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Aim: To investigate the usefulness of data augmentation in visual field (VF) trend analyses in patients with glaucoma., Method: This study included 6380 VFs from 638 eyes of 417 patients with open-angle glaucoma. Various affine transformations were applied to augment the VF data: (1) rotation, (2) scaling, (3) vertical and horizontal shift and (4) a combination of these different transformations. Using pointwise linear regression (PLR), the total deviation (TD) values of a patient's 10th VF were predicted using TD values from shorter VF series (from first to third VFs (VF1-3) to first to ninth VFs (VF1-9)) with and without VF data augmentation, and the root mean squared error (RMSE) was calculated., Results: With PLR, mean RMSE without VF augmentation averaged from 3.95 (VF1-3) to 19.01 (VF1-9) dB. The RMSE was significantly improved by applying the different transformations: (1) rotation (from VF1-3 to VF1-7), (2) scaling (from VF1-3 to VF1-6), (3) vertical and horizontal shifts (from VF1-3 to VF1-4) and (iv) a combination of these (from VF1-3 to VF1-7). Progression rates in VF1-10 had better agreement with those in shorter VF series when a combination of affine transformation was applied. The differences in rates were between 1.9 (VF1-3) and 0.39 (VF1-9) dB if augmentation was used, which was significantly smaller than that observed when augmentation was not applied (from 2.6 with VF1-3 to 0.26 dB with VF1-9)., Conclusion: It is useful to apply VF data augmentation techniques when predicting future VF progression in glaucoma using PLR, especially with short VF series., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We sought to investigate the genetic variants associated with the onset and progression of primary open-angle glaucoma (POAG)., Design: Case-control genetic association study., Methods: Japanese POAG patients (n = 505) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (non-IOP-related genetic variants). The total number of risk alleles of the 17 IOP-related and 5 non-IOP-related genetic variants were calculated as the genetic risk score (GRS), and the associations between the GRS and family history of glaucoma as an indicator of POAG onset and age at the diagnosis of glaucoma as an indicator of POAG progression were evaluated., Results: There was a significant association (P = .014; odds ratio 1.26 per GRS) between the non-IOP-related GRS, but not IOP-related GRS, and a family history of glaucoma in POAG. As the non-IOP-related GRS increased, the risk of a family history of glaucoma increased. In contrast, a significant association (P = .0014; β = -0.14) was found between the IOP-related GRS, but not non-IOP-related GRS, and age at the diagnosis of glaucoma. As the IOP-related GRS increased, age at the diagnosis of glaucoma decreased., Conclusion: The results indicate that non-IOP-related (optic nerve vulnerability) rather than IOP-related (IOP elevation) genetic variants may play an important role in the onset of POAG (family history of glaucoma) and that IOP-related rather than non-IOP-related genetic variants may play an important role in its progression (age at the diagnosis of glaucoma)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Poor persistence with glaucoma therapy can lead to disease progression and subsequent blindness. Persistence with second-line glaucoma combination treatment in a Japanese real-world setting and whether it differed from fixed and unfixed combination drugs was investigated., Methods: This was a retrospective, non-interventional, cohort study using data from a Japanese medical claims database. Patients with glaucoma aged ≥20 years with a first drug claim for glaucoma treatment between 01 July 2005 and 30 October 2014 and with data for > 6 months before and after this first prescription were included. The primary endpoint was duration of drug persistence among glaucoma patients with and without the use of fixed combination drugs in the year following initiation of second-line combination treatment., Results: Of 1403 patients included in the analysis, 364 (25.94%) received fixed combination drugs and 1039 (74.06%) received unfixed combination drugs as second-line treatment. Baseline characteristics were generally comparable between the groups. A total of 39.01% of patients on fixed combination drugs, compared with 41.67% of patients on unfixed combination drugs, persisted on their glaucoma drugs 12 months post second-index date. Median persistence durations for the fixed combination drugs and unfixed combination drugs groups were 6 (95% confidence interval [CI]: 5-8) and 7 months (95% CI 6-9), respectively. Patients who received prostaglandin analogs (PGAs) were the most persistent with their treatment (n = 99, 12.84%). Patients diagnosed with primary open-angle glaucoma were less likely to experience treatment modification (hazard ratio [HR]: 0.800, 95% CI 0.649-0.986, P = 0.036), while those diagnosed with secondary glaucoma were more likely to experience treatment modification (HR: 1.678, 95% CI 1.231-2.288, P = 0.001) compared with glaucoma suspects., Conclusions: In this retrospective claims database study, the persistence rate of second-line glaucoma combination treatment was low, with no difference in persistence between glaucoma patients receiving unfixed combination drugs compared with fixed combination drugs. Patients on PGA showed greater persistence rates compared with other treatments.

The aim of the study was to investigate the usefulness of processing visual field (VF) using a variational autoencoder (VAE). The training data consisted of 82,433 VFs from 16,836 eyes. Testing dataset 1 consisted of test-retest VFs from 104 eyes with open angle glaucoma. Testing dataset 2 was series of 10 VFs from 638 eyes with open angle glaucoma. A VAE model to reconstruct VF was developed using the training dataset. VFs in the testing dataset 1 were then reconstructed using the trained VAE and the mean total deviation (mTD) was calculated (mTD VAE ). In testing dataset 2, the mTD value of the tenth VF was predicted using shorter series of VFs. A similar calculation was carried out using a weighted linear regression where the weights were equal to the absolute difference between mTD and mTD VAE . In testing dataset 1, there was a significant relationship between the difference between mTD and mTD VAE from the first VF and the difference between mTD in the first and second VFs. In testing dataset 2, mean squared prediction errors with the weighted mTD trend analysis were significantly smaller than those form the unweighted mTD trend analysis.

Glaucoma is a neurodegenerative disorder characterized by the loss of retinal ganglion cells and optic nerve fibers, resulting in the loss of visual field. Primary open-angle glaucoma (POAG) is the most prevalent subtype of glaucoma. Recent genome-wide association studies (GWASs) identified more than 100 variants associated with POAG and multiple loci associated with endophenotypes including the disc area, vertical cup-to-disc ratio (VCDR), and intraocular pressure (IOP). Especially, several GWASs reported the association between VCDR and variants near CDKN2B/CDKN2B-AS1, ATOH7, and CHEK2, and between IOP and variants near TMCO1, CAV1/CAV2, GAS7, and ARHGEF12. However, the effect of each variant on endophenotypes is modest; therefore, it is useful to construct a genetic risk score (GRS) based on the effect on endophenotypes by combining susceptible genetic variants. Several studies demonstrated that higher GRS was closely associated with endophenotypes including the VCDR, IOP, and age of diagnosis. Henceforth, by quantifying GRS, identification of high risk group before the disease onset, prediction of visual prognosis and early intervention may be possible., (© 2020 Elsevier B.V. All rights reserved.)

Introduction: Few reports have investigated the status of adherence in Japan on a large scale. We aimed to investigate the status of adherence to topical glaucoma treatment and its associated factors., Methods: A nationwide survey was conducted as a prospective fashion. Participants in this survey were subjects with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic eyedrops and whose ophthalmologist considered prescribing any fixed combination of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects and their attending ophthalmologists independently completed a questionnaire by utilizing a fixed combination of ocular hypotensive eyedrops., Results: A total of 1358 ophthalmologists from 1071 medical institutions participated in this survey. We registered 4430 subjects (2049 males and 2381 females). In total, data from 3853 subjects (87.6%) were analyzed after inclusion of subjects based on inclusion and exclusion criteria. Good adherence was defined as not forgetting instillation during the past week. Rates of good adherence reported by subjects and ophthalmologists were 72.4 and 78.5%, respectively (P < 0.0001). The consistency of adherence evaluation between subjects and ophthalmologists was moderate [kappa score 0.5025 (95% confidence interval 0.4740-0.5309)]. Significant factors associated with adherence were size of clinic, age, gender, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge of glaucoma., Conclusion: Adherence to ocular hypotensive eyedrops among Japanese subjects was relatively good. Concordance of adherence between subjects' reports and ophthalmologists' responses was moderate. Size of clinic, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge of glaucoma were associated with adherence among Japanese glaucoma subjects.

Background/aims: To investigate the usefulness of the Octopus (Haag-Streit) EyeSuite's cluster trend analysis in glaucoma., Methods: Ten visual fields (VFs) with the Humphrey Field Analyzer (Carl Zeiss Meditec), spanning 7.7 years on average were obtained from 728 eyes of 475 primary open angle glaucoma patients. Mean total deviation (mTD) trend analysis and EyeSuite's cluster trend analysis were performed on various series of VFs (from 1st to 10th: VF1-10 to 6th to 10th: VF6-10). The results of the cluster-based trend analysis, based on different lengths of VF series, were compared against mTD trend analysis., Result: Cluster-based trend analysis and mTD trend analysis results were significantly associated in all clusters and with all lengths of VF series. Between 21.2% and 45.9% (depending on VF series length and location) of clusters were deemed to progress when the mTD trend analysis suggested no progression. On the other hand, 4.8% of eyes were observed to progress using the mTD trend analysis when cluster trend analysis suggested no progression in any two (or more) clusters., Conclusion: Whole field trend analysis can miss local VF progression. Cluster trend analysis appears as robust as mTD trend analysis and useful to assess both sectorial and whole field progression. Cluster-based trend analyses, in particular the definition of two or more progressing cluster, may help clinicians to detect glaucomatous progression in a timelier manner than using a whole field trend analysis, without significantly compromising specificity., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: The purpose of this study is to assess the association between the genetic variants that were previously reported to be associated with primary open-angle glaucoma (POAG) in the Japanese population and the phenotypic features., Methods: A total of 661 Japanese patients including 417 patients with POAG [normal tension glaucoma (NTG), n=210; high tension glaucoma (HTG), n=207] and 244 control subjects without glaucoma were analyzed for 3 genetic variants: rs547984 (near gene: ZP4), rs7081455 (PLXDC2), and rs7961953 (TMTC2). The allele frequency differences between POAG (NTG or HTG) patients and control subjects were estimated. The association between these genetic variants and the phenotypic features, including the maximum intraocular pressure (IOP) and the vertical cup-to-disc ratio, was evaluated., Results: There was a significant difference in the rs7081455 (PLXDC2) allele frequencies between the POAG (P=0.0050) patients and the control subjects. An almost 1.5 increase in the risk of POAG (P=0.0042, odds ratio 1.52) was found with a G allele of rs7081455 (PLXDC2). The maximum IOP [23.5±10.3 mm Hg (mean±SD)] in patients with the GG genotype of rs7081455 (PLXDC2) was significantly higher (P=0.0037) than that (19.9±7.4 mm Hg) in patients with the TT genotype., Conclusions: The genetic variant near the PLXDC2 gene was found to influence the risk of POAG by increasing IOP in the Japanese population.

To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1±1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7±1.8) in control subjects. The patients with GRS≥12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP≥22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.

Objective: The contributions of highly correlated cardiovascular risk factors to intraocular pressure (IOP) are not clear due to underlying confounding problems. The present study aimed to determine which metabolic syndrome parameters contribute to elevating IOP and to what extent., Design: Retrospective cohort study., Setting: A private healthcare centre in Japan., Participants: Individuals who visited a private healthcare centre and underwent comprehensive medical check-ups between April 1999 and March 2009 were included (20,007 in the cross-sectional study and 15,747 in the longitudinal study)., Primary and Secondary Outcome Measures: Changes in IOP were evaluated in terms of ageing and changes in metabolic syndrome parameters. Pearson's correlation coefficients and mixed-effects models were used to examine the relationship of changes in IOP with ageing and changes in metabolic syndrome parameters in cross-sectional and longitudinal studies, respectively., Results: In the cross-sectional study, IOP was negatively correlated with age and positively correlated with waist circumference, high-density lipoprotein cholesterol (HDL-C) levels, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting plasma glucose (FPG) levels. In the longitudinal multivariate analysis, the associated IOP changes were -0.12 (p<0.0001) mm Hg with male sex; -0.59 (p<0.0001) mm Hg with 10 years of ageing; +0.42 (p<0.0001) mm Hg with 1 mmol/L increase in HDL-C levels; +0.092 (p<0.0001) mm Hg with 1 mmol/L increase in triglyceride levels; +0.090 (p<0.0001) mm Hg with 10 mm Hg increase in SBP; +0.085 (p<0.0001) mm Hg with 10 mm Hg increase in DBP; and+0.091 (p<0.0001) mm Hg with 1 mmol/L increase in FPG levels., Conclusions: Elevation of IOP was related to longitudinal worsening of serum triglyceride levels, blood pressure and FPG and improvement in serum HDL-C levels., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: To investigate the changes in intraocular pressure (IOP) and associated factors over 10 years in subjects who participated in health examinations in 1999 and 2008., Subjects and Methods: Subjects with no clear history of ocular disease and who participated in health examinations at Yamanashi Koseiren Health Care Center, Japan, in 1999 and 2008 were enrolled in this study. IOP was evaluated using a noncontact tonometer. The right eye was analyzed in all subjects. The change in IOP between the 2 examinations and the factors that were significantly associated with the change in IOP were investigated., Results: A total of 3785 subjects were enrolled (mean age, 50.9±8.6 y), comprising 2022 males (mean age, 50.3±8.9 y) and 1763 females (mean age, 51.5±8.2 y). The mean IOPs of males and females in 1999 were 13.4±3.1 and 12.8±2.8 mm Hg, respectively (P<0.0001). IOP measured in 2008 was significantly lower than that in 1998 in males and females (mean change, -0.8 and -0.6 mm Hg, respectively; P<0.0001). Univariate regression analysis showed that changes in systolic blood pressure, diastolic blood pressure, total cholesterol, body mass index, and γ-glutamyl transpeptidase were positively correlated with change in IOP. Multivariate regression analysis showed that the change in IOP was positively associated with the changes in systolic blood pressure, diastolic blood pressure, and body mass index., Conclusions: IOP decreased significantly with age. Several systemic factors were significantly correlation with the change in IOP.

Purpose: To assess whether the genetic polymorphisms of estrogen receptor beta (ESR2) are associated with primary open-angle glaucoma (POAG)., Design: Case-control study., Methods: Four hundred and twenty-five Japanese patients with POAG, including normal-tension glaucoma (NTG, n = 213) and high-tension glaucoma (HTG, n = 212), and 191 control subjects without glaucoma were analyzed for polymorphisms of rs1256031 and rs4986938 in the ESR2 gene. The genotypic and allelic frequencies were compared between NTG or HTG patients and control subjects. The phenotypic features of patients with POAG were compared between each genotype., Results: There were significant differences in the genotype frequencies of rs1256031 and rs4986938 between the HTG patients and control subjects in women (P = .033 and P = .043 respectively). The frequencies of the C allele of rs1256031 and G allele of rs4986938 were significantly higher in patients with HTG in comparison to the control subjects in women (rs1256031: 53.6% vs 43.4%, P = .044; rs4986938: 89.2% vs 80.6%, P = .027). The maximum intraocular pressures in female POAG patients with the CC or TC genotypes of rs1256031 were significantly higher than that in female POAG patients with the TT genotype (P = .039, analysis of variance, P = .018 and P = .026 respectively)., Conclusion: The ESR2 gene polymorphism is therefore considered to be associated with an intraocular pressure elevation in female patients with POAG., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To assess the long-term effects of latanoprost monotherapy on intraocular pressure (IOP) reduction in Japanese patients with glaucoma., Methods: Those enrolled were patients with glaucoma who had been treated on an outpatient basis for more than 5 years at the Glaucoma Outpatient Clinic of the University of Yamanashi Hospital, with only latanoprost ophthalmic solution as the first drug of choice. Subjects who underwent treatment with a drug other than latanoprost, laser therapy, or surgery were eliminated from the study, and IOP reduction by latanoprost, the dropout rate and causative reasons, and the types of additional therapy were assessed in a retrospective manner., Results: Seventy-two patients (age: 68.3+/-13.0 y) were enrolled, including 40 men and 32 women for the checking of 72 eyes. There were 47 eyes with normal tension glaucoma (NTG) and 25 with primary open angle glaucoma (POAG). The mean duration of latanoprost monotherapy was 4.1+/-2.0 years (range: 5 mo to 7 y, median: 4.0 y). IOP reduction rates (cumulative dropout rates) relative to the mean IOP before the start of latanoprost monotherapy (17.8+/-3.4 mm Hg) were 11.5% (8.3%), 15.5% (8.3%), 13.0% (9.7%), 13.4% (13.9%), 13.5% (19.4%), and 10.6% (30.6%) at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after the start of monotherapy, respectively. Although latanoprost demonstrated significant IOP reduction in POAG and NTG, eyes with POAG showed significant IOP reduction than those with NTG. Two eyes presented with local adverse events resulting from the discontinuation of use of latanoprost, and 4 eyes required filtering surgery., Conclusions: Latanoprost stably reduced IOP over a long term and maintained visual field in approximately 70% of eyes with glaucoma after treatment for 5 years.

Purpose: To examine prospectively the effects of small-incision phacoemulsification and intraocular lens implantation (PEA+IOL) on anterior chamber depth (ACD) and intraocular pressure (IOP) using a newly developed scanning peripheral ACD analyzer (SPAC)., Materials and Methods: Twenty-eight eyes of 21 patients who underwent PEA+IOL without any complications were examined and divided into 7 eyes each of grades 1 to 4 according to the Van Herick technique. The SPAC measured ACD consecutively from the vicinity of the pupil center to the periphery at 0.4-mm intervals. Changes in ACD and IOP as a result of PEA+IOL were investigated, and the factors contributing to the changes in ACD and IOP were examined., Results: PEA+IOL increased ACD significantly at all groups. The average changing rates were 3.19 +/- 0.67 times (Van Herick grade 1), 2.00 +/- 0.80 times (Van Herick grade 2), 1.92 +/- 0.32 times (Van Herick grade 3), and 1.36 +/- 0.65 times (Van Herick grade 4), respectively. The closer to the pupil center the measurement point was, the larger was the increase in ACD. However, the rates of increase in ACD were similar among the measurement points. The increases in ACD were significantly large in patients having a shallow preoperative ACD and a small optic axis length. The IOP reduction became significantly large in eyes with a shallow preoperative ACD., Conclusions: The SPAC enabled quantitative measurement of changes in ACD from the vicinity of the pupil center to the periphery as a result of PEA+IOL. Changes in ACD resulting from PEA+IOL were thought to exert a greater effect on aqueous humor outflow facility as the postoperative ACD became shallower.

Purpose: To determine the proportion of age-related ophthalmologic diseases discovered in a healthy Japanese adult population, as well as to evaluate the age-related changes in intraocular pressure (IOP) in this population during a 10-year period., Methods: Ophthalmologic surveys were conducted in 1988 and 1998 at Tamaho-cho in Yamanashi Prefecture. The target population of the first survey was 1389 subjects over 40 years of age, and of these, 1250 subjects (473 men and 777 women) participated in the survey. Their mean age was 57.8 +/- 11.9 years. Of these 1250 subjects, 245 subjects participated in the second ophthalmologic survey in 1998. The cases of glaucoma or age-related ophthalmologic diseases developing over the intervening 10-year period were determined among the subjects who had been diagnosed with no ophthalmologic abnormalities in the 1988 survey. We also compared the IOP values of the 219 subjects who were diagnosed with no ophthalmologic abnormalities in either the 1988 or the 1998 survey., Results: The number of cases in the 1998 survey with newly discovered ocular diseases were as follows: two cases (0.82%) of normal-tension glaucoma, two cases (0.82%) of epiretinal membrane, one case (0.41%) of age-related macular degeneration, one case (0.41%) of angle-closure glaucoma, and one case (0.41%) of branch retinal vein occlusion. The mean IOP of the 219 subjects diagnosed with no ophthalmic abnormalities in either survey was 13.88 +/- 3.04 mmHg in 1988, which declined significantly to 13.16 +/- 2.75 mmHg in 1998 (P < 0.0001)., Conclusions: The 10-year follow-up of the 245 subjects participating in both surveys showed one or two de novo cases of age-related macular degeneration, epiretinal membrane, branch retinal vein occlusion, normal-tension glaucoma, or angle-closure glaucoma. IOP was found to decline significantly with age.

Glaucoma represents one of the most common eye diseases and is characterized by progressive loss of visual fields. In the more advanced stages bilateral blindness may result, due to optic nerve atrophy and an excavated optic nerve head. Open-angle glaucoma is one of the main disease subsets, which may be further divided into high tension primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Recently, the optineurin ( OPTN) gene was identified as a causative factor for NTG. Alterations in this gene were found in Caucasian families with NTG. In particular, c.458G>A, c.691-692insAG and c.1944G>A were shown to be risk factors. Since NTG is reported to be the most common form of glaucoma in Japan, and to identify if the OPTN gene plays a role in POAG, the DNAs from 148 unrelated Japanese patients with NTG, 165 patients with POAG and 196 unrelated controls who were not suffering glaucoma were investigated by appropriate genotyping techniques. No glaucoma-specific mutations were found in the OPTN gene in Japanese glaucoma patients. However, some novel single-nucleotide polymorphisms (SNPs) in the exons and introns are reported in this paper for the first time.

Objective: To investigate the effect of hospitalization on intraocular pressure (IOP) in patients with normal-tension glaucoma (NTG)., Methods: The study was conducted in 52 patients with a definite diagnosis of NTG. The correlation between IOP measured from 9.00 a.m. to 12.00 p.m. on an outpatient basis within 3 months each prior to and after hospitalization (ambulatory IOP) and IOP measured during the same time period after admission (inpatient IOP) was investigated in NTG patients., Results: Inpatient IOP (13.9 +/- 2.4 mm Hg) was significantly lower than ambulatory IOP (15.2 +/- 2.1 mm Hg), with a difference of 1.3 +/- 2.0 mm Hg (p < 0.01). The difference between inpatient IOP and ambulatory IOP was negatively correlated with inpatient IOP (r = 0.58, p < 0.01)., Conclusions: These results revealed that hospitalization decreased IOP in NTG patients, with the decrease being particularly pronounced in cases of low ambulatory IOP. Interpretation of inpatient IOP should be carefully included in glaucoma treatment., (Copyright 2003 S. Karger AG, Basel)

Aim: To investigate the effects of a non-steroidal anti-inflammatory drug (NSAID) ophthalmic solution on latanoprost induced intraocular pressure (IOP) reduction using normal volunteers., Methods: This study was conducted as a prospective and observer masked clinical trial. 13 normal volunteers were enrolled. After measurement of basal IOP and ophthalmic examination, latanoprost ophthalmic solution was initially administered to both eyes once daily. Four weeks later, an NSAID ophthalmic solution, sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate (refer to bromfenac sodium hydrate), was co-administered to one randomly selected eye (NSAID group) twice daily for 2 weeks. The other eye was employed as a control (non-NSAID group). After withdrawal of the NSAID ophthalmic solution, latanoprost ophthalmic solution was continuously administered for another 2 weeks and was then withdrawn. After a 4 week washout, only bromfenac sodium hydrate ophthalmic solution was administered to the eyes of the NSAID group for 2 weeks. During the study period, ophthalmic examination, including IOP measurement was performed in an observer masked fashion., Results: Before initiation of bromfenac sodium hydrate, baseline IOPs of the non-NSAID group and the NSAID group were 15.73 (SD 1.97) mm Hg and 15.86 (2.06) mm Hg, respectively (p=0.88). Although latanoprost ophthalmic solution significantly reduced IOP in both groups, co-administration of bromfenac sodium hydrate significantly inhibited latanoprost induced IOP reduction compared with the non-NSAID group. The IOPs of the non-NSAID and NSAID groups were 10.18 (1.17) mm Hg and 11.63 (1.35) mm Hg with a 2 week co-administration, respectively (p <0.01). Withdrawal of bromfenac sodium hydrate ophthalmic solution diminished the difference between the two groups. Re-administration of bromfenac sodium ophthalmic solution only did not affect IOP., Conclusion: These results indicate that NSAID ophthalmic solution may interfere with IOP reduction by latanoprost ophthalmic solution in normal volunteers and that we should take this into account when treating patients with glaucoma using latanoprost ophthalmic solution.

The intraocular metabolism of isopropyl unoprostone, a novel prostaglandin-related anti-glaucoma compound, was investigated using pigmented rabbits to clarify which metabolites are involved in actions in the eye. Tritium-labeled isopropyl unoprostone eyedrops were administered. The cornea, aqueous humor, iris, ciliary body and retina were then collected at 5, 15 or 30 min or at 2, 6 or 12 h after instillation. Isopropyl unoprostone and its metabolites were fractionated using high-performance liquid chromatography, and the radioactivity of each fraction was measured. Unmetabolized isopropyl unoprostone was never detected in any sample at any time point. In the cornea, only the de-esterificated metabolite, M1, and the further metabolized compound, M2, were detected; and the concentrations of these metabolites decreased with time. In the aqueous humor, M1, M2 and another metabolite, M3, were detected, with peak concentrations of M1 at 30 min and M2 at 2 h. The iris and ciliary body showed a similar metabolism with peak concentrations of M1 and M2 at 30 min. In the aqueous humor, iris and ciliary body, M2 was the dominant metabolite from 30 min. In the retina, only total radioactivity was detected. These results indicate that the main metabolites involved in actions in the eye are M1 and M2.

Aims: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. Methods: Genomic DNA was extracted from whole blood of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese origin. Results: Fifteen microsatellite markers within and/or near to the GLC1 B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. Conclusion: The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma. [ABSTRACT FROM AUTHOR]

Aim: Using the newly developed scanning peripheral anterior chamber depth analyser (SPAC), the effects of peripheral laser iridotomy (PLI) on peripheral anterior chamber depth (PACD) were determined quantitatively as was the association between PACD and chronic elevation of intraocular pressure (IOP) after PLI. Methods: 16 eyes of 15 patients with acute primary angle closure glaucoma (PACG) attack, 14 eyes of 14 patients with narrow angle and PACG attack in their fellow eyes, and 13 eyes of seven patients with chronic angle closure glaucoma (CACG) were enrolled. The SPAC scanned the anterior ocular segment from the optical axis to the limbus and took 21 consecutive slit lamp images at 0.4 mm intervals. A computer installed program automatically evaluated the PACD and the averaged values of three measurements were employed for analysis. Results: Pit significantly increased PACD and changed the iris contour from convex to flat or concave in all the enrolled eyes. The extent of the PLI induced PACD increase was enhanced with increasing distance from the optical axis. Comparing PACDs after PLI, eyes that received prophylactic P11 showed the greatest extent of PU induced PACD increase, followed by eyes with CACG and eyes with PACG attack. The PACD of eyes with PACG attack was almost the same as that of the fellow eyes of PACG attack before prophylactic P11. Eyes with PACG attack showed poorer lop control after PU than eyes with narrow angle and CACG with PLI. Conclusions: PLI significantly increases PACD and the small PLI induced opening of PACD may contribute to chronic IOP elevation after PLI. [ABSTRACT FROM AUTHOR]

AIM: To compare incidence of iridial pigmentation prospectively induced by long term treatment with latanoprost and isopropyl unoprostone (hereafter, unoprostone) in Japanese patients with glaucoma. METHODS: Patients with glaucoma treated with prostaglandin (PG) related ophthalmic solutions were sequentially enrolled. Patients treated for more than 30 months with PG related ophthalmic solutions were subjected to analysis. The entry criteria were no history of intraocular surgery, laser iridotomy, and/or laser trabeculoplasty within 12 months before and after the enrolment; and no history of uveitis; no changes in antiglaucoma drugs within 6 months before and after the enrolment. Photographs of the irides were taken under the same conditions and three glaucoma specialists evaluated the iridial pigmentation with masking of patient information. The correlation of iridial pigmentation with the background factors and the reduction of intraocular pressure (IOP) before and after the treatment were investigated. RESULTS: 48 eyes in 48 patients satisfied the enrolment criteria (25 eyes in the latanoprost group, 23 eyes in the unoprostone group). At the end of the follow up period, iridial pigmentation was present in 15 patients (60.0%) in the latanoprost group and seven patients (30.4%) in the unoprostone group. The correlation between development of iridial pigmentation and age, sex, concurrent use of other ophthalmic solutions, and IOP reduction was not significant. CONCLUSIONS: The incidence of iridial pigmentation induced by latanoprost or unoprostone is high in the case of long term treatment. Iridial pigmentation did not affect PG related ophthalmic solution induced IOP reduction. [ABSTRACT FROM AUTHOR]