Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy.

PURPOSE: To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. SUBJECTS AND METHODS: Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. RESULTS: Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P < 0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. CONCLUSIONS: Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events.

Involvement of genetic variants associated with primary open-angle glaucoma in pathogenic mechanisms and family history of glaucoma.

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.

Impact of patient access to Internet health records on glaucoma medication: randomized controlled trial.

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).

Successful transportation of human corneal endothelial tissues without cool preservation in varying Indian tropical climatic conditions and in vitro cell expansion using a novel polymer.

BACKGROUND: Though the transplantation of human corneal endothelial tissue (CET) separated from cadaver cornea is in practice, its transportation has not been reported. We report the successful transportation of CET in varying Indian climatic conditions without cool preservation and the in vitro expansion of Human Corneal Endothelial Precursor Cells (HCEPCs) using a novel Thermo-reversible gelation polymer (TGP). MATERIALS AND METHODS: CET from cadaver corneas (n = 67), unsuitable for transplantation, were used. In phase I, CET was transported in Basal Culture Medium (Group I) and TGP (Group II) and in Phase II, in TGP cocktail alone, from three hospitals 250-2500 km away, to a central laboratory. The transportation time ranged from 6 h to 72 h and the outdoor temperature between 20°C and 41°C. On arrival, CET were processed, cells were expanded upto 30 days in basal culture medium (Group A) and TGP scaffold (Group B). Cell viability and morphology were documented and Reverse transcription polymerase chain reaction (RT-PCR) characterization undertaken. RESULTS: In Phase I, TGP yielded more viable cells (0.11 × 10(6) cells) than Group I (0.04 × 10(6) cells). In Phase II, the average cell count was 5.44 × 10(4) cells. During expansion, viability of HCEPCs spheres in TGP was maintained for a longer duration. The cells from both the groups tested positive for B-3 tubulin and negative for cytokeratins K3 and K12, thereby proving them to be HCEPCs. CONCLUSION: TGP preserves the CET during transportation without cool preservation and supports in vitro expansion, with a higher yield of HCEPCs, similar to that reported in clinical studies.

Five-year incidence of angle closure among glaucoma health examination participants.

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.

Association between genetic variants associated with vertical cup-to-disc ratio and phenotypic features of primary open-angle glaucoma.

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.

Risk factors for anxiety and depression in patients with glaucoma.

AIM: To assess the risk factors for anxiety and depression in patients with glaucoma. METHODS: Anxiety and depression in 408 patients with glaucoma were evaluated using the hospital anxiety and depression scale (HADS) questionnaire, which consists of two subscales, representing HADS-anxiety (HADS-A) and HADS-depression (HADS-D). To identify the risk factors for anxiety and depression, the stepwise and multiple linear regression analyses were carried out with the HADS-A and HADS-D subscores as dependent variables and demographic and clinical features as independent variables. RESULTS: A stepwise linear regression analysis revealed the significantly related factors to be age for HADS-A (ß=-0.046, p=0.0007) and HADS-D (ß=0.035, p=0.011) and the mean deviation of the Humphrey Visual Field Analyzer 30-2 (HFA30-2) in the better eye for HADS-D (ß=-0.095, p=0.0026). Based on multiple linear regression analyses, significant relationships were confirmed between age and the HADS-A subscore (ß=-0.046, p=0.0008). Significant relationships were also confirmed between age (ß=0.037, p=0.0077) or the mean deviation of HFA30-2 in the better eye (ß=-0.094, p=0.0036) and the HADS-D subscore. CONCLUSION: A younger age was thus found to be a risk factor for anxiety, while an older age and increasing glaucoma severity were risk factors for depression in patients with glaucoma.

Comparison of the anterior ocular segment measurements using swept-source optical coherent tomography and a scanning peripheral anterior chamber depth analyzer.

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 (2) = 0.667, P < 0.0001) and the central ACD measurements (R (2) = 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.

Association between SRBD1 and ELOVL5 gene polymorphisms and primary open-angle glaucoma.

PURPOSE: The S1 RNA binding domain 1 (SRBD1) and elongation of long-chain fatty acids family member 5 (ELOVL5) have been reported to be susceptibility genes for early-onset normal-tension glaucoma (NTG). The present study we conducted to assess whether these genes were associated with primary open-angle glaucoma (POAG), including late-onset NTG and high-tension glaucoma (HTG). METHODS: Three hundred seventy Japanese patients with POAG, including 158 NTG and 212 HTG patients and 191 control subjects were analyzed for SRBD1 (rs3213787) and ELOVL5 (rs735860) gene polymorphisms. RESULTS: The A allele frequencies of rs3213787 were significantly higher in NTG (98.4%, P = 0.0003) and HTG (97.6%, P = 0.0013) patients than in the control subjects (92.7%). The A allele frequency was significantly higher (P = 0.014), even though the NTG patients were limited to those diagnosed at ages older than 60 years. The POAG patients with the CC or CT risk genotypes of rs735860 were significantly older (P = 0.032, analysis of variance, P = 0.043 and P = 0.015, respectively) than were the POAG patients with the TT genotype, and the frequency of a family history of glaucoma in POAG patients with the CC risk genotype was significantly higher (P = 0.015) than that in POAG patients with the TT genotype. CONCLUSIONS: SRBD1 gene polymorphism is associated with the development of HTG as well as NTG, including late-onset NTG. Typical POAG associated with ELOVL5 gene polymorphism may have a late rather than an early onset.

Estrogen receptor beta gene polymorphism and intraocular pressure elevation in female patients with primary open-angle glaucoma.

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.

Changes in anterior chamber depth due to contusion.

PURPOSE: We aimed to investigate changes in anterior chamber depth (ACD) prospectively in patients with recent unilateral contusion but no signs of angle recession, using a scanning peripheral anterior chamber depth analyzer (SPAC). METHODS: Among patients whose chief complaint was recent unilateral contusion and who showed no signs of angle recession by gonioscopy in 2006 and 2007, those who satisfied the following criteria were subjected to SPAC evaluation of ACD from the central to the peripheral region: no history of ocular diseases or ocular surgery including laser treatment, and similar refractory error in both eyes before trauma. RESULTS: Thirty-seven patients satisfied the criteria (29 males, 8 females; age: 28.6 +/- 23.5 years). Fourteen patients presented with commotio retinae. Fifteen showed no ocular manifestations related to the contusion. The mean SPAC-determined ACD grades of contused and noncontused eyes were 10.7 +/- 1.6 and 9.8 +/- 2.1, respectively, demonstrating that the contused eyes had significantly larger ACD values than the noncontused ones (p = 0.0005). The contused eyes had larger ACD values in both the central and the peripheral regions. The difference in ACD between the contused and noncontused eyes tended to increase with greater distance from the center. The equivalent refractive errors were -2.3 +/- 2.2 and -1.7 +/- 2.1 dpt, respectively (p = 0.004). There were no significant differences in best-corrected visual acuity and intraocular pressure between the contused and the noncontused eyes. CONCLUSION: Contusion may increase ACD particularly in the peripheral region even in patients who have no apparent manifestations in the anterior ocular segment.

Lack of association between p53 gene polymorphisms and primary open angle glaucoma in the Japanese population.

PURPOSE: To assess whether tumor protein p53 gene (p53) polymorphisms are associated with primary open angle glaucoma (POAG) in the Japanese population. 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 189 control subjects without glaucoma were analyzed for two p53 polymorphisms (rs1042522; a G-->C substitution at codon 72 in exon 4 and rs59758982; a 16 base pair insertion in intron 3) using allele specific primer PCR and a pyrosequencing technique respectively. The genotypic and allelic frequencies were compared between NTG or HTG patients and control subjects. RESULTS: No significant difference (NTG versus control, p=0.99, and HTG versus control, p=0.69, chi(2) test) was observed regarding the p53 genotype frequencies at codon 72 between the NTG (GG: 43.2%, GC: 44.6%, CC: 12.2%) or HTG (GG: 40.1%, GC: 48.1%, CC: 11.8%) patients and the control subjects (GG: 43.9%, GC: 43.9%, CC: 12.2%). In addition, there was no significant difference (NTG versus control, p=0.94; and HTG versus control, p=0.66, Fisher's exact test) in the p53 allele frequencies at codon 72 between the NTG (G allele: 65.5%, C allele: 34.5%) or HTG (G allele: 64.2%, C allele: 35.8%) patients and the control subjects (G allele: 65.9%, C allele: 34.1%). No 16 base pair insertion in intron 3 was found in this study. CONCLUSION: p53 polymorphisms were not associated with POAG in the Japanese population. Further studies in the other ethnic populations should therefore be performed to elucidate whether the p53 intron 3 insertion polymorphism is a genetic risk factor for POAG, because the intron 3 insertion polymorphism occurs very rarely in the Japanese population.

Long-term effects of latanoprost monotherapy on intraocular pressure in Japanese glaucoma patients.

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.

High prevalence of anxiety and depression in patients with primary open-angle glaucoma.

PURPOSE: To assess anxiety and depression in patients with primary open-angle glaucoma (POAG). DESIGN: Multicenter prospective case-control study. PARTICIPANTS: Two hundred thirty patients with POAG and 230 sex-matched and age-matched reference subjects with no chronic ocular conditions except cataracts. INTERVENTION: Anxiety and depression were evaluated using Hospital Anxiety and Depression Scale (HADS) questionnaire, which consists of 2 subscales with ranges of 0 to 21, representing anxiety (HADS-A) and depression (HADS-D). MAIN OUTCOME MEASURE: The prevalence of POAG patients with anxiety (a score of more than 10 on the HADS-A) or depression (a score of more than 10 on the HADS-D) was compared with that in the reference subjects. The prevalence of patients with depression was compared between the POAG patients with and without current beta-blocker eye drops. RESULTS: The prevalence (13.0%) of POAG patients with anxiety was significantly higher (P=0.030) than in the reference subjects (7.0%). The prevalence (10.9%) of POAG patients with depression was significantly higher (P=0.026) than in the reference subjects (5.2%). Between the POAG patients with and without beta-blocker eye-drops, no significant difference (P=0.93) in the prevalence of depression was noted. CONCLUSIONS: POAG was related to anxiety and depression. No significant relationship between the use of beta-blocker eye-drops and depression was noted.

Lysyl oxidase-like 1 gene polymorphisms in Japanese patients with primary open angle glaucoma and exfoliation syndrome.

PURPOSE: To assess whether lysyl oxidase-like 1 (LOXL1) polymorphisms are associated with primary open-angle glaucoma (POAG) and exfoliation syndrome (XFS). METHODS: Japanese patients with POAG (n=213) or XFS (n=89) and 191 control subjects were analyzed for LOXL1 polymorphisms (rs1048661: 758G/T, Arg141Leu and rs3825942: 794G/A, Gly153Asp). Demographic and clinical features of POAG patients and control subjects were compared in terms of the TT/GG compound genotype of rs1048661 and rs3825942. RESULTS: There was a significant difference in the genotype frequencies between XFS patients and control subjects (p<0.0001). Frequencies of the T allele of rs1048661 and the G allele of rs3825942 were significantly higher in XFS patients than in control subjects (rs1048661: 99.4% versus 55.0%; rs3825942: 99.4% versus 85.3%; p<0.0001). Except for one who had the TG/AG compound genotype, all XFS patients had the TT/GG compound genotype. An almost 250 fold increase in the risk of XFS (p<0.0001; odds ratio: 252.2; 95% confidence interval: 32.7 to more than 1000) was found in patients with the TT/GG compound genotype compared to those without the genotype. There were no significant differences in the genotype and allele frequencies between POAG patients and control subjects. Furthermore, no significant differences were noted in the demographic and clinical features of POAG patients as well as control subjects with and without the TT/GG high-risk compound genotype. CONCLUSIONS: LOXL1 polymorphisms were associated with XFS. However, the frequencies of the polymorphisms differed between Japanese and Caucasian XFS patients. These polymorphisms had no influence on the phenotypic features of POAG patients.

Effect of uncompensated corneal polarization on the detection of localized retinal nerve fiber layer defects.

PURPOSE: To investigate the effect of corneal polarization on the detection of retinal nerve fiber layer (RNFL) defects in an artificial eye using scanning laser polarimetry. METHODS: The model eye was composed of a film with a birefringence magnitude of 80 nm (single-pass retardance) in front of a plastic disc with a radial axis of birefringence, which was partially covered with a strip of black paper. The plastic disc, black paper and the film simulated the RNFL, the RNFL defect and the cornea, respectively. The model eye was located at 25 cm from the lens of the Nerve Fiber Analyzer II (NFA II) or GDx with variable corneal compensator (GDx-VCC). Using NFA II, the retardation of the laser beam was measured with/without the artificial cornea in differently simulated corneal birefringence axes that are 15 degrees nasally downward, and 15 degrees nasally upward. Using a GDx, the model eye with/without cornea was measured with a fixed corneal compensator (GDx-FCC) or GDx-VCC. RESULTS: Using NFA II or GDx-FCC, there were three areas in the RNFL thickness profile where an RNFL defect was detected, undetected and reversed. The mean thickness of the RNFL defects was not different from the mean thickness of RNFL in one model eye using NFA II (p = 0.3). Using GDx-VCC, all RNFL defects were detected in all model eye settings. CONCLUSIONS: The influence of incorrect compensation of the anterior segment birefringence is significant. With an FCC, there were particular locations in the retina where the RNFL defects were not detected. The GDx-VCC is a promising tool in glaucoma diagnosis because it detects RNFL defects in any corneal setting.

Case finding of angle closure glaucoma in public health examination with scanning peripheral anterior chamber depth analyzer.

PURPOSE: Despite the fact that the occurrence of angle closure glaucoma (ACG) or acute primary angle closure (PAC) can be prevented, in many cases, nonphysicians fail to detect them in regular health examinations before their onset. This study was aimed at examining the utility of a newly developed noncontact scanning peripheral anterior chamber depth analyzer (SPAC) in finding eyes at risk of ACG and acute PAC in a public health examination by nonphysicians. METHODS: A total of 535 local residents 40 years old or over were enrolled. In primary screening, nonphysicians use SPAC to determine up to 21 consecutive circumferential measurements of anterior chamber depth (ACD). The subjects were classified into 4 groups on basis of the previously established criteria: group 1: all ACD values above the minimum value of 72% confidence interval (CI); group 2: 1 or more ACD values below the minimum value of 72% or less than 4 ACD values below the minimum value of 95% CI; group 3: 4 or more ACD values below the minimum value of 95% CI; and group 4: no ACD data available. All the subjects from group 3 and those from group 2 or group 4 who were suspected to be at risk of ACG as diagnosed by a glaucoma specialist were subjected to a definitive examination. RESULTS: Fifty-seven (10.7%) subjects were recruited to the definitive examination. The final diagnoses were 1 subject with primary ACG (1.8%), 23 subjects with PAC (40.4%), 15 PAC suspect subjects (26.3%), and 18 subjects (31.6%) had eyes with open angle. All of them were from group 3. CONCLUSIONS: SPAC detected eyes at risk of ACG in a public health examination.

The OPA1 gene polymorphism is associated with normal tension and high tension glaucoma.

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.

Comparison between newly developed scanning peripheral anterior chamber depth analyzer and conventional methods of evaluating anterior chamber configuration.

PURPOSE: To compare the newly developed scanning peripheral anterior chamber depth analyzer (SPAC) with the Van Herick technique, the Shaffer grading system, and ultrasound biomicroscopy (UBM), in terms of accuracy of measurement of peripheral anterior chamber depth (ACD). METHODS: The subjects were well-controlled glaucoma patients who were being treated at the University of Yamanashi Hospital. Ten eyes from each of the 4 groups classified as Shaffer grades 1 to 4 were evaluated by SPAC, the Van Herick technique, and UBM. All measurements were performed independently on the temporal side in a masked fashion. SPAC evaluated ACD consecutively from the pupil center to the limbus at 0.4 mm intervals. UBM measurements were carried out at a depth of 500 mum (angle-opening distance 500) from the scleral spur. A dummy eye was used for evaluating SPAC measurement accuracy. RESULTS: The results of SPAC measurement were well correlated with those of the Van Herick technique and the Shaffer grading system. The SPAC measurement results were also significantly correlated with angle-opening distance 500. The correlation coefficients at distances of 2, 4, 4.8, and 5.6 mm from the pupil center were r=0.68, 0.69, 0.69, and 0.61, respectively, and the P values of all the correlations were less than 0.0001. Study of the dummy eye revealed that SPAC has high accuracy for measuring ACD and that the coefficient variances were less than 1.0% at all measured points. CONCLUSIONS: The results of SPAC measurement correlate well with those of the conventional methods.