Variants in optineurin gene and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma

PURPOSE: To investigate sequence variations in the optineurin (OPTN) gene and their association with TNF-alpha polymorphisms in Japanese patients with glaucoma. METHODS: The OPTN gene was analyzed in blood samples from 629 Japanese subjects. There were 194 patients with primary open-angle glaucoma (POAG), 217 with normal-tension glaucoma (NTG), and 218 with no eye disease (control subjects). The gene was screened for mutations by denaturing high-performance liquid chromatography. Genotyping of three polymorphisms of -308G-->A, -857C-->T, and -863C-->A in the TNF-alpha promoter region was performed. The associations between the genotypes and age, intraocular pressure (IOP), and visual field defects at the time of diagnosis were examined. RESULTS: A possible glaucoma-causing mutation, His26Asp, was identified in 1 of the 411 Japanese patients with glaucoma. A c.412G-->A (Thr34Thr) polymorphism in the OPTN gene was significantly associated with POAG (genotype frequency, P = 0.011; allele frequency, P = 0.003). The frequency of TNF-alpha/-857T and optineurin/412A carriers was significantly higher (P = 0.006) in patients with POAG than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-857T, the optineurin/412A carriers had significantly worse (P = 0.020) visual field scores than the non-optineurin/412A ones. The frequency of TNF-alpha/-863A and optineurin/603A (or Lys98) carriers was significantly higher in patients with POAG (P = 0.008) or NTG (P = 0.027) than in control subjects. Among the patients with POAG who were carriers of TNF-alpha/-863A, the ones with optineurin/603A (or Lys98) had significantly worse (P = 0.026) visual field scores than did those with non-optineurin/603A (or Lys98). CONCLUSIONS: These findings demonstrated that the OPTN gene is associated with POAG rather than NTG in the Japanese. Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-alpha genes that would increase the risk for glaucoma.     

Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients

PURPOSE: To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. RESULTS: The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p=0.0147) and NTG (4/28, 14.2%, p=0.0369) patients, and even in both the POAG and NTG patients combined (12/83, 14.4%, p=0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G > A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G > A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C > T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G > A showed significantly larger cup-to-disc ratios (p=0.0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p=0.0076), and a significantly higher rate of surgery and/or laser history (p=0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. CONCLUSIONS: Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G > A, may be a genetic risk factor for the progression of open- angle glaucoma in this Japanese population.     

角膜厚度与高眼压症及青光眼的眼压

目的 探讨高眼压症、正常眼压性青光眼、原发性开角型青光眼患者及正常人的角膜厚度差异,分析角膜厚度与眼压间的关系,以及角膜厚度的测定对各型青光眼的诊断意见。方法 用超声波角膜测厚仪检测７３例（７３只眼）高眼压症、７９例（７９只眼）正常人的中央角膜厚度,并将其测定结果进行比较。回顾性分析每只青光眼治疗前的最高眼压（Ｇｏｌｄｍａｎｎ）,包括２４ｈ眼压曲线,用Ｅｈｌｅｒ法通过中央角膜厚度对眼压进行校正。结     

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.     

Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma

PURPOSE: As suggested by findings of abnormal responses to posture in patients with normal-tension glaucoma (NTG), cardiovascular autoregulation may also be defective in primary open-angle glaucoma (POAG). PATIENTS AND METHODS: Both 24-hour ambulatory blood pressure monitoring and the head-up tilt test were performed in 17 subjects with NTG and in 13 subjects with high-tension POAG (ht-POAG). These groups were compared with 17 age-matched healthy individuals. Subjects undergoing cardiovascular therapy were excluded. RESULTS: No significant differences in diurnal and nocturnal blood pressure and heart rate were found between the groups. A significant reduction in diurnal heart rate variability was found in NTG (12.1 +/- 2.8 bpm) compared with the ht-POAG (15.0 +/- 2.4 bpm, P < 0.01) and control groups (15.8 +/- 3.0 bpm, P = 0.01]). Nocturnal diastolic blood pressure variability was also reduced in NTG (6.9 +/- 2.2 mm Hg) compared with controls (8.6 +/- 2.3 mm Hg, P < 0.05]) as was heart rate variability (6.3 +/- 1.4 vs 8.3 +/- 2.6 in ht-POAG, P < 0.05), suggesting blunted blood pressure and heart rate modulation in NTG subjects. Spectral analysis of short-term heart rate variability showed a significant reduction of total power in the supine position (1064 +/- 600 in NTG vs 1688 +/- 889 ms2 in controls, P < 0.05]). This was not accompanied either by a physiological reduction in total power or in a high-frequency component during the passive orthostatic stimulus. These differences tend to become more prominent in the clinically more severe forms of NTG (as identified by scores based on the extent of optic disk excavation, visual field damage, and progression of disease). This would suggest a correlation between the extent of autonomic disorder and severity of glaucoma. The alpha index (root-square of low-frequency heart rate to low-frequency blood pressure ratio) was lower in the supine position in NTG subjects (8.1 +/- 3.1 vs 10.6 +/- 3.3 ms/mm Hg in controls, P < 0.05), confirming the reduced baroreflex sensitivity. CONCLUSIONS: The results confirm the hypothesis that dysfunction of autonomic control of the cardiovascular response may be a contributing pathogenetic factor in NTG, inducing a chronic ischemia of the optic nerve.     

Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients

Purpose:To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Methods:Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. Results:The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p = 0.0147) and NTG (4/28, 14.2%, p = 0.0369) patients, and even in both the POAG and NTG patients combined (12/83, 14.4%, p = 0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G > A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G > A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C > T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G > A showed significantly larger cup-to-disc ratios (p = 0.0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p = 0.0076), and a significantly higher rate of surgery and/or laser history (p = 0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. Conclusions:Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G > A, may be a genetic risk factor for the progression of open-angle glaucoma in this Japanese population.     

Different optineurin mutation pattern in primary open-angle glaucoma

PURPOSE: The optineurin gene (OPTN) is the second gene besides MYOC in which mutations have been identified to be associated with primary open-angle glaucoma (POAG). In this study, sequence alterations in the OPTN gene associated with POAG in Chinese subjects were investigated. METHODS: All the coding exons of OPTN were screened, including the intron-exon boundaries, for sequence alterations in a Chinese sample of 119 sporadic patients with POAG and 126 unrelated control subjects by polymerase chain reaction-conformation-sensitive gel electrophoresis and DNA sequencing. RESULTS: Sixteen sequence changes were identified: 3 had been reported (T34T, M98K, and R545Q) and 13 were novel (T49T, E103D, V148V, P199P, T202T, H486R, IVS6-5T-->C, IVS6-10G-->A, IVS7+24G-->A, IVS8+20G-->A, IVS13+21C-->G, IVS15+10G-->A, and IVS15-48C-->A). Among them, only E103D, H486R, V148V, and IVS13+21C-->G were found exclusively in patients with POAG, whereas P199P, T202T, and IVS8+20G-->A were present only in control subjects. The genotype of IVS7+24G-->A showed a significant association with POAG (P = 0.02, Fisher two-tailed exact test) and with and increased cup-to-disc ratio in these patients (P = 0.005, Mann-Whitney test). CONCLUSIONS: The findings in the current study enrich the evidence on the OPTN gene as a causative gene for POAG and suggest a different mutation pattern of OPTN in Chinese than in whites. The wide spectrum of putative mutations detected in this study suggests that both structural and functional disruptions in OPTN may contribute to the pathogenesis of glaucoma.     

SNPs and interaction analyses of noelin 2, myocilin, and optineurin genes in Japanese patients with open-angle glaucoma

PURPOSE: To evaluate the noelin 2 gene as a disease-causing factor for open-angle glaucoma (OAG) and the interactions between the noelin 2 (OLFM2), optineurin (OPTN), and myocilin (MYOC) genes. METHODS: OLFM2 was analyzed in 770 Japanese subjects including 215 patients with elevated intraocular pressure (IOP), 277 with normal IOP, 38 with juvenile open-angle glaucoma, and 240 control subjects. Two single-nucleotide polymorphisms (SNPs) in OPTN (c.412G-->A and c.603T-->A) and one SNP in MYOC (c.227G-->A) were examined. Single genes were investigated by univariate analysis and the gene-gene interactions by logistic regression analysis. Associations between genotypes and clinical characteristics at the time of diagnosis were examined. RESULTS: In OLFM2, 12 sequence variants were identified in 770 Japanese subjects. Arg144Gln (exon 4) was identified in two (0.3%) of the patients and in none of the control subjects. Combinations of OLFM2/317A and OPTN/412A or OLFM2/1281T and OPTN/412A were associated with patients with elevated IOP (P = 0.018 or P = 0.012, respectively). The combination of OLFM2/317G and OPTN/603A was significantly associated with elevated IOP (P = 0.018). No significant association was detected between SNPs in OLFM2 and in MYOC. Patients with normal IOP and with OLFM2/678A+OPTN/412G or OLFM2/1281C+OPTN/412G had significantly worse visual field scores (P = 0.022 or 0.030, respectively). CONCLUSIONS: The Arg144Gln mutation in OLFM2 is a possible disease-causing mutation in Japanese patients with OAG. Common polymorphisms in OLFM2 and OPTN may interactively contribute to the development of OAG, indicating a polygenic etiology.     

Visual performance after photorefractive keratectomy with a 6-mm ablation zone.

PURPOSE: To prospectively examine the effect of photorefractive keratectomy with a 6-mm ablation zone on best-spectacle-corrected visual performance. METHODS: A prospective study was conducted of 164 eyes of 164 patients with an average (+/-SD) of -4.02 +/- 1.74 diopters (range, -0.63 to -8.38 diopters spherical equivalent). Best-spectacle-corrected high-contrast and low-contrast visual acuity (18% Weber contrast) was measured with both natural and dilated pupils. Patients were tested preoperatively and at 3, 6, and 12 months after photorefractive keratectomy. Photorefractive keratectomy was performed with an argon fluoride excimer laser. Fifty-five eyes of 55 patients also underwent astigmatic keratotomy. RESULTS: Twelve months after photorefractive keratectomy, best-spectacle-corrected high-contrast visual acuity with natural pupils showed no significant change from preoperative values; mean (+/-SD) change was 0.004 +/- 0.10 logMAR (t = 0.45, P = .65). Best-spectacle-corrected low-contrast visual acuity with natural pupils was significantly reduced compared to baseline; mean (+/-SD) change was 0.04 +/- 0.13 logMAR (t = 3.3, P = .001). The low-contrast loss was larger (1.5 lines) with dilated pupils; mean (+/-SD) change was 0.13 +/- 0.15 logMAR (t = 9.31, P < .001). Greater losses in dilated low-contrast visual acuity were associated with concurrent astigmatic ketatotomy (t = 2.28, P = .025) and corneal haze of grade 1 or greater (t = 2.71, P = .005). CONCLUSIONS: Reductions in visual performance occur after photorefractive keratectomy with a 6-mm zone. These changes are greatest for low-contrast visual acuity with dilated pupils. Corneal haze and concurrent astigmatic keratotomy are associated with greater losses in low-contrast visual acuity. Best-spectacle-corrected low-contrast visual acuity is a sensitive measure for evaluating visual performance after refractive surgery.     

Two-staged Baerveldt glaucoma implant for childhood glaucoma associated with Sturge-Weber syndrome

PURPOSE: To report the outcome and complications of 10 eyes of 9 children with Sturge-Weber syndrome (SWS) who underwent two-stage insertion of a Baerveldt glaucoma implant (BGI) for glaucoma. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: The authors reviewed the medical records of children under the age of 14 years with SWS who underwent two-stage BGI for glaucoma at two tertiary care referral centers. MAIN OUTCOME MEASURES: Intraoperative and postoperative complications, intraocular pressure (IOP), number of glaucoma medications, visual acuity, and further surgical intervention. RESULTS: Ten eyes of nine patients were included in the study. Ages of the nine patients at time of first stage BGI ranged between 6 weeks and 13 years. With average follow-up of 35 months (range, 10-50), all eyes had adequate IOP control (< or = 21 mmHg) without the need for additional glaucoma surgery. Intraocular pressure was reduced from a mean (+/- standard deviation) of 24.8 +/- 6.2 mmHg preoperatively to 16.9 +/- 2.3 mmHg at last follow-up visit (P = 0.001). The number of medications used for control of glaucoma was reduced from a mean (+/- standard deviation) of 1.8 +/- 1.0 preoperatively to 1.1 +/- 1.4 at last follow-up visit (P = 0.2). One eye had serous choroidal effusions with overlying serous retinal detachment that resolved spontaneously after 7 days with no permanent visual loss, and one eye had low choroidal effusion that lasted 4 days. There were no intraoperative or postoperative suprachoroidal hemorrhages. At last follow-up, visual acuity had improved by one or more lines in all patients in whom vision was measurable. CONCLUSIONS: Two-stage BGI surgery appears to be a safe and effective treatment for refractory glaucoma in children with SWS.     

Distribution of optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States

PURPOSE: Previous studies have suggested that Optineurin (OPTN) sequence variants contribute to low-tension glaucoma (LTG) in ethnically homogeneous populations. The purpose of this study is to evaluate the prevalence of OPTN sequence variants in an ethnically diverse population of LTG patients from the United States, and to describe the phenotype of patients with OPTN sequence variants preferentially found in LTG patients. METHODS: Genomic DNA purified from 67 LTG patients was screened for DNA sequence variants located in the exons and flanking introns of the OPTN gene using high-performance liquid chromatography analysis and direct genomic DNA sequencing. Eighty-six primary open-angle glaucoma probands and 100 control patients were also analyzed. RESULTS: Nine OPTN DNA sequence variants were identified in this patient population including the 2 previously identified heterozygous nonsynonymous single-nucleotide polymorphisms in exons 4 and 5. Four LTG patients with severe disease and positive family history of glaucoma, were found to have DNA sequence changes not found in primary open-angle glaucoma probands or control individuals including the previously reported E50K variation. CONCLUSIONS: The results of this study support the rare association of OPTN sequence variants with familial forms of LTG. The E50K mutation seems to be associated with a severe form of LTG, and although rare, the identification of this sequence variant in patients at risk may help direct appropriate therapy.     

Refractive change after dorzolamide use in patients with primary open-angle glaucoma and ocular hypertension.

The purpose of this study was to evaluate refractive and anterior chamber depth changes after short-term dorzolamide use in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study was prospective and non-comparative and included 34 patients. Baseline refraction and anterior chamber depth were compared to the refraction and anterior chamber depth 14 days after commencing dorzolamide to determine if refraction or anterior chamber depth had been affected. Before dorzolamide use, the mean refractive error was -0.88 +/- 3.53 D (+/-SD). The mean refractive error was -0.94 +/- 3.65 D (+/-SD) two hours post-dose after 14 days of dorzolamide use, which was not significantly different (P = 0.50). The mean pre-treatment anterior chamber depth was 3.088 +/- 0.385 mm (+/-SD), which did not differ significantly from the post-treatment anterior chamber depth mean of 3.092 +/- 0.389 mm (+/-SD) (P = 0.88). The results of the study show that refraction and anterior chamber depth are not significantly altered by short-term dorzolamide use in patients with POAG and OH with no history of previous dorzolamide use.     

Molecular genetic analysis of optineurin gene for primary open-angle and normal tension glaucoma in the Japanese population

PURPOSE: To determine whether mutations in the optineurin (OPTN) gene are associated with the incidence of primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese. METHODS: Eighty-nine unrelated Japanese patients with POAG and 65 unrelated patients with NTG were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and thirteen exons of the OPTN gene were amplified by polymerase chain reaction (PCR) and directly sequenced. RESULTS: Sequence alterations in exons 4 (His26Asp), 5 (Met98Lys), and 16 (Arg545Gln) were found. The His26Asp and Arg545Gln mutations were not detected in 100 ethnically matched controls. The frequency of the missense Met98Lys variant was higher in the POAG and NTG groups than in the control group (16.9% versus 5%, 15.4% versus 5%; P = 0.009 and P = 0.029, and odds ratio 3.85 and 3.45, respectively, for the dominant effect of the OPTN A allele). Polymorphisms in exons 4 and 12, and in introns 6 and 7 were also detected. CONCLUSIONS: The association of the allelic variation (Met98Lys) in the OPTN gene and the prevalence of POAG and NTG in unrelated Japanese patients suggest that they are involved in the pathogenesis of POAG and NTG.     

Analysis of optineurin (OPTN) gene mutations in subjects with and without glaucoma: the Blue Mountains Eye Study

BACKGROUND: The optineurin (OPTN) gene has been reported to possess both causal as well as risk-associated alleles for open-angle glaucoma. However, these findings have so far only been reported in family and clinic based studies. The aim of this study was to investigate the spectrum of mutations and gene variants in OPTN that might be present in people with glaucoma from a population-based study, the Blue Mountains Eye Study (BMES). METHODS: A total of 108 subjects of Caucasian origin were identified at baseline in the BMES as having open-angle glaucoma. Blood samples were available from 27 of these, of whom 18 had high-tension glaucoma and the remaining nine had normal-tension glaucoma. Ninety-four control subjects were chosen at random from the BMES, who satisfied the criteria of not having glaucoma at baseline and were over age 70 years. The 13 coding exons (exons 4-16 inclusive) and their intron-exon boundaries of OPTN were screened by the use of single-strand conformation polymorphism. Samples exhibiting mobility shifts were di-deoxy nucleotide sequenced. The M98K polymorphism was additionally screened using the restriction enzyme Stu1 in all cases and controls in this study. RESULTS: The M98K risk-associated alteration was identified in 2/18 (11%) subjects with high-tension glaucoma, 0/9 subjects (0%) with normal-tension glaucoma and 3/94 (3.2%) controls. However, association of this variant with disease was not significant (P = 0.2 for each phenotype) for either high-tension glaucoma or normal-tension glaucoma. A novel variant (P556P in exon 16) was found in one subject with open-angle glaucoma and a previously described variant (exon 7) was found in a further subject with open-angle glaucoma and in one control. No other OPTN variants were identified in this study cohort. CONCLUSIONS: Cross-sectional analysis from baseline observations of the BMES suggested that the M98K risk-associated allele appeared at a higher prevalence in high-tension glaucoma compared with controls, although this finding was not statistically significant.     

Systemic arterial stiffness in glaucoma patients

PURPOSE: To investigate systemic arterial stiffness in glaucoma patients. SUBJECTS AND METHODS: One hundred and forty glaucoma patients and 121 control subjects were enrolled in the study. Among these subjects, 51 glaucoma patients [normal-tension glaucoma (NTG), 31; primary open angle glaucoma or ocular hypertension (POAG/OH): 20] and 61 control subjects without glaucoma, who presented with no risk factors for arteriosclerosis, were extracted for further analysis of systemic arterial stiffness by glaucoma type. Subjects presenting with risk factors for arteriosclerosis were classified into group A, and those presenting with no risk factors were classified into group B. Brachial-ankle pulse wave velocity (baPWV), a marker of systemic arterial stiffness, was determined with a volume-plethysmographic apparatus. The correlation between baPWV and mean deviation obtained from Humphrey Field Analyzer program 30-2 test was compared between 13 each of age-matched and sex-matched NTG and POAG/OH patients. RESULTS: There was a significant difference in baPWV between groups A and B [P<0.0001; 1748+/-393 cm/s (group A) and 1467+/-282 cm/s (group B)]. The baPWVs of control, NTG patients, and POAG/OH patients with no risk factors showed no significant difference. baPWV was positively correlated with age in all the 3 groups, but there were no significant differences among the 3 groups. baPWV tended to be negatively correlated with mean deviation in NTG patients (r2=0.25, P=0.08); in contrast, no correlation was observed in POAG/OH patients. CONCLUSION: Systemic arterial stiffness seems not to be strongly associated with glaucoma.     

The role of the Met98Lys optineurin variant in inherited optic nerve diseases

AIMS: To investigate the role of the common OPTN Met98Lys variant as a risk allele in open-angle glaucoma (OAG), autosomal dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON). METHODS: The presence of the Met98Lys variant was determined in a total of 498 (128 with normal-tension glaucoma (NTG)) patients with OAG, 29 patients who had myocilin-related OAG, 101 patients from ADOA pedigrees, 157 patients from LHON pedigrees and 218 examined OAG age-matched normal controls. RESULTS: 17 of 218 (7.8%) controls had the Met98Lys variant. 28 (5.6%) patients with OAG were Met98Lys positive. More Met98Lys carriers were found in the NTG group than in the high-tension glaucoma (HTG) group (p = 0.033). However, no significant difference was observed between the NTG and control cohorts (p = 0.609). Two MYOC mutation carriers were found to have the variant. The variant was found in 1 of 10 pedigrees with ADOA and in 8 of 35 pedigrees with LHON. CONCLUSION: Data from this study do not support a strong role for the OPTN Met98Lys variant in glaucoma, ADOA or LHON. However, a weak association was observed of the variant with NTG compared with that with HTG. Meta-analysis of all published data on the variant and glaucoma confirmed that the association, although weak, is highly statistically significant in the cohort with glaucoma versus controls.     

Association of apolipoprotein E polymorphisms with normal tension glaucoma in a Chinese population

PURPOSE: To evaluate the role of apolipoprotein E (APOE) polymorphisms in primary open angle glaucoma (POAG). METHODS: A cohort of 400 unrelated Chinese POAG patients was examined, including 294 cases of high tension glaucoma (HTG) and 106 with normal tension glaucoma (NTG). Also studied were 300 unrelated Chinese control subjects. The genotypes of the APOE polymorphisms in exon 4 and in the promoter at positions -491, -427, and -219 were determined by polymerase chain reaction and restriction endonuclease analysis. Frequencies of the genotypes were compared between patients and controls by chi test or Fisher exact test. The association of APOE polymorphisms with POAG phenotypes including age at diagnosis, intraocular pressure (IOP) at diagnosis, highest IOP, cup-disc ratio, and visual field score was investigated by the Kruskal-Wallis test. RESULTS: No significant difference was detected in the frequencies of APOE promoter polymorphisms between POAG patients and control subjects (P>0.0125). For the exon 4 polymorphism, when compared with control subjects, the frequency of epsilon 4 carriers was significantly lower in patients with NTG (P=0.008; odds ratio=0.36, 95% confidence interval=0.17, 0.79) but not in HTG (P=0.07). Compared with -219TT, the -219G carriers had a significant higher age at diagnosis (P=0.0046). No significant association was found between other APOE polymorphisms and POAG phenotypes (P>0.07). CONCLUSIONS: Our findings suggest that the APOE epsilon 4 allele confers a protective effect against NTG, whereas the APOE promoter polymorphisms do not contribute to POAG risk. However, the APOE -219G carriers tended to have later-onset POAG.     

Central corneal thickness of normal tension glaucoma patients in Japan

PURPOSE: To compare central corneal thickness (CCT) of patients with normal tension glaucoma (NTG) with that of age-matched normal subjects, patients with open-angle glaucoma (POAG) and ocular hypertension (OH) subjects in Japan. METHODS: Central corneal thickness was measured in 79 NTG, 61 POAG, 73 OH, and 50 normal subjects with an ultrasonic pachymeter. One eye for 1 subject randomly selected in each group was used for inter-group comparison. The relationship between CCT and the maximum intraocular pressure (IOP) measured by Goldmann applanation tonometer with no ocular hypotensive medication (NTG, OH, and normal subjects) or under medication (POAG patients) was analyzed. RESULTS: The CCT of OH subjects (582 +/- 32 microm; mean +/- SD) was significantly greater than that of the other groups (P <.001), while no difference was seen in CCT among normal (552 +/- 36 microm), NTG (548 +/- 33 microm) and POAG (550 +/- 33 microm) subjects. In normal subjects, CCT and the maximum IOP were significantly correlated but the correlation coefficient was small (r = 0.420, P <.05). CONCLUSIONS: Central corneal thickness shows no significant difference among NTG, POAG, and normal subjects in Japan, while it is significantly greater in OH subjects. The CCT has little influence on the diagnosis of NTG in Japan.     

Long-term follow-up of trabeculectomy without antimetabolites in patients with uveitis

PURPOSE: To determine the long-term success rate after trabeculectomy without antimetabolites in patients with uveitis. METHODS: Review of data from all patients with uveitis who underwent trabeculectomy for uncontrolled intraocular pressure secondary to intraocular inflammation between May 1990 and December 1994. Results were compared with those from a group of patients with primary open-angle glaucoma matched for sex and surgeon. RESULTS: The uveitis group consisted of 32 eyes (20 patients). Maximum control of intraocular inflammation was achieved for a minimum of 2 months before surgery. Mean (+/-SD) age was 40.0 +/- 12.5 years (range, 14 to 67 years), with a median (+/-SE) follow-up of 53.0 +/- 1.8 months (range, 33 to 84 months). The primary open-angle glaucoma group consisted of 33 eyes (23 patients), with a mean age of 62.0 +/- 13.7 years (range, 26 to 81 years) and a median follow-up of 63.0 +/- 12.0 months (range, 34 to 299 months). The overall 5-year success rate (intraocular pressure < or =21 mm Hg with or without topical medication) for the uveitis group was 78% compared with 82% for the primary open-angle glaucoma group (P = .7). The absolute 5-year success rate (intraocular pressure < or =21 mm Hg with no medication) for the uveitis group was 53% compared with 67% for the primary open-angle glaucoma group (P = .87). CONCLUSIONS: In the absence of other risk factors, such as Afro-Caribbean race and previous intraocular surgery, and with adequate preoperative control of inflammation, trabeculectomy without antimetabolites may be considered the primary surgical procedure for increased intraocular pressure in patients with uveitis.