabsorbable hydrophilic implant.

BACKGROUND AND OBJECTIVE: To compare the efficacy and longevity of nonpenetrating glaucoma surgery with and without the use of a nonabsorbable hydrophilic implant at the Oxford Eye Centre, Johannesburg, South Africa, and the Glaucoma Unit, Jules Gonin Ophthalmic Hospital, Lausanne, Switzerland. PATIENTS AND METHODS: In a nonrandomized, prospective study between March 1997 and December 2001, 48 eyes of 32 patients aged 18 to 86 years with primary open-angle glaucoma underwent nonpenetrating glaucoma surgery; 25 eyes with the implant and 23 eyes without it. Intraocular pressure (IOP) was recorded preoperatively and postoperatively at 1, 7, and 14 days, at 1, 3, and 6 months, and thereafter every 6 months. RESULTS: The mean preoperative IOP was 27.5 +/- 11.8 mm Hg (range, 20 to 64 mm Hg) in the implant group and 24.8 +/- 7.1 mm Hg (range, 16 to 38 mm Hg) in the control group. During the first 18 months of follow-up, both groups showed identical IOP progression and the mean IOP remained less than 14 mm Hg. After 2 years of follow-up, the IOP started to rise in the control group but remained stable in the implant group. After 30 months, the mean IOP was 12.4 +/- 2 mm Hg and the IOP decrease in percentage was 62% +/- 6% in the implant group (n = 13) versus 16.1 +/- 3 mm Hg and 34% +/- 13% in the control group (n = 15) (mean IOP, P = .0022; mean IOP decrease in percentage, P = .01). CONCLUSIONS: During the first 18 months, there was no difference in the outcomes between the two groups. After 2 years of follow-up, the mean IOP was lower and the IOP decrease in percentage was greater in the implant group compared with the control group.

Macrodisco y glaucoma en individuos estudiados con tomografía óptica coherente

Introducción: El glaucoma representa la tercera causa de ceguera a nivel mundial y un diagnóstico oportuno requiere evaluar la excavación del nervio óptico que está relacionada con el área del mismo. Existen reportes de áreas grandes (macrodiscos) que pueden ser protectoras, mientras otros las asocian a susceptibilidad para glaucoma. Objetivo: Establecer si existe asociación entre macrodisco y glaucoma en individuos estudiados con Tomografía Optica Coherente (OCT ) en la Fundación Oftalmológica Nacional. Métodos: Estudio transversal de asociación que incluyó 25 ojos con glaucoma primario de ángulo abierto y 74 ojos sanos. A cada individuo se realizó examen oftalmológico, campo visual computarizado y OCT de nervio óptico. Se compararon por grupos áreas de disco óptico y número de macrodiscos, definidos según Jonas como un área de la media más dos desviaciones estándar y según Adabache como área ≥3.03 mm2 quien evaluó población Mexicana. Resultados: El área promedio de disco óptico fue 2,78 y 2,80 mm2 glaucoma Vs. sanos. De acuerdo al criterio de Jonas, se observó un macrodisco en el grupo sanos y según criterio de Adabache se encontraron ocho y veinticinco macrodiscos glaucoma Vs. sanos. (OR=0,92 IC95%=0.35 – 2.43). Discusión: No hubo diferencia significativa (P=0.870) en el área de disco entre los dos grupos y el porcentaje de macrodiscos para los dos grupos fue similar, aunque el bajo número de éstos no permitió concluir en términos estadísticos sobre la presencia de macrodisco y glaucoma.

Conjunctival inflammation in patients under topical glaucoma treatment with indication to surgery

PURPOSE: To compare the frequency of conjunctival HLA-DR expression (a surrogate marker for inflammation) in eyes treated with topical prostaglandin analogues versus eyes treated with other topical antiglaucomatous drugs. METHODS: Patients diagnosed with primary open-angle glaucoma presenting indication for trabeculectomy were divided in groups according to the use or not of prostaglandin analogues. All subjects were treated with the maximum tolerated dose of antiglaucomatous drugs until the date of the surgery. At the beginning of the surgical procedure, a 5 x 5 mm biopsy of the bulbar conjunctiva was collected, incubated with monoclonal anti-HLA-DR antibody and processed for histological analysis. RESULTS: Of the 31 eyes included (31 patients), 25 were under topical prostaglandin analogues (Group 1) and six under other topical pharmacological agents (Group 2). Fourteen eyes of Group 1 (56%) and three of Group 2 (50 %) were positive for the inflammatory marker HLA-DR (P=1.0). The percentage of stained cells ranged from 15.49 to 48.09% (median: 27.61) in Group 1, and from 18.35 to 28 (median: 20.71) in Group 2, with no differences statistically significant (p=0.33). CONCLUSION: The use of prostaglandin analogues did not increase conjunctival expression of HLA-DR compared to other topical antiglaucomatous agents.

Novel pressure-to-cornea index in glaucoma

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

Relationship between ocular perfusion pressure and retrobulbar blood flow in patients with glaucoma with progressive damage

PURPOSE: To evaluate the relationship between ocular perfusion pressure and color Doppler measurements in patients with glaucoma. MATERIALS AND METHODS: Twenty patients with primary open-angle glaucoma with visual field deterioration in spite of an intraocular pressure lowered below 21 mm Hg, 20 age-matched patients with glaucoma with stable visual fields, and 20 age-matched healthy controls were recruited. After a 20-minute rest in a supine position, intraocular pressure and color Doppler measurements parameters of the ophthalmic artery and the central retinal artery were obtained. Correlations between mean ocular perfusion pressure and color Doppler measurements parameters were determined. RESULTS: Patients with glaucoma showed a higher intraocular pressure (P <.0008) and a lower mean ocular perfusion pressure (P <.0045) compared with healthy subjects. Patients with deteriorating glaucoma showed a lower mean blood pressure (P =.033) and a lower end diastolic velocity in the central retinal artery (P =.0093) compared with normals. Mean ocular perfusion pressure correlated positively with end diastolic velocity in the ophthalmic artery (R = 0.66, P =.002) and central retinal artery (R = 0.74, P <.0001) and negatively with resistivity index in the ophthalmic artery (R = -0.70, P =.001) and central retinal artery (R = -0.62, P =.003) in patients with deteriorating glaucoma. Such correlations did not occur in patients with glaucoma with stable visual fields or in normal subjects. The correlations were statistically significantly different between the study groups (parallelism of regression lines in an analysis of covariance model) for end diastolic velocity (P =.001) and resistivity index (P =.0001) in the ophthalmic artery, as well as for end diastolic velocity (P =.0009) and resistivity index (P =. 001) in the central retinal artery. CONCLUSIONS: The present findings suggest that alterations in ocular blood flow regulation may contribute to the progression in glaucomatous damage.

Ascorbic acid concentration is reduced in the secondary aqueous humour of glaucomatous patients

P>Background: We aimed to evaluate the ascorbic acid concentration in secondary aqueous humour (AH) from glaucomatous patients and to compare it with primary AH from primary open-angle glaucoma patients and non-glaucomatous patients. Methods: Primary AH samples were prospectively obtained from clinically uncontrolled primary open-angle glaucoma patients and senile cataract patients (controls) prior to trabeculectomy and cataract surgery. Secondary AH samples were obtained from eyes with previous intraocular surgery, prior to trabeculectomy or cataract surgery. AH (0.1 mL) was aspirated by inserting a 26-gauge needle into the anterior chamber just before surgery and then immediately stored at -80 degrees C. The ascorbic acid concentration was determined in a masked fashion by high-pressure liquid chromatography. Results: A total of 18 patients with senile cataract, 16 glaucomatous patients with primary AH (no previous intraocular surgery) and 11 glaucomatous patients with secondary AH (previous intraocular surgery) were included. There was no difference in mean age between groups (P = 0.15). The mean +/- standard deviation concentration of ascorbic acid in the secondary AH from glaucomatous patients (504 +/- 213 mu mol/L [95% confidence interval {CI}, 383-624]) was significantly lower than the concentration of ascorbic acid found in the primary aqueous of primary open-angle glaucoma (919 +/- 427 mu mol/L [95% CI, 709-1128]) and control patients (1049 +/- 433 mu mol/L [95% CI, 848-1249]; P < 0.01, Kruskal-Wallis test). Conclusions: The ascorbic acid concentration in secondary AH of glaucomatous patients was approximately twofold lower in comparison with primary AH of glaucomatous and cataract patients. The implications of a reduced concentration of ascorbic acid in the secondary AH deserve further investigation.

Choroidal expansion during the water drinking test

To evaluate the correlation between intraocular pressure (IOP) rise, ocular pulse amplitude (OPA), and choroidal thickness (ChT) during the water drinking test (WDT). Primary open-angle glaucoma (POAG) patients were submitted to the WDT followed by serial IOP measurements using dynamic contour tonometry (DCT), Goldman tonometry (GAT), and ChT measurements using ultrasonographic A and B-scan (USG). A control group not submitted to the test was also evaluated using DCT, GAT, and USG. Intraclass correlation coefficient (ICC) was calculated in the control group in order to assess the reproducibility of measurements. Spearman`s coefficient (rho) was used to assess the correlation between the variables. Thirty eyes were included in the study. There was a significant IOP rise during the WDT using both GAT and DCT (p < 0.001). The OPA and ChT measurements also increased significantly (p < 0.001). Spearman`s correlation between the OPA values and ChT measurements was significant and moderate (rho = 0.40, p = 0.005). The average increase of OPA and ChT measurements occurred 15 min before the IOP rise. There was a significant increase of OPA and ChT measurements followed by an IOP rise during the WDT. Increased choroidal volume due to hemodynamic forces may be enrolled in the mechanism of IOP elevation during this stress test.

Immunohistochemical Expression of HLA-DR in the Conjunctiva of Patients Under Topical Prostaglandin Analogs Treatment

Purpose: Subclinical inflammation may be observed in patients, using topical antiglaucomatous drugs. The objective,e of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of a immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. Subjects and Methods: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides. and Prepared for immunohistochemical analysis. Results: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression (of HLA-DR in the conjunctiva (mild). After 1 month oil prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was round (P 0.27). Conclusions: The use of prostaglandin analogs eye drops provokes, a reaction, observed by HLA-DR subclinical inflammatory expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.