Amniotic membrane-assisted trabeculectomy for refractory glaucoma with corneal disorders.

PURPOSE: To report the cases of six consecutive patients who underwent amniotic membrane (AM)-assisted trabeculectomy (TLE) to treat refractory glaucoma with severe corneal disorders. METHODS: This study involved six patients (three males and three females, mean age: 69.5±15.8 years) with refractory glaucoma and severe corneal disorders. The surgical procedure for each patient involved trabecular tissue being excised, and human AM then being placed epithelial side up on the corneal surface, sutured at the limbal sclera, and flipped over onto the sclera to cover the TLE area. The remaining edge of the AM was then inserted into the subconjunctival space and sutured. Medical records of all cases were reviewed with regard to intraocular pressure (IOP), visual acuity, and condition of the filtering bleb and ocular surface. RESULTS: The mean observation period was 69.5±15.8 months, and mean IOP at presurgery and at 1, 3, and 7 years postoperative was 40.3±6.9, 23.0±12.1, 25.6±12.8, and 28.5±19.1 mmHg, respectively. Glaucoma medications decreased from 3.0±1.1 drugs (presurgery) to 0.8±1.0 drugs (7 years postoperative). However, in some cases, ocular surface conditions or visual acuity worsened during the follow-up period. CONCLUSION: Using AM as an internal patch for TLE, moderately good IOP control was obtained initially for the refractory glaucoma with severe corneal disorders; however, ocular surface conditions required special care, and the long-term IOP control was limited in some cases.

Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population.

Primary open-angle glaucoma (POAG) is the major type of glaucoma. To discover genetic markers associated with POAG, we examined a total of 1,575 Japanese subjects in a genome-wide association study (stage 1) and a subsequent study (stage 2). Both studies were carried out at a single institution. In the stage 1 association study, we compared SNPs between 418 POAG patients and 300 control subjects. First, low-quality data were eliminated by a stringent filter, and 331,838 autosomal SNPs were selected for analysis. Poorly clustered SNPs were eliminated by a visual assessment, leaving 255 that showed a significant deviation (P < 0.001) in the allele frequency comparison. In the stage 2 analysis, we tested these 255 SNPs for association in DNA samples from a separate group of 409 POAG and 448 control subjects. High-quality genotype data were selected and used to calculate the combined P values of stages 1 and 2 by the Mantel-Haenszel test. These analyses yielded 6 SNPs with P < 0.0001. All 6 SNPs showed a significant association (P < 0.05) in stage 2, demonstrating a confirmed association with POAG. Although we could not link the SNPs to the annotated gene(s), it turned out that we have identified 3 genetic loci probably associated with POAG. These findings would provide the foundation for future studies to build on, such as for the metaanalysis, to reveal the molecular mechanism of the POAG pathogenesis.

LOXL1 genetic polymorphisms are associated with exfoliation glaucoma in the Japanese population.

PURPOSE: We performed genetic association studies using a native Japanese population to examine the reproducibility of results of lysyl oxidase-like 1 (LOXL1) genetic association studies for exfoliation glaucoma (XFG) beyond the differences of ethnicity. We also quantified LOXL1 mRNA expression in the human lens capsule to examine the possible correlation between LOXL1 expression and XFG pathogenesis. METHODS: We performed a case-control study using 95 Japanese XFG patients and 190 controls. Real-time polymerase chain reaction (PCR) analysis was performed using lens capsules obtained during surgery. RESULTS: The TT genotype in the single nucleotide polymorphism (SNP) rs1048661 and the GG genotype in the SNP rs3825942 in exon 1 of LOXL1 were significantly associated with an increased risk of XFG under recessive models (chi(2) test, p=5.34 x 10(-34) and p=2.1 x 10(-8), respectively). Quantification of LOXL1 mRNA expression demonstrated no significant difference between XFG and senile cataract samples. CONCLUSIONS: Although the functional effects of the LOXL1 SNP appear to be qualitative rather than quantitative, the amino acid substitution (R141L) caused by SNP rs1048661 is not a simple decisive factor for XFG due to the inverted allele frequency between Japanese XFG and Caucasian XFG patients. Further genetic and functional studies are essential for clarifying XFG pathogenesis.

Effects of switching from topical beta-blockers to latanoprost on intraocular pressure in patients with normal-tension glaucoma.

AIMS: The effects of switching from topical beta-blockers (beta) to latanoprost (LA) on intraocular pressure (IOP) and IOP-reduction rate (IOP-RR) in patients with normal-tension glaucoma (NTG) were investigated. SUBJECTS AND METHODS: Sixty (60) NTG patients (60 eyes) were divided into three equal groups receiving carteolol hydrochloride (group A), nipradilol (group B), and betaxolol hydrochloride (group C) twice-daily for 3 months. The drugs were changed to topical LA administered once-daily for the next 3 months. RESULTS: Baseline IOP was 14.4 +/- 0.9, 14.6 +/- 0.6, and 14.6 +/- 0.9 mmHg in groups A, B, and C, respectively. At 3 months, IOP was 12.4 +/- 0.6, 13.4 +/- 0.6, and 12.9 +/- 0.8 mmHg and 10.5 +/- 0.5, 11.1 +/- 0.8, and 11.7 +/- 0.8 mmHg at 6 months in groups A, B, and C, respectively. At 3 months, IOP-RR was 10.4 +/- 5.5, 9.5 +/- 2.6, and 10.8 +/- 4.7% and 24.1 +/- 4.3, 22.9 +/- 5.9, and 19.4 +/- 3.8% at 6 months in groups A, B, and C, respectively. The groups did not significantly differ in the first 3 months regarding IOP and IOP-RR. Switching to LA significantly decreased IOP and increased IOP-RR in all groups. CONCLUSION: In NTG patients, LA reduced IOP more effectively than the beta tested.

[Relationship between compliance and background factors of glaucoma patients].

PURPOSE: To obtain useful information for the improvement of patient compliance in the medical treatment of glaucoma. SUBJECTS AND METHODS: An unsigned attitude survey on glaucoma and eye drops was conducted with 431 glaucoma patients. Correlation between compliance and individual(objective and subjective) factors was investigated. Objective factors were age, sex, number of eye drop products, duration of disease, and degree of visual field defects. Subjective factors were "stinging sensation with application of eye drops" and "worry about blindness". RESULTS: Thirty-eight percent of the glaucoma patients were compliant, instilling eye drops at the right time and with good technique. For the factor "duration of disease", patients who had glaucoma for 6-10 years had the best compliance. Compliance became poorer with an increasing number of eye drop products. In the subjective factors, less pain and worry led patients to better compliance. CONCLUSION: To improve compliance with medical treatment, we should categorize patients based on objective factors, eliminating their pain and worry, and instructing them not only in the frequency of instillation but also in the technique of administration.

Latanoprost nonresponders with open-angle glaucoma in the Japanese population.

PURPOSE: As some patients show little response to latanoprost, one of the most powerful topical glaucoma medications, we investigated the incidence and clinical profiles of latanoprost nonresponders (LNR) in the Japanese population. METHODS: We examined 62 glaucoma patients (62 eyes) who had received only latanoprost for more than 3 months. Their mean age was 63.8 +/- 1.8 years; the mean observation period was 9.7 +/- 0.4 months. At 1, 3, 6, and 12 months, their intraocular pressure (IOP) was measured, and the IOP reduction rate (RR) and the rate of LNR, defined as RR of 10% or less, were calculated. We statistically analyzed clinical factors involved in the LNR status of our study population. RESULTS: At 1, 3, 6, and 12 months, RR was 20.1 +/- 2.0%, 18.8 +/- 2.3%, 21.1 +/- 2.8%, and 23.0 +/- 2.6%, respectively. At the same time points, the LNR incidence was 23.1%, 28.1%, 23.5%, and 31.8%, respectively, and significantly higher in patients whose baseline IOP was less than 15 mmHg. Patient sex and age and the glaucoma type played no significant role in the LNR status. CONCLUSIONS: The incidence of LNR in the Japanese population, including normal-tension glaucoma (NTG) patients, is higher than among European or American patients. Only low baseline IOP was a significant clinical factor among LNR.

[A case of severe glaucoma with pseudopemphigoid successfully treated by filtration surgery using amniotic membrane].

BACKGROUND: It is necessary to decrease topical anti-glaucoma medication for severe glaucoma with pseudopemphigoid caused by anti-glaucoma eye drops. Glaucoma filtrating surgery is often needed instead of medication, but the prognosis is poor because it induces scar fomation and makes the filtrating bleb vanish. CASE: An 85-year-old male patient with exfoliation syndrome had twice undergone glaucoma surgery about ten years previously. His intra-ocular pressure (IOP) was high despite topical anti-glaucoma medication. At the first examination in our hospital, he had severe superficial punctate keratopathy, blephariticshortening and symblepharon, and we therefore diagnosed severe pseudopemphigoid induced by anti-glaucoma eye drops. Because his IOP could not be controlled by topical and general medication, we conducted a glaucoma filtrating operation using amniotic membrane. CONCLUSION: The administration of oral anti-inflammatory drugs before and after surgery and the use of amniotic membrane prevented post-operative scar formation and the progress of symblepharon, resulting in the successful control of IOP after surgery.

Evaluation of the pressure phosphene tonometer as a self-tonometer.

PURPOSE: Different from conventional tonometers, the pressure phosphene tonometer (FPT) measures intraocular pressure (IOP) through the upper eyelid without corneal applanation. We evaluated the usefulness of the FPT as a self-tonometer by comparing FPT IOP readings with those obtained with the Goldmann applanation tonometer (GAT). We also evaluated the influence of central corneal thickness (CCT) on IOP measurements obtained with the two different devices. METHODS: We confirmed the repeatability of FPT measurements in a preliminary study. The main investigation formed part of a prospective clinical trial, in which IOP was measured in 101 eyes of 101 participants (55 normal and 46 glaucomatous eyes) using GAT and FPT. FPT measurements were self-acquired by each participant. CCT was measured with an ultrasonic pachymeter. The agreement between FPT and GAT measurements was evaluated by the method of Bland and Altman. Using individual IOP and CCT values, we determined the correlation coefficients and performed regression analysis. RESULTS: FPT met the British Standard criteria for reproducibility. Among 101 participants, seven patients with glaucoma were unable to detect the pressure phosphene and to measure IOP using the FPT. By the statistical method of Bland and Altman there was a significant difference between FPT readings self-measured by the remaining 94 participants and GAT readings obtained by an ophthalmologist. There was no correlation between FPT and CCT readings in 65 participants with no prior history of anti-glaucoma medications or glaucoma surgery. CONCLUSIONS: Self-tonometer FPT readings differed from GAT readings. However, we suggest that the FPT may be a clinically acceptable device because it enables patients to self-measure their IOP easily and safely. As FPT readings are not affected by CCT, this tonometer may be of clinical and practical value for the at-will measurement of IOP in patients with corneal changes.

APC0576 decreases production of pro-inflammatory chemokine and extracellular matrix by human Tenon's capsule fibroblasts.

PURPOSE: To control intraocular pressure in patients treated by trabeculectomy, progressive inflammation, fibroblast proliferation, and the enhanced expression of extracellular matrix (ECM), causes of scar formation at the bleb, must be prevented. Using human Tenon's capsule fibroblasts (TCFs), we examined the effect of APC0576, a suppressor of NF-kappaB-dependent gene activation of human vascular endothelial cells that does not adversely affect cell viability, on the production of pro-inflammatory chemokine and ECM. Its effect on TCF proliferation was also assessed. METHODS: Enzyme-linked immunosorbent assay was used to detect the pro-inflammatory cytokines IL-8 and MCP-1 in the supernatant of TCFs stimulated with IL-1alpha in the presence or absence of APCO576 and ECM proteins, COOH-terminal peptide of type I procollagen (PIP), fibronectin (FN), and laminin (LN) in supernatants and lysates of TCFs stimulated with IL-1alpha or TGF-beta. The proliferative response of IL-1alpha-stimulated TCFs was examined using the SF formazan solution reaction. RESULTS: APC0576 significantly suppressed the production by TCFs of IL-8 (p<0.0001), MCP-1(p<0.0001), PIP (supernatants: p<0.0001, cell lysates: p<0.0001), LN (supernatants: p<0.0001, lysates: p<0.0001), and FN (supernatants: p<0.0001, lysates: p<0.0001) as well as their proliferation (p<0.0001). CONCLUSIONS: APC0576 suppressed pro-inflammatory chemokine and ECM production in TCFs as well as their proliferation. It may represent a novel candidate for the postoperative management of patients treated by trabeculectomy.

Evaluation of intraocular pressure change after laser in situ keratomileusis using the pressure phosphene tonometer.

PURPOSE: To evaluate the applicability of pressure phosphene tonometry in measuring intraocular pressure (IOP) after laser in situ keratomileusis (LASIK). SETTING: Baptist Eye Clinic, Kyoto, Japan. METHODS: Thirty-six eyes of 22 consecutive patients who had had LASIK for myopia were enrolled in this prospective comparative study. The mean age of the patients was 32.6 years +/- 9.0 (SD). The IOP was measured using the pressure phosphene tonometer (FPT), Goldmann applanation tonometry (GAT), and noncontact tonometry (NCT). The patients themselves took measurements with the FPT before and 1 week after surgery. One-way analysis of variance followed by a Bonferroni/Dunn multiple comparison post hoc test was administered to compare the preoperative and postoperative measurements with each tonometer. These data were represented graphically using a method described by Bland and Altman. The relationship between each tonometric change and the central corneal thickness (CCT) or keratometry (K) changes after LASIK were evaluated with by Pearson correlation coefficient. RESULTS: Statistically significant differences were found between preoperative and postoperative measurements with GAT and NCT but not with FPT. Preoperative and postoperative FPT readings conformed to the British Standard for reproducibility of a standard test method for IOP estimation. No significant correlation between FPT changes and CCT or K changes was found. CONCLUSIONS: Pressure phosphene tonometry measures IOP through the upper eyelid, and changes in corneal shape do not appear to have an effect on the IOP. The IOP measurements with FPT were constant before and after LASIK.

A new technique for removing the inner wall of Schlemm's canal using cyanoacrylate.

PURPOSE: To introduce a new technique for removing the inner wall of Schlemm's canal using cyanoacrylate. METHODS: Two donor eyes were used in this study. A limbal-based scleral flap was dissected. The external wall of Schlemm's canal was opened and the inner wall of Schlemm's canal was exposed. Ethyl-2-cyanoacrylate was applied uniformly to the inner wall. After it had solidified, it was removed with fine forceps. The operated sites were then studied by light microscopy. RESULTS: After cyanoacrylate removal, the aqueous humour was seen percolating through the thin remaining trabecular meshwork. Histopathological findings at the operated sites revealed that the lining of the Schlemm's endothelial cells was irregular. Endothelial cell nuclei were rarely seen along the canal wall. Microperforation to the anterior chamber was not seen. CONCLUSION: This new technique is potentially a safer method for removing the inner wall of Schlemm's canal than the conventional method.

cDNA microarray analysis of gene expression changes induced by dexamethasone in cultured human trabecular meshwork cells.

PURPOSE: To profile gene expression changes induced by dexamethasone in cultured human trabecular meshwork (TM) cells and identify genes related to the occurrence of steroid-induced glaucoma. METHODS: At confluence, dexamethasone (final concentration 10(-7) M in 0.1% ethanol) or vehicle alone (control, 0.1% ethanol) was applied to cultured human TM cells from eyes of four normal subjects. After 7 days of application, a labeled cDNA probe was synthesized from extracted total RNA and hybridized to a human cDNA microarray containing 2400 genes. After hybridization, the tyramide signal was amplified, and the fluorescent signals on each microarray were scanned and analyzed. RESULTS: In dexamethasone-treated TM cells, simultaneous analysis of 2400 human genes indicated a more than twofold increase in 30 genes. Five of them, myocilin (MYOC), decorin, insulin-like growth factor binding protein 2, ferritin L chain, and fibulin-1C, were the most upregulated genes with higher-than-control expression levels in all four experiments. Their upregulation was further confirmed by semiquantitative RT-PCR. Downregulation, with fluorescent signals decreased to less than a half, was found in 34 genes. The dexamethasone-induced expression changes in most of these TM cell genes have not been reported previously. CONCLUSIONS: cDNA microarray is a useful tool for gene expression analysis that confirms previous reports of upregulated mRNA expression of MYOC after treatment with dexamethasone in human TM cells. Changes in other genes subsequent to the treatment with dexamethasone may also reduce outflow facility, providing new insights into the pathogenesis of steroid-induced glaucoma.