Reduced-serum vitamin C and increased uric acid levels in normal-tension glaucoma.

BACKGROUND: Vitamin A, B(9), C, E, and uric acid are well-known antioxidants and may prevent age-related eye disorders. The aim of the present study was to investigate the levels of antioxidant vitamins, A, B(9), C, E, and antioxidative substance, uric acid in the serum of Japanese patients with normal-tension glaucoma and compare the results with normal controls. METHODS: All subjects with suspicion of primary open-angle glaucoma who came to the glaucoma subspeciality clinic of Keio University Hospital were enrolled in this study. Sixty patients (28 males, 32 females; mean age +/- standard deviation: 59.9 +/- 9.8 years) with newly diagnosed primary open-angle glaucoma patients were consecutively enrolled in this study. After the diagnosis of primary open-angle glaucoma, the patients underwent 24-h IOP measurements. Forty-seven newly diagnosed consecutive normal-tension glaucoma patients (18 males, 29 females; mean age +/- standard deviation: 59.5 +/- 10.2 years) were enrolled in this study. The control subjects were recruited from subjects who came to the clinic for annual refractive check-up. The 44 consecutive control subjects of the current study, (16 males, 28 females; 62.7 +/- 14.8 years) did not have any ocular diseases. The serum levels of vitamins A, B(9), C, E, and uric acid were measured. The values were compared between the normal-tension glaucoma and control groups by the Mann-Whitney U test. RESULTS: Serum levels of vitamin C were significantly lower in normal-tension glaucoma patients than in normal healthy controls (P = 0.04; normal-tension glaucoma; 4.6 +/- 4.0 microg/ml control; 6.3 +/- 3.9 microg/ml). Uric acid level was significantly higher in normal-tension glaucoma patients than in controls (P = 0.01; normal-tension glaucoma; 5.8 +/- 1.5 mg/dl control; 4.9 +/- 1.4 mg/dl). No statistically significant difference was seen in vitamin A (P = 0.41; normal-tension glaucoma; 82.1 +/- 26.7 microg/dl control; 77.1 +/- 30.1 microg/dl), B(9) (P = 0.37; normal-tension glaucoma; 8.7 +/- 4.3 ng/ml control; 8.0 +/- 3.1 ng/ml)and E (P = 0.83; normal-tension glaucoma; 1.5 +/- 0.6 control; 1.5 +/- 0.6) levels between normal-tension glaucoma and control groups. CONCLUSION: Normal-tension glaucoma patients had lower serum levels of vitamin C and increased levels of uric acid. These observations may pave the way for possible alternative treatment for normal-tension glaucoma.

Diagnosis of steroid-induced glaucoma after photorefractive keratectomy.

PURPOSE: To report steroid-induced glaucoma after photorefractive keratectomy (PRK). METHODS: A 50-year-old Japanese woman was referred for endstage glaucoma 9 months after PRK. Topical fluorometholone 0.1% was administered for corneal subepithelial haze in both eyes for 9 months after PRK. Pneumatic non-contact tonometry values of intraocular pressure (IOP) remained normal (range: 11 to 17 mmHg), until she was diagnosed with end-stage steroid-induced glaucoma with extensive restriction in visual fields. At the patient's initial examination in our hospital, IOP measured by Goldmann applanation tonometry was 34 mmHg in the right eye and 32 mmHg in the left eye, but the estimated IOP as corrected by central corneal thickness measurement was >40 mmHg in both eyes. RESULTS: The patient underwent uneventful bilateral trabeculectomies, resulting in reduction of IOP to <10 mmHg in both eyes. CONCLUSIONS: The underestimation of IOP after PRK led to advanced visual field loss. Careful evaluation of IOP, optic disc, and visual field tests are indispensable to avoid such a devastating outcome after PRK.

Microcirculation in eyes after rhegmatogenous retinal detachment surgery.

PURPOSE: To investigate the tissue blood flow in the neuroretinal rim of the optic disk and macula after rhegmatogenous retinal detachment (RRD) surgery. METHODS: Tissue blood flow in the neuroretinal rim of the optic disk and macula was measured with the Heidelberg retina flowmeter in 53 eyes of 53 patients who had undergone successful surgery for unilateral RRD. Patients were divided into three groups; those who had the RRD treated by conventional encircling scleral buckling (group E), by local buckling (group L), and by primary vitrectomy (group V). Blood flow measurements were made more than 6 months after surgery in a 10 degrees x 2.5 degrees area of the superior and inferior margins of the neuroretinal disk rim and of the superior and inferior macula area. The mean blood flow (MBF) and the ratio of the MBF in the affected eye to the healthy fellow eye (a/f ratio) were compared among the three groups. The influence of several clinical factors on the MBF was also investigated. RESULTS: The MBF rate and mean a/f ratios of the MBF of the three groups were not significantly different. Multiple regression analysis revealed that the averaged MBF both at superior and inferior disk rims was significantly correlated with only the gas tamponade procedure. CONCLUSIONS: The ocular microcirculation is normal 6 months after scleral buckling or vitrectomy for RRD. However, the use of gas tamponade might have a subclinical adverse effect on the circulation in the neuroretinal disk rim.

Association between open-angle glaucoma and gene polymorphism for heat-shock protein 70-1.

PURPOSE: Heat-shock proteins (HSPs) or antibodies against them may contribute to glaucomatous optic neuropathy. We investigated the associations of HSP70-1 polymorphisms with open-angle glaucoma (OAG) in a Japanese population. METHODS: In 241 normal Japanese controls and 501 Japanese OAG patients, including 211 with primary open-angle glaucoma (POAG) and 290 with normal-tension glaucoma (NTG), two single-nucleotide polymorphisms, A-110C and G+190C, of HSP70-1 were identified by using an Invader assay and polymerase chain reaction-restriction fragment length polymorphism, respectively. Genotype distributions were compared between controls and OAG patients. Age at diagnosis, untreated maximum intraocular pressure, and visual field defects at diagnosis were examined for associations with the polymorphisms. RESULTS: Distribution of the A-110C genotype (AA versus AC+CC) differed significantly between controls and OAG patients (P = 0.007), POAG patients (P = 0.007), or NTG patients (P = 0.032). The genotype distribution of the G+190C polymorphism did not differ significantly between the controls and any patient group. No significant differences in the clinical characteristics of the patients were detected between genotype-defined groups by logistic regression analysis. CONCLUSION: The A-110C polymorphism of HSP70-1 may be associated with OAG pathogenesis in Japanese patients.

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.

Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma.

PURPOSE: The human trabecular meshwork and ciliary body, which express beta-adrenergic receptors (ADRB1 and ADRB2), control aqueous humor dynamics. We investigated associations of ADRB polymorphisms with open-angle glaucoma (OAG), because ADRB gene polymorphisms alter receptor function. METHODS: We studied 240 Japanese controls and 505 Japanese OAG patients including 211 with primary open-angle glaucoma (POAG), and 294 with normal-tension glaucoma (NTG). Associations of four polymorphisms (Ser49Gly and Arg389Gly in the ADRB1 gene; Arg16Gly and Gln27Glu in the ADRB2 gene) were compared between patients and controls. Age, intraocular pressure (IOP), and visual field defects at diagnosis were examined for associations with polymorphisms. RESULTS: The Arg389Gly polymorphism in the ADRB1 gene showed significantly different allele and genotype frequencies in patients with NTG than in controls (p = 0.004 and 0.006, respectively). Other polymorphisms did not show a significant frequency difference. In POAG patients, carriers of Gly16 in the ADRB2 gene were significantly younger at diagnosis than noncarriers (p<0.001). The IOP at diagnosis was significantly higher in OAG patients carrying 27Glu in the ADRB2 gene than in patients without this allele (p<0.001). Clinical characteristics of OAG patients did not differ significantly in relation to other polymorphisms. CONCLUSIONS: Certain polymorphisms of the ADRB1 and ADRB2 genes influence the pathophysiology of OAG in Japanese patients.

Mitochondrial DNA mutations with Leber's hereditary optic neuropathy in Japanese patients with open-angle glaucoma.

PURPOSE: Abnormal optic disc excavations are found in patients with Leber's hereditary optic neuropathy (LHON). The purpose of this study was to determine whether heteroplasmy for the major three LHON mutations or for the rare LHON mutations are risk factors for open-angle glaucoma. METHODS: Blood samples from 835 Japanese subjects were screened with the Invader assay for ten LHON-associated mutations: three major mutations (G3460A, G11778A, T14484C) and seven rare mutations (T9101C, G9804A, C14482A, C14482G, G14459A, T14498C, and A14510G). Of the 835 subjects, 241 were patients with primary open-angle glaucoma (POAG), 310 were patients with normal-tension glaucoma (NTG), and 284 were healthy controls. RESULTS: Five POAG patients and three NTG patients had one of five mutations, C9099A, T9101G, T9101C, G9804A, or G11778A, but none of these patients had LHON. The C9099A (Ile191Met) and T9101G (Ile192Ser) mutations were novel and identified within the probes by lack of signal in the assay. Two patients with the G11778A mutation showed heteroplasmy, with 15% mutant mtDNA in the male patient and 80% in the female patient. The remaining LHON-associated mutations were not detected in any of the subjects. A case-control study did not show a significant difference (P = 0.099): eight potentially disease-associated variants in 551 patients versus zero variants in the 284 controls. CONCLUSIONS: Rare LHON-associated mitochondrial DNA mutations were found in Japanese patients with open-angle glaucoma (OAG). However, whether mitochondrial DNA mutations are risk factors for OAG is still open to question.

Genetic polymorphisms in the angiotensin II receptor gene and their association with open-angle glaucoma in a Japanese population.

PURPOSE: The local renin-angiotensin system (RAS) is present in the ciliary body and plays a role in regulating aqueous humor dynamics and thus intraocular pressure (IOP). The purpose of this study was to determine whether gene polymorphisms in the RAS increase the risk of development of glaucoma in the Japanese. METHODS: A case-control study was performed in 698 Japanese subjects: 190 patients with primary open-angle glaucoma (POAG), 268 patients with normal-tension glaucoma (NTG), and 240 normal subjects. Ten polymorphisms in seven genes-AGT/Thr174Met and AGT/Met235Thr; REN/I8-83G-->A; ACE/insertion(I)-deletion(D); CMA/-1930A-->G; AGTR1/-731T-->G, AGTR1/-521C-->T, and AGTR1/1166A-->C; AGTR2/3123C-->A; and CYP11B2/-344T-->C were examined. The age, IOP, and visual field defects, all at diagnosis, were examined to determine whether they were associated with the polymorphisms. The effects of oral angiotensin II receptor blocker (ARB) on IOP were examined in association with the AGTR1 and AGTR2 polymorphisms in 20 normal subjects. RESULTS: Of the 10 polymorphisms, the AGTR2/3123C-->A polymorphisms had a significantly different distribution in female patients with NTG; the frequency of the CA+AA genotypes was significantly higher than in female control subjects (P = 0.0095 for CC versus CA+AA). Although no significant difference was seen in the clinical characteristics of female patients with NTG who carried the AGTR2/3123C-->A genotype, patients with CC in the AGTR2 gene had significantly worse visual field scores if they carried ACE/ID+DD (i.e., D carriers; P = 0.012). ARB significantly lowered IOP in normal subjects, but the male subjects with the AGTR2/3123A genotype had significantly less lowering of IOP than those with the C genotype (P = 0.014). CONCLUSIONS: Angiotensin II receptor gene polymorphisms may be associated with the risk of glaucoma in the Japanese population.

Association between glaucoma and gene polymorphism of endothelin type A receptor.

PURPOSE: Endothelin 1 (ET-1), a potent vasoconstrictor, may affect regulation of intraocular pressure and ocular vessel tone. Thus, ET-1 and its receptors may contribute to development of glaucoma. We investigated whether gene polymorphisms of ET-1 (EDN1) and its receptors ETA (EDNRA) and ETB (EDNRB) were associated with glaucoma phenotypes and clinical features. METHODS: We studied 224 normal Japanese controls and 426 open angle glaucoma (OAG) patients including 176 with primary open angle glaucoma (POAG) and 250 with normal tension glaucoma (NTG). Nine single nucleotide polymorphisms were detected among the participants using the Invader assay; four for EDN1 (T-1370G, +138/ex1 del/ins, G8002A, K198N), four for EDNRA (G-231A, H323H, C+70G, C+1222T), and one for EDNRB (L277L). Genotype distributions were compared between normal controls and OAG. Age at diagnosis, untreated maximum intraocular pressure (IOP), and visual field defects at diagnosis were examined for association with polymorphisms. RESULTS: Of the 9 polymorphisms, genotype distributions showed no significant differences between OAG patients and controls adjusted by age. The GG genotype of EDNRA/C+70G was associated with worse visual field defects in NTG patients (p=0.014; Mann-Whitney U test, and p=0.027; logistic regression analysis). CONCLUSIONS: The polymorphism of EDNRA/C+70G may be related to NTG risk factors.

Effect of topical unoprostone isopropyl on optic nerve head circulation in controls and in normal-tension glaucoma patients.

PURPOSE: To evaluate the effect of unoprostone isopropyl on microcirculation in the optic nerve head (ONH) of controls and patients with normal-tension glaucoma (NTG). METHODS: Thirty healthy volunteers were randomly placed in a placebo group or a control group. For ten NTG patients, one eye was selected to receive the placebo drops and the contralateral eye received the unoprostone in a masked fashion. In both studies, the intraocular pressure (IOP) and the parameters of the blood hemodynamics of the ONH were obtained before and at 1 and 2 h after the instillation. Blood flow measurements were made with a scanning laser Doppler flowmeter. RESULTS: In both control subjects and NTG patients, the changes in the IOPs after the instillation of either unoprostone or the placebo were not significant because almost all of the NTG patients had IOPs lower than 15 mmHg. Although the hemodynamic parameters were not significantly changed in the placebo-treated eyes of the controls, the eyes of the controls treated with unoprostone had mean blood velocity and flow values that were significantly higher than the baseline values 1 and 2 h after instillation (P < 0.01). The velocity values of the controls treated with unoprostone were significantly higher than in those controls receiving the placebo at 2 h postinstillation (P = 0.027). The values for the three circulation parameters (volume, velocity, flow) were significantly higher than the baseline values after instillation in the eyes of the NTG patients treated with unoprostone (P < 0.05). In contrast, none of these parameters was significantly different from the baseline in the eyes of NTG patients treated with placebo. CONCLUSIONS: These results showed that unoprostone significantly increased microcirculation in the ONH in control subjects and in NTG patients without reducing the IOP significantly.

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.

Novel MYOC gene mutation, Phe369Leu, in Japanese patients with primary open-angle glaucoma detected by denaturing high-performance liquid chromatography.

PURPOSE: To screen for mutations in the MYOC gene in Japanese patients with primary open-angle glaucoma (POAG) using denaturing high-performance liquid chromatography (DHPLC). PATIENTS AND METHODS: Blood samples were collected from 171 patients with POAG and 100 controls from seven institutions in Japan. For high-throughput analysis, seven exonic regions were amplified by polymerase chain reaction using DNA pooled from three patients; each DNA pool was then analyzed chromatographically. For analysis of a small number of samples, 7 exonic regions were amplified separately but simultaneously with annealing at 58 degrees C in each patient and then chromatographed, using 7 wells of the same 96-well plate per sample. When chromatographic patterns were abnormal by either method, the PCR products of the individual samples were sequenced. RESULTS: Four glaucoma-causing mutations were identified in five POAG patients (2.9%). One missense mutation, Phe369Leu, is new; and three others, Ile360Asn, Ala363Thr, and Thr448Pro, have been reported in Japanese patients. Phe369Leu was associated with adult onset POAG. CONCLUSIONS: Mutations in the MYOC gene were demonstrated chromatographically in 2.9% of our Japanese POAG patients. The use of pooled DNAs with DHPLC analysis is a time- and labor-saving technique. All mutations detected appear to be specific to Japanese patients.

[Long-term efficacy and safety of combined topical antiglaucoma therapy--timolol & unoprostone vs. betaxolol & unoprostone].

PURPOSE: To evaluate long-term efficacy and safety of treatment combining topical beta-blockers and isopropyl unoprostone in primary open-angle glaucoma and normal-tension glaucoma patients. METHODS: A prospective, open-label, parallel-group clinical comparison trial was performed to evaluate efficacy and safety of treatment combining 0.5% betaxolol and 0.12% isopropyl unoprostone (B&U) or 0.5% timolol and 0.12% isopropyl unoprostone (T&U). Forty eyes of 40 patients, which were matched in the aging and the stage of glaucomatous visual field defect, were studied. Twenty patients were treated with B&U and the other twenty patients with T&U twice daily for 24 months. Goldmann intraocular pressure(IOP), Humphrey automated perimetry, blood pressure, heart rate, and peak flow were done every six months in each group. RESULTS: In the B&U treatment group, mean IOP was 21.2 mmHg at baseline and 18.3 mmHg(p < 0.005) after 2 years, and in the T&U treatment group it was 21.1 mmHg at baseline and 17.9 mmHg (p < 0.001) after 2 years. The cases in which MD value decreased over 2 dB were one in the B&U treatment group and three in the T&U treatment group. The average MD value was significantly improved from -7.40 dB to -5.90 dB after 2 years with B&U treatment(p < 0.05), but there was no difference with the T&U treatment. None of the patients stopped combined therapy because of side effects, though heart rate was significantly reduced only in T&U treatment group. CONCLUSION: Both combined treatments were effective for IOP reduction in glaucoma patients, and the data from the B&U treatment group suggested that B&U was more effective in maintaining visual field than T&U.

[A comparison of visual field and optic disc appearance depending on the peak intraocular pressure in patients with normal-tension glaucoma].

PURPOSE: To investigate the clinical differences between the two groups depending on the peak intraocular pressure(IOP) in patients with normal-tension glaucoma(NTG). METHODS: We studied 96 eyes of 48 NTG patients who were hospitalized for diurnal IOP measurement. Then we selected the eye whose peak IOP was higher than the other, or the right eye if the peak IOP of both eyes was equal. We divided these eyes into a "high-teen" group (peak IOP > or = 16 mmHg) and a "low-teen" group(peak IOP < or = 15 mmHg). We compared these two groups by age, gender, refraction, IOP, visual field defect, optic disc appearance, and tomograph. We used a Humphrey C 30-2 program to estimate the visual field defect and classified the optic disc into four types according to Nicolela's criteria. 22 eyes were imaged with Heidelberg Retina Tomograph (HRT) to obtain topographic parameters of the optic disc. RESULTS: There were no significant differences in age, gender, refraction, optic disc appearance, or tomograph between two groups. The trough and variation range of diurnal IOP were significantly larger in the high-teen group(p < 0.01). The value of mean deviation(MD) given by STATPAC was statistically lower in the high-teen group(p < 0.01). CONCLUSIONS: In patients with NTG, the visual field damage tended to be greater in the high-teen group than in the low-teen group. We surmise that the IOP might influence the progression of visual field defect in NTG.

Selective laser trabeculoplasty for elevated intraocular pressure following subtenon injection of triamcinolone acetonide.

PURPOSE: To report on the efficacy of selective laser trabeculoplasty (SLT) for elevated intraocular pressure (IOP) following subtenon injection of triamcinolone acetonide. METHOD: SLT was performed on four of 148 eyes in which IOP was elevated after a subtenon injection of triamcinolone acetonide and could not be maintained within normal limits by conventional medications. Postoperative IOP and relative reduction of IOP were evaluated. RESULTS: IOP was reduced in three eyes to within the normal range without any medications six months after SLT alone, but trabeculotomy was performed on one eye. Percentage reduction in IOP after SLT was 21.6% at one month, 45.0% at three months, and 52.7% at nine months. CONCLUSION: SLT may be effective in reducing elevated IOP following subtenon injection of triamcinolone acetonide and should be considered before glaucoma surgery.

Trabeculectomy with or without intraoperative sub-tenon injection of triamcinolone acetonide in treating secondary glaucoma.

PURPOSE: To investigate the efficacy of intraoperative sub-Tenon injection of triamcinolone acetonide (TA) in increasing the success rate of trabeculectomy for the treatment of secondary glaucoma. DESIGN: Prospective randomized controlled clinical trial. METHODS: Fifty-three consecutive eyes scheduled for trabeculectomy were randomly allocated in an institutional setting. In the study group (n = 26), TA was injected in the sub-Tenon at the conclusion of the surgery. In the control group (n = 27) surgery was completed without TA injection. Surgical success was defined as a complete success if the intraocular pressure (IOP) was 21 mm Hg or less with an IOP reduction of greater than or equal to 20% without any antiglaucoma medication. Success rates in both groups were compared using Kaplan-Meier survival curves and the log-rank test. The morphologic characteristics of the filtering blebs were evaluated using the Indiana Bleb Appearance Grading Scale. RESULTS: Fifty-three eyes completed the study (26 in the study group and 27 in the control group), with a follow-up of 12 months. Complete success rates were 65.4% for the study group and 63.0% for the control group (P = .77) at 12 months. The morphologic characteristics of the filtering blebs and postoperative complications were similar in the study and the control eyes (P > .40). IOP measurements in both groups were similar at all visits (P > .05). CONCLUSIONS: Trabeculectomy with intraoperative sub-Tenon injection of TA for the treatment of secondary glaucoma neither increased the intermediate-term success rate nor decreased postoperative complications.

Lead accumulation as possible risk factor for primary open-angle glaucoma.

We evaluated the association between hair lead concentrations and primary open-angle glaucoma. Ninety-eight Japanese patients (40 males, 58 females; average age 57.6 ± 10.8 years) with primary open-angle glaucoma and control subjects (131 males, 114 females; average age 56.0 ± 12.8 years) were recruited in this study. Hair lead levels were measured by inductively coupled plasma mass spectrometry. Hair lead concentrations between primary open-angle glaucoma and control groups were compared using Mann-Whitney U test. As a subgroup analysis, we compared hair lead concentrations between low-tension glaucoma, high-tension glaucoma, and control groups using one-factor analysis of variance. Lead accumulation levels were significantly higher in the female subjects with primary open-angle glaucoma compared to the control group (P=0.03). Lead accumulation levels were significantly higher in female patients with low intraocular pressure compared to control group 2 (P=0.02). A higher hair lead level, which reflects the total body burden of lead, was observed to be associated with primary open-angle glaucoma in females especially with low-tension glaucoma. Accumulation of lead may be an unrecognized risk factor of non-pressure-dependent glaucomatous optic neuropathy.

Reduced choroidal blood flow can induce visual field defect in open angle glaucoma patients without intraocular pressure elevation following encircling scleral buckling.

PURPOSE: To determine the cause of the progressive glaucomatous visual field defects in three patients after an encircling scleral buckle for a rhegmatogenous retinal detachment (RRD). METHODS: Scanning laser Doppler flowmetry and visual field tests were performed on three cases with unilateral progressive visual field defect after an encircling scleral buckling for a RRD. Similar measurements were made after the buckle was removed. RESULTS: After implanting the scleral buckle, the intraocular pressure was normal and chamber angle was open. The blood flow in the neuroretinal rim of the optic disk was lower than that in the healthy fellow eye. After removing the buckle, the blood flow improved to normal levels and a further worsening of the visual field was not detected. CONCLUSIONS: These results suggest that an encircling scleral buckle may impair choroidal circulation and lead to visual field defects similar to eyes with normal tension glaucoma.

Decreased blood flow at neuroretinal rim of optic nerve head corresponds with visual field deficit in eyes with normal tension glaucoma.

PURPOSE: To determine the relationship between the blood flow parameters of the optic disc rim and the glaucomatous visual field changes. DESIGN: Observational cross-sectional study. METHODS: Tissue blood flow in the neuroretinal rim within the optic disc was determined with the Heidelberg retina flowmeter(HRF) in 54 eyes of 54 patients with normal tension glaucoma (NTG). Patients were selected whose visual field defects were confined to either the superior or inferior hemifield. Blood flow measurements were made in a 10 degrees x 2.5 degrees area of the superior and inferior neuroretinal rim within the optic disc. The mean blood flow (MBF) was calculated by the automatic full-field perfusion image analyzer program, and the ratio of the MBF in the superior to the inferior rim areas (the S/I ratio) was calculated from the same HRF image in order to minimize the variation of measurement condition. RESULTS: Inferior rim blood flow is less than superior rim blood flow in patients with superior hemifield defect, and superior rim blood flow is reduced compared to inferior in patients with inferior hemifield defect. The mean S/I ratios of the MBF in the patients with superior hemifield defect (1.46, n=37) was significantly higher than that in the patients with inferior hemifield defect (0.79, n=17; P<0.0001, Mann-Whitney U-test). CONCLUSIONS: The blood flow in the neuroretinal rim was found to correspond to the regional visual field defect in eyes with NTG. Reductions in flow were associated with reductions in function.

Paraoxonase 1 gene polymorphisms influence clinical features of open-angle glaucoma.

BACKGROUND: The purpose of this study was to determine whether genetic polymorphisms affecting high-density lipoprotein (HDL)-associated antioxidant enzymes were associated with open-angle glaucoma (OAG). The rationale for this study was that the modification of low-density lipoprotein (LDL) by HDL prevents oxidative modification which can then cause dysfunction of endothelial cells. METHODS: We studied 284 normal Japanese controls and 555 Japanese patients with OAG, including primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). The possible associations of polymorphisms of PON1/L55M, PON1/Q192R, PON2/S311C, and PAF-AH/V279F with OAG were investigated. We compared the genotype distributions and allele frequency in controls and patient groups. The age at diagnosis, intraocular pressure (IOP) at diagnosis, and visual field score at diagnosis were examined for association with polymorphisms. RESULTS: The distributions of genotypes and allele frequency for the four polymorphisms were not significantly different between any patient group and controls. In NTG patients, 55M carriers of the PON1 gene were significantly older at diagnosis than 55M non-carriers (P=0.001). The IOP at diagnosis was significantly higher in glaucoma patients carrying 192R in the PON1 gene than in patients not carrying 192R (P=0.006). No significant differences were seen in clinical characteristics of OAG patients in relation to other polymorphisms. CONCLUSION: PON1 gene polymorphisms may influence the features of Japanese patients with OAG.