Marcelo Hatanaka

The Effect of Prostaglandin Analogs and Prostamide on Central Corneal Thickness

OBJECTIVE The aim of this study was to verify the influence of prostaglandin analogs and prostamide on central corneal thickness (CCT). METHODS A prospective analysis was done of CCT in glautomatous patients submitted to monotherapy with prostaglandin analogs (latanoprost 0.005% or travoprost 0.004%) or prostamide (bimatoprost 0.03%) during an 8-week period. A control group of patients without any ocular medication was also evaluated. CCT measurements were performed with a commercially available ultrasound pachymeter. A total of 73 patients were included in this study. Mean age was 68.5 +/- 9.2 (range, 48-85) years old. RESULTS A statistically significant reduction in CCT was observed in all groups, except the control group (n = 21): Bimatoprost 0.03% group (n = 21): 544.41 +/- 35.4 vs. 540.35 +/- 35.9 microm (P = 0.039); travoprost 0.004% group (n = 17): 538.47 +/- 32.0 vs. 532.25 +/- 30.4 microm (P = 0.009); latanoprost 0.005% group (n = 14): 548.57 +/- 32.4 vs. 543.88 +/- 35.6 microm (P = 0.036). CONCLUSION Topical therapy with prostaglandin analogs and bimatoprost is associated with CCT reduction over a period of at least 8 weeks.

An eight-week, multicentric, randomized, interventional, open-label, phase 4, parallel comparison of the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure.

PurposeTo compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks. Patients and MethodsThis 8-week, multicentric, interventional, randomized, open-label, parallel group study was conducted at 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM, 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit. ResultsA total of 210 patients were randomized (brimonidine/timolol, n=111; dorzolamide/timolol, n=99). Mean baseline IOP was 23.43±3.22 mm Hg and 23.43±4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P=0.993). Mean diurnal IOP reduction after 8 weeks were 7.02±3.06 mm Hg and 6.91±3.67 mm Hg, respectively (P=0.811). The adjusted difference between groups (analysis of covariance) at week 8 was not statistically significant (P=0.847). Mean baseline WDT peak was 27.79±4.29 mm Hg in the brimonidine/timolol group and 27.68±5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94±3.76 mm Hg (P<0.001) and 20.98±4.19 (P<0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P=0.469). No statistical difference in terms of adverse events was found between groups. ConclusionsBoth fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both fixed combinations are well tolerated with few side effects.

Reproducibility of intraocular pressure peak and fluctuation of the water-drinking test

The water‐drinking test has been used as a stress test to evaluate the drainage system of the eye. However, in order to be clinically applicable,a test must provide reproducible results with consistent measurements. This study was performed to verify the reproducibility of intraocular pressure peaks and fluctuation detected during the water‐drinking test in patients with ocular hypertension and open‐angle glaucoma.

Reproducibility of the water drinking test in treated glaucomatous patients

To evaluate the reproducibility of intraocular pressure peaks and fluctuation elicited during the water drinking test in treated glaucomatous patients with a long follow‐up interval.

Reproducibility of the Mean, Fluctuation, and IOP Peak in the Diurnal Tension Curve

Purpose:To verify the reproducibility of the mean, peak, and fluctuation of intraocular pressure (IOP) observed during modified diurnal tension curves (mDTC) performed on ocular hypertensive and primary open-angle glaucoma patients. Methods:Prospective analysis of 88 eyes from 88 ocular hypertensive and primary open-angle glaucoma patients subjected to 2 consecutive mDTCs (IOP measurements obtained at 8:00 AM, 11:00 AM, 2:00 PM, and 4:00 PM) on 2 consecutive days. Mean IOP was calculated as the average of all IOP measurements obtained during each mDTC. Peak and minimum IOP levels were considered as the highest and lowest IOP level during each mDTC, respectively. IOP fluctuation was calculated using 2 different approaches: the difference between IOP peak and minimum IOP detected during each mDTC and as the SD of all mDTC measurements. Reproducibility was assessed using the intraclass correlation coefficient (ICC). Results:IOP fluctuation between 2 days in the modified diurnal curve, calculated as the difference between peak IOP and minimum IOP and as the SD of all mDTC measurements, was less reproducible than the mean IOP and peak IOP (ICC values 0.60, 0.62, 0.91, and 0.85, respectively; all ICC values, P<0.001). Conclusions:Mean IOP and peak IOP observed during the mDTC had good reproducibility, whereas the reproducibility of IOP fluctuation was only fair.

Long ciliary processes with no ciliary sulcus and appositional angle closure assessed by ultrasound biomicroscopy.

PurposeNonpupil block mechanisms and appositional angle closure after laser iridotomy (LI) have been reported as common findings in Asians. We evaluated the presence of these findings in a cohort of Brazilian patients using ultrasound biomicroscopy (UBM). MethodsThis observational case-control study included 22 open angle eyes and 31 eyes with occludable angles on gonioscopy (defined by 2 examiners). UBM radial scans through a typical ciliary process were obtained in both light and dark conditions, at 6 and 12-o′clock positions. Long ciliary processes with no ciliary sulcus were determined on the basis of a reference line drawn perpendicular to the iris plane passing through a point located 750 μm from scleral spur. Trabecular ciliary processes distance was measured on 6-o′clock UBM images. ResultsAfter LI, 52% of occludable angle eyes had appositional angle closure in both 6 and 12-o′clock UBM images. We also observed this finding in 14% and 23% of the control eyes (in 6 and 12-o′clock UBM images, respectively). A long ciliary process with no ciliary sulcus was observed in 61% of occludable angle eyes, and also in 32% of control eyes (6-o′clock UBM images). Control eyes had longer trabecular ciliary processes distance than occludable angle eyes (P<0.001). ConclusionsThe UBM finding of long ciliary processes associated with the absence of ciliary sulcus is not necessarily related to an anterior positioning of the ciliary processes. Whether UBM appositional angle closure after LI is associated with further angle closure process and/or poor intra-ocular pressure control remains to be evaluated.

Additive intraocular pressure reduction effect of fixed combination of maleate timolol 0.5%/dorzolamide 2% (Cosopt) on monotherapy with latanoprost (Xalatan) in patients with elevated intraocular pressure: a prospective, 4-week, open-label, randomized, controlled clinical trial.

Purpose:To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods:In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results:Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34±2.96 mm Hg and 15.24±2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60±3.09 and 14.44±3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47±3.68 mm Hg and 17.02±3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02±3.81 mm Hg and 20.39±4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions:In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.

Twenty-four-hour repeatability of diurnal intraocular pressure patterns in glaucomatous and ocular hypertensive individuals

OBJECTIVE: To verify the 24-hour repeatability of diurnal intraocular pressure patterns in glaucomatous and ocular hypertensive individuals. METHODS: A prospective analysis of 88 eyes from 88 ocular hypertensive or open-angle glaucoma patients was conducted on diurnal tension curves obtained by the same examiner on two consecutive days. The intraclass correlation coefficient test was used for statistical analysis. RESULTS: Eighty-eight eyes from 88 patients were analyzed. Fifty-seven patients (64.8%) were female. The mean age of all participants was 68.7 (SD 10.8, range 51–79) years. The intraclass correlation coefficient values for measurements at 8 AM, 11 AM, 2 PM, and 4 PM were 0.80, 0.82, 0.83, and 0.86, respectively (all intraclass correlation coefficient values, p<0.001). CONCLUSION: Diurnal intraocular pressure data collected on a single day characterize the diurnal intraocular pressure variability over 24 hours in primary open-angle glaucoma and ocular hypertensive patients.

A comparison of bimatoprost 0.03% versus the fixed-combination of latanoprost 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 significant difference in IOP increase (absolute and percentage) between groups; however, there was a significant decrease in mean heart rate in the latanoprost/timolol group. Finally, no significant 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.

Comparison of the Intraocular Pressure Variation Provoked by Postural Change and by the Water Drinking Test in Primary Open-angle Glaucoma and Normal Patients.

Purpose:To evaluate the intraocular pressure (IOP) peak and variability detected by moving the body from sitting to supine position (postural test) and by the water drinking test (WDT) in normal and primary open-angle glaucoma (POAG) subjects. Patients and Methods:Prospective, cross-sectional observational analysis of 14 eyes of 14 normal subjects and 31 eyes of 31 patients with POAG. All POAG subjects were under clinical therapy. IOP measurements were all performed on the same day. Results:When the subjects moved to the supine position, there was an IOP increase of 1.36±1.34 and 2.84±2.21 mm Hg in the normal and POAG groups, respectively (P=0.011). During the WDT, mean IOP peak and fluctuation in the POAG group was 19.29±4.10 and 4.13±2.33 mm Hg, respectively. These levels were significantly higher in comparison with the normal group (16.50±3.76 and 2.71±0.99 mm Hg; P=0.018 and 0.022, respectively). The mean peak IOP observed in the WDT was significantly higher than the IOP in the supine position (19.29±4.10 vs. 17.32±4.66 mm Hg, P=0.013). The mean IOP increase during the WDT was also significantly higher when compared with the postural test (4.13±2.33 vs. 2.84±2.21 mm Hg, P=0.019). Conclusions:POAG eyes demonstrated a significant IOP increase when assuming the supine position and during the WDT. The IOP increase during the WDT was significantly higher than the IOP increase after postural test. Hence, the results of both tests are not interchangeable.