Impact of Morphological Factors on the Future Growth of Unruptured Posterior Communicating Artery Aneurysms.

BACKGROUND: No previous study has established the factors associated with intracranial aneurysm growth using imaging data obtained before the appearance of morphological changes. Therefore, we investigated the factors related to future aneurysm growth in posterior communicating artery (Pcom) aneurysms. METHODS: Using a longitudinal database of intracranial aneurysm cases, we reviewed the findings for consecutive patients with unruptured Pcom aneurysms admitted to our institute from 2012 to 2021. Magnetic resonance images obtained over time were used to evaluate aneurysm growth. Aneurysms showing growth over time (group G) and unchanged aneurysms (group U) were compared in terms of background data and morphological factors. RESULTS: 93 Pcom aneurysms (group G: 25 aneurysms, 25%; group U: 68 aneurysms, 75%) were eligible for the present study. Six aneurysm rupture events occurred in group G (24%). Among morphological factors, Pcom diameter (1.2 ± 0.3 mm vs. 0.8 ± 0.7 mm, P < 0.01), bleb formation (group G: 39% vs. group U: 10%; odds ratio, 5.6; P = 0.01), and the lateral projection of the dome (group G: 52% vs. group U: 13%; odds ratio, 3.2; P = 0.023) were significantly different between the 2 groups. The sensitivity and specificity of a cutoff Pcom diameter of 0.73 mm for predicting enlargement were 96% and 53%, respectively. CONCLUSIONS: Pcom diameter, bleb formation, and lateral dome projection were associated with growth of Pcom aneurysms. Aneurysms with these risk factors require careful follow-up imaging, which may facilitate early detection of aneurysm growth and prevention of rupture through therapeutic interventions.

Risk factors for progression of normal-tension glaucoma under ß-blocker monotherapy.

PURPOSE: To prospectively study prognostic factors for normal-tension glaucoma (NTG) under treatment with topical ß-blocker. METHODS: One hundred and forty-six eyes of 146 patients with NTG with a mean untreated intraocular pressure (IOP) of 14 mmHg, mild to moderate visual field damage and mean spherical equivalent refraction of -3.5 (-8.0 to +2.0) dioptre were randomized to topical nipradilol or timolol and followed for 3 years. The Humphrey full threshold 30-2 visual field test was performed every 6 months, and optic disc photographs were obtained every 12 months. Progression was defined as visual field progression, optic disc and/or peripapillary nerve fibre layer change, and factors relating to progression were evaluated using Cox proportional hazards models. RESULTS: IOP decreased by 1.0 mmHg over the 3-year period, during which 35% showed progression according to the aforementioned criteria. Optic disc haemorrhage (hazard ratio [HR] 4.00, p < 0.001) and less extent of myopia (per dioptre, HR 1.15, p = 0.013) were significant risk factors. When progression was defined by visual field progression only, less extent of myopia was again a significant risk factor (HR 1.17, p = 0.038). CONCLUSION: Beside optic disc haemorrhage, less extent of myopia was a risk factor for progression in the current NTG population where most patients were mildly myopic and IOP during follow-up averaged 13.2 mmHg under topical ß-blocker.

[Double-masked, phase III comparative study of the combination ophthalmic solution of the 1% dorzolamide hydrochloride/0.5% timolol maleate (MK-0507A) in patients with glaucoma and ocular hypertension].

OBJECTIVE: To investigate the IOP-lowering effect and safety of a combined ophthalmic solution (MK-0507A) of 1% dorzolamide hydrochloride and 0.5% timolol maleate in comparison to 0.5% timolol maleate (timolol), and 1% dorzolamide hydrochloride and 0.5% timolol maleate concomitant therapy (concomitant therapy). SUBJECTS AND METHODS: This study was conducted in patients with either primary open angle glaucoma or ocular hypertension. The patients with IOP > or = 18 mmHg following the administration of timolol for 4 weeks during the observation period (474 patients) were randomized to receive either MK-0507A (189 patients), timolol (92 patients) or concomitant therapy (193 patients) during the treatment period and when evaluated for IOP at Week 8. The primary evaluation criteria were change in 2 hour IOP from baseline to Week 8. RESULTS: The least square means of the changes in hour 2 IOP from baseline to Week 8 were -2.50 mmHg, -1.82 mmHg and -2.78 mmHg in the MK-0507 A group, timolol group and concomitant therapy group, respectively. MK-0507A demonstrated a significant reduction in IOP compared to timolol. Further- more, the 95% confidence interval of the difference between MK-0507A and concomitant groups satisfied the pre-specified criteria for non-inferiority confirming the non-inferiority of MK-0507A relative to the concomitant therapy. In addition, MK-0507A had safety comparable to that of timolol and concomitant therapy. CONCLUSION: MK-0507A has a significantly superior IOP-lowering effect relative to timolol. MK-0507A also showed a non-inferior IOP-lowering effect relative to the concomitant therapy. MK-0507A was safe compared to both timolol and concomitant therapy.

Does the enlargement of retinal nerve fiber layer defects relate to disc hemorrhage or progressive visual field loss in normal-tension glaucoma?

PURPOSE: We investigated the difference in clinical characteristics between cases with enlarged retinal nerve fiber layer defects (RNFLD) and stable RNFLDs in normal-tension glaucoma (NTG). PATIENTS AND METHODS: We retrospectively reviewed NTG patients that were diagnosed and followed up for at least 3 years at 1-month to 2-month intervals by the same examiner, and selected eyes with distinct RNFLD borders. Using fundus photographs, for which we extracted only a blue ingredient and processed it into black and white, we measured RNFLD angles and divided NTG cases into 2 groups, enlarged RNFLD and stable RNFLD, and compared the clinical characteristics between both groups. RESULTS: Ninety-three eyes from 93 patients (mean follow-up, 8.2 y) were selected and enlargement of RNFLD was detected in 55 eyes. Disc hemorrhage (DH) was found in 35 of 55 eyes (63.6%) in the enlarged group and in 6 of 38 eyes (15.8%) in the stable group (P<0.0001). Twenty-one eyes (38.2%) from the enlarged group exhibited recurrent DH. In 48 eyes (87.3%) from the enlarged group, the enlargement of RNFLD was toward the fovea. When DHs located apart from RNFLD were excluded, RNFLD enlarged in the direction of DH in 21 of 25 eyes (84.0%). The cumulative probability of non progression in the visual field was significantly lower in the enlarged group (10-year survival rate: 0.52±0.11) than in the stable group (10-year survival rate: 0.89±0.08) (P=0.0019). CONCLUSIONS: The enlargement of RNFLD in NTG was closely associated with DH occurrence and the deterioration of visual field.

Visual field loss in patients with normal-tension glaucoma under topical nipradilol or timolol: subgroup and subfield analyses of the nipradilol-timolol study.

PURPOSE: To estimate the deterioration rates of visual field loss in Japanese normal-tension glaucoma (NTG) patients under either topical nipradilol or timolol, and to explore intergroup differences in the treatment results. METHODS: A total of 146 NTG patients with mild to moderate damage were randomized to either nipradilol or timolol and followed for 3 years with a periodic comprehensive ophthalmological visual field examination (30-2 Humphrey perimeter program) every 6 months (the Nipradilol-Timolol Study). The time course of mean deviation (MD), the average total deviation (TD(mean)) in four subfields, and the corrected pattern standard deviation (CPSD) were compared between the two groups using regression analysis with a linear mixed effect model. RESULTS: The estimated slope for MD (dB/year) was -0.03 in the nipradilol and -0.05 in the timolol group (P > 0.4). In both groups, TD(mean) in the superior-central subfield and CPSD showed significant changes (-0.3 and 0.2-0.3, P

[A review of the Eye Health Care Project in Tajimi].

The results of the Eye Health Care Project in Tajimi, conducted concurrently with the Tajimi Study, a population-based prevalence survey of glaucoma by the Japan Glaucoma Society, are summarized. The project was carried out from September, 2000 to October, 2001. The target population was 50,165, out of which 14,779 citizens participated, which yielded a response rate of 29.5%. A study on the efficacy of the van Herick method showed that 65.9% of eyes with grade 1 or 2 had gonioscopically narrow angles with grade 2 or less of the Shaffer classification and that 17.9% of eyes with van Herick grade 1 were angle-closure suspects and 5.6% of grade 2 were also suspect. In a disc hemorrhage study, hemorrhage was found in 8.2% of glaucoma cases and 0.2% of non-glaucoma participants. Similarly, superior segmental optic hypoplasia was found in 0.3% of the participants studied. The central corneal thickness (CCT) averaged 517.5 +/- 29.8 microm (mean +/- standard deviation). True IOP was estimated by the equation: Estimated IOP (mmHg) = Measured IOP - 0.012 * (CCT (microm) - 520), which means that a 100 microm change in CCT may cause a 1.2 mmHg measurement error in IOP. The average IOP in ophthalmologically normal eyes was 14.1 +/- 2.3 mmHg. The IOP showed negative correlation with age, corneal radius of curvature, and refractive error, and it was positively correlated with CCT, systolic blood pressure, and body mass index. In addition, the points of discussion of the original papers are described.

The additive effects on intraocular pressure of combining nipradilol 0.25% and latanoprost 0.005% ophthalmic solutions: a prospective, randomized, multicenter study.

PURPOSE: To investigate the effectiveness of combining nipradilol 0.25% and latanoprost 0.005% ophthalmic solutions in improving the intraocular pressures (IOPs) in glaucoma patients. METHODS: We divided the 53 patients into two groups, those who had been treated with latanoprost and those who had been treated with nipradilol. We administered to the first group one dose of latanoprost daily for 12 weeks and to the second group one dose of nipradilol daily for 12 weeks. Each group then received both solutions for another 12 weeks; the latanoprost group received nipradilol and the nipradilol group received latanoprost. IOPs were measured at each 4-week visit. RESULTS: In the patients previously treated with latanoprost, the mean IOP was 19.6+/-2.5 mmHg at baseline, and 14.9+/-2.4 mmHg (23.7% reduction) after 12 weeks of latanoprost monotherapy. The addition of nipradilol decreased the IOP to 13.8+/-1.9 mmHg (29.0% reduction). In the group previously treated with nipradilol, the mean IOP was 20.2+/-3.1 mmHg at baseline, and 16.7+/-3.5 mmHg (17.1% reduction) after 12 weeks of nipradilol monotherapy. Addition of latanoprost decreased the IOP to 14.2+/-3.2 mmHg (29.5% reduction). CONCLUSION: Latanoprost and nipradilol are more effective as a combination therapy than each one by itself.

Clinical efficacy of topical nipradilol and timolol on visual field performance in normal-tension glaucoma: a multicenter, randomized, double-masked comparative study.

PURPOSE: To compare the effects of topical nipradilol and timolol on the visual field in Japanese normal-tension glaucoma (NTG) patients. METHODS: We enrolled 146 NTG patients. At baseline, age, intraocular pressure (IOP), and mean deviation (MD) by the Humphrey field analyzer were 47.6 (SD 8.5), 14.2 (1.7) mmHg, and -4.5 (3.0) dB. Seventy-two patients were randomly assigned to the 0.25% nipradilol group and 74 patients to the 0.5% timolol ophthalmic solution group twice daily for the 3-year study period. The Humphrey full-threshold 30-2 visual field test was performed every 6 months. The primary end point was the nonparametric O'Brien summary score (sum of the ranks of six slopes calculated from the average of the total deviation in each cluster) in each patient. The secondary analyses were differences in the MD slope, average of the total deviation in each cluster, the corrected pattern standard deviation (CPSD), and the time course of IOP. RESULTS: No significant intergroup differences were found in baseline characteristics, or in the parameters of the primary and secondary analyses. In both groups, central superior clusters showed negative slopes and IOP decreased by about 1 mmHg from baseline. CONCLUSION: No significant difference in visual field performance or IOP reduction was seen between the nipradilol and timolol groups.

[Tajimi Study review].

The results of The Tajimi Study (a population-based prevalence survey of glaucoma in Tajimi City performed by the Japan Glaucoma Society) are summarized. The Tajimi Study was carried out from September, 2000 to October, 2001 to investigate the prevalence of glaucoma among residents aged 40 years old or over in Tajimi. Seventy-eight point one % of 3,870 eligible people from 4,000 subjects who had been randomly selected from the 54,165 over 40 years old residents in Tajimi participated in the study. Estimated prevalence of all glaucoma and glaucoma/suspected glaucoma were 5.0 (95% confidence interval [CI], 4.2-5.8)% and 7.5 (95% CI, 6.5-8.4)%. The prevalence of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and secondary glaucoma (SG) were 3.9 (95% CI, 3.2-4.6)%, 0.6 (95% CI, 0.4-0.9)%, and 0.5 (95% CI, 0.2-0.7)%, respectively. Including suspected cases, the prevalence of POAG, PACG, and SG was 6.0 (5.1-6.8)%, 0.8 (0.5-1.2)%, 0.7 (0.4-1.0)%. High intraocular pressure, myopia, and older age were shown to be statistically significant risk factors for POAG. It was suggested that the Frequency Doubling Technology is a good candidate as a screening test for glaucoma. The leading cause of low vision was cataracts. Investigation of refractive status showed that the prevalence of myopia(spherical equivalence [SE] < 0.5 diopters) and high myopia (SE < -5.0 diopters) was 41.8 (40.0-43.6)% and 8.2 (7.2-9.2)%, respectively.

Performance of frequency-doubling technology perimetry in a population-based prevalence survey of glaucoma: the Tajimi study.

OBJECTIVE: To evaluate the performance of frequency-doubling technology (FDT) perimetry in a population-based glaucoma prevalence survey. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants older than 40 years randomly selected from the population of Tajimi City. METHODS: Each participant underwent screening ophthalmic examinations including a visual field test using FDT with the C-20-1 screening protocol. A diagnosis of glaucoma was determined by glaucoma specialists with another detailed visual field test using Humphrey Field Analyzer (HFA; Humphrey Instruments, San Leandro, CA) with the 30-2 Swedish interactive threshold algorithm standard protocol and stereoscopic disc photographs. MAIN OUTCOME MEASURES: The ratios of reliable FDT results and the sensitivity and specificity for detecting glaucoma in a general population. RESULTS: Of 5784 eyes of 2892 participants (age range, 40-92 years; refractive error, -23 to 11 diopters) in whom FDT was performed in both eyes, reliable results (< or =33% fixation loss and < or =33% false-positive errors) were obtained in 5707 eyes (98.7%), including 2871 right eyes (99.3%) and 2836 left eyes (98.1%) with a significant bilateral difference (P<0.001, chi-square test). The rate of reliable FDT results did not differ between men and women (P = 0.81) but decreased with age. In 5582 eyes with reliable FDT results, FDT showed 1 or more abnormal points in the visual field in 502 eyes (9.0%), including 388 (7.3%) of 5295 normal eyes, 19 (16.4%) of 116 eyes of glaucoma suspects, and 95 (55.6%) of 171 eyes with definite glaucoma. The sensitivity and specificity values for detecting definite glaucoma were 55.6% and 92.7%, respectively. The positive and negative predictive values were 18.9% and 98.5%, respectively. In further analyses stratified with the mean deviation (MD) of the HFA, the sensitivities were 32.1%, 48.4%, 73.7%, and 96.6% for detecting definite glaucoma with an MD of more than -2 dB, an MD of -2 dB or less and more than -5 dB, an MD of -5 dB or less and more than -8 dB, and an MD of -8 dB or less, respectively. CONCLUSIONS: In a population-based glaucoma screening study, FDT perimetry with the C-20-1 screening protocol was reliably performed in more than 98% of participants. The sensitivity for detecting glaucomatous visual field damages, especially early damage, was not sufficiently high, whereas the specificity was high.

Aqueous humor dynamics associated with the phorbol ester-induced decrease in intraocular pressure in the rabbit.

PURPOSE: To determine the effects of injection of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) into the anterior chamber of the eye on intraocular pressure (IOP) and aqueous humor dynamics. METHODS: IOP was measured for 24 h after intracameral injection of PMA (3 to 50 pmol) in unanesthetized rabbits. Aqueous humor dynamics (aqueous flow, total outflow facility, and uveoscleral outflow) were determined approximately 6 h after injection of 50 pmol of PMA in animals pretreated with indomethacin. RESULTS: Intracameral injection of 50 pmol of PMA induced a biphasic effect on IOP, consisting of a transient increase apparent at 0.5 and 1 h and a sustained decrease apparent after 2 h. This effect of PMA was dose dependent. Whereas pretreatment with indomethacin attenuated the PMA-induced increase in IOP, the sustained decrease in IOP remained apparent in the pretreated rabbits. Intracameral injection of 4alpha-PMA, an inactive PMA analog, had no effect on IOP. PMA also significantly increased uveoscleral outflow, but it had no effect on aqueous flow or total outflow facility. CONCLUSION: Intracameral injection of PMA reduced IOP in the rabbits by increasing the rate of uveoscleral outflow. This IOP-lowering effect of PMA may be mediated by activation of PKC.

Prevalence and causes of low vision and blindness in a Japanese adult population: the Tajimi Study.

OBJECTIVE: To determine the prevalence and causes of low vision and blindness in a Japanese adult population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Randomly selected residents (n = 3870) of Tajimi City, Japan, who were 40 years of age or older. METHODS: Of the 3021 study participants (78.1% of 3870 eligible persons), 2977 (76.9%) underwent a complete ophthalmologic examination including measurement of the best-corrected visual acuity (BCVA) with full subjective refraction using a Landolt ring chart at 5 m. Age- and gender-specific prevalence rates of low vision and blindness were estimated and causes were identified. MAIN OUTCOME MEASURES: Low vision and blindness were defined as BCVA in the better eye worse than 20/60 to a lower limit of 20/400 and worse than 20/400, respectively (World Health Organization [WHO] criteria) and worse than 20/40 but better than 20/200 and 20/200 or worse, respectively (United States criteria). RESULTS: The overall prevalence of blindness according to the WHO or U.S. criteria was 0.14% (n = 4; 95% confidence interval [CI], 0.06-0.32). The primary causes were optic atrophy, myopic macular degeneration, retinitis pigmentosa, and uveitis. The overall prevalence of low vision according to the WHO criteria was 0.39% (95% CI, 0.18%-0.60%) and according to the U.S. criteria was 0.98% (95% CI, 0.66%-1.30%), which was significantly greater in women and in the older half of the participants than in the younger half (P = 0.0079 and <0.0001, respectively). The leading causes of low vision in descending order were cataract followed by glaucoma, and those of monocular blindness were myopic macular degeneration, glaucoma, and trauma. CONCLUSIONS: The prevalence of low vision and blindness in Japanese adults was one of the lowest among those reported. The major causes of low vision were cataract and glaucoma, and the leading cause of monocular blindness was myopic macular degeneration.

Risk factors for open-angle glaucoma in a Japanese population: the Tajimi Study.

PURPOSE: To identify the risk factors associated with primary open-angle glaucoma (POAG) in the Tajimi Study. DESIGN: Population-based cross-sectional epidemiologic study. PARTICIPANTS: One hundred nineteen POAG patients and 2755 controls. METHODS: Univariate and multivariate comparison of ocular factors and systemic factors between POAG patients and controls. MAIN OUTCOME MEASURES: Difference in factors between POAG patients and controls, factors associated with POAG patients, and their odds ratio (OR). RESULTS: Intraocular pressure (IOP), age, myopia, and history of hypertension differed between POAG patients and controls in univariate analyses. Multivariate analysis with logistic regression with stepwise selection of variables demonstrated that higher IOP (OR, 1.12 [95% confidence interval (CI), 1.04-1.21]), myopia (ORs, 1.85 [95% CI, 1.03-3.31] for low myopia and 2.60 [95% CI, 1.56-4.35] for moderate to high myopia), and older age (OR, 1.06 [95% CI, 1.04-1.08]) were associated with an increased risk of having POAG. CONCLUSIONS: Although the majority (92%) of POAG patients diagnosed in the Tajimi Study had IOP within the normal range, IOP was still identified as a significant risk factor for POAG. Together with IOP, myopia and age were significant risk factors for having POAG.

Incidence of disc hemorrhages in open-angle glaucoma before and after trabeculectomy.

PURPOSE: To investigate the effects of reduction of intraocular pressure (IOP) by surgical intervention on the frequency of disc hemorrhages in eyes with primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). DESIGN: Retrospective study. METHODS: We studied 99 eyes of 99 patients with POAG and 50 eyes of 50 patients with NTG, who underwent trabeculectomy with adjunctive mitomycin C (MMC) and were followed regularly at 1 to 3-month intervals at the Glaucoma Service of Gifu University Hospital. We applied Kaplan-Meier life-table analysis for the detection of disc hemorrhages before and after trabeculectomy. RESULTS: Trabeculectomy significantly reduced IOP (in POAG: 19.6 +/- 4.4 down to 11.1 +/- 4.2 mm Hg; in NTG: 15.3 +/- 1.5 down to 11.3 +/- 4.5 mm Hg; mean +/- SD). Life-table analysis revealed that the final cumulative probability of detecting a disc hemorrhage after surgery in POAG was 5.5 +/- 2.2% (calculated probability +/- SE) and was significantly lower than that (33.4 +/- 7.8%) before surgery (P < 0.0001, log-rank test). Likewise, the final probability after surgery in NTG was 23.1 +/- 6.3% and was significantly lower than that (42.1 +/- 8.8%) before surgery (P = 0.0063, log-rank test). CONCLUSIONS: IOP reduction via surgical intervention significantly decreases the frequency of disc hemorrhages in open-angle glaucoma patients.

Morphometric evaluation of changes with time in optic disc structure and thickness of retinal nerve fibre layer in chronic ocular hypertensive monkeys.

We examined the time course of changes in optic disc structure by means of a scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT) in ocular hypertensive (experimental glaucoma) monkeys, and clarified the relationships between the histological RNFL thickness and HRT parameters. Further, the time course of changes in retinal nerve fiber layer (RNFL) thickness in individual eyes was measured using a scanning laser polarimeter with fixed corneal polarization compensator (GDx FCC). In the present study, two separate experiments were carried out. A chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eye in 11 cynomolgus monkeys. In Experiment 1, the HRT and GDx parameters were measured 12 weeks after the laser treatment in 10 eyes in five monkeys. In Experiment 2, the time course of changes in the HRT and GDx parameters was examined before and 1, 3, 4, 5, 6, 8, 10, 12, 14, and 16 weeks after the laser treatment in 12 eyes in six monkeys. The retardation values (thickness parameters) obtained from the GDx were used to derive thickness and ratio parameters in the superior, inferior, nasal and temporal quadrants. Ratio parameters were expressed as a ratio of superior and inferior quadrant to nasal quadrant. After the last measurements, each eye was enucleated, and retinal cross sections were prepared for histological analysis. In the left (hypertensive) eyes, IOP was persistently elevated throughout the observation periods in both Experiments 1 and 2. In the HRT measurements in Experiment 1, seven out of eight global topographic parameters (exception, disc area) were statistically different between the hypertensive and control eyes 12 weeks after the laser treatment. In Experiment 2, the HRT parameters changed in a time-dependent manner, but each of them almost plateaued at about 4 weeks after the laser treatment. Significant correlations were seen between the histological mean RNFL thickness at 1.5 disc diameters from the optic disc margin and the HRT parameters in 21 eyes from 11 monkeys in Experiments 1 and 2. Especially good correlations with histological mean RNFL thickness were seen for the rim volume and cup volume. In Experiment 1, good correlations were found between GDx ratio parameters and histological RNFL thickness in individual right control eyes (n=5). In individual left experimental glaucoma eyes of Experiment 2 (n=6), GDx ratio parameters declined in a time-dependent manner alongside the IOP elevation. In conclusion, alongside the IOP elevation, time-related changes in optic disc topography and RNFL thickness were demonstrated in monkey eyes using HRT and GDx. HRT (rim and cup) parameters showed good correlations with histological RNFL thickness, and significant interrelations.

Phase III long-term study and comparative clinical study of nipradilol ophthalmic solution in patients with primary open-angle glaucoma and ocular hypertension.

Nipradilol (CAS 81486-22-8) is a non-selective beta-blocker with alpha-1 blocking and nitroglycerin-like vasodilating activities. In the present communication, the long-term efficacy and safety of nipradilol were investigated and the efficacy, safety and utility of topical nipradilol and timolol (CAS 91524-16-2) were compared in patients with primary open-angle glaucoma or ocular hypertension. In the long-term study, nipradilol for 1 year (52 weeks) was performed by registration method. 67 out of 68 patients were subjected to analysis and 57 patients (83.8 %) completed 52-week instillation. 0.25 % nipradilol was applied twice daily to patients. As a result, intraocular pressure (IOP) decreased significantly by 4.0 mmHg to 4.8 mmHg compared with the baseline without tachyphylaxis. The incidence of adverse events was 12.5 % at 52 weeks by analysis with Kaplan-Meier life-table method. It showed no significant trend of increase after 3 months. In the multi-centered double-masked comparative randomized study, 0.25 % nipradilol was assigned to 96 patients and 0.5 % timolol to 100 patients. Each patient was instilled nipradilol or timolol twice daily for 8 weeks. IOP significantly decreased by 4.2 mmHg and by 4.7 mmHg at 8 weeks and the incidence of adverse events was 10.5 % and 12.1 % in the nipradilol and timolol group, respectively. No significant between-group difference in IOP reduction or incidence of adverse events was seen. Topical nipradilol showed long-term ocular hypotensive effects and clinical safety in a 52-week study, and its efficacy and safety equivalent to timolol was confirmed in a 8-week comparative study.

The Tajimi Study report 2: prevalence of primary angle closure and secondary glaucoma in a Japanese population.

PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG), secondary glaucoma (SG), and all glaucoma in a Japanese population as a part of the Tajimi Study. DESIGN: Population-based epidemiological survey. PARTICIPANTS: A random sample of residents 40 years or older from Tajimi, Japan. INTERVENTION: Each subject underwent a screening program comprising an interview and an ophthalmic examination, including Goldmann applanation tonometry, slit-lamp examination, a van Herick test, fundus photography, and a screening visual field (VF) test using frequency-doubling technology. If glaucoma was suspected, the subject was referred for a definitive examination that included slit-lamp examination, gonioscopy, intraocular pressure measurement, a VF test, and optic disc and fundus examination. A diagnosis of PACG or SG was made based on slit-lamp examination, gonioscopy, optic disc appearance, and perimetric results. MAIN OUTCOME MEASURES: Prevalences of PACG, SG, and all cases of glaucoma. RESULTS: Of 3870 eligible people, 3021 (78.1%) participated in the study. Estimated prevalences of PACG and SG in those over 40 years were 0.6% (95% confidence interval [CI], 0.4%-0.9%) and 0.5% (95% CI, 0.2%-0.7%), respectively. Prevalences of all glaucoma and glaucoma/suspected glaucoma were estimated to be 5.0% (95% CI, 4.2%-5.8%) and 7.5% (95% CI, 6.5%-8.4%), respectively. CONCLUSIONS: Prevalences were 0.6%, 0.5%, and 5.0%, respectively, for PACG, SG, and all glaucoma in subjects over 40 years from Tajimi, Japan.

Statistical evaluation of the diagnostic accuracy of methods used to determine the progression of visual field defects in glaucoma.

OBJECTIVE: To evaluate trend-type analyses to judge the progression of visual field damage (VFD) of glaucoma in terms of ratios of making judgments of progression and specificity, and to report a new method. DESIGN: Retrospective analysis of visual field (VF) results of actual glaucoma cases and those simulated by computer, and receiver operating characteristic curve analysis of performance of methods to judge the progression of VFD. PARTICIPANTS: One hundred five eyes of 105 open-angle glaucoma (OAG) patients with progressing VFD and 355 eyes of 355 clinically stable OAG patients for VF simulation from 4 university-based referral practices. METHODS: Methods using regression analysis of total deviation (TD), mean deviation (MD), mean TD of a sectored VF, and original scoring used in the Advanced Glaucoma Intervention Study (AGIS) were compared. A VF test was repeated twice in a short period on the 355 stable OAG eyes, and test-retest fluctuation, including variance at each test point and covariance between 2 test points, was calculated to simulate stable glaucomatous VF series by computer. The sensitivity of each method was calculated with 105 progressing VF series, and specificity was calculated with 10,000 simulated stable glaucomatous VF series. MAIN OUTCOME MEASURES: Sensitivity (ratios of making judgments of progression), specificity, and diagnostic power. RESULTS: The methods using the TD slope on one test location showed a sensitivity of 0.848 to 1.000, with a specificity of 0.105 to 0.721, and on 2 adjacent test locations showed a sensitivity of 0.848, with a specificity of 0.722. A significant negative MD slope with P<0.05 showed a sensitivity of 0.524, with a specificity of 0.945. The method using a sectored VF showed a sensitivity of 0.695, with a high specificity of 0.946. The AGIS method showed a sensitivity of 0.305 to 0.467, with a very high specificity of 0.999 to 1.000. The method using previously reported mathematically sectored VFs showed a sensitivity of 0.790, with a specificity of 0.900, and higher diagnostic power (1.69) than the others in this study population. CONCLUSIONS: Most of the methods using the TD slope were characterized by high sensitivity, the AGIS method had a very high specificity, and those using VF sectors had reasonable sensitivity and specificity.

The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study.

PURPOSE: To assess the prevalence of primary open-angle glaucoma (POAG) and its association with intraocular pressure (IOP) in Tajimi City in central Japan. DESIGN: A cross-sectional epidemiologic study in a defined population. PARTICIPANTS: Subjects randomly selected from the population older than 40 years in Tajimi City. INTERVENTION: Each subject underwent a screening examination comprised of an interview and ophthalmic examinations, including measurement of IOP by a Goldmann applanation tonometer, central corneal thickness (CCT), slit-lamp examination, fundus photography, and a screening visual field test using frequency doubling technology. When ocular diseases were suspected, the subjects were referred for definitive examination. During the definitive examination, slit-lamp examination, IOP measurement, a visual field test using Humphrey Field Analyzer 30-2 SITA Standard program (Humphrey Instruments, San Leandro, CA), optic disc and fundus examination, and gonioscopy were performed and stereoscopic disc photographs were obtained. A diagnosis of glaucoma was made based on optic disc appearance, perimetric results, and other ocular findings. MAIN OUTCOME MEASURES: Prevalence of POAG, mean IOP, and mean CCT. RESULTS: Of 3870 eligible people, 3021 (78.1%) participated in the study. The estimated prevalence of POAG in the population older than 40 years was 3.9% (95% confidence interval [CI]), 3.2%-4.6%). The prevalence of cases of POAG with IOP levels of 21 mmHg or less was 3.6% (95% CI, 2.9%-4.3%), whereas the prevalence for those with IOP levels of more than 21 mmHg was 0.3% (95% CI, 0.1%-0.5%). The average IOP for eyes with POAG was 15.4+/-2.8 (standard deviation) in the right eye (n = 115) and 15.2+/-2.8 mmHg in the left eye (n = 115), which was significantly higher than that of nonglaucoma subjects (14.5+/-2.5 in the right eye; n = 2759; P = 0.0004; and 14.4+/-2.6 mmHg in the left eye; n = 2757; P = 0.0026). The mean CCT of POAG eyes with IOP levels of 21 mmHg or less was 518+/-29 (n = 109) in the right eye and 519+/-29 microm (n = 110) in the left eye, levels that were not significantly different from that of nonglaucoma eyes (520+/-32 microm [n = 2690]; and 522+/-32 microm [n = 2692]; P>0.05). CONCLUSIONS: The prevalence of POAG in this population was 3.9%. In 92% patients with POAG, the IOP was 21 mmHg or less.