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Top-ten 22nd Meeting of the Japan Glaucoma Society
Akita, Japan, September 23-25, 2011
Takeshi Yoshitomi
- Effects of oral administration of black currant anthocyanins on
plasma endothelin-1 concentration and visual field defects in patients
with glaucoma
A randomized, placebo-controlled, double-masked, 24-month cohort study was conducted to evaluate the effects of oral administration of black currant anthocyanins (BCACs) on plasma endothelin-1 (ET-1) concentration and visual field deterioration in patients with glaucoma. Thirty-eight patients with early to moderate stages of glaucoma treated by anti-glaucoma drops were included in the present study. BCACs (50 mg/day, n = 19) or its placebos (n = 19) were orally administrated once daily for a 24-month period. Plasma ET-1 concentrations of both groups were significantly lower than those of normal subjects at the trial baseline. Those of BCACs group increased to the levels of normal subjects, while those of placebos group remained unchanged during the 24-month period. In addition, administration of BCACs caused beneficial effects on visual field deterioration during the trial period. However, no significant effects were observed in systemic conditions and ocular conditions, including intraocular pressures and visual acuities during the trial period. These results suggested that oral administration of BCACs may be a promising supplement for patients with glaucoma in addition to anti-glaucoma medication. (Ikuyo Ohguro and Hiroshi Ohguro, Sapporo, Japan) - A step-configuration of the scleral bed in myopic eyes
Recently, examination of peripapillary structures using SD-OCT seems to have attracted considerable attention. In myopic eyes of young patients, we found characteristic alterations of deep structures within PPA beta, a step-configuration of the scleral bed, which had the significant relationship to myopic refraction and visual field defect. Compared to eyes without, eyes with this configuration had significantly longer axial length, greater ovality index of the optic disc, and greater maximal width of PPA beta. A step-configuration of the scleral bed seems to be related to myopic changes of optic discs such as disc tilting and peripapillary atrophy, and in addition, might be associated with visual field loss in eyes of young myopes. (Atsushi Nonaka, Kyoto, Japan) - The effect of aqueous MCP-1 on surgical results of trabeculectomy
in patients with open-angle glaucoma
Cytokines and growth factors (including monocyte chemotactic protein (MCP)-1 and associated pro-inflammatory cytokines) in aqueous humor are likely associated with the formation and maintenance of filtration blebs. However, our knowledge of the clinical relevance of those factors is far from satisfactory. To investigate roles of MCP-1 in aqueous humor in patients with open-angle glaucoma (OAG), aqueous humor samples were collected from 41 patients with phakic OAG and 23 patients with pseudophakic OAG. A multiplex bead-based immunoassay was used to measure levels of MCP-1. Statistical analyses were performed to elucidate the relationship between levels of MCP-1 in aqueous humor and patients' clinical backgrounds including the surgical outcome of trabeculectomy. In OAG patients, a positive association between previous cataract surgery and MCP-1 concentration was found in the multiple regression analysis (P < 0.0001). Multivariate analyses by the Cox proportional hazards model showed that the aqueous MCP-1 level was a significant prognostic factor for the surgical outcome of trabeculectomy in both all OAG patients (P = 0.007) and phakic OAG patients (P = 0.012). In summary, the increased aqueous MCP-1 level was induced by cataract surgeries and may cause a short-term failure of trabeculectomy in OAG patients. (Toshihiro Inoue, Kumamoto, Japan) - Choroidal thickness changes accompanied by acute intraocular pressure
drop using enhanced depth imaging optical coherence tomography
Choroidal thickness (ChT) changes accompanied by acute intraocular pressure (IOP) drop right after the laser suturelysis (LSL) following trabeculectomy were evaluated in 41 eyes of 33 cases using enhanced depth imaging optical coherence tomography (EDI-OCT, Topcon). The results showed that EDI-OCT provides detailed measurable choroidal images even in the hypotonic situation after trabeculectomy. Significant increase of ChT under the fovea from 231.4 ± 54.3 to 249.3 ± 62.8 micrometer (p < 0.001) and correlation between ChT increments and IOP drops (r = -.48, p < 0.05) suggests the possibility of ChT influenced by IOP dynamically. (Yu Ishida and Kazuhiko Mori, Kyoto, Japan) - Correlation between optic disc rotation, torsion and ovality with
spherical equivalent and mean deviation
We measured rotation, torsion and ovality to assess optic disc changes according to previously reported methods. First, the line through the center of optic disc and central fovea was defined as a base line of each eye. Torsion was defined as an angle between the base line and a horizontal line. Rotation was defined as an angle between the long axis of the optic disc and a vertical line to the base line. Ovality was defined as the ratio of minimum to maximum disc diameter. We measured these parameters in 171 eyes of 171 patients with (101 eyes) and without (70 eyes) glaucoma. Multiple regression analysis was done to correlate the three parameters with age, spherical equivalent (SE), mean deviation (MD) of Humphrey 24-2 SITA-STANDARD. Disc rotation was negatively correlated with SE (p < 0.001, r = 0.399). Disc torsion was positively correlated with age (p = 0.014, r = 0.241). Ovality was positively correlated with SE (p = 0.002, r = 0.297). In conclusion, the optic disc showed more rotation with higher myopia, and more torsion with older patients. (Satoshi Mrooka, Kyoto, Japan) - Effects of high myopia on spectral-domain optical coherence tomography
parameters
To evaluate the effects of high myopia on spectral-domain optical coherence tomography (SD-OCT) parameters as well as on their ability to detect glaucoma, Ninety glaucoma and 87 non-glaucoma patients were designated as emmetropic (89 subjects, spherical equivalent £ 1 dioptres [D] and 3 -1D) or highly myopic (88 subjects, £ -5 D). Macular ganglion cell complex (GCC) and circumpapillary retinal nerve fiber layer (cpRNFL) measurements obtained from the algorithms of the SD-OCT system were compared. Only average cpRNFL thickness was significantly affected by high myopia and the interaction between high myopia and glaucoma. The areas under the curve (AUC) for average cpRNFL between high myopia (AUC = 0.839) and emmetropia (AUC = 0.938) was nearly significant (p = 0.050); no differences were noted for the other GCC parameters. The effect of high myopia might confuse glaucoma detection using cpRNFL. GCC parameters are a useful complementary technique to RNFL thickness assessment for clinically evaluating patients with concomitant glaucoma and high myopia. (Takuhei Shoji, Saitama, Japan) - Central corneal thickness changes in patients with long time using
prostaglandine analogues
Central corneal thickness (CCT) changes were evaluated in 50 eyes of 50 glaucoma patients who underwent latanoprost monotherapy for more than four years using the Pentacam® (Oculus Optikgeräte GmbH, Wetzlar, Germany) anterior segment tomography instrument at pretreatment, midpoint, and final follow-up (more than four years from the first observations). The mean CCT significantly decreased from 541 ± 36 μm at pre-treatment to 530 ± 34 μm at the final follow-up (p < 0.0001). Interestingly, there was no significant difference between the mean CCT at midpoint and that at final follow-up, while the mean CCT significantly decreased to 533 ± 33 μm in the first two years (p = 0.00049). Latanoprost eye drops significantly reduce CCT during the initial stage of their usage. (Yuko Maruyama, Kyoto, Japan) - The association of altered aquaporin-9 expression with apoptosis
of retinal ganglion cells
The association of altered aquaporin-9 expression with apoptosis of retinal ganglion cells Aquaporins are a family of integral membrane proteins that allow water to cross the plasma membrane. They are critically involved in the maintenance of ionic and osmotic balance in the central nervous system. In human eyes, aquaporin 9(AQP9) is expressed. AQP9, expressed in amacrine cells and retinal ganglion cells (RGCs), is an aquaglyceroporin that is also permeable to non-charged solutes such as lactate, which can serve as fuel for neurons. Previously we reported that elevated intraocular pressure reduced the AQP9 expression in RGCs. This study tested the association of altered AQP9 expression with apoptotic death of RGCs using serum-deprived RGC5 cells in vitro and rat optic nerve transection (ONT) model in vivo. Western blotting and immunohistochemistry demonstrated that both serum deprivation and ONT reduced AQP9 protein contents and accelerated apoptosis in RGCs. The AQP9 knockdown increased apoptotic death of RGC5 cells. These results indicate that AQP9 plays a critical role in RGC survival and that the reduced expression of AQP9 may induce apoptotic death of RGCs. (Akiko Miki, Kobe, Japan) - Altered stability of mRNAs associated with glaucoma progression
in human trabecular meshwork cells following oxidative stress
To determine if oxidative stress on human trabecular meshwork (HTM) cells influences the stability of key mRNAs containing AU rich elements known to be associated with glaucoma progression. HTM cells were treated with 150μM H2O2 for two hours in the presence of 5μg/ml actinomycin D, and compared with cells without H2O2 treatment. The selected mRNAs (IL-6, IL-8, myocilin, SPARC, MMP-3) from the cells were analyzed by using Q-PCR. Immunohistochemistry for HuR was performed in addition to Western blots of HuR using TM-1 cells. H2O2 increased IL-6 mRNA stability 0.142 (0.057/0.195) to 0.239 (0.184/0.475) [normalized ratio, median (inter-quartile range)] (n = 9) while IL-8 mRNA was increased marginally. [from 0.518 (0.372/0.612) to 0.686 (0.545/0.767)] (n=7). The differences were statistically significant (p = 0.0039, p = 0.0313, respectively; Wilcoxon signed-rank test). The mRNAs of myocilin, SPARC and MMP-3, which do not have AREs, were stable after actinomycin D treatment and were not altered with oxidation. Western blot and immunohistochemistry demonstrated that H2O2 treatment induces the translocation of HuR from the nucleus to the cytoplasm. Oxidative stress stabilizes IL-6 mRNA significantly while IL-8 mRNA stability was marginally increased. The decay of certain mRNAs associated with glaucoma may be altered in the TM of glaucoma patients. (Hideki Mochizuki, Hiroshima, Japan) - The effects of prostaglandin analogues on intracellular Ca2+ in
ciliary arteries of wild type and prostanoid receptor-deficient mice
Prostaglandin (PG) analogues induce vasodilation in mouse ciliary artery, possibly by reduction of the intracellular free calcium concentration ([Ca2+]i). The purpose of this study was to determine if prostaglandin (PG) analogues reduce ciliary artery[Ca2+]i. We also used PG receptor-deficient mice to clarify the roles of prostanoid receptors. Changes of [Ca2+]i in isolated ciliary artery segments were monitored by fluorescence photometry. High K solution increased [Ca2+]i in wild type ciliary arteries. In high K-stimulated arteries, the PG analogues (10μM) latanoprost, unoprostone, and tafluprost induced concentration dependent decreases of [Ca2+]i. The amplitudes of [Ca2+]i decrease induced by these three drugs were unchanged with the NO synthase inhibitor L-NAME (10-4 M) or the cyclo-oxygenase inhibitor indomethacin (10-5 M). The decrease in [Ca2+]i induced by the PG analogues latanoprost and unoprostone was partially blocked in prostanoid FP receptor-deficient ciliary arteries. For the PG analogue tafluprost, the reduction in [Ca2+]i was enhanced in ciliary arteries deficient in prostanoid EP2 receptors. Thus, we conclude that the three PG analogues decrease[Ca2+]i in mice ciliary arteries. The mechanism was not dependent on endothelial-derived factors. Moreover, prostanoid FP and EP receptors might play small roles in these [Ca2+]i reductions. (Sanae Abe, Akita, Japan)