Language：Japanese  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/iae.0000000000003644

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.2176-23

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Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

DOI： 10.1002/humu.24492

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/humu.24492

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ajoc.2022.101729

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Posterior microphthalmos (PM) is a rare condition with poor visual prognosis even after amblyopia treatment. We report a case of PM with achievement of good visual acuity and disappearance of papillomacular retinal folds (PFs) over a period of 7 years.

Case presentation

A girl aged 3 years and 5 months was referred to our hospital, after poor visual acuity was identified at a medical checkup for 3-year-olds. She had severe spherical hyperopia: + 17.25 D in the right eye (RE) and + 18 D in the left eye (LE). Her corrected visual acuity was 20/200 in the RE and 20/250 in the LE. PFs were observed in both eyes on optical coherence tomography (OCT), and the diagnosis of PM was made based on the normal corneal diameter and anterior chamber depth. During the course of the disease, a gradual decrease in the height of the PFs was observed on OCT. The corrected visual acuity at age 10 years was 20/20 in the RE and 20/25 in the LE.

Conclusions

The visual prognosis of PM is poor, and only one case with good visual acuity has been reported in the literature. The patient in the present case not only developed good visual acuity, but also showed improvement in macular morphology, which was not noted in previous reports. Early diagnosis of PM and early amblyopia treatment is important for the visual development in PM.

DOI： 10.1186/s12886-022-02648-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10384-022-00954-9

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Language：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：日本緑内障学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Although eyelid reconstruction by transplanting an autologous free tarsoconjunctival graft (FTG) is a well-established technique, few studies have examined the postoperative course of FTG transplantation for East Asian eyelids, including those of Japanese patients. Therefore, this study investigated complication and reoperation rates after FTG transplantation in the reconstruction of East Asian (Japanese) eyelids. This study included 42 eyelids wherein posterior lobe reconstruction after resection of a malignant tumour of the eyelid was performed by FTG transplantation between 2007 and 2019 at Niigata University Medical and Dental Hospital. We investigated complications and need for revision surgery during the patients' postoperative courses. The relationship between postoperative complications, tumour diameter, and eyelid defect width was statistically examined. Of 42 cases reconstructed with FTG, the upper eyelid was reconstructed in 23. Postoperative complications were observed in 12 cases (52%): entropion in eight and corneal epithelial disorder in four. Revision surgery was required in three of those cases (13%). There were 19 cases of lower eyelid reconstruction. Postoperative complications were observed in seven cases (32%): ectropion in three and corneal epithelial disorder in two and one lower eyelid ptosis. Two of these cases (11%) required revision surgery. There was no statistically significant difference in tumour diameter between cases with and without postoperative complications. There was also no significant association between the width of the eyelid defect and the presence/absence of complications. Entropion and ectropion were more likely to occur in the upper and lower eyelids, respectively. For Japanese eyelids, complication rates after FTG transplantation were approximately 50% and 30% for the upper and lower eyelids, respectively. The revision surgery rate was approximately 10% for both upper and lower eyelids. As these revision surgery rates are low, FTG transplantation may be an option for the reconstruction of Japanese eyelids.

DOI： 10.1016/j.jpra.2022.04.003

PubMed

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Authorship：Last author  

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Authorship：Last author  

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Authorship：Last author  

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>We non-invasively evaluated macular non-perfused areas (m-NPAs) of branch retinal vein occlusion (BRVO) using optical coherence tomography (OCT) angiography and the Humphrey visual field analyser 10-2 programme (HFA 10-2). We enrolled 30 patients (30 eyes) with macular oedema secondary to BRVO. OCT angiography was used to photograph the macula at 6 × 6-mm; sizes of m-NPAs in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured in four areas. For HFA 10-2, we divided the actual measurement threshold of 68 points into four areas and calculated the mean central visual field sensitivity (CVFS). The correlation between the mean m-NPA and mean CVFS (dB) in each area was examined. There was a strong correlation between the m-NPA of each region detected in SCP and DCP, and the mean CVFS of each corresponding area (SCP: r = − 0.83, r = − 0.64, r = − 0.73, and r = − 0.79; DCP: r = − 0.82, r = − 0.71, r = − 0.71, and r = − 0.70), p values were &lt; 0.001 for all. m-NPAs were associated with decreased visual field sensitivity in BRVO. Non-invasive m-NPA evaluation was possible using OCT angiography and HFA 10-2.

DOI： 10.1038/s41598-021-84240-7

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Other Link： http://www.nature.com/articles/s41598-021-84240-7

Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：日本緑内障学会  

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To assess the effect of maintenance therapy on visual outcomes in preventing recurrences one year after first onset in patients with aquaporin-4 antibody (AQP4Ab)-positive optic neuritis. STUDY DESIGN: Retrospective study. METHODS: The medical charts of 56 patients with optic neuritis (22 with AQP4Ab-positive and 34 with AQP4Ab-negative) at Niigata University Medical and Dental Hospital were retrospectively analyzed. Clinical characteristics, including visual acuity and number of recurrences one year after first onset, were compared among patients who were AQP4Ab-positivie with and those without maintenance therapy such as oral prednisolone and azathioprine, as well as those who were AQP4Ab-negative. RESULTS: The mean ages were 49.3 and 45.2 years in the AQP4Ab-positive and the AQP4Ab-negative groups. The female to male ratio was 21:1 and 18:16 in the two groups, respectively. Multiple between-group comparison showed a statistically significant difference in visual acuity one year after first onset between the AQP4Ab-positive without maintenance therapy group and the AQP4Ab-negative group (0.05 (median, same applies below) vs. 1.0, p < 0.01). There was also a statistically significant difference in the number of recurrences in the year after first onset between the AQP4Ab-positive with and without maintenance therapy groups (1 vs. 0, p < 0.01). CONCLUSION: This study demonstrates that patients with AQP4Ab-positive optic neuritis without maintenance therapy had the poorest visual acuity and the most recurrences one year after first onset. These results indicate that reducing the number of recurrences with maintenance therapy could improve the visual outcomes in patients with AQP4Ab-positive optic neuritis.

DOI： 10.1007/s10384-021-00858-0

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Language：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：(株)メディカル葵出版  

視神経乳頭陥凹拡大は緑内障に特徴的な所見であるが、非緑内障性の視神経疾患や頭蓋内疾患でもみられる。「緑内障と間違えやすい視神経疾患」第2回目の本稿では、非緑内障性視神経疾患の乳頭所見や視野障害の特徴、緑内障との鑑別のポイントについて概説する。(著者抄録)

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Language：Japanese   Publisher：(株)メディカル葵出版  

「緑内障と間違えやすい視神経疾患」の第1回は、緑内障と間違えやすい視神経乳頭の形状異常である上方視神経乳頭低形成と巨大乳頭について、症例を交えて概説する。どちらも非進行性の先天異常で治療の必要はないが、緑内障を合併することがあり、注意が必要である。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10384-021-00830-y

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Other Link： https://link.springer.com/article/10.1007/s10384-021-00830-y/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

PURPOSE: Patients with an eye disease often report nyctalopia, hemianopia, and/or photophobia. We hypothesized that such symptoms are related to the disease impacting the dynamic range of lightness perception (DRL). However, there is currently no standardized approach for measuring DRL for clinical use. We developed an efficient measurement method to estimate DRL. STUDY DESIGN: Clinical trial METHODS: Fifty-five photophobic patients with eye disease and 46 controls participated. Each participant judged the appearance of visual stimuli, a thick bar with luminance that gradually changed from maximum to minimum was displayed on uniform background. On different trials the background luminance changed pseudo-randomly between three levels. The participants repeatedly tapped a border on the bar that divided the appearance of grayish white/black and perfect white/black. We defined the DRL as the ratio between the luminance values at the tapped point of the border between gray and white/black. RESULTS: The mean DRL of the patients was approximately 15 dB, significantly smaller than that of the controls (20 dB). The center of each patient's DRL shift depending on background luminance, which we named index of contextual susceptibility (iCS), was significantly larger than controls. The DRL of retinitis pigmentosa was smaller than controls for every luminance condition. Only the iCS of glaucoma was significantly larger than controls. CONCLUSIONS: This measurement technique detects an abnormality of the DRL. The results support our hypothesis that the DRL abnormality characterizes lightness-relevant symptoms that may elucidate the causes of nyctalopia, hemeralopia, and photophobia.

DOI： 10.1007/s10384-020-00808-2

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)医学書院  

＜文献概要＞目的:片眼の水痘帯状疱疹ウイルス(VZV)による急性網膜壊死(ARN)の発症10年後に僚眼にも同ウイルスによるARNが発症し,初発眼および10年後の再発眼ともPCR定量を行った症例の報告。症例:66歳,男性。前医にて10年前に右眼にVZV(前房水にて6.8×106copies/ml)によるARNを罹患し,網膜剥離を発症した。治療として,抗ウイルス療法や硝子体手術により加療されていた。左眼のARNの疑いで当院を受診した。当院受診時の矯正視力は右(0.1),左(0.5)であり,左眼の角膜後面沈着物,眼底上方の黄白色滲出斑を認めた。臨床所見と反対眼の経過から,僚眼にARNが発症したと判断した。即日入院とし,アシクロビルの点滴とステロイドの全身投与を行った。当院受診時に採取した前房水からは6.8×104copies/mlのVZVが検出され,10年前に測定した初発眼に比べて1/100であった。治療後,左眼の硝子体混濁は増悪なく,最終視力は左(0.6)であった。現時点でも網膜剥離の発症はない。結論:片眼のARN発症から10年後に僚眼に再発することがあり,右眼に比べてウイルス量が少ない左眼は予後が良好であった。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01537&link_issn=&doc_id=20210406030023&doc_link_id=10.11477%2Fmf.1410213970&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213970&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞目的:生来健康な若年男性で,非感染性ぶどう膜炎との鑑別が困難であった内因性細菌性眼内炎の症例を経験したので報告する。症例:18歳,男性。皮膚潰瘍の治療中に突然の右眼の眼痛・視力低下が生じた。所見:右眼視力は指数弁で,前房に前房蓄膿,線維素析出があり,強い硝子体混濁を認めた。左眼に異常を認めなかった。非感染性ぶどう膜炎と感染性眼内炎との鑑別に難渋したが,抗菌薬硝子体内注射に反応し,皮膚病巣からメチシリン耐性黄色ブドウ球菌(MRSA)が検出されたため,内因性細菌性眼内炎を強く疑い,速やかに硝子体切除術を施行した。術中に採取した前房水からは細菌,真菌ともに培養されず,MRSAも検出されなかったが,硝子体手術後に炎症所見と視機能は改善した。結論:眼内炎の診断では,感染性か非感染性かの鑑別は非常に大切である。

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Authorship：Last author  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メディカル葵出版  

緑内障患者65例のGoldmann型視野計と自動視野計による視野障害等級について検討した。Goldmann型視野計での周辺視野角度、両眼中心視野角度と、自動視野計での両眼開放Estermanテスト視認点数、10-2プログラム両眼視認点数を求めて視野障害等級判定を実施した。Goldmann型視野計での周辺視野角度が両眼ともに80°以下の群では、6例全例(100.00%)が異級となった。一眼のみが80°以下の群では、同級が14例(46.67%)、異級が16例(53.33%)、両眼ともに81°以上の群では、同級が19例(65.52%)、異級が10例(34.48%)であった。二つの視野計での視野障害等級は、視野の残存状態、視覚特性、測定原理や検査条件の違いから乖離が生じる。このことに医療者は留意する必要がある。(著者抄録)

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Language：English  

The purpose of this study was to investigate the clinical characteristics of Japanese patients with optic nerve hypoplasia (ONH), with particular attention to the prevalence of brain abnormalities. We retrospectively analysed the medical charts of 16 patients who were diagnosed with ONH and who underwent magnetic resonance imaging (MRI) at Niigata University Medical and Dental Hospital. We recorded the age, sex, laterality, initial eye and visual symptoms, best-corrected visual acuity, and brain abnormalities on MRI (excluding ONH). The median age at the first visit to the Ophthalmology Clinic was 2.4 years old. Four patients were male and 12 were female. ONH was bilateral in 11 patients and unilateral in five. Best-corrected visual acuity ranged from no light perception to 20/20. Seven patients (43.8%) had brain abnormalities including agenesis of the septum pellucidum, pituitary gland hypofunction, cerebral dysplasia, and West syndrome. Five of these seven patients had general manifestations since the neonatal or infantile period. Our study revealed the prevalence of brain abnormalities associated with optic nerve hypoplasia in Japanese patients at a single institute. Because two of 11 patients had no general manifestations since the neonatal or infantile period but demonstrated brain abnormalities, MRI should be performed to investigate all patients with ONH.

DOI： 10.1080/01658107.2020.1844758

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
Steep Trendelenburg position (ST) during robot-assisted radical prostatectomy (RARP) poses a risk of increase in intraocular pressure (IOP) in men receiving robot-assisted radical prostatectomy (RARP). The aim of the study was to identify clinicopathological factors associated with increased IOP during RARP.


</sec><sec>
<title>Methods</title>
We prospectively studied 59 consecutive prostate cancer patients without glaucoma. IOP was measured at 6 predefined time points before, during and after the operation (T1 to T6).


</sec><sec>
<title>Results</title>
Compared with T1, IOP decreased after beginning of anesthesia(T2) (by − 6.5 mmHg, <italic>p</italic> &lt; 0.05), and increased 1 h after induction of pneumoperitoneum in the steep Trendelenburg position (ST) (T3) (+ 7.3 mmHg, <italic>p</italic> &lt; 0.05). IOP continued to increase until the end of ST (T4) (+ 10.2 mmHg, p &lt; 0.05), and declined when the patient was returned to supine position under general anesthesia (T5) (T1: 20.0 and T5: 20.1 mmHg, p above 0.05). The console time affected the elevation of IOP in ST; IOP elevation during ST was more prominent in men with a console time of ≥4 h (<italic>n</italic> = 39) than in those with a console time of &lt; 4 h (<italic>n</italic> = 19) (19.8 ± 6.3 and 15.4 ± 5.8 mmHg, respectively, <italic>p</italic> &lt; 0.05). Of the 59 patients, 29 had a high baseline IOP (20.0 mmHg or higher), and their IOP elevated during ST was also reduced at T5 (T1: 22.6 and T5: 21.7 mmHg, p above 0.05). There were no postoperative ocular complications.


</sec><sec>
<title>Conclusions</title>
Console time of &lt; 4 h is important to prevent extreme elevation of IOP during RARP. Without long console time, RARP may be safely performed in those with relatively high baseline IOP.


</sec>

DOI： 10.1186/s12894-020-00595-5

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Other Link： http://link.springer.com/article/10.1186/s12894-020-00595-5/fulltext.html

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本神経眼科学会  

目的:高血圧性網膜症による乳頭腫脹と鑑別を要した特発性頭蓋内圧亢進症によるうっ血乳頭の1例を報告する.症例:当科初診時42歳,女性.無治療の高血圧があり,網膜出血・軟性白斑の他に網膜趨壁を伴う旺盛な乳頭腫脹がみられ,程度が強い乳頭腫脹であることからうっ血乳頭を積極的に疑い,頭部画像検査・髄液検査を行って特発性頭蓋内圧亢進症の診断に至った.結論:本症例は診断に至るまでに高血圧性網膜症による乳頭腫脹との鑑別を要したため,特発性頭蓋内圧亢進症の診断を考える上で重要な症例であった.うっ血乳頭の診断には頭部画像検査・髄液検査を積極的に行うことが重要であることが改めて示唆された.(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>Mitophagy plays an important role in the maintenance of mitochondrial homeostasis. PTEN-induced kinase (PINK1), a key regulator of mitophagy, is degraded constitutively under steady-state conditions. During mitophagy, it becomes stabilized in the outer mitochondrial membrane, particularly under mitochondrial stress conditions, such as in treatment with uncouplers, generation of excessive mitochondrial reactive oxygen species, and formation of protein aggregates in mitochondria. Stabilized PINK1 recruits and activates E3 ligases, such as Parkin and mitochondrial ubiquitin ligase (MUL1), to ubiquitinate mitochondrial proteins and induce ubiquitin-mediated mitophagy. Here, we found that the anticancer drug gemcitabine induces the stabilization of PINK1 and subsequent mitophagy, even in the absence of Parkin. We also found that gemcitabine-induced stabilization of PINK1 was not accompanied by mitochondrial depolarization. Interestingly, the stabilization of PINK1 was mediated by MUL1. These results suggest that gemcitabine induces mitophagy through MUL1-mediated stabilization of PINK1 on the mitochondrial membrane independently of mitochondrial depolarization.

DOI： 10.1038/s41598-020-58315-w

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Language：Japanese   Publisher：(公社)日本視能訓練士協会  

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

We aimed to evaluate choroid structural changes using swept-source optical coherence tomography (SS-OCT) following hemodialysis initiation in diabetic and nondiabetic patients with end-stage kidney disease (ESKD). In this multicenter, prospective, cross-sectional study, diabetic (DM group; 30 eyes; 16 patients) and nondiabetic patients (NDM group; 30 eyes; 15 patients) with ESKD were evaluated after hemodialysis initiation. SS-OCT findings were analyzed using a manual delineation technique and binarization method before the first and last hemodialysis sessions, conducted approximately 2 weeks apart. Subfoveal choroidal thickness changes and mean large choroidal vessel layer thickness were significantly greater in the DM group (-13.3% ± 2.5% and -14.5% ± 5.2%, respectively) than the NDM group (-9.5% ± 3.1% and -9.2% ± 3.4%, respectively; p = 0.049 and p = 0.02, respectively). Binarized SS-OCT analysis revealed that the mean subfoveal choroidal area was significantly larger in the DM group (-21.9% ± 6.5%) than the NDM group (-17.2% ± 5.9%; p = 0.032). The change ratio in mean luminal area values was significantly greater in the DM group (-27.7% ± 8.7%) than the NDM group (-17.7% ± 5.8%; p = 0.007). The DM group exhibited substantial changes in the choroidal layer, possibly reflecting choroidal vascular disorders caused by diabetes.

DOI： 10.1371/journal.pone.0239072

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本神経眼科学会  

眼球運動制限を伴う固定内斜視を呈する強度近視性斜視に対する術式として上外直筋結合術の効果は確立されている。一方、画像上眼球の筋円錐からの脱臼がみられるが眼球運動制限を伴わない強度近視性斜視に対する上外直筋結合術の効果についての報告は少ない。我々は眼球運動制限を伴わない強度近視性内斜視に対して上外直筋結合術を施行し、術後約6年間経過観察を行うことができた症例を経験した。画像上両眼に筋円錐からの脱臼がみられたが、程度のより強い右眼に上外直筋結合術を施行した。術後、内斜視は改善したが術眼が上斜視となり僚眼の下直筋後転法を施行した。経過良好だったが上外直筋結合術施行から5年後に水平性複視が増悪し、プリズム組込眼鏡装用で複視は改善した。本症例の経過と既報から眼球運動制限がなく両眼に眼球の脱臼がみられる強度近視性症例では、両眼の上外直筋結合術を計画するのが良いと考えられた。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01767&link_issn=&doc_id=20200930580009&doc_link_id=%2Fex4sinke%2F2020%2F003703%2F010%2F0317-0321%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fex4sinke%2F2020%2F003703%2F010%2F0317-0321%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

PURPOSE: To investigate the spatial and temporal relationship between disc hemorrhage (DH) and structural progression in patients with primary open-angle glaucoma (POAG) in a 3-year prospective study. DESIGN: Prospective cohort study. PARTICIPANTS: Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs. METHODS: Fundus photographs were taken at baseline and every 3 months for 3 years. Disc hemorrhage and structural progression were detected independently by flicker chronoscopy. If present, clock-hour disc locations in the right eye format and colocalization were determined. Statistical comparisons were based on mixed-effects models accounting for the correlation between different disc sites within the same eye and between fellow eyes in the same patient. MAIN OUTCOME MEASURES: Relationship between DH and structural progression at the same site. RESULTS: Among 195 eyes of 115 patients, DH appeared in 85 sites in 65 eyes (33.3%) and was most frequently at the 7 o'clock disc location (29.4%, P < 0.0001). Structural progression occurred at 63 sites of 52 eyes (26.7%) comparably in both superior and inferior hemidiscs, which was mostly detected as widening of the retinal nerve fiber layer defects (RNFLDs). Temporal RNFLD widening was common, whereas nasal widening occurred exclusively in the vertical quadrants (P = 0.035). Of 41 progression sites in eyes with DH, 28 sites (68.2%) had both DH and progression. Progression sites with DH were less common in the superior quadrant than in the inferior and temporal quadrants (P = 0.011). Eyes with DH had a significantly higher risk of progression than eyes without DH (hazard ratio, 3.72; P < 0.0001). For 63 progression sites, DH recurrence and more visits with DH at the progression site were significantly associated with shorter time to progression from baseline (P = 0.021, P = 0.017, respectively), whereas colocalization of DH and progression were not. CONCLUSIONS: In a 3-year prospective study with a Japanese POAG cohort, the relationship between DH and RNFLD and the pattern of RNFLD progression differed by disc location. The association between more frequent DH at the progression site and shorter time to progression indicates that DH may reflect vulnerability to same-site structural deterioration.

DOI： 10.1016/j.ogla.2020.08.008

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

<italic>Purpose</italic>. To clarify the clinical features of patients with exfoliation glaucoma (XFG) requiring surgical intervention. <italic>Study Design</italic>. Retrospective study. <italic>Methods</italic>. The study included 46 eyes from 36 XFG patients, 85 eyes from 53 primary open-angle glaucoma (POAG) patients, and 54 eyes from 35 normal-tension glaucoma (NTG) patients. Age, duration of previous glaucoma treatment, intraocular pressure, medication scores, visual function, and surgical procedure were compared among the three patient groups. <italic>Results</italic>. The XFG group had the highest mean age (XFG: 75.7 ± 8.3 years, POAG: 65.8 ± 12.8 years, and NTG: 53.3 ± 12.8 years; <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.001</mml:mn></mml:math>) and the shortest mean duration of previous treatment with glaucoma medication (XFG: 5.1 ± 3.5 years, POAG: 8.9 ± 6.9 years, and NTG: 8.9 ± 5.9 years; <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.001</mml:mn></mml:math>). Intraocular pressure and medication scores were slightly higher in the XFG group than in the POAG group, although the differences were not significant. Among XFG patients, trabeculectomy was performed in 20 eyes from 16 patients (55.6%) and trabeculotomy was performed in 16 eyes from 14 patients (44.4%). Both trabeculectomy (3 eyes) and trabeculotomy (14 eyes) were performed in combination with cataract surgery. <italic>Conclusions</italic>. The XFG patients referred to our department for initial examination were older than the POAG and NTG patients, and their duration of treatment before referral was shorter. Moreover, intraocular pressure and the eye drop medication score were higher in the XFG patients. A significantly higher percentage of XFG patients required surgical intervention compared to patients with other disease types.

DOI： 10.1155/2020/9423756

PubMed

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Other Link： http://downloads.hindawi.com/journals/joph/2020/9423756.xml

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/aos.14506

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/aos.14506

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

PRECIS: The foveal avascular zone (FAZ) in optical coherence tomography angiography is significantly correlated with retinal inner layer thickness, Humphrey field analyzer (HFA) 10-2 sensitivity threshold, and mean deviation (MD) value in open-angle glaucoma patients. PURPOSE: The purpose of this study was to measure the FAZ area using optical coherence tomography angiography and investigate its relationship with retinal inner layer thickness and visual field defects in eyes with open-angle glaucoma. PARTICIPANTS AND METHODS: A total of 52 eyes with open-angle glaucoma from 52 patients. FAZ area was measured using optical coherence tomography angiography in angio-macula mode. Thicknesses of retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), and ganglion cell complex (GCC) were determined using a 7 mm×7 mm macular (V) map via 3D-OCT. Correlations of FAZ area with sensitivity threshold measurements, foveal threshold (FT), and MD value in the HFA10-2 visual field were analyzed for each inner retinal layer. RESULTS: FAZ area was 0.26±0.07 mm; overall mean thicknesses were 19.14±6.55 μm (RNFL), 57.34±5.93 µm (GCL+IPL), and 75.87±10.96 μm (GCC); mean FT was 35.23±3.15 dB, and sensitivity threshold was 20.81±7.22 dB in the HFA10-2 visual field. FAZ area was significantly correlated with the thickness of individual retinal layers in the entire field (RNFL, P<0.001; GCL+IPL, P<0.001; GCC, P<0.001), sensitivity threshold (P=0.01), FT (P<0.001), and MD value (P=0.011). CONCLUSION: FAZ area was significantly negatively correlated with retinal inner layer thickness, sensitivity threshold, FT, and MD value in the HFA10-2 visual field.

DOI： 10.1097/ijg.0000000000001492

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Glaucomatous optic neuropathy (GON) is the pathohistological feature of glaucoma in the optic nerve. The pathogenesis of GON has been hypothesized, to either originate from compromised mechanical conditions at the lamina cribrosa or as associated with pathological vascular involvement. From a historical perspective, glaucoma is the degeneration of retinal ganglion cells (RGC) due to the elevation of intraocular pressure (IOP). The consensus of glaucoma treatment is generally accepted as sufficient IOP reduction. Is there an additional option to treat GON from the perspective of the vascular theory? In this section, two distinguished leaders in glaucoma research advance their views and discuss the current opinions surrounding the two theories regarding the causes of GON in primary open angle glaucoma (POAG) and normal tension glaucoma (NTG).

DOI： 10.1007/s10384-020-00736-1

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)医学書院  

＜文献概要＞目的:急性網膜壊死(ARN)は高率に網膜剥離(RD)をきたし,視機能不良に至る症例が多い疾患である。RDを合併した例とRDを合併しなかった例で,臨床的経過・所見にどのような差があるのか,RDの原因となる臨床的所見や素因について比較検討した。検討には2015年の診断分類における臨床診断群も加えた。対象と方法:対象は2006年9月〜2018年12月にARNを発症し,新潟大学医歯学総合病院眼科(当科)で初診・治療された患者20例22眼。うち確定診断群18眼,臨床診断群4眼であった。これらのうちRDを発症した例(剥離例)と発症しなかった例(非剥離例)に分け,比較検討を行った。結果:両眼発症を20例中2例に認めた。原因ウイルスは水痘・帯状疱疹ウイルス15眼,単純ヘルペスウイルス3眼,PCR陰性4眼であった。12眼にRDを生じ,10眼はRDを生じなかった。年齢は,剥離例で50.3±18.7歳,非剥離例で69.0±16.6歳と,剥離例で有意に若年の傾向を認めた(p=0.049)。剥離例は非剥離例と比較し,有意差はなかったものの,比較的病変の範囲が狭い例が多かった(p=0.106)。剥離例と非剥離例の間の視神経乳頭所見・硝子体混濁・後部硝子体剥離の差はなかった。結論:当科では,RD例が非剥離例と比較して有意に若年の傾向を認めた。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01537&link_issn=&doc_id=20200414020014&doc_link_id=10.11477%2Fmf.1410213522&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213522&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

PURPOSE: To estimate the central 10-degree visual field of glaucoma patients using en-face images obtained by optical coherence tomography (OCT), and to examine its usefulness. PATIENTS AND METHODS: Thirty-eight eyes of 38 patients with primary open angle glaucoma were examined. En-face images were obtained by swept-source OCT (SS-OCT). Nerve fiber bundles (NFBs) on en-face images at points corresponding to Humphrey Field Analyzer (HFA) 10-2 locations were identified with retinal ganglion cell displacement. Estimated visual fields were created based on the presence/absence of NFBs and compared to actual HFA10-2 data. κ coefficients were calculated between probability plots of visual fields and NFBs in en-face images. RESULTS: Actual HFA10-2 data and estimated visual fields based on en-face images were well matched: when the test points of <5%, <2%, and <1% of the probability plot in total deviation (TD) and pattern deviation (PD) of HFA were defined as points with visual field defects, the κ coefficients were 0.58, 0.64, and 0.66 in TD, respectively, and 0.68, 0.69, and 0.67 in PD. In eyes with spherical equivalent ≥ -6 diopters, κ coefficients for <5%, <2%, and <1% were 0.58, 0.62, and 0.63 in TD and 0.66, 0.67, and 0.65 in PD, whereas for the myopic group with spherical equivalent < -6 diopters, the values were 0.58, 0.69, and 0.71 in TD and 0.72, 0.71, and 0.71 in PD, respectively. There was no statistically significant difference in κ coefficients between highly myopic eyes and eyes that were not highly myopic. CONCLUSIONS: NFB defects in en-face images were correlated with HFA10-2 data. Using en-face images obtained by OCT, the central 10-degree visual field was estimated, and a high degree of concordance with actual HFA10-2 data was obtained. This method may be useful for detecting functional abnormalities based on structural abnormalities.

DOI： 10.1371/journal.pone.0229867

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：新潟医学会  

【目的】眼科健診、人間ドックで緑内障を疑われ魚沼基幹病院眼科外来を受診した患者の緑内障の有無、緑内障の病型、重症度、受診後の動向を調査した。【方法】2015年6月から2019年10月までに魚沼基幹病院眼科を初診した症例のうち、緑内障に関わる病名を付与されたものを電子カルテネットワーク上で検索し、カルテを縦覧した。眼科健診、人間ドックで緑内障を疑われ受診した症例を抽出し、眼科医による問診や細隙灯顕微鏡検査、視力、眼圧測定、眼科学的画像解析、視野検査結果から緑内障の有無、緑内障の病型、重症度、診断後の治療内容、通院継続の有無を調査した。【結果】眼科健診、人間ドックにより緑内障を疑われ初診した症例数は108例(男性51例、女性57例)だった。そのうち緑内障患者は18例、緑内障を疑う眼底所見を呈しながらも視野障害を認めない前視野緑内障と診断されたのは14例、正常範囲内と判断されたのは70例だった。緑内障と診断された症例は緑内障点眼液一剤の処方または厳重な経過観察を開始された。定期的な経過観察を指示された71症例の中で受診が途絶えた症例が12例存在した。【結論】眼科健診で緑内障を疑われて受診した症例の16.7%に緑内障を認め、検出率は既報と同等だった。経過観察を行うと緑内障患者を含めて15.5%が通院中断しており、通院継続率を向上させる取り組みが必要である。(著者抄録)

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Language：English   Publisher：(公財)日本眼科学会  

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Language：English   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公財)日本眼科学会  

目的:正常眼圧緑内障の加療中に視交叉部腫瘍の合併が明らかになった4例を提示し,腫瘍合併を疑うべき所見について検討する.症例:合併した視交叉部腫瘍は,3例は下垂体腺腫,1例は鞍結節部髄膜腫であった.いずれの症例も急速な視野障害進行と片眼もしくは両眼の視力低下を伴っていた.2例では乳頭蒼白を伴っていたが,2例ではなかった.症例1の両耳側半盲所見は,10°内視野測定で初めて検出された.結論:緑内障症例に視交叉部腫瘍合併を疑う眼科的所見として,垂直経線を境界とする視野障害,急激な視力低下・視野悪化,乳頭蒼白などが挙げられるが,進行した緑内障症例では耳側半盲所見が判別しづらいことがあり,10°内視野測定が有用な場合がある.疑われる場合には積極的に頭蓋内画像検索を行うことが勧められる.(著者抄録)

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Language：Japanese   Publisher：日本視能矯正学会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：金原出版(株)  

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Publishing type：Research paper (scientific journal)   Publisher：Association for Research in Vision and Ophthalmology (ARVO)  

DOI： 10.1167/iovs.19-27184

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Publishing type：Research paper (scientific journal)   Publisher：BMJ  

<sec><title>Objective</title>This study aimed to examine the natural course and relapse rate of IgG4-related ophthalmic disease (IgG4-ROD) after debulking surgery in Japanese patients.

</sec><sec><title>Methods and analysis</title>This retrospective review included patients with IgG4-ROD who did not undergo further treatment following debulking surgery. The patients were diagnosed between January 2009 and December 2018 at the Department of Ophthalmology and Pathology, Niigata University Medical and Dental Hospital. The main outcome measures included postoperative IgG4-ROD recurrence rate and differences between patients with and without recurrent disease.

</sec><sec><title>Results</title>Fifteen patients (six male, 9 female; 61.8±16.2 years) were included. Twelve patients (80.0%) had dacryoadenitis disease and three patients (20.0%) had orbital fat tissue disease. About 70%–100% of the lesion was resected in the debulking surgery and the pathological diagnosis was rendered. A definitive diagnosis was made in 13 cases (86.7%) and a probable diagnosis in 2 cases (13.3%). Patients were followed up for 39.0±25.5 months following operation. All patients had lesion volume reduction and patients with dacryoadenitis had eyelid swelling improvement after surgery. Two patients (13.3%) had disease recurrence and six patients (40.0%) had extraophthalmic lesions. There was no statistically significant difference in clinical features between relapsed and non-recurring cases.

</sec><sec><title>Conclusion</title>We observed a 13.3% relapse rate following debulking surgery in patients with IgG4-ROD who did not undergo further treatment. This rate is lower than the documented relapse rate of 30%–70% following oral prednisolone therapy. Therefore, debulking surgery may be a treatment option for IgG4-ROD.

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DOI： 10.1136/bmjophth-2019-000295

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Language：Japanese   Publisher：日本眼科紀要会  

目的:90歳を超える超高齢ながら拡大読書器(CCTV)を使いこなしている加齢黄斑変性の2例のロービジョンケア経過を報告する。症例:症例1は現在90歳の男性で新聞を読みたいというニーズがあり、83歳時にロービジョン外来を初診。矯正視力は左右眼ともに0.2であった。中心視野障害のため光学的視覚補助具ではニーズを満たすことができなかったが、CCTVは有用であった。現在視力は右眼0.04、左眼0.02であるが、現在も読書と書字が可能である。症例2は現在93歳の男性。ニーズは読書と書字であった。85歳で初診したときの右眼矯正視力は0.02、左眼矯正視力は0.15で両眼の中心視野障害を認めた。当初は光学的視覚補助具を処方したが視機能低下が進行したため88歳時にCCTVを入手した。現在の視力は右眼0.03、左眼0.01未満であるが、CCTVを使用して新聞を毎日読んでいる。結論:90歳を超える高齢視覚障害者に対しても、読み書きのニーズを満たすCCTVの情報提供および指導は患者のquality of life(QOL)向上に有効である。(著者抄録)

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Language：Japanese   Publisher：(公社)日本視能訓練士協会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.oret.2018.04.020

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Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.2147/opth.s174277

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

PurposeTraffic accidents are associated with the visual function of drivers, as well as many other factors. Driving simulator systems have the advantage of controlling for traffic-and automobile-related conditions, and using pinhole glasses can control the degree of concentric concentration of the visual field. We evaluated the effect of concentric constriction of the visual field on automobile driving, using driving simulator tests.MethodsSubjects meeting criteria for normal eyesight were included in the study. Pinhole glasses with variable aperture sizes were adjusted to mimic the conditions of concentric visual field constrictions of 10 degrees and 15 degrees, using a CLOCK CHART (R). The test contained 8 scenarios (2 oncoming right-turning cars and 6 jump-out events from the side).ResultsEighty-eight subjects were included in the study; 37 (mean age =52.9 +/- 15.8 years) subjects were assigned to the 15 degrees group, and 51 (mean =48.6 +/- 15.5 years) were assigned to the 10 degrees group. For all 8 scenarios, the number of accidents was significantly higher among pinhole wearing subjects. The average number of all types of accidents per person was significantly higher in the pinhole 10 degrees group (4.59 +/- 1.81) than the pinhole 15 degrees group (3.68 +/- 1.49) (P = 0.032). The number of accidents associated with jump-out scenarios, in which a vehicle approaches from the side on a straight road with a good view, was significantly higher in the pinhole 10 degrees group than in the pinhole 15 degrees group.ConclusionsConcentric constriction of the visual field was associated with increased number of traffic accidents. The simulation findings indicated that a visual field of 10 degrees to 15 degrees may be important for avoiding collisions in places where there is a straight road with a good view.

DOI： 10.1371/journal.pone.0193767

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

PurposeTo compare the additive effects and safety of 1% brinzolamide/0.5% timolol fixed combination (BTFC) versus the low-dose regimen of 1% dorzolamide/0.5% timolol fixed combination (DTFC) in patients with open-angle glaucoma and ocular hypertension (OAG/OH) following treatment with prostaglandin analogues (PGAs).
MethodsA prospective, randomized, double-masked, multicentre, parallel-group and active-controlled study included 201 Japanese OAG/OH patients whohad been treated with PGA. Efficacy was assessed as the change in intra-ocular pressure (IOP) from baseline after weeks 4 and 8. Safety was assessed with adverse event rates, ocular discomfort score, blur scale, bloodpressure and heart rates, best-corrected visual acuity (BCVA) and slit lamp examinations.
ResultsIntra-ocular pressure (IOP) change from baseline at 9AM/11AM pooled over the 8weeks was -3.3/-3.3mmHg in the BTFC group and -2.9/-3.4mmHg in the DTFC group, demonstrating non-inferiority of BTFC to DTFC. Ocular irritation was frequently seen in DTFC group. Although blurred vision was frequently seen in BTFC group, it was transient and blurring became the equivalent 3min after instillation between two groups. No noteworthy issue was observed in other safety outcome.
ConclusionNon-inferiority of BTFC to DTFC in IOP reduction was demonstrated after adding onto PGA therapy in Japanese OAG/OH patients. Although the score of blurred vision was transiently higher in BTFC than DTFC, treatment difference decreased and disappeared with time. Thus,BTFC can be considered as a safe and effective agent for glaucoma treatment.

DOI： 10.1111/aos.13401

Web of Science

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本視能訓練士協会  

【目的】網膜色素変性(RP)患者の黙読能力の他覚的評価を試みた。【対象及び方法】新潟大学医歯学総合病院通院中のRP患者11名(37.4±17.6歳)と健常者(N)20名(46.9±17.2歳)。視線解析装置(Tobii Tx300)にて横書き文黙読時の平均停留時間およびsaccade時間、100文字あたりの読み時間、停留回数を算出した。また読書時のsaccadeを幅と角度の2変数から混合ガウスモデルによるクラスタ分類およびクラス分類し、その割合をχ2検定で検討した。【結果】平均停留時間はRP群256.3±41.6msec、N群215.7±24.9msec(p<0.01)、saccade時間RP群44.28±8.26msec、N群50.78±11.45msec(P=0.11)、停留回数はRP群31.1±7.9回、N群32.7±10.6回(p=0.66)、読み時間はRP群9.4±3.0sec、N群8.8±3.4sec(p=0.65)で、RP群において停留時間が延長した。各saccadeは短・長順行、逆行、行替えに分類されその構成に両群間で有意差を認めた(p=0.03)。RP群において短順行、長順行saccadeが多く、逆行saccadeが少なかった(p<0.01)。【結論】RP群は平均停留時間が延長しsaccadeパターンに変化がみられたが、読み時間は延長しなかった。今後は視野異常の重症度に着目した解析が必要である。(著者抄録)

DOI： 10.4263/jorthoptic.046F128

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Language：Japanese   Publisher：(公社)日本視能訓練士協会  

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Language：Japanese   Publisher：(公社)日本視能訓練士協会  

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メディカル葵出版  

目的:広義・原発開放隅角緑内障(POAG)眼の中心窩閾値(FT)と矯正視力との相関、Humphrey視野(HFA)10-2プログラムの傍中心窩測定点視野感度閾値(PFT)との相関について調べた。対象および方法:対象はHFA10-2測定を行ったPOAG眼103例103眼である。年齢は54.4±9.7(23〜70)歳、等価球面度数-4.5±3.9(+2.0〜14.5)ジオプトリー、病型は狭義POAG56眼、正常眼圧緑内障47眼である。FTは直近3回のHFA24/30-2もしくは10-2測定時の測定値を平均し、矯正視力(logMAR)は直近2回の測定値を平均した。FTと矯正視力の相関、またFTとHFA10-2傍中心4点の実測感度閾値(PFT)との相関を調べた。結果:FTと矯正視力は統計学的に有意に相関した(r2=0.537、p<0.001)。FTとPFTは単回帰分析では4点とも有意に相関し、その程度は耳側上方(r2=0.481、p<0.001)、耳側下方(r2=0.443、p<0.001)、鼻側下方(r2=0.210、p<0.001)、鼻側上方(r2=0.055、p=0.017)の順であった。FTとPFTの重回帰分析では、耳側上方と下方、鼻側下方の3点が有意に相関した。結論:広義POAG眼においてFTと矯正視力は有意に相関し、FT測定は広義POAG眼の矯正視力推定に有用な可能性がある。FT低下とHFA10-2における傍中心視野障害のパターンには関連があると考えられた。(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メディカル葵出版  

目的:Humphrey 10-2視野(HFA10-2)における視野感度低下領域とシラスHD-OCT(カールツァイスメディテック)のganglion cell analysis(GCA)判定の相関を検討した。対象および方法:広義原発開放隅角緑内障53名53眼を対象とした後ろ向き研究。HFA10-2における測定点をGCA解析に準じて6セクターに分割し、トータル偏差で感度低下(1%以下)がみられるものを異常点とした。GCA各セクターにおける菲薄化をディビエーションマップからスコア化した(>5%、0;≦5%かつ>1%、1;≦1%、2)。半視野当たりのHFA異常点数とGCAスコア合計との相関について調べ、セクターごとの整合性についても検討した。結果:半視野当たりのHFA異常点数と対応するGCAスコアはいずれも有意な相関がみられた(上半0.74、下半0.53)。上鼻側セクターにおいて感度と特異度は高く(90%、100%)、下方および耳側セクターでは低くなる傾向があった。結論:GCA解析による判定は中心10°内視野障害を反映していると考えられる。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Objectives
To evaluate the vascular architecture of the radial peripapillary capillaries (RPCs) and its relation with visual function in patients with open-angle glaucoma (OAG) and normal-tension glaucoma using spectral-domain optical coherence tomography (SD-OCT) angiography.
Subjects and methods
Clear OCT angiography images of blood vessels in the optic disc and peripapillary retina were obtained from 52 patients (52 eyes) aged 55.42 +/- 10.64 (range 28-72) years with primary OAG. The mean spherical equivalent was -3.19 +/- 2.31 diopters, and the mean deviation (MD) of the central 24/30-2 threshold test using the Humphrey Field Analyzer (HFA) was -10.47 +/- 7.99 dB. The correlations between the disappearance angle of the RPCs on OTC images, flow density (FD) and the circumpapillary retinal nerve fiber layer (cpRNFL) thickness, the angle of retinal nerve fiber layer (RNFL) defect, the MD and pattern standard deviation (PSD) values of the HFA central 24/30-2 threshold test using the Swedish interactive thresholding algorithm, the sensitivity threshold, age, corneal thickness, and refractive value were analyzed. In addition, the correlation between FD and the cpRNFL thickness was analyzed at FD measurement points.
Results
FD was significantly correlated with cpRNFL thickness, PSD value, MD value, and sensitivity threshold, whereas the disappearance angle of the RPCs was significantly correlated with the angle of the RNFL defect (P &lt; 0.001), MD value (P &lt; 0.01), and sensitivity threshold (P &lt; 0.01). There was a negative correlation between FD and age (P &lt; 0.05). The Pearson correlation coefficient of FD and cpRNFL thickness in the area surrounding the optic disc revealed the most significant correlation in the inferior visual field (r = 0.851, P &lt; 0.001), followed by the superior visual field (r = 0.803, P &lt; 0.001) and then the temporal visual field (r = 0.653, P &lt; 0.001).
Conclusion
SD-OCT angiography enabled thorough observation of the RPCs. FD and the disappearance angle of the RPCs were significantly and independently correlated with glaucomarelated functional and morphological changes in the optic nerve, suggesting that these two factors are novel functional and morphological indicators of visual defects due to glaucoma.

DOI： 10.1371/journal.pone.0184301

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メディカル葵出版  

Soemmerring輪を伴って発症した続発閉塞隅角症(以下、本症)の2例を経験した。症例1は78歳、男性。10年前に両眼に超音波水晶体乳化吸引術、眼内レンズ挿入術(以下、PEA+IOL)を受けた。左眼に浅前房と眼圧上昇(25mmHg)を生じ、細隙灯顕微鏡検査、および超音波生体顕微鏡(以下、UBM)所見から、本症と診断した。Soemmerring輪の手術的除去と周辺部前後嚢切開術を行い、前房深度は改善、隅角は開大し、眼圧は下降した。症例2は77歳、女性。11年前に左眼にPEA+IOLを受けた。左眼霧視と頭痛を主訴に受診した。左眼眼圧は77mmHgで浅前房と全周に周辺虹彩前癒着を認めた。同様に細隙灯顕微鏡検査、UBM所見から本症と診断し、Soemmerring輪の手術的除去と隅角癒着解離術を行った。術後、前房深度は改善し、眼圧は下降した。結論:まれではあるがPEA+IOL後の長期合併症の一つとしてSoemmerring輪を伴う続発閉塞隅角症がある。本症にはさまざまな隅角閉塞のメカニズムが関与している可能性が考えられる。診断にはUBMが有用で、正確に本症と診断された場合には、Soemmerring輪を手術的に除去することで眼内レンズを温存したまま治療できる可能性がある。(著者抄録)

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Language：Japanese   Publisher：日本眼科紀要会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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GNAQ and GNA11 mutations are thought to be important for the tumorigenesis of uveal melanoma. Although previous studies have reported on mutation rates in cases of uveal melanoma, presently, no such report for the Japanese population exists. In this study, we examined the frequency of GNAQ and GNA11 somatic mutations in cases of uveal melanoma in Japan and their relationship with clinicopathologic features or Ki-67-positive cell rates (Ki-67 labeling index: Ki-67 LI) using immunofluorescence methods. The study involved 19 cases of uveal melanoma. We extracted the template DNA from formalin-fixed, paraffin-embedded specimens using a DNA extraction kit. We amplified the DNA sequences of GNAQ and GNA11 using polymerase chain reaction and analyzed mutations by direct sequencing. We evaluated Ki-67 LI using immunofluorescence methods. The frequencies of GNAQ and GNA11 somatic mutations were 26.3% (5/19) and 31.6% (6/19), respectively. The GNAQ and GNA11 mutations were mutually exclusive, as indicated in previous reports. The frequency of GNA11 mutations was significantly higher in epithelioid cells; however, no significant association between GNAQ mutations and cell type was evident, and there was no significant difference in Ki-67 LI between the mutation-positive and mutation-negative tumors. GNAQ and GNA11 mutations were identified in cases of uveal melanoma in Japan, although at lower frequencies than in white counterparts. The mutation frequency of GNA11 was significantly higher in epithelioid cells.

DOI： 10.1097/PAI.0000000000000505

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Objective
To investigate the relationship between silent reading performance and visual field defects in patients with glaucoma using an eye tracking system.
Methods
Fifty glaucoma patients (Group G; mean age, 52.2 years, standard deviation: 11.4 years) and 20 normal controls (Group N; mean age, 46.9 years; standard deviation: 17.2 years) were included in the study. All participants in Group G had early to advanced glaucomatous visual field defects but better than 20/20 visual acuity in both eyes. Participants silently read Japanese articles written horizontally while the eye tracking system monitored and calculated reading duration per 100 characters, number of fixations per 100 characters, and mean fixation duration, which were compared with mean deviation and visual field index values from Humphrey visual field testing (24-2 and 10-2 Swedish interactive threshold algorithm standard) of the right versus left eye and the better versus worse eye.
Results
There was a statistically significant difference between Groups G and N in mean fixation duration (G, 233.4 msec; N, 215.7 msec; P = 0.010). Within Group G, significant correlations were observed between reading duration and 24-2 right mean deviation (r(s) = -0.280, P = 0.049), 24-2 right visual field index (r(s) = -0.306, P = 0.030), 24-2 worse visual field index (rs = -0.304, P = 0.032), and 10-2 worse mean deviation ((r)s = -0.326, P = 0.025). Significant correlations were observed between mean fixation duration and 10-2 left mean deviation (r(s) = -0.294, P = 0.045) and 10-2 worse mean deviation (r(s) = -0.306, P = 0.037), respectively.
Conclusions
The severity of visual field defects may influence some aspects of reading performance. At least concerning silent reading, the visual field of the worse eye is an essential element of smoothness of reading.

DOI： 10.1371/journal.pone.0170230

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：眼科臨床紀要会  

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© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd Purpose: To report the 5-year incidence of visual impairment after mitomycin C-augmented trabeculectomy (MMC trabeculectomy) and the risk factors for visual impairment. Methods: This is a multicentre prospective observational cohort study. Among glaucoma patients registered in the Collaborative Bleb-related Infection Incidence and Treatment Study performed in Japan, the patients with eyes meeting the following qualifications were included: eyes with primary open-angle glaucoma; eyes with primary angle-closure glaucoma; eyes with exfoliative glaucoma; eyes with ≥3/60 in blindness analysis; and eyes with ≥20/60 in low-vision analysis and visual acuity loss analysis. The patients were followed at 6-month intervals for 5 years. The entry data and follow-up data were analysed to determine the incidence of blindness (<3/60), low vision (≥3/60 and <20/60) and visual acuity loss (≥0.2 logMAR) during the follow-up period. Risk factors for visual impairment were also analysed. Results: A total of 694 eyes of 694 or 559 eyes of 559 glaucoma patients were subjected to the blindness analysis or the low-vision and visual acuity loss analysis, respectively. Visual acuity significantly deteriorated (p < 0.0001): 12.2% (95%CI: 9.8–14.7%) of the patients became blind; 12.1% (95%CI: 9.4–14.9%) were judged to have low vision at the final examination; 28.3% (95%CI: 24.5–32.0%) were judged to have visual acuity loss. Glaucoma subtypes, poor preoperative visual function and postoperative complications are the main risk factors for visual impairment. Conclusions: Visual acuity was significantly reduced after MMC trabeculectomy in 5 years, and we identified several risk factors associated with this complication.

DOI： 10.1111/aos.13058

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メディカル葵出版  

目的:エクスプレス併用濾過手術後の角膜内皮細胞所見について検討した。対象および方法:対象はエクスプレス併用濾過手術を施行し、術後3ヵ月以上スペキュラーマイクロスコープによって角膜内皮細胞を観察できた32例37眼である。年齢は70.8±10.4歳で、病型は広義・原発開放隅角緑内障眼19例21眼(POAG群)、落屑緑内障群10例13眼(XFG群)、その他3例3眼であった。このうち眼内レンズ挿入眼は28例32眼であった。内皮細胞密度(CD)、六角形細胞出現率(6A)、変動係数(CV)の経時変化について検討した。結果:CDは術前2,292±563/mm2に対して、平均術後観察期間13.7±8.5ヵ月の最終観察時に2,059±614mm2と有意に減少した(p=0.0002)。病型別にPOAG群CDは術前2,359±487/mm2が術後最終2,244±574/mm2に対して、XFG群CDは術前2,196±671/mm2が術後最終1,808±555mm2と、XFG群で有意に大きく減少していた(p=0.037)。6A、CVでは有意な差はみられなかった。術後にCDが500以上減少した例は6眼、20%以上減少した眼は7眼であった。結論:エクスプレス併用濾過手術後に角膜内皮細胞密度が低下する可能性がある。落屑緑内障眼ではより減少する可能性がある。(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公財)日本眼科学会  

目的:本邦における緑内障診療データの管理・共通化の現状について調査し,今後の緑内障診療・研究の向上のための課題と方向性について明らかにすること.対象と方法:日本緑内障学会内に設置されたデータ共通化委員会に参画し,緑内障診療に積極的に取り組んでいる14大学に対して文書によってアンケート調査を行った.結果:すべての大学において病院情報システムが導入され,3社の眼科部門カルテによる診療データの電子化が行われていた.しかしながら,電子カルテから電子的な診療データ提供体制が整っていた大学は30.8%にとどまり,データの二次利用が具体的に進んでいる大学眼科は14.3%のみであった.地域医療機関との電子データによる診療連携を進めている大学眼科は35.7%であり,眼科内で診療データの電子的管理を行っていたのは42.9%にとどまっていた.結論:アンケートの結果から診療データの管理や共通化について多くの課題が明らかになった.(著者抄録)

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Purpose: Ｗe conducted a survey to evaluate the current status of glaucoma-related medical data management and standardization, aiming to improve the development of glaucoma care and research in Japan.
Materials and methods: The survey was performed as a paper-based questionnaire of 14 universities that both participate in the glaucoma-related data standardization committee, established by the Japan Glaucoma Society in 2014, and actively perform glaucoma care.
Results: All enrolled university hospitals installed an electronic hospital information system and used any of three ophthalmology-limited electronic chart systems. However, only 30.8% of the hospitals established a data extraction system from an electronic medical chart system, and only 14.3% could practically apply medical data for secondary research purposes. In all, 35.7% of the hospitals operate a medical cooperation system with local medical institutions and 42.9% electronically managed medical data inside their departments.
Conclusion: This survey clarified the current state of medical data management and standardization.

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Dove Medical Press Ltd  

Purpose: To investigate the correlation coefficients between intraocular pressure (IOP) before and after adjusting for central corneal thickness (CCT) and corneal biomechanical properties. Patients and methods: A total of 218 eyes of 218 patients with primary open-angle glaucoma (mean age =71.5 years
mean spherical equivalent =-0.51 D
mean deviation determined by Humphrey visual field analyzer =-3.22 dB) were included in this study. The tIOP and tIOPCCT, which were adjusted by the CCT (with tIOP meaning IOP not adjusted by CCT, as determined using the CT-1P
and tIOPCCT meaning IOP adjusted by CCT, as determined using the CT-1P), were determined using a noncontact tonometer. The IOPg and IOPCCT, which were adjusted by CCT, and IOPcc adjusted by corneal biomechanical properties were determined using a Reichert 7CR (with IOPg meaning IOP not adjusted by CCT or corneal biomechanical properties, as determined using the Reichert 7CR
IOPCCT meaning IOP adjusted by CCT, as determined using the Reichert 7CR
and IOPcc meaning IOP adjusted by corneal biomechanical properties, as determined using the Reichert 7CR). The GT and GTCCT adjusted by CCT were determined using a Goldmann applanation tonometer (with GT meaning IOP not adjusted by CCT, as determined using the Goldmann applanation tonometer
and with GTCCT meaning IOP adjusted by CCT, as determined using the GAT). Pearson’s correlation coefficients among the IOPs were calculated and compared. P-values &lt
0.05 were considered as statistically significant. Results: The tIOP, tIOPCCT, IOPg, IOPCCT, IOPcc, GT, and GTCCT were 14.8±2.5, 15.0±2.4, 13.1±3.2, 13.3±3.1, 13.7±2.9, 13.2±2.4, and 13.4±2.3 mmHg (mean ± standard deviation), respectively. The correlation coefficient between tIOPCCT and tIOP (r=0.979) was significantly higher than that between tIOPCCT and the other IOPs (r=0.668-0.852
P&lt
0.001, respectively). The correlation coefficient between IOPCCT and IOPg (r=0.994) or IOPcc and IOPg (r=0.892) was significantly higher than that between IOPCCT or IOPcc and the other IOPs (r=0.669-0.740
P&lt
0.001, respectively). The correlation coefficient between GTCCT and GT (r=0.989) was significantly higher than that between GTCCT and the other IOPs (r=0.669-0.740
P&lt
0.001, respectively). Conclusion: The IOP adjusted by CCT or corneal biomechanical properties depends on the measurement instrument itself, rather than the adjustment methods, for eyes of patients with primary open-angle glaucoma.

DOI： 10.2147/OPTH.S106836

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DOI： 10.11477/mf.1410211796

CiNii Article

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Other Link： http://search.jamas.or.jp/link/ui/2016229848

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

ObjectiveNeuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia-neuron interaction in NMOsd.
MethodsThirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP.
ResultsThe AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Muller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON.
InterpretationSevere and widespread neuroaxonal damage and unique dynamics of astrocytes/Muller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd. Ann Neurol 2016;79:605-624

DOI： 10.1002/ana.24608

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

We evaluated the rate of progression of total, upper, and lower visual field defects in patients with treated primary open-angle glaucoma (POAG) with high myopia (HM).
Seventy eyes of 70 POAG patients with HM [a parts per thousand currency signa'8 diopters (D)] were examined. The mean deviation (MD) slope and the upper and lower total deviation (upper TD, lower TD) slopes of the Humphrey Field Analyzer were calculated in patients with high-tension glaucoma (HTG) (&gt; 21 mmHg) versus normal-tension glaucoma (NTG) (a parts per thousand currency sign21 mmHg). The mean age of all the patients (29 eyes with HTG and 41 eyes with NTG) was 48.5 +/- A 9.6 years. The MD slope, and upper and lower TD slopes of the HM group were compared to those of the non-HM group (NHM) (&gt;-8 D) selected from 544 eyes in 325 age-matched POAG patients. In all, 70 eyes with HM and NHM were examined.
The mean MD slope was -0.33 +/- A 0.33 dB/year in the HM, and -0.38 +/- A 0.49 dB/year in the NHM. There were no statistical differences between the HM and NHM (p = 0.9565). In the comparison of HTG versus NTG patients in both groups, the MD slope, and upper and lower TD slopes were similar.
The rate of progression of total, upper, and lower visual field defects was similar among patients with HM and NHM. Although HM is a risk factor for the onset of glaucoma, HM may not be a risk factor for progression of visual field defects as assessed by the progression rate under treatment.

DOI： 10.1007/s10384-016-0427-3

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本眼科紀要会  

目的:新潟大学ロービジョン外来における75歳以上の後期高齢者を対象とし、ロービジョンケアの内容を分析し、評価した。方法:2000年9月〜2014年5月の間に受診した初診時年齢75歳以上の111例(平均79.9±4.0歳)。視覚障害の原因疾患、身体障害者手帳の取得状況、聴取したニーズ、ニーズに対応したロービジョンケア(情報提供・指導、処方)を検討した。結果:原因疾患で最も多かったのは緑内障48例(43.2%)であった。身体障害者手帳は34例(30.6%)が取得していた。ニーズは読書98件(88.3%)、羞明の緩和38件(34.2%)、書字36件(32.4%)、歩行17件(15.3%)であった。指導、情報提供数は拡大読書器が最も多く、処方数は遮光眼鏡が最も多かった。結論:高齢ロービジョン患者のニーズは多岐にわたっており、ニーズを最大限に引き出しロービジョンケアにあたる必要がある。(著者抄録)

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS INC  

Background: It has been hypothesized that dysfunction of the solute carrier family 1, member1 gene (SLC1A1), which encodes the glutamate aspartate transporter, may play a role in normal tension glaucoma. In this study we investigate whether SLC1A1 is associated with normal tension glaucoma in Japanese patients.
Methods: A total of 292 Japanese patients with normal tension glaucoma and 500 healthy control subjects were recruited. We genotyped 12 single-nucleotide polymorphisms in SLC1A1. We also performed an imputation analysis to evaluate the potential association of un-genotyped SLC1A1 single-nucleotide polymorphisms, and 165 single-nucleotide polymorphisms were imputed.
Results: We observed an increased frequency of the G allele of rs10739062 in patients compared to controls (p = 0.043, OR = 1.25). The rs10739062 polymorphism exhibited a dominant effect: individuals with genotype GG and GC showed a 1.91-fold increase in risk compared to genotype CC (p = 0.0082). However, the statistical significance disappeared after Bonferroni correction for multiple testing (pc&gt;0.05). We did not find any significant association between any of the remaining 176 single-nucleotide polymorphisms and disease risk.
Conclusions: Our study showed a lack of association between SLC1A1 variants and normal tension glaucoma in Japanese patients, suggesting that the SLC1A1 gene does not play a critical role in the development of the disorder in this patient population. However, further genetic studies with larger sample sizes are needed to clarify whether SLC1A1 may make some contribution that affects the risk of developing normal tension glaucoma.

DOI： 10.3109/13816810.2015.1028649

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Purpose. To evaluate the restoration of the ellipsoid zone (EZ) and its influence on visual prognosis 1 year after surgical macular hole (MH) closure. Method. Subjects were patients with stage 2, 3, or 4 idiopathic MH who underwent primary vitrectomy that resulted in successful hole closure. Nineteen eyes with both EZ disruption with foveal detachment and a continuous external limiting membrane on optical coherence tomography during the early postoperative period were included in this study. Result. EZ disruption was restored in 10 eyes (53%, Group A) and remained in 9 eyes (47%, Group B) at 1 year after surgery. In Group B, the diameter of the residual EZ disruption was 54.7 +/- 33.1 mu m. LogMAR visual acuity (VA) 1 year after surgery was significantly better than preoperative VA in each group (Group A: -0.007 +/- 0.102; P &lt; 0.001; Group B: 0.051 +/- 0.148; P &lt; 0.001), but there was no significant difference between the 2 groups (P = 0.332). There was no significant correlation between logMAR VA and EZ disruption diameter at 1 year after surgery. Conclusion. EZ was restored in 53% of eyes at 1 year after surgical closure of idiopathic MH. Mean residual EZ disruption diameter was 54.7 +/- 33.1 mu m. Neither resolved nor residual EZ disruption influenced postoperative VA.

DOI： 10.1155/2016/1769794

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DOI： 10.1038/eye.2016.190

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Other Link： http://orcid.org/0000-0003-2853-1308

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Other Link： http://search.jamas.or.jp/link/ui/2016052839

Language：Japanese   Publisher：新潟医療福祉学会  

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DOI： 10.1155/2015/181269

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DOI： 10.11477/mf.1410211402

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DOI： 10.11477/mf.1410211417

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：Japanese   Publisher：(株)医学書院  

目的:新潟大学病院で過去7年間に加療した急性網膜壊死(ARN)の報告。対象と方法:2013年までの7年間に当院を受診したARNの12例12眼を検索し,その治療成績を解析した。男性7例,女性5例で,年齢は25〜76歳,平均53歳であった。結果:全例が片眼発症であった。初診時に採取した前房水から,単純ヘルペスウイルスが3眼,水痘・帯状疱疹ウイルスが9眼で陽性であった。経過中に網膜剥離が7眼に発症し,5眼には発症しなかった。網膜剥離の有無は,ARN発症から受診までの日数とは相関がなかった。網膜剥離の原因は,2眼では増殖膜により牽引,5眼では裂孔原性であった。初診時に硝子体混濁が7眼にあり,うち6眼に網膜剥離が生じた。網膜剥離の全例に対して硝子体手術を行い,シリコーンオイル充填などを併用した。全7眼で網膜が復位した。結論:当院でのARNはすべて片眼性であった。経過中の網膜剥離発症は,初診時に硝子体混濁のある例に多かった。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: To report a case of acute glaucoma due to complete ring cyst of the ciliary body.
Patients and Methods: A 33-year-old woman experienced blurred vision in her left eye. Intraocular pressure of the left eye was elevated accompanied with a very shallow anterior chamber. Anterior segment-optical coherence tomography and ultrasound biomicroscopy detected ring-shaped ciliary masses in the both eyes. Myopic change and contact between the ciliary mass and lens in the left eye suggested the presence of aqueous misdirection resulting in forward displacement of the lens-iris diaphragm. Because elevated intraocular pressure was refractory to conservative management, the left eye underwent clear lens aspiration and implantation of intraocular lens.
Results: Although the anterior chamber became deep in the left eye initially after lens extraction in conjunction with core vitrectomy, possible aqueous misdirection recurred. Second vitrectomy in the left eye together with posterior and anterior capsulotomies, to establish humoral communication between the anterior and posterior chambers, deepened the anterior chamber and lowered the intraocular pressure. The anterior chamber in the fellow right eye remained deep a year after the episode.
Conclusions: This is the first reported case of bilateral ring cysts of the ciliary body. The manifestation caused secondary glaucoma, which was resolved by lensectomy and vitrectomy.

DOI： 10.1097/IJG.0b013e31827a088c

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Purpose: To report the 5-year incidence of bleb-related infection after mitomycin Ceaugmented glaucoma filtering surgery and to investigate the risk factors for infections.
Design: Prospective, observational cohort study.
Participants: A total of 1098 eyes of 1098 glaucoma patients who had undergone mitomycin Ceaugmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation performed at 34 clinical centers.
Methods: Patients were followed up at 6-month intervals for 5 years, with special attention given to bleb-related infections. The follow-up data were analyzed via Kaplan-Meier survival analysis and the Cox proportional hazards model.
Main Outcome Measures: Incidence of bleb-related infection over 5 years and risk factors for infections.
Results: Of the 1098 eyes, a bleb-related infection developed in 21 eyes. Kaplan-Meier survival analysis revealed that the incidence of bleb-related infection was 2.2 +/- 0.5% (cumulative incidence +/- standard error) at the 5-year follow-up for all cases, whereas it was 7.9 +/- 3.1% and 1.7 +/- 0.4% for cases with and without a history of bleb leakage, respectively (P = 0.000, log-rank test). When only eyes with a well-functioning bleb were counted, it was 3.9 +/- 1.0%. No differences were found between the trabeculectomy cases and the combined surgery cases (P +/- 0.398, log-rank test) or between cases with a fornix-based flap and those with a limbal-based flap (P = 0.651, log-rank test). The Cox model revealed that a history of bleb leakage and younger age were risk factors for infections.
Conclusions: The 5-year cumulative incidence of bleb-related infection was 2.2 +/- 0.5% in eyes treated with mitomycin Ceaugmented trabeculectomy or trabeculectomy combined with phacoemulsification and intraocular lens implantation in our prospective, multicenter study. Bleb leakage and younger age were the main risk factors for infections. (C) 2014 by the American Academy of Ophthalmology.

DOI： 10.1016/j.ophtha.2013.11.025

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Purpose:To investigate the significance of vision-specific quality of life (QOL) in glaucoma patients based on the location of visual field defects.Patients and Methods:We examined 336 eyes of 168 patients. The 25-item National Eye Institute Visual Function Questionnaire was used to evaluate patients' QOL. Visual field testing was performed using the Humphrey Field Analyzer; the visual field was divided into 10 clusters. We defined the eye with better mean deviation as the better eye and the fellow eye as the worse eye. A single linear regression analysis was applied to assess the significance of the relationship between QOL and the clustered visual field.Results:The strongest correlation was observed in the lower paracentral visual field in the better eye. The lower peripheral visual field in the better eye also showed a good correlation. Correlation coefficients in the better eye were generally higher than those in the worse eye. For driving, the upper temporal visual field in the better eye was the most strongly correlated (r=0.509). For role limitation and peripheral vision, the lower peripheral visual field in the better eye had the highest correlation coefficients at 0.459 and 0.425, respectively.Conclusions:Overall, clusters in the lower hemifield in the better eye were more strongly correlated with QOL than those in the worse eye. In particular, the lower paracentral visual field in the better eye was correlated most strongly of all. Driving, however, strongly correlated with the upper hemifield in the better eye.

DOI： 10.1097/IJG.0b013e318265bbdc

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORPORATION  

Purpose. To evaluate the effect on intraocular pressure (IOP) of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG). Methods. 27 NTG patients (54 eyes) were compared IOP, superficial punctuate keratitis (SPK) scores, and conjunctival injection scores in eyes treated with prostaglandin (PG) or PG analog/beta-blocker (PG/b) fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4 +/- 1.59 mm Hg in eyes receiving PG therapy only and 17.4 +/- 1.69 mm Hg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1 +/- 1.79 mm Hg (P &lt; 0.001) (-24.71% reduction from baseline) at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P = 0.028). The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P = 0.463). Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.

DOI： 10.1155/2014/720385

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORPORATION  

Purpose. To compare a new digital Goldmann applanation tonometer (dGAT) that measures intraocular pressure (IOP) in 0.1 mmHg increments to a standard Goldmann applanation tonometer (sGAT). Methods. This study included 116 eyes of 60 subjects. A single examiner first measured IOP in triplicate using either sGAT or dGAT, which was randomly chosen. After a 5-minute interval, the next set of three consecutive IOP was measured using the other GAT. Results. The mean IOP measured with sGAT was 16.27 +/- 6.68 mmHg and 16.35 +/- 6.69 mmHg with dGAT. Pearson's correlation coefficient was 0.998 (P &lt; 0.01). The subjects were divided into three groups based on the mean IOP: IOP &lt; 14 mmHg, 14-20 mmHg, or &gt;20 mmHg. The Pearson's correlation coefficient within each group was 0.935, 0.972, and 0.997 (P &lt; 0.01), respectively. The difference within the three consecutive IOP measurements (maximum-minimum) for dGAT (0.72 +/- 0.34 mmHg) was significantly smaller than those with sGAT (0.92 +/- 0.42 mmHg, P &lt; 0.01). Even in patients with equal IOP (zero left-right difference) with sGAT (n = 30), dGAT detected IOP differences between the left and right eyes (0.47 +/- 0.31 mmHg). Conclusion. Compared to sGAT, dGAT measurements are highly reproducible and less variable.

DOI： 10.1155/2014/461681

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DOI： 10.4263/jorthoptic.042F023

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Purpose:The purpose of this study was to analyze the relationship between the mean deviation (MD) slope as the progressive rate of visual field defects and the follow-up intraocular pressure (IOP) in open-angle glaucoma (OAG) patients.Methods:This study was a retrospective, nonrandomized comparative study. A total of 287 eyes from 287 Japanese OAG patients were examined. The MD slope of the Humphrey Field Analyzer was calculated and compared with the follow-up IOP. OAG was classified into the high-tension group (&gt;21 mm Hg) and the normal-tension group (21 mm Hg) on the basis of the highest recorded IOP without treatment, and then the 2 groups were compared. After setting a threshold for the progression rate at -0.3 dB/y, related factors were compared between the fast-progression and slow-progression eyes in each group.Results:The correlation line between the follow-up IOP and the MD slope was statistically significant in the high-tension group but not in the normal-tension group. Compared with eyes with slow progression, eyes with fast progression in the high-tension group were older and had a higher mean IOP, greater highest and lowest IOPs, and a smaller mean IOP reduction ratio, whereas eyes with fast progression in the normal-tension group had a greater SD of the mean IOP, a larger IOP range, and a greater highest IOP.Conclusions:Eyes with a faster visual field progression tended to have a higher follow-up IOP in the high-tension group and larger IOP fluctuations in the normal-tension group of OAG patients. We should monitor both the follow-up IOP and fluctuations in IOP to provide a safer and more reliable visual field prognosis for OAG.

DOI： 10.1097/IJG.0b013e318264b779

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Other Link： http://search.jamas.or.jp/link/ui/2014137475

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本眼科手術学会  

目的:マイトマイシンC併用トラベクレクトミー(MMCレクトミー)既往眼に対する白内障手術後の眼圧経過について検討した。対象および方法:対象は2001〜2008年に白内障手術を行われたMMCレクトミー既往眼のうち、術後24ヵ月以上経過観察が可能であった開放隅角緑内障37例48眼である。白内障手術術前眼圧値と術後24ヵ月までの眼圧値を比較し、検討した。結果:全症例および病型ごとで術前、術後12ヵ月、24ヵ月の時点での平均眼圧値に有意な差はなかった。術後24ヵ月で術前より3mmHg以上上昇は9眼(18.8%)、2mmHg以上上昇は17眼(35.4%)だった。術前眼圧12mmHg未満の24眼のうち、術後24ヵ月に12mmHg以上となったのは12眼(50.0%)で、12mmHg未満維持の12眼より白内障手術前眼圧値が有意に高く、MMCレクトミーから白内障手術までの期間が有意に短かった。結論:MMCレクトミー既往眼に対する白内障手術後の眼圧経過について術前・術後で全体の平均眼圧に統計学的な差はなかった。しかし、一部の症例では眼圧は上昇しており、注意を要する。(著者抄録)

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Reading performance in glaucoma patients has yet to be studied. We hypothesized that glaucomatous visual field loss affects reading performance even in patients with good acuity and evaluated their reading performance quantitatively.
A cross-sectional, comparative, non-interventional study. Forty-nine patients with early-moderate glaucomatous visual field loss OU with visual acuity better than 1.0 in the better and 0.7 in the worse eye. Reading performance in glaucoma patients was examined by the Japanese version of the Minnesota Reading Acuity Chart (MNREAD) were compared to that of age-matched normal subjects (n = 30).
The study subjects consisted of the 21 men and 28 women. The mean age was 53.3 +/- A 12.6 years. Diagnosis included primary open-angle glaucoma (n = 22), normal-tension glaucoma (n = 22), developmental glaucoma (n = 4) and exfoliation glaucoma (n = 1). Reading parameters of glaucoma patients examined by MNREAD were: maximum reading speed (MRS), 329.9 +/- A 55.4 characters per min.; critical print size (CPS), 0.24 +/- A 0.14 logMAR; reading acuity (RA), 0.02 +/- A 0.12 log MAR, significantly lower than those of normal subjects (MRS 363.0 +/- A 42.9, CPS 0.09 +/- A 0.13 logMAR, RA -0.13 +/- A 0.10 logMAR, P &lt; 0.01 for three parameters by unpaired t test). CPS in glaucoma subjects was negatively correlated with mean deviation of Humphrey Field Analyzer 10-2 and 30-2 programs in the better eye (r = -0.402, P &lt; 0.005; r = -0.304, P &lt; 0.05; respectively, by linear regression analysis).
The reading performance deteriorated even in glaucoma patients with good acuity.

DOI： 10.1007/s10384-013-0259-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

We describe a method that enables the introduction of 2 suture loops for scleral fixation of an intraocular lens (IOL) by a single ab externo procedure. A long needle carrying a polypropylene suture loop is inserted through the scleral fixation site and docked with a hollow needle inserted through the opposite fixation site. The hollow needle pulls the suture needle out, but the suture loop end is left external. Another polypropylene suture loop is placed through the first loop. As the first (leading) suture is pulled, the second (trailing) suture is drawn into the eye. The suture loops are retrieved through the main incision. The IOL haptics are secured with a polypropylene loop by cow hitches. After the IOL is placed in the eye, the sutures are fixated to the sclera. This technique enhances efficiency and control during the introduction of suture loops for scleral fixation of IOLs.

DOI： 10.1016/j.jcrs.2013.07.003

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DOI： 10.11477/mf.1410104856

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Other Link： http://hdl.handle.net/10191/36093

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

To investigate the incidence of adverse effects on eyelids and eyelashes related to treatment with prostaglandin analogs (PGAs) in patients who apply the medication in only one eye.
A clinical examination of 39 glaucoma patients treated for over 3 months continuously in one eye with one of four PGAs. Face photographs were used to judge adverse effects of PGA treatment on eyelids and eyelashes of the treated eyes by comparing them with the eyelids and eyelashes of the contralateral eyes. Each of three examiners then calculated scores for the eyelids and eyelashes by counting how many adverse effects were present (out of five possible effects for eyelids and two for eyelashes). The findings for the eyelids or eyelashes were considered "positive" if two or more examiners judged that at least one adverse effect was present.
Thirty-five (89.7 %) patients were judged to have positive eyelid findings and 37 (94.9 %) patients were judged to have positive eyelash findings. There was a significant correlation between the period of PGA administration and eyelid score (P = 0.0218).
There was a high incidence of adverse effects caused by PGAs in the eyelids and eyelashes. The frequency of adverse effects of the eyelid seemed to increase as the use of PGAs was prolonged. The cosmetic complications caused by PGA use should be considered, and patients should be informed of them in advance.

DOI： 10.1007/s10384-012-0199-3

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Although family studies and genome-wide association studies have shown that genetic factors play a role in glaucoma, it has been difficult to identify the specific genetic variants involved. We tested 669 single nucleotide polymorphisms (SNPs) from the region of chromosome 2 that includes the GLC1B glaucoma locus for association with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese population. We performed a two-stage case-control study. The first cohort consisted of 123 POAG cases, 121 NTG cases and 120 controls: the second cohort consisted of 187 POAG cases, 286 NTG cases, and 271 controls. Out of six SNPs showing significant association with POAG in the first round screening, seven SNPs were tested in the second round. Rs678350 in the HK2 gene coding sequence showed significant allelic (p = 0.0027 in Stage Two, 2.7XE-4 in meta-analysis) association with POAG, and significant allelic (p = 4.7XE-4 in Stage Two, 1.0XE-5 in meta-analysis) association with NTG. Although alleles in the TMEM182 gene did not show significant association with glaucoma in the second round, subjects with the A/A allele in TMEM182 rs869833 showed worse visual field mean deviation (p = 0.01). Even though rs2033008 in the NCK2 gene coding sequence did not show significant association in the first round, it had previously shown association with NTG so it was tested for association with NTG in round 2 (p = 0.0053 in Stage Two). Immunohistochemistry showed that both HK2 and NCK2 are expressed in the retinal ganglion cell layer. Once multi-testing was taken into account, only HK2 showed significant association with POAG and NTG in Stage Two. Our data also support previous reports of NCK2 association with NTG, and raise questions about what role TMEM182 might play

DOI： 10.1371/journal.pone.0054115

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

PURPOSE: To determine whether polymorphisms in the Toll-like receptor 4 (TLR4) gene are associated with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and exfoliation glaucoma (XFG) in Japanese individuals.
DESIGN: Genetic association study.
METHODS: SETTING: Multicenter study. STUDY POPULATION: One hundred eighty-four unrelated Japanese patients with POAG, 365 unrelated patients with NTG, and 109 unrelated patients with XFG from 5 hospitals. PROCEDURES: Genomic DNA was extracted from leukocytes of the peripheral blood, and 8 polymorphisms in the TLR4 genes were amplified by polymerase chain reaction (PCR) and directly sequenced. Allele and genotype frequencies and the inferred haplotypes were estimated. MAIN OUTCOME MEASURES: Differences in allele and genotype frequencies and haplotypes between subjects with POAG, NTG, and XFG.
RESULTS: The allele frequency of rs2149356 of the TLR4 gene in the POAG, NTG, and XFG groups was the most significantly different from that of the control group (minor allele frequency 0.446, 0.395, 0.404, vs 0.308; P = .000058, P = .0030, and P = .015). The allele frequencies of the 5 TLR4 SNPs were higher in all of the glaucoma groups than that in the control group. The statistics of genotypes of TLR4 were approximately the same for all allele frequencies. The haplotypic frequencies with Tag SNPs studied earlier showed that only POAG was statistically significant. Other haplotypes, such as rs10759930, rs1927914, rs1927911, and rs2149356, had higher statistical significance (overall P = .00078 in POAG, overall P = .018 in NTG, and overall P = .014 in XFG).
CONCLUSIONS: This study demonstrated that TLR4 polymorphisms are associated with NTG in the Japanese, and they also play a role in the pathogenesis of POAG and XFG. (Am J Ophthalmol 2012;154:825-832. (C) 2012 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2012.03.050

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：B M J PUBLISHING GROUP  

Background/aims To analyse quantitatively the anterior segment configuration in eyes with nanophthalmos before and after cataract surgery.
Methods This was a retrospective, non-comparative, interventional case series. Eleven eyes in eight patients with nanophthalmos who underwent phacoemulsification and intraocular lens implantation were identified from the department's surgical log, and their clinical records were retrospectively reviewed. Main outcome measures were as follows: visual acuity, intraocular pressure (IOP), axial length and the following ultrasound biomicroscopy parameters: angle opening distance at 500 mm anterior to the scleral spur (AOD500), trabecular-iris angle (TIA) and trabecular ciliary process distance.
Results The mean axial length of the eyes was 17.3 +/- 1.7 mm. AOD500 and TIA increased after cataract surgery (p&lt;0.005). Smaller axial length, AOD500 and TIA before cataract surgery were observed in eyes with preoperative IOP elevation than those without preoperative IOP elevation (p&lt;0.05). Lower postoperative IOP was correlated with greater AOD500 and TIA before cataract surgery (p&lt;0.05).
Conclusions Cataract surgery deepened the anterior chamber and widened the anterior chamber angle in nanophthalmic eyes. Cataract surgery may have beneficial effects on IOP in eyes with nanophthalmos.

DOI： 10.1136/bjophthalmol-2012-301496

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Fibrin pupillary-block glaucoma is a rare complication after cataract surgery. The treatment for this condition is still controversial, since Nd:YAG laser fibrin membranotomy tends to reocclude and laser peripheral iridotomy entails the risk of damaging the corneal endothelium in the presence of corneal edema associated with elevated intraocular pressure.
Case presentation: A 62-year-old man with diabetes mellitus developed acute elevation of intraocular pressure with a shallow anterior chamber five days after uneventful cataract surgery. Initially, slit lamp examination provided only limited information due to severe corneal edema. After resolution of corneal edema with systemic glaucoma therapy, a complete fibrin membrane was observed across the pupil by slit lamp examination. Anterior segment optic coherence tomography clearly revealed a thin fibrin membrane covering the entire pupillary space, a shallow anterior chamber, and a deep posterior chamber. The intraocular lens was not observed by anterior segment optic coherence tomography. In contrast, ultrasound biomicroscopy, which has superior penetration depth, was able to visualize the intraocular lens deep in the posterior chamber. Injection of tissue plasminogen activator into the anterior chamber resulted in complete fibrinolysis and released the pupillary block.
Conclusion: This case suggests that ocular anterior segment imaging modalities, especially ultrasound biomicroscopy, serve as powerful diagnostic tools to identify mechanisms of acute angle closure glaucoma, which is often accompanied by poor intraocular visibility. This is the first reported case of fibrin pupillary-block glaucoma after cataract surgery successfully treated with intracameral tissue plasminogen activator.

DOI： 10.1186/1471-2415-12-3

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We compared two types of visual field index including mean deviation (MD) and the visual field index (VFI) for assessing the relationship between quality of life (QOL) and the loss of visual field in open-angle glaucoma patients.
We examined 336 eyes of 168 consecutive glaucoma patients. All participants completed the Japanese version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Visual field testing using the Humphrey Field Analyzer (HFA) was performed to obtain both MD and VFI in the bilateral eyes of each patient. We defined eyes of better MD or VFI as the better eye and the fellow eyes as the worse eye. Visual field data and scores of NEI VFQ-25 were compared between patients with normal tension glaucoma (NTG) and patients with primary open-angle glaucoma (POAG). A single linear regression analysis was applied to assess the significance of the relationship between QOL and visual field, and to compare the strength of correlations between MD and the VFI. An unpaired t test was used for the comparison the data between NTG and POAG.
A significant relationship was observed between QOL and visual field in nine subscales and the composite in both the better eye and the worse eye. The relationship was stronger in the better eye than in the worse eye. The correlation coefficients of the VFI were slightly higher than those of MD overall. The highest correlation coefficients were demonstrated in ten subscales and the composite in the better eye of the VFI. Only the score for general vision was significantly higher in NTG patients than POAG patients.
A significant relationship was found between QOL and both the VFI and MD, but the VFI had a marginally better correlation than that of MD. While QOL was better related with visual field loss in the better eye than in the worse eye, the difference was not large. Not much of a difference was found in the status of QOL between NTG patients and POAG patients.

DOI： 10.1007/s00417-011-1779-5

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DOI： 10.1016/j.ajo.2010.11.028

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To verify the advantages of trabeculotomy combined with phacoemulsification, intraocular lens implantation and sinusotomy (PTOS) in eyes with exfoliation glaucoma (XFG) and a coexisting cataract.
Sixty-six eyes of 62 Japanese XFG patients that received either PTOS, phacotrabeculectomy (PTE) or MMC trabeculectomy (LEC) were followed for up to 36 months at Niigata University Medical and Dental Hospital. The outcomes of postoperative intraocular pressure (IOP) and visual acuity as well as complications were compared among the patients who underwent the three surgical procedures.
The average preoperative IOP in the PTOS cases was 22.4 +/- A 5.13 mmHg, but decreased to 12.3 +/- A 2.33 mmHg at 12 months post-surgery and was maintained for up to 36 months. The preoperative IOPs, which were 21.9 +/- A 4.18 mmHg in the PTE group and 26.6 +/- A 7.57 mmHg in the LEC group, decreased to 13.3 +/- A 2.79 mmHg in the PTE group and 12.6 +/- A 6.00 mmHg in the LEC group at 12 months. There were no statistical differences among the three groups at any time point after 3 months. While the postoperative corrected visual acuities were similar between the PTOS and PTE groups, the average time in which the best postoperative visual acuity was reached was significantly shorter in the PTOS group (1.37 +/- A 1.74 months) than in the PTE group (4.92 +/- A 4.36 months).
PTOS can be recommended as an initial glaucoma surgery for XFG eyes with coexisting cataracts, because PTOS is not a filtering surgery, but can obtain similar IOP effects as PTE for XFG eyes.

DOI： 10.1007/s10384-011-0024-4

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メディカル葵出版  

目的:落屑緑内障眼の角膜内皮細胞所見について検討した。対象および方法:対象は緑内障手術の適応となった落屑緑内障患者47例で、手術眼を落屑緑内障手術群(XFG手術群)とし、その僚眼を落屑緑内障非手術群(XFG非手術群)とした。原発開放隅角緑内障患者63例63眼(OAG群)、加齢白内障患者47例47眼(CAT群)と比較した。スペキュラーマイクロスコープにより細胞密度(CD)、平均細胞面積、六角形細胞出現率、変動係数を計測し比較した。結果:XFG手術群、非手術群、OAG群、CAT群のCDはそれぞれ2408±236、2514±254、2601±295、2829±306(cells/mm2)で、XFG非手術群とOAG群間以外のすべての群間で有意差がみられた。XFG手術群のCDと発見時眼圧、経過観察期間との間に有意な相関がみられた。結論:落屑緑内障眼ではCDは有意に小さかった。発見時眼圧が高く経過観察期間が長いほどCDが小さい傾向がみられた。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOLECULAR VISION  

Purpose: To investigate whether the solute carrier family 1, member 3 (SLC1A3) gene, which encodes the glutamate aspartate transporter, is associated with normal tension glaucoma (NTG) in Japanese patients.
Methods: Two hundred and ninety-five Japanese patients with NTG and 518 Japanese healthy controls were recruited. Patients exhibiting comparatively early NTG onset were selected because early onset suggests that genetic factors may show stronger involvement. We genotyped 5 single-nucleotide polymorphisms (SNPs) in SLC1A3 and assessed the allelic and genotypic diversity among cases and controls.
Results: There were no statistically significant differences in the frequency of SLC1A3 alleles and genotypes between cases and controls.
Conclusions: Our study showed no association between SLC1A3 and NTG, suggesting that the SLC1A3 gene may not be an associated factor in NTG pathogenesis.

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Purpose: To evaluate the correlation between quality of vision (QOV) and visual function in glaucoma patients. Patients and methods: The relationship between QOV and visual function was investigated in 200 Japanese glaucoma patients. QOV was assessed using the Japanese version of the 25-item National Eye Institute Visual Function Questionnaire. The better eye and the worse eye were defined based on the mean deviation (MD) value of the Humphrey Field Analyzer program 30-2. A single linear regression analysis was applied to assess the relationship. Results: The lowest subscale score was observed in general health followed by general vision and driving. Visual acuity and the central 10° MD value in the better eye and the central 30° MD value in the worse eye were highly correlated with QOV. Threshold MD values at which patients began to have lower QOV ranged from -2 to -12 dB in the better eye and from -7 to -16 dB in the worse eye. Conclusion: Loss of visual function in both the better and the worse eye is significantly correlated to QOV. QOV of glaucoma patients begins to decrease in the early stages of visual field defects. © 2011 Sawada et al.

DOI： 10.2147/OPTH.S16989

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PURPOSE: To report corneal lamellar grafting to repair the late-onset complications after MMC trabeculectomy. METHODS: Multiple case reports. RESULTS: A 76-year-old male with primary open-angle glaucoma (POAG) and a 55-year-old male with late developmental glaucoma complicated by bleb leaks from a microhole 10 and eight years after surgery, respectively. Severe ciliochoroidal detachment and a shallow anterior chamber were persistent in one case and bleb-related infection recurred in another. Additionally, a 46-year-old male with POAG had hypotony maculopathy with a giant ischemic bleb 18 months after surgery. Although these patients were quite resistant to medical and surgical treatments, they were successfully treated by corneal lamellar grafting without complications. CONCLUSIONS: Tectonic corneal lamellar grafting is a reliable and final surgical method to improve severe cases of hypotony maculopathy or bleb leak after mitomycin C trabeculectomy.

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Purpose: To investigate whether the GLC1F locus is associated with normal tension glaucoma (NTG) in Japanese patients.
Methods: We recruited 242 unrelated Japanese subjects, including, 141 NTG patients and 101 healthy controls. The patients exhibiting a comparatively early onset were selected as they suggest that genetic factors may show stronger involvement. Genotyping and assessment of allelic diversity was performed on 11 highly polymorphic microsatellite markers in and around the GLC1F locus.
Results: Individuals carrying the 163 allele of D7S1277i had a statistically significant increased risk of NTG (p=0.0013, pc=0.016, OR=2.47, 95% CI=1.42-4.30). None of the other markers identified significant loci (pc&gt;0.05) after Bonferroni's correction.
Conclusions: These findings suggested that the genes in the GLC1F locus may be associated with the pathogenesis of NTG.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To investigate the concentration of tumor necrosis factor (TNF)-alpha in the aqueous humor of patients with glaucoma, including correlations with glaucoma subtypes and intraocular pressure.
METHODS. The study population comprised 84 patients with open-angle glaucoma who were scheduled for filtration or cataract surgery. Glaucoma subgroups included 29 cases of primary open-angle glaucoma (POAG), 28 cases of normal-tension glaucoma (NTG), and 27 cases of exfoliation glaucoma (ExG). Seventy-nine patients with senile cataract were recruited as control subjects. The concentrations of TNF-alpha in the aqueous humor were measured with an enzyme-linked immunosorbent assay. The percentages of samples positive for TNF-alpha and the measured concentrations in the glaucoma and cataract groups were compared. In addition, the relationships with the glaucoma subtypes, intraocular pressure, and glaucoma severity were analyzed.
RESULTS. A significantly higher percentage of subjects in the glaucoma group were positive for TNF-alpha compared with the cataract group (P = 0.011). The mean TNF-alpha concentrations among the positive cases were not different between the groups (P = 0.689). TNF-alpha-positive samples were higher in the POAG (13.7%) and NTG (10.7%) subgroups than in the cataract group without significance, but higher in ExG subgroup (29.6%) with significance (P = 0.001). Relationships between the TNF-alpha concentration and the intraocular pressure or the clinical stage of glaucoma were not observed.
CONCLUSIONS. TNF-alpha levels were significantly higher in the glaucoma group than in the cataract group, with a particularly large difference observed in those with ExG. The results suggest that TNF-alpha plays a key role in the progression of glaucoma. (Invest Ophthalmol Vis Sci. 2010; 51: 903-906) DOI:10.1167/iovs.09-4247

DOI： 10.1167/iovs.09-4247

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Purpose: Normal tension glaucoma (NTG) is a subtype of glaucoma in which intraocular pressure is within the statistically normal range. NTG may be associated with an immune disorder. The aim of this study was to determine whether specific alleles in the human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 genes correlated with NTG in Japanese patients. Methods: We genotyped the HLA-DRB1 and HLA-DQB1 alleles in 113 Japanese patients with NTG and in 184 healthy Japanese control subjects using the polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) Luminex method. We assessed the allelic diversity in patients and controls. Results: There were no statistically significant differences in the allele frequency of HLADRB1 and HLA-DQB1 between NTG patients and control subjects, and no HLA-DRB1-HLA-DQB1 haplotypes demonstrated any significant association with NTG. Conclusions: Our findings suggest that HLA-DRB1 and HLA-DQB1 polymorphisms have no significant effect on the development of NTG in Japanese patients. © 2010 Molecular Vision.

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Purpose: We evaluated the progression rate of total, and upper and lower visual field defects in treated open-angle glaucoma patients. Patients and methods: This study was a retrospective, nonrandomized, comparative study. Five-hundred forty-four eyes from 315 Japanese open-angle glaucoma patients were examined. The mean deviation (MD) and total deviation (TD) for both the upper and lower slopes on the Humphrey Field Analyzer were calculated and compared in high-tension glaucoma (&gt
21 mmHg) and normal-tension glaucoma (≤21 mmHg). Results: Patients with over -20 dB of MD and over -23 dB of upper or lower TD were enrolled into each analysis. Patients with -7.75 ± 5.30 (mean ± standard deviation) dB of MD, -9.16 ± 10.80 dB of upper TD, or -7.11 ± 6.02 dB of lower TD were followed up for 4-19 years. The mean MD slope was -0.41 ± 0.50 dB/year, the upper TD slope was -0.46 ± 0.65 dB/year, and the lower TD slope was -0.32 ± 0.53 dB/year. Comparing high-tension glaucoma and normal-tension glaucoma, the upper TD slope was similar for both types of glaucoma, but the MD and lower TD slopes in high-tension glaucoma were significantly lower than those in normal-tension glaucoma. Conclusions: The progression rates in lower visual field defects in high-tension glaucoma might be faster than those in normal-tension glaucoma. The results of this study might be used to predict the prognosis of visual field defects, as well as the quality of vision in patients with open-angle glaucoma. © 2010 Fukuchi et al.

DOI： 10.2147/OPTH.S13101

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The exact role of cyclooxygenase-2 (COX-2) in neurodegeneration of retinal ganglion cells (RGCs) in vivo following ischemia-reperfusion injury of the retina was unknown. We made transgenic mice in which the Thy-1.2 promoter drives the expression of EGFP cDNA (Thy-1-EGFP) in RGCs to monitor RGC survival and death in retinal whole mount preparations and in live animals. We show that celecoxib, a selective COX-2 inhibitor, blocks RGC death after ischemic injury. Furthermore, in COX-2 knockout (COX-2(-/-)) mice, RGCs are resistant to ischemia-reperfusion injury. Finally, we performed time-lapse monitoring of RGC death after ischemia in Thy-1-EGFP; COX-2(-/-) mice. Our data show that COX-2 plays a crucial role in ischemia-reperfusion injury-induced RGC death. Inhibition of COX-2 activity may therefore be an effective therapy for neurodegenerative diseases of the retina and optic nerve. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2009.08.008

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Purpose: Toll-like receptor 2 (TLR2) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands, and interacts with heat-shock proteins, which are reportedly involved in normal tension glaucoma (NTG). We investigated whether TLR2 polymorphisms are associated with NTG.
Methods: 200 Japanese patients with NTG and 128 healthy Japanese controls were recruited. We genotyped five single-nucleotide polymorphisms (SNPs) in the TLR2 gene and assessed the allele and haplotype diversities between cases and controls for all SNPs.
Results: No significant differences in the frequency of TLR2 alleles and haplotypes in the NTG cases were detected, compared with the controls.
Conclusions: Our study showed no evidence for an association between TLR2 polymorphisms and NTG. TLR2 polymorphisms may not play an important role in NTG pathogenesis in the Japanese population.

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DOI： 10.1007/s10384-009-0742-z

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To examine the composition of scleral sulfated proteoglycans in three nanophthalmic eyes by electron microscopic histochemistry.
Scleral tissues from three cases of nanophthalmos were collected from the Niigata University Hospital for transmission electron microscopic examination. Sulfated proteoglycans were studied using the cuprolinic blue (CB) dye binding method in conjunction with enzymatic digestion.
Compared with the controls, the nanophthalmic sclerae were much thicker, and the collagen fibrils showed a less orderly arrangement. Twisting or fraying of collagen fibrils was noted in some areas, and fine fibrous materials surrounded the abnormal fibrils. CB-positive proteoglycan filaments were found around the collagen fibrils and in the fine fibrous materials in the nanophthalmic specimens. The number of proteoglycan filaments was smaller than that in the normal specimens. After enzymatic digestion, the CB-positive filaments were identified as dermatan/chondroitin sulfate proteoglycans. Although the number of dermatan sulfate filaments in nanophthalmos sclerae was similar to that in the controls, there were many fewer chondroitin sulfate filaments.
A loss of chondroitin sulfate proteoglycan was observed in nanophthalmic sclerae. The alteration may be related to the abnormal organization of collagen fibrils and the onset of uveal effusion.

DOI： 10.1007/s10384-008-0641-8

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PURPOSE: To investigate whether the GLC3A locus harboring the CYP1B1 gene is associated with normal tension glaucoma (NTG) in Japanese patients. MATERIALS AND METHODS: One hundred forty-two Japanese patients with NTG and 101 Japanese healthy controls were recruited. Patients exhibiting a comparatively early onset were selected as this suggests that genetic factors may show stronger involvement. Genotyping and assessment of allelic diversity was performed on 13 highly polymorphic microsatellite markers in and around the GLC3A locus. RESULTS: There were decreased frequencies of the 444 allele of D2S0416i and the 258 allele of D2S0425i in cases compared to controls (P = 0.022 and P = 0.034, respectively). However, this statistical significance disappeared when corrected (Pc > 0.05). We did not find any significant association between the remaining 11 microsatellite markers, including D2S177, which may be associated with CYP1B1, and NTG (P > 0.05). CONCLUSIONS: Our study showed no association between the GLCA3 locus and NTG, suggesting that the CYP1B1 gene, which is reportedly involved in a range of glaucoma phenotypes, may not be an associated factor in the pathogenesis of NTG.

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BACKGROUND: To investigate whether the GPDS1 locus, a potential causative locus of pigment-dispersion syndrome, is associated with normal-tension glaucoma (NTG) in Japanese patients. MATERIALS AND METHODS: We used polymerase chain reaction amplification with sequence-specific primers to analyze 20 polymorphic microsatellite markers in and around the GPDS1 locus with an automated DNA analyzer and automated fragment detection by fluorescent-based technology. The DNA samples used for these analyses were obtained from ethnicity- and gender-matched patients, including 141 Japanese patients with NTG and 101 healthy controls. Patients exhibiting a comparatively early onset were selected as this suggests that genetic factors may show stronger involvement. RESULTS: One allele of D7S2462 exhibited a frequency that was significantly decreased in NTG cases compared to controls (P = 0.0013, Pc = 0.019, OR = 0.48, 95% CI = 0.30-0.75). Alleles at another six microsatellite loci were positively or negatively associated with NTG, but these associations did not retain statistical significance after Bonferroni correction (P < 0.05, Pc > 0.05). CONCLUSION: Our study showed a significant association between the GPDS1 locus and NTG, suggesting that there may be some genetic risk factor(s) in the development of NTG.

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Purpose: To investigate the levels of oxidative stress markers in human eyes with senile cataracts. Methods: We conducted a retrospective, case-controlled study of 57 patients with senile cataracts. To assess oxidative stress markers in the eye, we measured the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as the total protein levels in aqueous humor. Results: In aqueous humor, SOD and CAT activity levels were 0.133 0.020 and 1.223 0.081 U/ml, respectively; protein levels were 2.372 0.166 mg/ml (means SEM). We observed a significant increase in SOD activity and the protein level in progressed nuclear cataracts. No significant age-associated difference in antioxidant enzyme levels was detected. Conclusion: Significant increases in the levels of SOD activity and total protein correlated with the severity of the cataract but not with patient age, suggesting that progressed cataract is associated with molecules leaking from the lens capsule.

DOI： 10.1080/02713680802500960

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PURPOSE. Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands and interacts with heat shock proteins, which are reportedly involved in normal tension glaucoma (NTG). This study was undertaken to investigate whether TLR4 polymorphisms are associated with NTG.
METHODS. Two hundred fifty Japanese patients with NTG and 318 Japanese healthy control subjects were recruited. Eight single-nucleotide polymorphisms (SNPs) in the TLR4 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects.
RESULTS. Strong linkage disequilibrium was observed among all SNPs (D&apos; &gt;= 0.85), which were located in one haplotype block. With respect to allelic diversity, the minor allele of three SNPs (rs10759930, rs1927914, and rs7037117) carried a significantly increased risk of NTG. With regard to genotypic diversity, individuals with the minor allele of six SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, and rs7037117) had a 1.47- to 1.65-fold increased risk of NTG. rs7037117, located in the 3&apos;-untranslated region of TLR4, was most strongly associated with NTG, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 0.0038, P(c) = 0.0095).
CONCLUSIONS. Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.

DOI： 10.1167/iovs.07-1575

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Purpose: To present midterm results and problems pertaining to nonpenetrating lamellar trabeculectomy (NPT) with mitomycin C (MMC) for Japanese glaucoma patients.
Methods: Thirty-nine patients (39 eyes) with primary open-angle glaucoma or normal-tension glaucoma underwent NPT. The results were compared with those in patients treated by penetrating trabeculectomy (PT) with MMC. In addition, the NPT patients were classified into two groups (group A, 24 patients treated between April 1998 and April 1999; group B, 21 patients treated from May 1999 onward), and the results were compared.
Results: The average intraocular pressure (IOP) was 12.6 +/- 2.8mmHg with NPT and 12.4 +/- 3.0mmHg with PT. No statistical differences between NPT and PT were identified with respect to IOP at any time after surgery. A life-table analysis showed that the probability of success (good IOP control) was 37.2% with NPT and 62.5% with PT. No significant difference was detected in postoperative IOP change or in the probability of success between NPT groups A and B.
Conclusions: While postoperative IOP is similar between PT and NPT, the probability of success is better with PT than with NPT. Postoperative laser treatment after NPT is effective but sometimes has a negative influence on IOP control.

DOI： 10.1007/s10384-006-0381-6

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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 -&gt; A and c. 603T -&gt; A) and one SNP in MYOC ( c.227G -&gt; 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
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.

DOI： 10.1167/iovs.06-0196

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Purpose: To verify that postoperative management affects the outcome of mitomycin C (MMC) trabeculectomy and suture lysis.
Methods: A total of 108 eyes in 108 Japanese patients were treated with MMC trabeculectomy. They were divided into two groups based on when the operation was performed: group A, 57 eyes in 1998, and group B, 51 eyes in 2001. The results, including postoperative intraocular pressure (IOP), complications, and postoperative management, were compared between groups. In addition, they were evaluated by a Kaplan-Meier life-table analysis.
Results: Postoperative IOP was lower and the probability of success by life-table analysis was higher in group B than in group A. Postoperative management, including laser suture lysis and subconjunctival injection of 5-fluorouracil, was started significantly earlier in group B than in group A patients. Although more postoperative complications occurred in group B, none were severe and all were adequately managed.
Conclusions: Starting postoperative management earlier, particularly laser suture lysis, may be necessary to achieve lower and longer IOP control in MMC trabeculectomy.

DOI： 10.1007/s10384-006-0346-9

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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.

DOI： 10.1007/s00417-005-0200-7

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Purpose: To analyze the results of mitomycin C (MMC) trabeculectomy and laser suture lysis using either fornix-based (1713) or limbus-based (LB) conjunctival flaps.
Methods: Eighty-two Japanese glaucoma patients were treated by MMC trabeculectomy, with 38 eyes receiving an FB conjunctival flap and 44 eyes receiving an LB conjunctival flap. Postoperative intraocular pressure (IOP), the probability of success, and complications were compared between the FB and LB groups.
Results: The IOP of the FB group decreased from 21.6 +/- 7.90 mmHg to 9.75 +/- 3.23 mmHg at 12 months postoperation, and the IOP of the LB group decreased from 21.3 +/- 6.77 mmHg to 9.30 +/- 3.16 mmHg. The postoperative IOPs were similar in the two groups at all postoperative time points. A life-table analysis (Kaplan-Meier method) showed that the survival rate was similar in the two groups but tended to be lower in the early postoperative period in the FB group. Complications were similar also, with the exception of increased leakage in the FB group.
Conclusions: MMC trabeculectomy results were similar between FB and LB conjunctival flaps, in agreement with previous reports. However, increased care may be warranted when an FB flap is used in MMC trabeculectomy.

DOI： 10.1007/s10384-005-0323-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOLECULAR VISION  

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 &lt; 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 &lt; 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.

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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.Tl4484C) 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.

DOI： 10.1007/s10384-005-0290-0

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Other Link： http://search.jamas.or.jp/link/ui/2006046187

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Muller cells, the predominant glial cells in the retina, are thought to play important roles in the survival of retinal neurons. Previous studies have demonstrated that Muller cells express brain-derived neurotrophic factor (BDNF), which has a pronounced neurotrophic effect on retinal ganglion cells. In this study, we investigated whether Muller cells express and release BDNF in culture. Reverse transcriptase-PCR, immunocytochemistry and Western blotting revealed that Muller cells produce BDNF mRNA and protein. Using the enzyme-linked immunosorbant assay, BDNF protein levels in Muller cells and their conditioned medium were quantified, demonstrating that Muller cells produce and release high levels of BDNF. Noradrenaline administration caused an upregulation of BDNF mRNA and protein expression by cultured Muller cells. These results suggest that Muller cells may act as an endogenous source of BDNF in the retina. Furthermore, induction of BDNF expression by adrenergic agonists may provide a therapeutic approach to retinal neurodegenerative disorders.

DOI： 10.1007/s11064-005-7936-7

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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 -&gt; A; ACE/insertion(I)-deletion(D); CMA/-1930A -&gt; G; AGTR1/-731T -&gt; G, AGTR1/-521C -&gt; T, and AGTR1/1166A -&gt; C; AGTR2/3123C -&gt; A; and CYP11B2/-344T -&gt; 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 -&gt; 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 -&gt; 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.

DOI： 10.1167/iovs.04-1100

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Aims: This study sought to elucidate the effects of timolol and dorzolamide on intraocular pressure (IOP) and retinal ganglion cell (RGC) death in an experimental model of glaucoma in rat.
Methods: Mild elevation of IOP was induced in rats by intracameral injection of India ink and subsequent laser trabecular photocoagulation. IOP was measured before the surgical procedures and weekly thereafter. Timolol (0.5%), timolol XE (0.5%), dorzolamide (1%), and artificial tears ( vehicle) were topically applied daily. Retinal sections were prepared for histology to determine RGC number.
Results: Timolol, timolol XE, and dorzolamide induced a significant reduction in IOP (p&lt;0.05) and counteracted the reduction in RGC number that occurred in vehicle treated glaucomatous eyes (p&lt;0.05). The coefficient of correlation between RGC number and IOP was significant in the dorzolamide treated group (r=-0.908, p&lt;0.005), but not in other groups (p&gt;0.05).
Conclusions: Both timolol formulation and dorzolamide reduced IOP and protected RGCs in a rat model of experimental glaucoma. It cannot be ruled out that timolol might protect RGCs by additional mechanisms other than simply lowering of IOP.

DOI： 10.1136/bjo.2004.052860

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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--&gt;A, -857C--&gt;T, and -863C--&gt;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--&gt;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.

DOI： 10.1167/iovs.03-1403

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Purpose: In this study, we sought to elucidate changes in the levels of neurotrophin-3 (NT-3) in the rat retina throughout postnatal development and aging.
Methods: We demonstrated NT-3 localization in the retina by immunohistochemistry. Protein and mRNA levels of NT-3 were quantified by enzyme-linked immunosorbant assay and semiquantitative reverse transcriptase-polymerase chain reaction, respectively. NT-3 protein levels were assayed in the various regions of the central nervous system. Age-associated changes in protein and mRNA levels of NT-3 in the retinas were assessed.
Results: NT-3-immunoreactivity localized in the ganglion cell layer, inner nuclear layer, and outer nuclear layer. NT-3 content in the retina was relatively high in the examined regions of the central nervous system. Retinal NT-3 protein levels decreased after eye opening, whereas mRNA levels were constant. Both mRNA and protein levels of NT-3 in the retinas of aged animals remained constant.
Conclusions: Our observations suggest that NT-3 regulation in the retina is independent of increasing visual stimuli after eye opening. Stable expression of NT-3 in the adult retina suggests a possible role in the maintenance of the retinal environment throughout later life. (C) Japanese Ophthalmological Society 2004.

DOI： 10.1007/s10384-004-0093-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER DIABETES ASSOC  

Although neurotrophins have been assessed as candidate therapeutic agents for neural complications of diabetes, their involvement in diabetic retinopathy has not been fully characterized. We found that the protein and mRNA levels of brain-derived neurotrophic factor (BDNF) in streptozotocin-induced diabetic rat retinas were reduced to 49% (P&lt;0.005) and 74% (P&lt;0.05), respectively, of those of normal control animals. In addition, dopaminergic amacrine cells appeared to be degenerating in the diabetic rat retinas, as revealed by tyrosine hydroxylase (TH) immunoreactivity. Overall TH protein levels in the retina were decreased to one-half that of controls (P&lt;0.01), reflecting reductions in the density of dopaminergic amacrine cells and the intensity of TH immunoreactivity within them. To confirm the neuropathological implications of BDNF reduction, we administered BDNF protein into the vitreous cavities of diabetic rats. Intraocular administration of BDNF rescued dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of TH expression, demonstrating its therapeutic potential. These findings suggest that the early retinal neuropathy of diabetes involves the reduced expression of BDNF and can be ameliorated by an exogenous supply of this neurotrophin.

DOI： 10.2337/diabetes.53.9.2412

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Other Link： http://search.jamas.or.jp/link/ui/2004040891

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. This study sought to elucidate changes in the levels and distribution of brain-derived neurotrophic factor (BDNF) in the retina throughout aging and depending on visual experience.
METHODS. Protein and mRNA levels of BDNF were quantified by enzyme-linked inummosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RTPCR), respectively. Levels were assayed in the retinas of rats on postnatal day (P)2, P7, and P14 (approximate time of eye opening) and at 1 month (M), 3M, 8M, and 18M of age. Changes in BDNF expression and localization in the retina were assessed by immunohistochemistry. The effect of monocular deprivation during infancy on retinal BDNF expression was also examined, by ELISA and immunohistochemistry.
RESULTS. Both protein and mRNA levels of BDNF in the rat retina increased after P14. Immunohistochemical analyses revealed that the increase in BDNF protein levels occurred in retinal ganglion cells (RGCs) between P14 and 1M. BDNF immunoreactivity in Muller cell processes was observed in the inner nuclear layer at 1M, but not at P14. The levels of BDNF protein in the retinas of visually deprived eyes were lower than those of control eyes, as quantified by ELISA. Immunohistochemistry showed that BDNF immunoreactivity in RGCs was diminished by visual deprivation, whereas Muller cells were unaffected.
CONCLUSIONS. These observations indicate that BDNF expression in RGCs is upregulated in an activity-dependent manner, whereas that in Muller cells is regulated only by development.

DOI： 10.1167/iovs.02-1089

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Purpose: To examine the expression and localization of heat shock proteins (HSPs) in the retinas of normal and experimentally induced primate glaucoma eyes. These proteins are known to be produced in response to a variety of stresses.
Methods: Experimental glaucoma was induced in the right eyes of three adult monkeys by repeated applications of argon laser to the chamber angle. Immunostaining with a panel of antibodies against HSP 90, 70, 60, 47, and 27 was performed on retinal sections prepared from the normal and glaucomatous monkey eyes.
Results: The intensity of immunostaining for HSP 90, 60, and 27 was greatly enhanced in the retinas of glaucomatous eyes. Prominent reactivity was observed in the inner retinal layers, especially in the ganglion cell and nerve fiber layers. The staining intensity for HSP 70 was also moderately increased, while immunoreactivity against HSP 47 remained almost unchanged in glaucomatous retinas. Immunostaining against glial fibrillary acidic protein was increased and the immunolabeling pattern appeared to be identical with that of HSP 90 in glaucoma retinas.
Conclusions: The level of HSP 90, 70, 60, and 27 in primate retinas was increased in experimentally induced ocular hypertension. The differences in expression pattern suggest that each HSP may have its unique role in responding to damage or injury related to intraocular pressure elevation. Jpn J Ophthalmol 2003;47:42-52 (C) 2003 Japanese Ophthalmological Society.

DOI： 10.1016/S0021-5155(02)00627-5

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In the central nervous system (CNS), Thy-1 is expressed predominantly on neurons and serves as a specific marker for neurons. In the present study, we established a two-site enzyme-linked immunosorbant assay (ELISA) that detects trace amounts of Thy-1 protein. Recombinant Thy-1 protein expressed in Escherichia coli was purified and used as a standard. Of the regions of the nervous system examined, the highest Thy-1 concentration was found in the striatum followed by the hippocampus, neocortex, cerebellum, spinal cord, retina and optic nerve. We found that injection of a neurotoxin, N-methyl-D-aspartate, into the vitreous cavity reduced the Thy-1 level in the retina. Thy-1 ELISA will be useful for quantitative assessment of neurodegeneration in the CNS. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(02)00654-7

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Purpose. To report two patients with glaucoma who exhibited severe damage to the corneal endothelium after a trabeculectomy with mitomycin C (MMC). Methods. This study includes clinical histories and specular microscopic pictures of the cases. Results. Both patients were middle-aged women, underwent trabeculectomy with MMC, had moderate to severe cornea guttata preoperatively, and developed a shallow to flat anterior chamber, classified as grade 2 according to Spaeth early in the postoperative period. Stromal opacity caused by corneal edema associated with severe Descemet's membrane folds appeared within 2 to 5 days in both cases. The density of the corneal endothelium was decreased on specular microscopic examination. The severe corneal endothelial damage seen after the trabeculectomy with MMC was likely owing to a combination of the preexisting cornea guttata, the flat anterior chamber, and possibly the administration of MMC. Conclusion. Severe endothelial damage after trabeculectomy with MMC may occur in patients with glaucoma and associated cornea guttata. The use of tight sutures on the scleral flap or a modified operative method, nonpenetrating trabeculectomy, may be effective in preventing a shallow to flat anterior chamber postoperatively.

DOI： 10.1097/00003226-200204000-00012

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DOI： 10.11477/mf.1410909019

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Purpose: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF) in the optic nerve head in an experimentally induced glaucoma model. Methods: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after photocoagulation. The optic nerve head was examined for expression of TGF-β1, -β2 and -β3 and PDGF-A and -B in frozen sections and by the biotin ExtraAvidin-alkali phosphatase method. Results: Normal monkey eyes showed TGF-β1, -β2 and -β3, and PDGF-A and -B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF-β1 and -β2 in the glial cells around the lamina cribrosa. The staining intensities for TGF-β3, PDGF-A and -B were the same as in normal eyes. Conclusions: Eyes with experimental glaucoma showed higher expression of TGF-β1 and -β2 around the lamina cribrosa. These findings may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma. © 2001 Japanese Ophthalmological Society.

DOI： 10.1016/S0021-5155(01)00414-2

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Purpose: The distribution of the cell adhesion glycoproteins, laminin, fibronectin, tenascin, vitronectin, thrombospondin, and entactin/nidogen, was examined in the human lamina cribrosa. Methods: Frozen sections of the optic nerve head from 7 normal human elderly donors were stained by immunohistochemistry. Results: All six glycoproteins were detected in this tissue. While laminin and entactin/nidogen were observed linearly, reflecting the localization of basement membranes, fibronectin was identified diffusely. Marked tenascin immunoreactivity was apparent in the lamina cribrosa, but little or no tenascin staining was detected in the sclera. Vitronectin showed a fine fibrillar staining pattern in the lamina cribrosa, and, to a lesser extent, in the sclera and pial septa. Thrombospondin staining was apparent only in the sclera and the lamina cribrosa, which traversed the optic nerve. Conclusions: These results indicate that extracellular matrix components in the lamina cribrosa differ from those in the sclera or pial septa. This study is the first report that the human lamina cribrosa includes vitronectin and thrombospondin. Copyright © 2001 Japanese Ophthalmological Society.

DOI： 10.1016/S0021-5155(01)00331-8

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We examined ultrastructurally the localization of myocilin (formerly called trabecular meshwork inducible glucocorticoid response, or TIGR) protein in cultured human trabecular meshwork (TM) cells and in normal human TM tissues. The TM, a specialized tissue located at the chamber angle of the eye, is believed to be responsible for the development of glaucoma. The myocilin gene has been directly linked to both juvenile and primary open-angle glaucomas, and multiple mutations have been identified. Human TM cells were treated with 0.1 mM of dexamethasone (DEX) to induce myocilin expression. This protein was immunolocalized by colloidal gold electron microscopy using an anti-human myocilin polyclonal antibody. Double labeling with different sizes of gold particles was also performed with additional monoclonal antibodies specific for cell organelles and structures. In both DEX-treated and untreated cultured cells, myocilin was associated with mitochondria, cytoplasmic filaments, and vesicles. In TM tissues, myocilin was localized to mitochondria and cytoplasmic filaments of TM cells, elastic-like fibers in trabecular beams, and extracellular matrices in the juxtacanalicular region. These results indicate that myocilin is localized both intracellularly and extracellularly at multiple sites. This protein may exert diverse biological functions at different sites.

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Purpose : To examine collagen fibrils in 3 nanophthalmos sclerae and to compare them with normal control sclerae morphometrically. Materials and methods : Three cases of nanophthalmos associated with uveal effusion were studied. When sclerectomy was performed, scleral specimens were collected and fixed with 3% glutaraldehyde/2.5% paraformaldehyde. After epon-embedding and ultrathin sectioning, they were examined by transmission electron microscopy. Collagen fibrils from both nanophthalmos and normal control sclerae were compared in diameters and numbers per ̀m 2 areas. Results : All scleral tissues from the three cases were associated with irregularly woven and unclear collagen bundles. Several abnormal findings, such as twisting or fraying, were also detected in a few collagen fibrils. The diameter and density of normal - appearing collagen fibrils that occupied most areas of nanophthalmos sclerae were the same as those from normal control sclerae morphometrically. Conclusions : Although nanophthalmos sclerae even with uveal effusion showed thick irregular collagen bundles and a few abnormal collagen fibrils, most collagen fibrils appeared the same as normal controls.

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DOI： 10.11477/mf.1410906513

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC CATARACT REFRACTIVE SURGERY  

Purpose: To examine the 3-dimensional collagen fibrillar architecture of Bowman's layer after radial keratotomy (RK).
Setting: Department of Ophthalmology, Niigata University School of Medicine, Niigata, Japan.
Methods: This study used monkey eyes in which 0.3 mm deep radial incisions were made on the cornea 2 weeks and 1, 6, and 12 months before the animals were killed. Corneal buttons were immersed in a fixative and the cells macerated with sodium hydroxide 10%. Scanning electron microscopy (SEM) was performed : according to standard procedures. A part of the specimens was embedded in epoxy resin for light microscopic (LM) observation for comparison.
Results: The 5-dimensional collagen fibrillar architecture of Bowman's layer was revealed by SEM. The rupture of Bowman's layer could be seen 12 months after surgery, and there was no continuity of collagen fibrils in the ruptured area. in LM observations, the width of the stromal incisions gradually became narrower near 12 months after surgery.
Conclusion: Our cell-maceration/SEM method showed that the rupture of Bowman's layer remained up to 12 months after RK. This suggests that discontinuity of Bowman's layer may be responsible far globe rupture after RK.

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Purpose. To examine the three-dimensional organization of collagen fibrils in the lamina cribrosa of normal monkey eyes and monkey eyes with laser-induced glaucoma.
Methods. Intraocular pressure elevation and glaucomatous optic discs were obtained in one eye of three adult monkeys by repeated applications of argon laser to the chamber angle. The monkey eyes were enucleated, and the collagen fibrillar network was investigated by scanning electron microscopy after cell maceration with 10% sodium hydroxide and conductive staining.
Results. In normal monkey eyes, round to oval shaped regular laminar pores through which axon bundles exited were observed in the lamina cribrosa. The straight, column-like pores or openings were formed by multilayered laminar plates that aligned vertically in parallel with the optic nerves. The surface of the laminar plates was covered by delicate, loosely arranged collagen fibrils. The inner surface of the pores was smooth, made up of well-packed collagen fibers. In glaucomatous eyes, the laminar pores were clogged by tightened collagen fibrils. The inner surface of the pores was irregular, and the pores were narrowed or distorted.
Conclusions. Alterations in the three-dimensional organization of collagen fibrils were demonstrated in the optic nerve head of glaucomatous monkey eyes. The architectural changes may affect the flexibility and resilience required of the lamina cribrosa in supporting optic nerve fibers.

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Purpose: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-β and platelet derived growth factor (PDGF) in the optic nerve heads in experimentally induced glaucoma. Methods: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after treatment. The optic nerve head was examined for expression of TGF β 1, β 2, and β 3, and PDGF A and B in frozen sections and by the biotin-ExtrAvidin-Alkali Phosphatase method. Findings: Normal monkey eyes showed TGF β 1, β 2, and β 3, and PDGF A, and B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF β 1 and β 2 in the glial cells around the lamina cribrosa. The staining intensities for TGF β 3, PDGF A, and PDGF B were the same as in normal eyes. Conclusion: Eyes with experimental glaucoma showed higher expressions of TGF β 1 and β 2 around the lamina cribrosa. This finding may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.

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DOI： 10.11477/mf.1410906157

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To evaluate the characteristics of 10 glaucomatous cases with microcornea, we measured corneal diameter, curvature, axial length, and depth of anterior chamber, and examined the eyes with a specular microscope and an ultrasound biomicroscope. The ten cases examined in this study included 1 case of cornea plana, 2 cases of sclerocornea, 2 cases of nanophthalmos, and 5 cases of anterior microphthalmos. Three of the 10 cases were combined with open angle glaucoma, and the others with closed angle glaucoma. Open-angle glaucoma seemed like developmental glaucoma with angle maldevelopment. The closed angle type may appear at a younger age than in patients who have simple pupilary block. There are probably complex mechanisms related with closed angle glaucoma with microcornea. While differential diagnosis among these cases is relatively easy, we should evaluate how or why the intraocular pressure rises as far as possible before forming a treatment plan for each patient.

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A simple and reproducible rodent glaucoma model is required to elucidate the pathophysiology of damage to the optic nerve. We developed chronically elevated intraocular pressure (IOP) unilaterally in rats by injecting india ink into the anterior chamber of one eye using a 30-gauge needle. One week later, trapped carbon particles in the chamber angle formed a black band along the corneal limbus in the injected eyes. We performed direct laser photocoagulation without a gonio lens, and selectively burned the trabecular meshwork. Intraocular pressure was measured every week and laser photocoagulation was repeated until mean IOP in the experimental eyes rose above 25 mmHg. Unilateral IOP elevation was attained in all rats within 4 weeks. Twelve weeks after ink injection, we sacrificed the rats and excised the eyes for histologic analysis. The anterior chamber angle showed peripheral anterior synechia caused by laser photocoagulation, and carbon particles were engulfed by macrophages that infiltrated the ciliary cleft. In the optic nerve head, a remarkable decrease in the nerve fiber layer and cavernous degeneration were observed, suggesting glaucomatous optic nerve damage. This experimental rodent model should facilitate the study of the complex mechanisms involved in glaucoma. Copyright (C) 1998 Japanese Ophthalmological Society.

DOI： 10.1016/S0021-5155(98)00026-4

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We used a specular microscope to evaluate the corneal endothelial cells in 119 eyes before and 2 to 3 weeks after trabeculectomy with topical mitomycin C. The endothelial cell density per square millimeter averaged 2,569±487 (mean±standard deviation) before surgery and 2,444±536 after surgery, showing a decrease of 4.98%. The hexagonality decreased by 1.7%, the coefficient of variation increased by 1.9, and the average cell area increased by 6.82%. There were no statistical differences as a whole in these values. Decrease in hexagonality was more frequent in eyes with prior intraocular or glaucoma surgery. Eyes treated by laser trabeculoplasty showed a decrease in endothelial cell density, an increase in coefficient of variation and an increase in hexagonality. Eyes with postoperative flat anterior chamber showed significant changes in each parameter. The findings show that trabeculectomy with topical mitomycin C does not significantly affect the corneal endothelial cells at 2 to 3 weeks after surgery.

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We tried to create an experimental glaucoma which is simple and highly reproducible in rodents. India ink was injected into the anterior chamber with a 30-gauge needle. The carbon particles were trapped in the chamber angle and formed a black band along the corneal limbus one week later. This area was then photocoagulated anteroposteriorly with an argon laser. Photocoagulation was repeated until the intraocular pressure was elevated to 25 mmHg or more by pneumotonometry performed at a one-week interval. The above procedure was applied to one eye of 7 rats with the fellow eye serving as control. Chronic elevation of intraocular pressure was obtained in all the 7 treated eyes. The eyes were then enucleated and examined by light microscopy. Carbon particles were phagocytosed by macrophages in the intertrabecular spaces. Peripheral anterior synechias were also present. The optic nerve-head showed remarkable decrease in nerve fibers and cavernous degeneration suggestive of glaucomatous optic nerve damage. This experimental model promises to be of value in further studies of glaucomatous optic nerve damage.

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DOI： 10.11477/mf.1410905741

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER MEDICAL ASSOC  

Objective: To examine the 3-dimensional collagen fibril organization in the Bowman layer of keratoconus corneas.
Methods: Eight keratoconus corneas, 8 corneas with other diseases, and 5 normal human corneas were studied. A cell maceration method in combination with scanning electron microscopy was used to examine the collagen network in the Bowman layer.
Results: In normal corneas, the surface of the Bowman layer was smooth and collagen fibrils were regularly arranged. By contrast, sharply edged defects in the Bowman layer were found in keratoconus corneas. Latticelike configurations of the ruptured Bowman layer and collagenous scar tissue were observed, to varying degrees, in all keratoconus corneas examined. None of the other diseased corneas exhibited the ruptures.
Conclusions: Scanning electron microscopy demonstrated alterations in the Bowman layer specific to keratoconus. Fragmentation of the Bowman layer may be an early change leading to keratoconus conditions.

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To provide evidence for diagnosing malignant glaucoma, as well as to elucidate the pathogenetic mechanism of the disease, ultrasound biomicroscopy (UBM) is a useful tool. We examined the anterior segments of three patients with post-operative malignant glaucoma with UBM regarding the state before operation, the state of the opposite eye, and the state after the release of the cilio-lenticular block. Case 1 was a 76-year-old female who was diagnosed as having chronic angle-closure glaucoma (CACG) and was treated by trabeculectomy, phacoemulsification, aspiration (PEA), and simultaneous intraocular lens (IOL) implantation. Case 2 was a 22-year-old male diagnosed as having CACG secondary to plateau iris syndrome and was treated by trabeculectomy. Case 3 was a 73-year-old female diagnosed as having normal- tension glaucoma with narrow angle and was treated by PEA and IOL implantation. Slit-like anterior chamber angle and anteriorly positioned ciliary body were observed in all 3 cases, which were identical to those Pavlin reported in 8 cases with plateau iris syndrome. UBM seems to be an important pre-operative examination to evaluate the risk of malignant glaucoma and to consider which surgical procedure and post-operative management is proper. The pre-operative configuration of the ciliary body may be associated with the onset of malignant glaucoma in some patients with CACG or narrow angle.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER VERLAG  

Background: The aim of the study was to evaluate the effects of mitomycin C on the cell replication activity in wound healing following experimental filtration surgery. Methods: Trabeculectomy with or without application of mitomycin C was performed on albino rabbit eyes. At 1, 4, 7, 14, and 28 days after surgery, the expression of proliferating cell nuclear antigen, a marker of cell proliferation, in the filtering site was examined immunohistochemically using a streptavidin-biotin complex method. Results: In control eyes that underwent trabeculectomy but did not receive mitomycin C, the number of immunoreactive cells increased 4-7 days after operation and decreased markedly at around 14 days. The filtering site was obstructed histologically at 4-7 days after operation. In the mitomycin C-treated eyes, immunoreactive cells appeared 4 days after surgery but disappeared by 7 days at the surgical site. The number of immunoreactive cells in the treated eyes was much lower than that in control eyes. Conclusion: The cell replication activity was markedly inhibited by administration of mitomycin C. The filtering site remained open for 28 days after surgery, whereas it was completely obstructed within 7 days in control eyes. Immunocytochemistry for proliferating cell nuclear antigen, as used in this study, is a simple and reliable method for detection of cell replication activity.

DOI： 10.1007/BF00941765

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We examined the distribution and expression of three proteinase inhibitors, α1-proteinase inhibitor (α1-PI), α1-antichymotrypsin (α1- ACT), and α2-macroglobulin (α2-M) in the human trabecular meshwork. Immunohistochemistry, in situ hybridization, and reverse transcription- polymerase chain reaction (RT-PCR) were used. By immunostaining, all three inhibitors were identified in the human trabecular meshwork with enhanced staining in the uveal meshwork. In situ hybridization showed mild but positive accumulation of the silver grains on the trabecular meshwork cells, which indicates mRNA expression. Specific distribution or cell selectivity were not detectable probably due to weak expression of these inhibitors in this tissue. Instead mRNAs for α1-PI, α1-ACT, and α2-M as well as antithrombin III, plasminogen activator inhibitor-1 could be identified by RT-PCR using trabecular meshwork culture cells. In this study, we concluded that some proteinase inhibitors were distributed in the human trabecular meshwork as well as in the cornea and the ciliary body. At least part of these were probably produced by the trabecular meshwork cells. The balance between proteinases and proteinase inhibitors might play an important role even in the human trabecular meshwork to maintain the outflow route. The alterations in the primary or secondary glaucomatous eyes are curious.

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Purpose. Keratoconus is characterized by thinning and scarring of the central region of the cornea The authors have shown, in corneas obtained from patients with keratoc nus, that lysosomal enzyme activities are elevated, whereas levels of protease inhibitors such as alpha 1-proteinase inhibitor (alpha 1-PI) are reduced. This study was undertaken to examine further the gene expression of cathepsin G, acid phosphatase, and alpha 1-PI in keratoconus corneas.
Methods. Corneal buttons were collected from patients with keratoconus, normal subjects, and patients with other corneal diseases. In situ hybridization was performed on paraffin sections using a tritium-labeled probe for cathepsin G or alpha 1-PI. Competitive polymerase chain reaction (PCR) was used to determine the messenger RNA (mRNA) levels for lysosomal acid phosphatase and alpha 1-PI in epithelial and stromal cells of keratoconus corneas.
Results. Silver grains, indicative of positive in situ hybridization products, were observed in all three cell types of normal corneas for both DNA probes. Compared with normal and other diseased controls, the labeling was enhanced for cathepsin G but was diminished for alpha 1-PI in the epithelium of keratoconus corneas. Competitive PCR showed that the mRNA level, for acid phosphatase was higher and that the mRNA level for alpha 1-PI was lower in keratoconus corneas.
Conclusions. These results indicate that the mRNA level for degradative enzymes is increased and that for alpha 1-PI it is reduced in keratoconus corneas. This study provides the first evidence that the altered expression of multiple enzymes and inhibitors in keratoconus occurs at the gene level. Furthermore, it implicates a possible role of coordinated transcriptional regulation of gene expressions in keratoconus.

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We examined the immunohistochemical distribution of six types of cell adhesion glycoproteins in the human retrobulbar optic nerve. The pial septa had laminin and entactin on the surface at the border with the optic nerve fibers, and fibronectin and vitronectin were distributed in the stroma of the septa. Some tenastin was also detectable both on the surface and in the stroma of the septa. Thrombospondin was associated with capillaries within the stroma. The surface of the arachnoid membrane, the pia mater, and the dura mater was covered by laminin and entactin. Diffuse staining with antifibronectin antibody was seen in all these meningeal tissues, but vitronectin showed a fine fibrillar appearance in these tissues. No significant staining could be found for tenastin. Thrombospondin showed only faint staining on the capillaries of the pia mater and the dura mater. These findings can provide clues for the discussion of how the extracellular matrix works and what roles it plays in disorders involving the retrobulbar optic nerve, such as optic neuritis and glaucoma.

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DOI： 10.11477/mf.1410905081

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Axonal transport abnormality has been reported to be deeply related to glaucomatous optic nerve injury. These reports mainly investigated the axonal transport blockage using the model of acute elevation of intraocular pressure in normal primates. We studied such axonal transport abnormality especially of slow flow in laser-induced glaucomatous monkey eyes by tissue autoradiography. Abnormal silver grain accumulation suggesting axonal transport damage was seen in the areas of distorted lamina cribrosa in glaucomatous eyes. Accumulation of grains was also seen in the retro-laminar optic nerve in some areas. Normal control eyes showed almost homogenous grain distribution in the prelamina, lamina and post-lamina areas. Areas of slightly elevated, accumulation of grains were seen around the lamina cribrosa and disc margin suggesting physiological blockage of axonal transport.

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Purpose. To investigate the response of trabecular meshwork cells to phagocytic events.
Methods. Cultured bovine trabecular meshwork cells were established and exposed to latex microspheres for 40 to 44 hours. After phagocytosis, the cohesiveness of cells to their underlying matrix was measured by the susceptibility to trypsin, as indicated by the time needed to be liberated from culture plates. The amounts of two cell attachment proteins, fibronectin and laminin, in both the phagocytically challenged and the control cultures were measured at various postphagocytosis time points with an enzyme-linked immunosorbent assay. The fibronectin and laminin network was visualized with immunostaining. The mRNA levels were analyzed by Northern blot. Zymography using gelatin-containing gels was also performed to examine the gelatinase activities.
Results. Compared with controls, cells in phagocytically challenged cultures were more sensitive to trypsin. At the 4- and 8-hour postphagocytosis time points, the trypsinization time needed to suspend cells from tissue culture plates was significantly shorter for phagocytically challenged cells. Also, at these two time points, reduced amounts of fibronectin and laminin, as well as disruption of the fibronectin-laminin network, were observed in the phagocytically challenged trabecular meshwork cultures. The mRNA level for fibronectin was reduced, and a slightly increased gelatinase activity was noted. The fibronectin and laminin levels returned to normal by 24 hours.
Conclusions. Results suggest that after phagocytosis, trabecular meshwork cells exhibit a shortterm loss in cell-matrix cohesiveness. Such a loss may be related to diminished levels of cell attachment proteins.

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We examined the ultrastructural changes in the lamina cribrosa in monkeys with experimental chronic glaucoma. In normal monkey eyes, the extracellular matrix consists of tightly packed collagen fibers, elastic fibers and less ground substance in the beams, and basement membranes associated with vascular cells and astrocytes in the lamina cribrosa. In the experimental glaucomatous eyes there was a marked destruction of collagenous bundles. The empty spaces were expanded and filled with fine fibrillar materials. There were normal by appearing parts and clearly destroyed parts mixed in the same region. Elastic fibers looked isolated from the collagenous bundles around them. Basement membranes were generally thick, multi-laminated, and bent. In addition, basement membrane-like materials, separated from the cells, were often seen in the laminar beams. The lamina cribrosa in experimental chronic glaucoma showed evidence of both destruction and healing or remodeling. These changes might have a influence to the worse for the tissue characterization of the lamina cribrosa, such as resistence to intraocular pressure changes. In conclusion, this may he a factor related with the progression of glaucomatous optic nerve damage.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS UNITED KINGDOM