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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. [ABSTRACT FROM AUTHOR]

Purpose: To examine the correlation between the van Herick system and the Shaffer system in a large-scale epidemiological survey conducted on healthy Japanese subjects. Methods: The van Herick technique was performed on 14 779 subjects aged 40 years and over who participated in an ophthalmic epidemiological survey conducted in Tajimi City, Gifu Prefecture. Eyes classified as grade 1 or 2 according to the van Herick technique were diagnosed as narrow angle eyes, and those eyes were subjected to secondary examination using a gonioscope. In the secondary examination, glaucoma specialists evaluated angle width based on the Shaffer system. Results: Nine hundred and twenty-three eyes of 505 subjects (108 men and 397 women) were determined to be narrow-angle eyes among the 14 779 subjects surveyed. There were 78 grade 1 eyes and 845 grade 2 eyes. Three hundred and eighty-three subjects (75.8%) underwent gonioscopic examination, and 426 eyes (65.9%) had an angle as narrow as or narrower than Shaffer grade 2. Among the 51 eyes evaluated as van Herick grade 1, 44 (86.3%) had an angle an narrow as or narrower than Shaffer grade 2, while among the 595 eyes evaluated as van Herick grade 2, 382 (64.2%) had an angle as narrow as or narrower than Shaffer grade 2. Conclusions: The van Herick technique closely coincided with the Shaffer system and was found to have a potential for use as a simple method for evaluating narrow-angle eyes in Japanese. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is one of the leading causes of blindness. Reduction of intraocular pressure is the only proven way to prevent progression of glaucomatous optic neuropathy. The majority of glaucoma patients need to use antiglaucoma ophthalmic solutions over the course of their life. Thus, good adherence and persistency of glaucoma treatment are important factors for better glaucoma care.Objective: The purpose of this study was to investigate the impact of an Internet-based glaucoma care support system on glaucoma medication use.Methods: Patients were randomly divided into two groups. The non-Internet access (NIA) group consisted of patients who had access to the Internet-based glaucoma care support system during the 4-year period only when they were examined by ophthalmologists. The Internet access (IA) group consisted of patients who had the same Internet-based glaucoma care support system access as the NIA group for the first 2 years following enrollment but who were also given free access to the glaucoma care support system for the remaining 2 years. Changes in glaucoma medication use were investigated.Results: In total, 81 patients in the IA group and 90 patients in the NIA group satisfied the study protocol. The number of antiglaucoma ophthalmic solutions used during the study period significantly increased in the NIA group (P<.03) but not in the IA group. The percentages of patients with unchanged, increased, and decreased antiglaucoma ophthalmic solution use during the study period were 61.1% (55/90), 17.8% (16/90), and 3.3% (3/90), respectively, in the NIA group, and 56.8% (46/81), 8.6% (7/81), and 13.6% (11/81), respectively, in the IA group (P<.001). Internet access significantly shifted from an increasing intraocular pressure trend to a decreasing trend in the IA group (P=.002) among the patients who did not have any medication changes.Conclusions: Allowing patients to browse their medical data may reduce the use and improve the effectiveness of glaucoma medication.Trial Registration: UMIN-CTR Clinical Trial Number: UMIN000006982; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000008238&language=E (Archived by WebCite at http://www.webcitation.org/6MRPQeEAv). [ABSTRACT FROM AUTHOR]

Background and aim: To investigate incidence of angle closure (AC) and its associated factors through a community-based longitudinal study over a 5-year period. Methods: Japanese residents aged 40 years or over who underwent two glaucoma health examinations held in 2005 and 2010 were enrolled. Of the participants of the first glaucoma health examination (first examination), those who satisfied exclusion criteria such as having eyes with angle closure, glaucoma, incisional ocular surgery, or other conditions that could influence the results were eliminated from the second glaucoma health examination (second examination). In addition to routine ophthalmic examination, a scanning peripheral anterior chamber depth analyzer (SPAC) was employed to investigate the anterior chamber configuration. The incidence of angle closure over the 5-year period and its associated factors were investigated. Results: Of the 754 participants of the first examination, 569 participants were invited for the second examination and 331 participants (87 males and 244 females, age: 62.6 ± 12.7 years), or 619 eyes, were analyzed after eliminating eyes matching exclusion criteria. In the 5-year period, the incidence of AC was 5.4 % (95 % CI: 3.5-8.4 %) of participants or 5.5 % (95 % CI: 4.0-7.6 %) of eyes, including eight eyes (1.3 %) with primary angle-closure glaucoma. Eyes that developed AC had a much smaller SPAC grade at the first examination and a greater decrease in SPAC grade than those that did not develop AC, whereas age and sex were not associated. Conclusions: AC was developed by 5.4 % of senior Japanese residents over the 5-year period. The shallow anterior chamber and the marked decrease in anterior chamber depth were associated with AC development. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association between the genetic variants associated with the optic nerve vertical cup-to-disc ratio (VCDR) and the phenotypic features in patients with primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG) and high-tension glaucoma (HTG). Design: Case-control study. Participants and Controls: Japanese patients with NTG (n = 213) and HTG (n = 212) and 191 control subjects without glaucoma. Methods: DNA samples were genotyped for 7 single nucleotide polymorphisms (SNPs) associated with VCDR: rs1063192 (near gene: CDKN2B), rs10483727 (SIX1), rs17146964 (SCYL1), rs1547014 (CHEK2), rs1900004 (ATOH7), rs1926320 (DCLK1), and rs12015126 (RERE). Main Outcome Measures: The VCDR was compared between genotypes, and allele frequency differences were compared between NTG or HTG subjects and control subjects. Demographic and clinical features were compared between alleles in patients with NTG or HTG. Results: There were significant VCDR differences (P = 0.0077 and P = 0.019) between the genotypes for rs1063192 (CDKN2B) and rs1547014 (CHEK2), respectively. There were significant differences in the rs1063192 (CDKN2B) and rs1900004 (ATOH7) allele frequencies between the NTG subjects and control subjects (P = 0.0023 and P = 0.028, respectively) and a significant difference (P = 0.013) in the rs1547014 (CHEK2) allele frequencies between the HTG subjects and control subjects. Ages at diagnosis were significantly different in the NTG subjects with and without the rs10483727 (SIX1) C allele (P = 0.017) or the rs1926320 (DCLK1) T allele (P = 0.040). Likewise, the age at diagnosis was significantly different (P = 0.037) in the HTG subjects with and without the rs12025126 (RERE) T allele. There were no significant associations between the maximum intraocular pressure (IOP) and 7 genotyped SNP alleles in patients with NTG or HTG. Conclusions: The rs1063192 (CDKN2B) and rs1900004 (ATOH7) seem to be non–IOP-related genetic risk factors for NTG, and the rs1547014 (CHEK2) is a genetic risk factor for HTG. Although the rs10483727 (SIX1), rs1926320 (DCLK1), or rs12025126 (RERE) alone may not be sufficient for the development of POAG, the association of these SNPs with a phenotypic feature in patients with NTG or HTG suggests that these loci contribute to the pathogenesis of POAG. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Age related Macular Degeneration (AMD) is a disease of the retina that leads to deterioration in vision and eventually permanent blindness. As yet there are no definitive ways of repairing the damage caused by AMD. Recently evidence is mounting that cell-based therapy using Retinal Pigment Epithelium (RPE) could be a feasible option for treating this disease. For example, autologous RPE transplantation has been successful at providing a functioning replacement for the diseased retina in animal models and humans. However, degeneration can re-occur requiring more RPE cells from the patient. Therefore, considering the option of onetime harvested RPE tissue from the periphery of the patient's eye, safe transportation between clinics/hospitals, efficient in vitro RPE expansion at the destination and long-term cryopreservation for future applications, we have developed a biodegradable RPE carrying medium in 3D, made from a growth factor-free Thermoreversible gelation polymer (TGP - Mebiol gel). RPE cell layers harvested from cadaver eyes were embedded in the TGP hydrogel and divided into three groups: Group 1, were processed immediately, Group 2 after 18-24 hours and Group 3 after 40-48 hrs of harvesting. Each group had one control sub-group grown in conventional media and one TGP sub-group grown embedded in TGP scaffold. No growth factors were used in the culture, when grown for three weeks. RPE cell counts were done at regular intervals during the expansion phase, and were then characterized by RT-PCR to confirm their RPE phenotype. The cells in all the three TGP preserved groups and the controls were equally viable after different periods of preservation, with a maximum duration of 48 Hrs. In cultivation, TGP preserved RPE cells formed a monolayer with a typical honeycomb/cobblestone appearance characteristic of native RPE. The degree of pigmentation is increased in the TGP group compared to the control group indicating that the RPE possesses a native RPE phenotype. The proliferative capacity of RPE was also increased when embedded in TGP. Cells from both the groups expressed Cellular Retinaldehyde-Binding Protein (CRALBP) and RPE65, which are abundantly expressed in the RPE cells and Mueller cells of the retina. We have established a simple and efficient transportation module for RPE at varying climatic conditions without the need for cool preservation using a polymer hydrogel cocktail and a culture method without using any growth factors. These cells can be a potential source for transplantation in treating retinal disorders upon further confirmation of their functional characteristics. [ABSTRACT FROM AUTHOR]

Purpose: To compare the anterior ocular segment measurements of two non-contact devices, i.e., anterior segment swept-source optical coherence tomography (SS-OCT) and the scanning peripheral anterior chamber depth analyzer (SPAC), in patients with glaucoma. Patients and methods: This was a cross-sectional study of glaucoma patients visiting the Yamanashi University Hospital. The consistency and correlation of various parameters were studied between the SS-OCT and SPAC measurements, including the central corneal thickness (CCT), the central anterior chamber depth (ACD), the trabecular-iris angle (TIA), the angle opening distance (AOD), the area of the recessed angle (ARA), and the trabecular-iris space area (TISA) from the SS-OCT measurements, and the CCT, central ACD, SPAC grade, and SPAC-evaluated anterior chamber angle (ACA) from the SPAC measurements. Results: Seventy right eyes of 70 patients (27 men, 43 women) with glaucoma were enrolled in the study. The mean patient age was 65.9 ± 14.5 years. The CCT measurements by SS-OCT and the SPAC were 528.3 ± 32.0 and 516.1 ± 28.5 μm, respectively ( P < 0.001). The central ACD measurements by SS-OCT and the SPAC were 2.39 ± 0.44 and 2.73 ± 0.50 mm, respectively ( P < 0.001). The two devices showed a significant correlation in terms of the CCT measurements ( R = 0.667, P < 0.0001) and the central ACD measurements ( R = 0.86, P < 0.0001), but SS-OCT give a significantly shallower central ACD measurement and a thinner CCT measurement compared with the SPAC. AOD, TIA, TISA, and the ARA were all significantly correlated with the SPAC grade and the ACA. Consistency between the two devices was reduced among eyes with primary angle closure. Conclusions: Based on our results, the SS-OCT and SPAC measurements of the anterior segment were significantly correlated, but the values cannot be considered to be directly interchangeable. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether genetic polymorphisms of optic atrophy 1 (OPA1) are associated with primary open-angle glaucoma (POAG). Design: Prospective case control association study. Methods: Japanese patients with normal tension glaucoma (NTG, n = 194), and high tension glaucoma (HTG, n = 191), and 185 control subjects were analyzed for the OPA1 intervening sequence (IVS) 8+4 cystosine thymine (C/T) and IVS 8+32 thymine cystosine (T/C) polymorphisms using pyrosequencing technique. Results: There was a significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the NTG patients and control subjects (P = .0074), and the frequency of the cystosine (C) allele was significantly higher in the NTG patients compared with the control subjects (19.3% vs 11.6%, P = .0036). Adjusted for age, gender, refractive error, and intraocular pressure, an almost two-fold increased risk of NTG (P = .004, odds ratio 2.27, 95% confidence interval 1.30 to 3.97) was found with the OPA1 IVS 8 +32 C allele. Although there was no significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the HTG patients and control subjects (P = .24), the age at the time of diagnosis (53 ± 11.0 years, median value ± median absolute deviation) in the HTG patients with the OPA1 IVS 8 +32 C allele was significantly younger than that (57 ± 12.0 years) in the HTG patients without C allele (P = .048). Conclusions: The OPA1 IVS 8 +32 T/C polymorphism is associated with NTG, and may be used as a marker for this disease association. This polymorphism also influences the phenotypic feature in patients with HTG and should be considered to be a genetic risk factor not only for NTG, but also for HTG. [Copyright &y& Elsevier]

Abstract: Using cultured rat retinal glial cells, the changes in the expression of glutamate transporters (GLTs) under such conditions as the degree of confluence of the cells, hypoxia, glutamate loading, and potassium loading, were assessed. After the retinal glial cells were isolated from 3-day-old Sprague–Dawley rats, GLAST, GLT-1, and EAAC1 mRNA expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and their protein expression was confirmed by Western blot analysis and immunostaining. Changes in the expression of the GLTs at 6 h after passage and at confluence, during culture in 5% oxygen, during glutamate loading and during potassium loading were assessed using real-time PCR. Although the GLAST mRNA expression was increased during glutamate and potassium loading, no changes in the expression were observed during hypoxia and at confluence. By contrast, the GLT-1 mRNA expression was increased during hypoxia and at confluence, but not during glutamate and potassium loading, and the EAAC1 mRNA expression was not changed only during glutamate loading. The expression of EAAC1 in the cultured retinal glial cells was confirmed. The expression of the GLTs varied according to the environment and the type of load suggests that the involvement of the GLTs in retinal physiology and pathology varies depending on the subtype. [Copyright &y& Elsevier]

The aim of this study was to compare the effects of hypoxia on nitric oxide synthase (NOS) expression and the production of NO between isolated retinal ganglion cells (RGCs) and retinal glial cells. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to examine the presence of neuronal NOS mRNA, inducible NOS mRNA, and endothelial NOS mRNAs in the two cell types. RGCs and retinal glial cells were separately cultured under hypoxic (10% O2) or control (20% O2) conditions. Changes in NOS-mRNA expression were quantified by real-time PCR, and nitrite in the medium was measured up to 96 h of culture. The effects of non-NOS- and iNOS-selective inhibitors on hypoxia-induced release of nitrite in the culture medium were evaluated. RT-PCR revealed the presence of three types of NOSs in the two types of cultured cells. Hypoxic culture conditions significantly changed the expression of all NOS mRNAs in retinal glial cells but not in RGCs. NO production showed significant changes corresponding to those of NOS mRNAs in retinal glial cells but not in RGCs, and both NOS inhibitors significantly reduced hypoxia-induced nitrite release in retinal glial cells. Retinal glial cells but not RGCs may be the major source of NO under hypoxic conditions. [Copyright &y& Elsevier]

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 &y& Elsevier]

Purpose: To investigate the associations between the non-intraocular pressure (IOP)-related genetic variants (genetic variants associated with vulnerability of the optic nerve independent of IOP) and primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG) and high-tension glaucoma (HTG), and between the non-IOP-related genetic variants and a family history of glaucoma., Design: Case-control study., Methods: Japanese patients with NTG (n = 213) and HTG (n = 212) and 191 control subjects were genotyped for 5 non-IOP-related genetic variants predisposing to POAG near the SRBD1, ELOVL5, CDKN2B/CDKN2B-AS1, SIX1/SIX6, and ATOH7 genes. The load of these genetic variants was compared between the control subjects and patients with NTG or HTG and between the POAG patients with and without a family history of glaucoma., Results: The total number of POAG risk alleles and the product of the odds ratios (POAG risk) of these genetic variants were significantly larger (P < .0025) in patients with both NTG and HTG than in the control subjects, and were significantly larger (P = .0042 and P = .023, respectively) in POAG patients with a family history of glaucoma than in those without. As the number of relatives with glaucoma increased, the total number of risk alleles and the product of the odds ratios increased (P = .012 and P = .047, respectively)., Conclusions: Non-IOP-related genetic variants contribute to the pathogenesis of HTG as well as NTG. A positive family history of glaucoma in cases of POAG is thought to reflect the influence of genetic variants predisposing to POAG., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Glaucoma is one of the leading causes of blindness. Reduction of intraocular pressure is the only proven way to prevent progression of glaucomatous optic neuropathy. The majority of glaucoma patients need to use antiglaucoma ophthalmic solutions over the course of their life. Thus, good adherence and persistency of glaucoma treatment are important factors for better glaucoma care., Objective: The purpose of this study was to investigate the impact of an Internet-based glaucoma care support system on glaucoma medication use., Methods: Patients were randomly divided into two groups. The non-Internet access (NIA) group consisted of patients who had access to the Internet-based glaucoma care support system during the 4-year period only when they were examined by ophthalmologists. The Internet access (IA) group consisted of patients who had the same Internet-based glaucoma care support system access as the NIA group for the first 2 years following enrollment but who were also given free access to the glaucoma care support system for the remaining 2 years. Changes in glaucoma medication use were investigated., Results: In total, 81 patients in the IA group and 90 patients in the NIA group satisfied the study protocol. The number of antiglaucoma ophthalmic solutions used during the study period significantly increased in the NIA group (P<.03) but not in the IA group. The percentages of patients with unchanged, increased, and decreased antiglaucoma ophthalmic solution use during the study period were 61.1% (55/90), 17.8% (16/90), and 3.3% (3/90), respectively, in the NIA group, and 56.8% (46/81), 8.6% (7/81), and 13.6% (11/81), respectively, in the IA group (P<.001). Internet access significantly shifted from an increasing intraocular pressure trend to a decreasing trend in the IA group (P=.002) among the patients who did not have any medication changes., Conclusions: Allowing patients to browse their medical data may reduce the use and improve the effectiveness of glaucoma medication., Trial Registration: UMIN-CTR Clinical Trial Number: UMIN000006982; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000008238&language=E (Archived by WebCite at http://www.webcitation.org/6MRPQeEAv).