Effects of Switching from Timolol to Brimonidine in Prostaglandin Analog and Timolol Combination Therapy.

PURPOSE: To assess the efficacy and safety of switching from timolol 0.5% to brimonidine 0.1% in patients with glaucoma treated with a prostaglandin analog (PGA) and timolol combination. METHODS: This prospective, open-label multicenter study enrolled patients with open-angle glaucoma or ocular hypertension who were being treated with a PGA and timolol. After baseline measurements, timolol was switched to brimonidine 0.1%, and patients were followed for 12 weeks. Patients visited at 4 and 12 weeks after switching. The main outcome measure was the change in intraocular pressure (IOP). For safety evaluations, hyperemia, formation of conjunctival follicles, superficial punctate keratopathy as a local side effect, blood pressure (BP), and heart rate (HR) were evaluated. RESULTS: One hundred seven patients participated in this study. Among them, 103 patients completed the study. The IOP values at baseline, 4 weeks, and 12 weeks after the transition were 15.7 ± 2.7, 14.3 ± 2.8, and 14.0 ± 2.8 mmHg, respectively. IOP was significantly reduced at 4 and 12 weeks compared with baseline (p<0.001). There were no significant changes in hyperemia or follicle formation. The superficial punctate keratopathy score was significantly reduced at 12 weeks compared with baseline (p<0.05). Systolic and diastolic BP values were significantly reduced and HR significantly increased after switching (p<0.05). CONCLUSION: Switching from timolol 0.5% to brimonidine 0.1% may not change IOP in the combination use of timolol 0.5% and a PGA and was well tolerated by patients without severe ocular or systemic side effects.

A placebo-controlled 3-year study of a calcium blocker on visual field and ocular circulation in glaucoma with low-normal pressure.

PURPOSE: To study the 3-year effect of oral nilvadipine, a calcium antagonist, on visual field performance and ocular circulation in open-angle glaucoma (OAG) with low-normal intraocular pressure (IOP). DESIGN: A randomized, placebo-controlled, double-masked, single-center trial. PARTICIPANTS: Patients with OAG who were younger than 65 years and had untreated IOP consistently of 16 mmHg or less. INTERVENTION: Oral nilvadipine (2 mg twice daily) or placebo was assigned randomly to patients fulfilling the criteria by the minimization method of balancing the groups according to age, refraction, and the mean deviation (MD) value (Humphrey Perimeter 30-2 SITA Standard Program; Humphrey Instruments, Inc., San Leandro, CA) of the eye with less negative MD. No topical ocular hypotensive drugs were prescribed. Visual field testing was performed every 3 months; fundus examination and IOP, blood pressure, and pulse rate measurements were carried out every month; and quantitative indexes of circulation in the optic disc rim (NB(ONH)) and choroid in the foveal area (NB(fovea)) were determined using the laser speckle method at 0, 3, 6, 12, 18, 24, 30, and 36 months. MAIN OUTCOME MEASURES: The time courses of MD, NB(ONH), and NB(fovea) in the eye with less negative MD. RESULTS: Thirty-three patients were enrolled; 17 were assigned to nilvadipine and 16 were assigned to placebo; 13 in each group completed the study. No significant intergroup difference was seen in age, refraction, or baseline values of any of the parameters. During the 3-year period, the IOP averaged 12.6 mmHg in the nilvadipine group and 12.8 mmHg in the placebo group (P>0.1), and no significant change from baseline or intergroup difference was seen in blood pressure or pulse rate. The estimated slope of change in the MD was less negative in the nilvadipine than in the placebo group (-0.01 vs. -0.27 decibels/year; P = 0.040). The NB(ONH) and NB(fovea) values remained increased compared with baseline for the study period by approximately 30% to 40% only in the nilvadipine group, and the intergroup difference was significant (P = 0.003 for NB(ONH) and P = 0.007 for NB(fovea)). CONCLUSIONS: Nilvadipine (2 mg twice daily) slightly slowed the visual field progression and maintained the optic disc rim, and the posterior choroidal circulation increased over 3 years in patients with OAG with low-normal IOP.

Intraocular metabolites of isopropyl unoprostone.

PURPOSE: It is still unknown which metabolite of isopropyl unoprostone is responsible for reducing intraocular pressure. This study was carried out to measure intraocular metabolites of isopropyl unoprostone in the aqueous humor of primate and human eyes. METHODS: Nine monkeys were randomly divided into three groups, all of which received isopropyl unoprostone. In group I, the drug was scheduled to be instilled at 0 hr, in group II at 1 hr, and in group III at 2 hr, prior to aqueous humor aspiration in order to determine metabolite concentration. Furthermore, 27 patients scheduled for cataract surgery and intraocular lens implantation were divided into five groups that received isopropyl unoprostone. In group A, the drug was scheduled to be instilled at 0 hr, in group B at 1 hr, in group C at 2 hr, in group D at 3 hr, and in group E at 4 hr, prior to surgery. At the beginning of the operation, the aqueous humor was aspirated. Metabolites of isopropyl unoprostone in the aqueous humor were determined by high-performance liquid chromatography. RESULTS: M1 (3-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]propionic acid) (unoprostone free acid) and M2 ((Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]hept-5-enoic acid), an intraocular oxidized metabolite of isopropyl unoprostone, were measured. M1:M2 in monkeys was respectively 0:0 ng/ml in group I, 150.2 +/- 45.1:9.5 +/- 1.7 (p < 0.05) in group II, and 74.6 +/- 31.4:19.2 +/- 5.3 (p < 0.01) in group III. M1:M2 in humans was respectively 0:0 ng/ml in group A, 50.6 +/- 22.3:3.2 +/- 1.3 (p < 0.05) in group B, 125.0 +/- 23.1:12.2 +/- 3.4 (p < 0.001) in group C, 144.9 +/- 33.8:24.5 +/- 6.2 (p < 0.01) in group D, and 56.7 +/- 21.5:18.7 +/- 5.3 (p < 0.05) in group E. CONCLUSIONS: A free acid of isopropyl unoprostone is the major intraocular metabolite of isopropyl unoprostone that is expected to act on target tissues in the eyes of both monkeys and humans.

Frequency doubling technology and scanning laser tomography in eyes with generalized enlargement of optic disc cupping.

PURPOSE: To characterize functional and structural changes in eyes with generalized enlargement of optic disc cupping (vertical cup/disc ratio > or = 0.8), normal intraocular pressure, normal standard achromatic automated perimetry (SAP) results, and no other ophthalmoscopic findings suggesting glaucoma (large C/D eyes) using frequency doubling technology (FDT) and the Heidelberg Retina Tomograph (HRT). METHODS: This comparative observational case series included 30 large C/D eyes (30 subjects), 17 eyes (17 patients) with early-stage normal tension glaucoma with generalized enlargement of optic disc cupping (NTG eyes), and 25 eyes from 25 normal subjects (normal eyes). Results with Humphrey 30-2, FDT N-30 threshold programs, and HRT were compared among these groups. Large C/D eyes were subdivided into FDT-normal and -abnormal eyes according to the predetermined criteria and HRT parameters were compared among them. RESULTS: No significant difference was seen in HRT parameters between the large C/D and NTG eyes. In the large C/D eyes, FDT mean deviation was lower than in the normal eyes and higher than in the NTG eyes, whereas FDT pattern standard deviation was smaller than in the NTG eyes (P = 0.02-0.03). Among HRT parameters, only cup shape measure (CSM) showed significant negative correlation with FDT mean deviation in the large C/D eyes. Between FDT-normal and -abnormal subgroups, only CSM showed significant difference (P < 0.01). CONCLUSION: Frequency doubling technology showed abnormalities in large C/D eyes. Only CSM showed significant correlation with FDT result and difference between those with normal and abnormal FDT results. In management of large C/D eyes, FDT and CSM will be useful to detect functional and structural change.

Case of optic nerve involvement in metastasis of a gastrointestinal stromal tumor.

BACKGROUND: The gastrointestinal stromal tumor (GIST) belongs to the leiomyosarcoma or leiomyoma group, and metastasis of leiomyosarcoma to the orbit is extremely rare. The most common sign of the metastasis of leiomyosarcoma to the orbit is proptosis; the primary lesion is usually found in skin or soft tissue. CASE: A 60-year-old man, who had a history of multiple metastases of GIST, suffered sudden unilateral blindness. OBSERVATIONS: His history and computed tomographic scans suggested that the lesion was a metastasis of GIST to the cavernous sinus around the root of the optic nerve. CONCLUSION: To the best of our knowledge, this is the first case of metastasis of GIST to the orbit.

Long-term follow-up of visual field progression after trabeculectomy in progressive normal-tension glaucoma.

OBJECTIVE: To evaluate the long-term effects of trabeculectomy on the progression of visual field damage in patients with progressive normal-tension glaucoma (NTG). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-three patients with NTG who had significant progression of visual field damage preoperatively and underwent trabeculectomy using antimetabolites. METHODS: Visual field testing using the Humphrey Visual Field Analyzer was periodically performed before and for at least 5 years after surgery (mean, 6 years). The time course of the mean deviation (MD) and mean of total deviations (TD(mean)) in four separate subfields, superior and inferior cecocentral and superior and inferior arcuate fields, were analyzed using a linear mixed effects model. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), preoperative and postoperative regression coefficients of the time course of MD or TD(mean) in the four subfields, corresponding to the rate of progression of visual field damage. RESULTS: IOP significantly decreased from 16.2 +/- 1.8 mmHg preoperatively to approximately 11 mmHg during the postoperative follow-up period (P < 0.001). The preoperative regression coefficient of MD change was significantly negative (-1.05 [95% confidence interval, -1.28 to -0.82] dB/year, P < 0.001). After surgery, it increased significantly to -0.44 (95% confidence interval, -0.64 to -0.24) dB/year (P < 0.001), but the postoperative value was still significantly negative (P < 0.001). In the superior cecocentral, superior and inferior arcuate fields, preoperative regression coefficients of TD(mean) change were significantly negative (P < 0.001) and significantly increased after surgery (P < 0.01). In the inferior cecocentral field, the preoperative regression coefficient was not significantly different from 0 (P = 0.72) and did not change significantly after surgery (P = 0.15). CONCLUSIONS: Trabeculectomy was statistically associated with slowing further progression of visual field damage in patients with progressive NTG. The progression, however, did not completely stop over the 6-year postoperative follow-up period.