Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

This study investigated the influence of asymmetric corneal hysteresis (CH) on asymmetric visual field impairment between right and left eyes in patients with primary open-angle glaucoma (POAG) without a history of intraocular surgery. CH, corneal resistance factor (CRF), and corneal compensated intraocular pressure (IOPcc) were measured using the Ocular Response Analyzer. Differences between the eyes (right eye–left eye: DIFRL) and CH-based and in target parameters (higher CH eye–lower CH eye: DIFCH) were calculated in the same patient. In 242 phakic eyes of 121 patients, older age (p < 0.001), lower CH (p = 0.001), and lower CRF (p = 0.007) were significantly associated with worse standard automated perimetry (SAP) 24-2 mean deviation (MD). The DIFsRL in axial length (p = 0.003), IOPcc (p = 0.028), and CH (p = 0.001) were significantly associated with the DIFRL in SAP24-2 MD, but not in central corneal thickness (CCT), Goldmann applanation tonometry (GAT) measurement, and CRF. When dividing the patients into two groups based on the median of the CH DIFsCH (0.46), the DIFsCH in CRF (p < 0.001), IOPcc (p < 0.001), CCT (p = 0.004), SAP24-2 MD (p < 0.001), and SAP10-2 MD (p = 0.010) were significantly different between the groups. Large inter-eye asymmetry in CH is an important explanatory factor for disease worsening in patients with POAG.

DOI： 10.3390/jcm12134514

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DOVE MEDICAL PRESS LTD  

Purpose: To evaluate the effect of trabeculectomy (Trab MMC) on visual field (VF) progression in eyes with glaucoma and high myopia.Patients and Methods: Patients diagnosed with primary open-angle glaucoma or exfoliation glaucoma who underwent Trab MMC as the first glaucoma surgery along with >3 VF tests preoperatively and postoperatively were enrolled. High myopia was defined as an axial length >26.5 mm. Postoperative reductions in intraocular pressure (IOP) were assessed by survival analysis using IOP measurements obtained preoperatively. The longitudinal trends of the outcome measures were evaluated using linear mixed models.Results: Thirty-five eyes of 32 patients were included in this study, including 22 eyes of 20 patients in non-highly myopic group and 13 eyes of 12 patients in highly myopic group. IOP decreased after Trab MMC, and the survival rate did not differ significantly in relation to axial length. Linear mixed-model analyses suggested that the inhibitory effects of Trab MMC on the rate of mean deviation (MD) changes were significant in the non-highly myopic group (-0.53 & PLUSMN; 0.15 dB/year preoperatively to -0.16 & PLUSMN; 0.13 dB/year postoperatively; P = 0.004), but not in the highly myopic group (-0.66 & PLUSMN; 0.19 dB/year preoperatively to -0.48 & PLUSMN; 0.18 dB/year postoperatively; P = 0.32).Conclusion: Trab MMC reduced IOP in both highly myopic and non-highly myopic eyes, and IOP reduction was very similar in both groups. The VF deterioration rate decreased in both groups, but the change was weaker and nonsignificant in the highly myopic group.

DOI： 10.2147/OPTH.S415654

Web of Science

PubMed

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

The purpose of the study was to investigate the number of examinations required to precisely predict the future central 10-degree visual field (VF) test and to evaluate the effect of fitting non-linear models, including quadratic regression, exponential regression, logistic regression, and M-estimator robust regression model, for eyes with glaucoma. 180 eyes from 133 open angle glaucoma patients with a minimum of 13 Humphrey Field Analyzer 10-2 SITA standard VF tests were analyzed in this study. Using trend analysis with ordinary least squares linear regression (OLSLR), the first, second, and third future VFs were predicted in a point-wise (PW) manner using a varied number of prior VF sequences, and mean absolute errors (MAE) were calculated. The number of VFs needed to reach the minimum 95% confidence interval (CI) of the MAE of the OLSLR was investigated. We also examined the effect of applying other non-linear models. When predicting the first, second, and third future VFs using OLSLR, the minimum MAE was obtained using VF1-12 (2.15 ± 0.98 dB), VF1-11 (2.33 ± 1.10 dB), and VF1-10 (2.63 ± 1.36 dB), respectively. To reach the 95% CI of these MAEs, 10, 10, and 8 VFs were needed for the first, second and third future VF predictions, respectively. No improvement was observed by applying non-linear regression models. As a conclusion, approximately 8-10 VFs were needed to achieve an accurate prediction of PW VF sensitivity of the 10-degree central VF.

DOI： 10.1038/s41598-022-23604-z

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

The effect of trabecular meshwork (TM)-targeted minimally invasive glaucoma surgery (MIGS) on the vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) has not been established. In this prospective, longitudinal study, we investigated changes in the deep vasculature following TM-targeted MIGS using AS-OCTA for open-angle glaucoma in 31 patients. AS-OCTA images of the sclera and conjunctiva at the nasal corneal limbus were acquired preoperatively and 3 months postoperatively, and the vessel densities (VDs) of the superficial (conjunctival) and deep (intrascleral) layers were calculated. The VDs before and after MIGS were compared, and the factors associated with the change in VD following MIGS were analyzed. The mean deep VD decreased from 11.98 ± 6.80% at baseline to 10.42 ± 5.02% postoperatively (P = 0.044), but superficial VD did not change (P = 0.73). The multivariate stepwise regression analysis revealed that deep VD reduction was directly associated with IOP reduction (P < 0.001) and preoperative IOP (P = 0.007) and inversely associated with preoperative deep VD (P < 0.001). The deep VD reduction following MIGS was significant in the successful group (21 eyes) (P = 0.032) but not in the unsuccessful group (10 eyes) (P = 0.49). The deep VDs assessed using AS-OCTA decreased following TM-targeted MIGS, especially in the eyes with good surgical outcomes.

DOI： 10.1038/s41598-022-22104-4

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

課題に対する本計画の論点は,「光干渉断層血管撮影(OCT-A)はフルオレセイン蛍光眼底造影検査(FA)の代わりになり得る検査なのか?」である.侵襲的な眼科検査とは,痛み・接触・羞明を伴うもの,造影剤を使用するもの,時間がかかるもの,生検であり,これらを軽減できる検査方法の改良や代替検査の開発は検査の低侵襲化といえる.また検査精度の向上は疾病の早期発見を可能にし,結果的に治療の低侵襲化につながる.なかでも,FAは頻度は少ないが重篤な合併症を引き起こす可能性のある比較的侵襲性の高い検査であり,検査時間が長く,散瞳に伴う羞明や末梢静脈路の確保に関連した痛みも伴う.しかしながら,多くの眼底疾患の診断や治療に欠かせない検査であり,代替検査の開発・普及は眼科診療の発展に大きく貢献できると期待される.OCT-Aは,造影剤を使用せずに高いコントラストで網膜血管像を描出することができる機器であり,比較的低侵襲なFAの代替検査として注目されているが,市販機が登場して5年以上が経った現在でもFAの代わりとして単純に置き換えることは不可能である.読影方法や治療方針の決定,効果判定を行う所見の取り方に関する科学的根拠も,半世紀以上の歴史を経て確立されたFAと比較して極端に少なく,またそもそも臨床機器として未熟である.画質が不安定であり,定量のしやすさとは裏腹に定量の不安定さが存在することは臨床機器としては致命的な欠点である.我々は,OCT-AがFAの代替検査として成熟するために,今後成長が必要な項目を明らかにし,OCT-Aの臨床機器としての完成度を高めることを計画した.I.OCT-Aにおける血管描出能の基礎的な検討 OCT-Aにおける血管の描出方法はFAとはまったく異なる.理論的な部分は理解できても,画像処理により抽出された血流信号が実際の網膜微小循環の動態とどのような対応をしているのかを直接観察した報告はなく,未知である.今後の成長を眺めれば,なぜ映り,なぜ映らないのかを網膜微小循環を直接可視化した状態で検証することは,まさに永くブラックボックスであった領域を照らすことであり,避けては通れない.補償光学走査レーザー検眼鏡を用いて血球の動きを可視化し,血球密度や流れる血球の種類がOCT-Aの描出能に与える影響について,細胞レベルで検証した.II.高画質化に関する検討 Volume scanから再構成するOCT-Aはその画質の安定化が大きな課題の一つである.加算平均,人工知能(AI)を用いた高画質化や,それが定量評価に与える影響について検討した.III.広画角化に関する検討 OCT-Aの画角の狭さは当初より問題であった.近年では画角が広くなりつつあるが,一方で画角と画質はトレードオフの関係にあり,単純な広画角化が画質の低下につながることもクローズアップされてきている.現状,OCT-Aが眼底のどれほどの範囲を撮影することができ,それが臨床的にどの程度有用であるかを調査した.IV.FAを超えるOCT-Aの機能に関する検討 FAの代替検査として期待される一方で,FA検査では得難い情報が得られるのはOCT-Aの大きな強みであり,OCT-Aが注目される大きな理由となっている.前眼部OCT-A,脈絡毛細血管板の可視化と定量評価について検討した.(著者抄録)

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Optical coherence tomography angiography (OCTA) is a new technique for non-invasive imaging of blood vessels, allowing combined evaluation of both deep and surface vessels. The purpose of this study was to evaluate the post-trabeculectomy longitudinal changes in complete avascular area (CAA) of filtering blebs using anterior segment (AS-) OCTA and their association with surgical outcomes. This study included 57 eyes of 53 patients who had undergone trabeculectomy with mitomycin C. AS-OCTA images of filtering bleb were acquired at 3 and 6 months after trabeculectomy, and at 1 month in possible cases. CAAs, regions where complete blood flow was not depicted in AS-OCTA images, were evaluated for their presence, extent, and change over time. CAAs were detected in 37 eyes (65%) and 33 eyes (58%) at 3 and 6 months postoperatively, respectively. The extent of CAAs reduced over time after surgery in most cases. No parameters related to CAAs were significantly associated with surgical success (i.e., intraocular pressure (IOP) ≤ 12 mmHg and IOP reduction > 20% without medication). In conclusion, although it is difficult to predict surgical success by CAA itself, AS-OCTA may be useful for the objective evaluation of the vascularity of filtering blebs.

DOI： 10.1038/s41598-021-02871-2

PubMed

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

DOI： 10.1167/tvst.10.11.17

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

We performed a prospective, longitudinal study to investigate the association between the preoperative intrascleral vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) and surgical outcomes of trabecular meshwork-targeted micro- or minimally invasive glaucoma surgery (MIGS). We included 37 patients with primary open-angle glaucoma. Preoperative AS-OCTA images of the sclero-conjunctiva of the nasal corneal limbus were acquired in the superficial (conjunctival) and deep (intrascleral) layers. The vessel densities (VDs) of each layer were measured separately in the entire area, limbal side, and fornix area. Surgical success was determined by postoperative intraocular pressure (IOP) and IOP reduction. Twenty-three and 14 eyes were classified as having successful and unsuccessful outcomes, respectively. The deep VDs of the entire area and fornix area were significantly lower in the successful group (P = 0.031 and P = 0.009). The success rate was significantly higher for eyes with a lower deep VD than for eyes with a higher deep VD. A greater IOP reduction was significantly associated with lower deep VD in the fornix area (P = 0.022) and higher preoperative IOP (P < 0.001). These results indicate that intrascleral vasculature assessed using preoperative AS-OCTA was negatively correlated with surgical success and IOP reduction resulting from trabecular meshwork-targeted MIGS. AS-OCTA images might help predict MIGS outcomes.

DOI： 10.1038/s41598-021-97290-8

PubMed

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PURPOSE: To investigate the association between the use of topical β-blockers and subsequent asthma attacks in glaucoma patients with asthma. METHODS: This was a retrospective longitudinal cohort study using an administrative claims database. All patients aged 20 years or older who were registered in the health insurance claims database updated and managed by JMDC Inc. (Tokyo, Japan). Patients who were newly prescribed eye drops for glaucoma treatment were identified between 2011 and 2017. The patients with glaucoma were divided into two groups: β-blocker users and non-β-blocker users, based on the presence of a β-blocker in the prescribed eye drops. We investigated whether the incidence of asthma attacks in patients with previously treated asthma differed between the two groups. RESULTS: We categorized 17,666 patients in the β-blocker-user group and 12,609 patients in the non-β-blocker-user group. A total of 580 patients in the β-blocker group (3.28%) and 847 in the non-β-blocker group (6.72%) underwent asthma treatment before the prescription of anti-glaucoma eye drops (P < 0.001). Furthermore, 94 patients in the β-blocker-user group (0.53%) and 278 in the non-β-blocker user group (2.20%) were undergoing current treatment for asthma (P < 0.001). The adjusted hazard ratios of asthma attacks were 0.73 (95% confidence interval, 0.46-1.16, P = 0.18) in patients with a history of asthma treatment and 1.22 (95% confidence interval, 0.56-2.70, P = 0.62) in patients with current asthma treatment, compared to the non-β-blocker-user group. CONCLUSION: Our results clarified that several patients with asthma were prescribed topical β-blockers for glaucoma treatment. However, asthma attacks may not be significantly attributed to topical β-blockers, even in glaucoma patients under current asthma treatment. The administration of topical β-blockers to asthma patients could be a treatment option in the absence of other treatment options, if adequate informed consent is obtained. Further studies are needed to draw a firm conclusion on this clinical question.

DOI： 10.1007/s00417-021-05357-z

PubMed

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PURPOSE: To investigate the effect of denoise processing by artificial intelligence (AI) on the optical coherence tomography angiography (OCTA) images in eyes with retinal lesions. METHODS: Prospective, observational, cross-sectional study. Optical coherence tomography angiography imaging of a 3 × 3-mm area involving the lesions (neovascularization, intraretinal microvascular abnormality, and nonperfusion area) was performed five times using OCT-HS100 (Canon, Tokyo, Japan). We acquired AI-denoised OCTA images and averaging OCTA images generated from five cube scan data through built-in software. Main outcomes were image acquisition time and the subjective assessment by graders and quantitative measurements of original OCTA images, averaging OCTA images, and AI-denoised OCTA images. The parameters of quantitative measurements were contrast-to-noise ratio, vessel density, vessel length density, and fractal dimension. RESULTS: We studied 56 eyes from 43 patients. The image acquisition times for the original, averaging, and AI-denoised images were 31.87 ± 12.02, 165.34 ± 41.91, and 34.37 ± 12.02 seconds, respectively. We found significant differences in vessel density, vessel length density, fractal dimension, and contrast-to-noise ratio (P < 0.001) between original, averaging, and AI-denoised images. Both subjective and quantitative evaluations showed that AI-denoised OCTA images had less background noise and depicted vessels clearly. In AI-denoised images, the presence of fictional vessels was suspected in 2 of the 35 cases of nonperfusion area. CONCLUSION: Denoise processing by AI improved the image quality of OCTA in a shorter time and allowed more accurate quantitative evaluation.

DOI： 10.1097/IAE.0000000000003101

PubMed

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Descemet’s membrane detachment (DMD) is a rare but serious complication of phacoemulsification surgery. A small DMD may resolve spontaneously, but extensive DMD often requires intracameral injection of air, nonexpansile gases, or expansile gases. A 92-year-old man who underwent phacoemulsification and aspiration with intraocular lens placement in the right eye had significantly reduced visual acuity, with a hazy cornea after surgery. Anterior segment optical coherence tomography (AS-OCT) examination revealed extensive DMD throughout the cornea. He was treated with intracameral injection of 20% sulfur hexafluoride. As a result, the Descemet membrane was successfully reattached, and the corneal edema resolved. AS-OCT was helpful in confirming the presence and extent of DMD, provided useful information to determine the appropriate treatment, and was useful for monitoring DMD.

DOI： 10.1159/000517351

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

PURPOSE: To evaluate the association between daily coffee consumption and intraocular pressure (IOP) in healthy persons without glaucoma and the association between daily coffee consumption and history of glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. METHODS: All participants underwent a standardized ophthalmic examination. Self-reporting questionnaires were completed by all participants. First, the association between habitual coffee consumption and IOP among nonglaucoma individuals was evaluated by a multivariate linear regression analysis, adjusting for possible confounders. Second, the association between habitual coffee consumption and history of glaucoma also was evaluated using a multivariate logistic regression analysis. MAIN OUTCOME MEASURES: The association between habitual coffee consumption and IOP among nonglaucoma individuals. RESULTS: Of 9850 participants, 9418 did not have history of glaucoma. Among these participants, the mean ± standard deviation IOP of both eyes was 14.7 ± 2.9 mmHg. The multivariate regression analysis revealed that habitual coffee consumption was associated significantly with IOP (P < 0.001): the higher the consumption of coffee, the lower the IOP of an individual. The IOP of the group who consumed coffee most frequently (3 times daily or more) was 0.4 mmHg lower (95% confidence interval, 0.2-0.5 mmHg lower) than that of the group that consumed coffee least frequently (less than once daily). However, the logistic regression analysis showed that habitual coffee consumption was not associated significantly with history of glaucoma (P = 0.53). CONCLUSIONS: Frequent coffee consumption was associated with a slightly lower IOP in people without glaucoma but was not associated with a decreased risk of glaucoma developing. Additional experimental studies are needed to examine the effects of coffee on IOP and glaucoma risk.

DOI： 10.1016/j.ogla.2020.09.019

PubMed

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

BACKGROUND AND OBJECTIVE: Investigations of morphological changes in photoreceptors in Behçet's disease (BD) using adaptive optics scanning light ophthalmoscope (AOSLO) are lacking. The authors aimed to evaluate macular cone density and regularity in BD patients with or without a history of uveitis with good visual acuity (VA). PATIENTS AND METHODS: The authors included 16 patients (29 eyes) with BD and 12 healthy volunteers (12 eyes) as controls. All subjects had VA of 20/20 or higher. Subjects underwent AOSLO to evaluate the photoreceptor status including cone density (numbers/mm2) and proportion of hexagonal Voronoi domains. RESULTS: Hyporeflective patches that were not detected in color fundus photograph or optical coherence tomography were observed by AOSLO in BD patients both with and without past uveitis history; these were not detected in the control group. Cone density was significantly reduced in BD patients with a history of uveitis compared to controls (P = .002). The proportion of hexagonal Voronoi domains was significantly reduced in BD eyes both with and without history of uveitis relative to controls (P < .001). CONCLUSION: Macular photoreceptor damage was observed in BD patients with and without a history of uveitis. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:218-225.].

DOI： 10.3928/23258160-20210330-06

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

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PURPOSE: To assess the characteristics of glaucoma patients who received systemic or topical steroid treatment. METHODS: Patients who received steroid treatment were selected from a total of 4256 patients at our tertiary referral center of glaucoma management between August 2011 and October 2017. Clinical characteristics of the subjects were extracted from clinical records. To evaluate the factors influencing highest intraocular pressure during observation (max-IOP) or mean deviations (MDs) of visual field at the first and last visits, univariate and multivariate regression analyses were performed using a generalized estimating equation. RESULTS: Three hundred and eighty-two eyes of 196 patients were included in this study. The most frequent disease as the reason for steroid treatment was atopic dermatitis (58 eyes) followed by autoimmune diseases. The patients with atopic dermatitis were significantly younger (38.0 ± 11.2 years old, p < 0.001) and had lower MD (- 9.3 ± 9.1 dB at first visit, p = 0.01; - 10.6 ± 9.2 dB at last visit, p = 0.004) than those with other diseases. In multivariate regression analysis, age and MD at first visit, max-IOP, and atopic dermatitis were correlated with MD at last visit. CONCLUSIONS: The results of the present study suggest that patients with atopic dermatitis carry the risk of irreversible visual field loss even in youth. For earlier detection of high intraocular pressure, reinforcement of ophthalmological screening in management of atopic dermatitis should be recommended.

DOI： 10.1007/s00417-020-04925-z

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Glaucoma is a multifactorial optic neuropathy, possibly involving vascular dysfunction, leading to the death of retinal ganglion cells and their axons. Disc hemorrhage (DH) is known to be closely associated with the widening of retinal nerve fiber layer defect (NFLD); however, it has not been well elucidated how DH affects retinal microvasculature. We aimed to investigate the association between DH history and longitudinal changes in superficial retinal microvasculature in NFLD. We enrolled 15 glaucoma patients with DH history (32 glaucomatous NFLD locations, with or without DH history). NFLD-angle, superficial retinal vessel density (VD), and decreased superficial retinal microvasculature (deMv)-angle were assessed using optical coherence tomography angiography for at least three times over time. The mean follow-up period and OCT/OCTA scan interval were 21.3 ± 5.4 months (range, 12-28) and 6.8 ± 0.4 months (range, 2-18), respectively. Linear mixed-effects models showed that the presence of DH history was significantly associated with an additional NFLD-angle widening of 2.19 degree/year (P = 0.030), VD decrease of 1.88%/year (P = 0.015), and deMv-angle widening of 3.78 degree/year (P < 0.001). These changes were significantly correlated with each other (P < 0.001). Thus, the widening of NFLD was closely associated with deMv, and DH was associated with a subsequent decrease in superficial retinal microvasculature in NFLD.

DOI： 10.1038/s41598-020-79151-y

PubMed

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: To investigate the short-term effects of different types of anti-glaucoma eyedrop on sclero-conjunctival vasculatures and their associations with intraocular pressure (IOP) reduction. METHODS: This was a prospective study including 20 healthy subjects. A single instillation of ripasudil or bimatoprost was introduced into the right eyes of the participants. The superficial (conjunctival) and deep (intrascleral) vasculatures of the corneal limbus using anterior-segment optical coherence tomography angiography (OCTA) and IOP were examined in both eyes at baseline and 15 min and 2 h after instillation. RESULTS: In the ripasudil group, the vessel density (VD) (median) at baseline (deep, 13.1%; superficial, 28.5%) significantly increased in both layers at 15 min (deep, 19.9%; superficial, 37.3%) and the deep layer at 2 h (deep, 14.8%; superficial, 31.6%). In the bimatoprost group, the superficial VD significantly changed over time, but the deep VD did not. The greater effect of ripasudil on IOP reduction was significantly associated with a lower baseline VD in the deep layer (at 15 min, p = 0.004; at 2 h, p = 0.018). CONCLUSIONS: Differences in the timing, depth, and extent of the effects on vasculature after instillations, could be detected using OCTA. The IOP-lowering effects of ripasudil might be associated with the deep vasculature.

DOI： 10.3390/jcm9124016

PubMed

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Purpose: To investigate longitudinal changes in the retinal nerve fiber bundle in eyes with primary open angle glaucoma using adaptive optics scanning laser ophthalmoscopy. Methods: A prospective observational case series. Fourteen eyes from 12 patients with primary open angle glaucoma that exhibited retinal nerve fiber layer defects on fundus photography were imaged with adaptive optics scanning laser ophthalmoscopy over time. Results: The expansion of retinal nerve fiber bundle narrowing was observed on adaptive optics scanning laser ophthalmoscopy in 8 eyes (57.1%) over a period of 1.44 ± 0.42 years. Retinal nerve fiber bundle narrowing expanded horizontally in 2 eyes and vertically in 6 eyes. In 3 eyes, changes in the retinal nerve fiber layer were only detectable on adaptive optics scanning laser ophthalmoscopy images. Conclusions and Importance: The expansion of retinal nerve fiber bundle narrowing was observed using adaptive optics scanning laser ophthalmoscopy. Accordingly, this tool may be a useful tool for detecting glaucoma-related changes in retinal nerve fibers in a short time.

DOI： 10.1016/j.ajoc.2020.100732

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Although strabismus is a well-known complication of glaucoma implant surgery, its surgical treatment is still challenging. We present a case with refractory strabismus after Baerveldt glaucoma implant (BGI) surgery, which was not sufficiently improved by strabismus surgery, but by removal of the BGI and fibrous adhesion. The patient was a 35-year-old woman who had multiple surgeries for secondary glaucoma. She had severe limitations of the movement of her right eye and binocular diplopia in all gaze positions after BGI surgery. Although she underwent two strabismus surgeries, the strabismus was not resolved. The surgery was performed by two specialists in glaucoma and strabismus. The BGI plate and the fibrous capsule were carefully removed. The fibrous tissue involved the muscle bellies of the inferior and particularly lateral rectus (LR) muscles and induced tight and wide adhesion between the muscle bellies and sclera. The adhesion was released after tenotomy at the insertion of the LR muscle, and the LR muscle was additionally resected by 6.0 mm. The ocular position and movement dramatically improved; however, intraocular pressure (IOP) increased immediately after the surgery. Then, Ahmed glaucoma valve implantation was performed 5 days after BGI removal. The IOP decreased and has been controlled. The improvement of ocular position and movement remained 9 months postoperatively and she obtained cosmetic satisfaction without diplopia or worsening of visual acuity. Removal of BGI and fibrous adhesion is a potential option for refractory mechanical strabismus following BGI surgery; however, it is important to prepare additional procedures for the subsequent IOP increase in advance.

DOI： 10.1159/000508067

Scopus

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PURPOSE: To investigate the effect of image averaging on qualitative and quantitative assessments of optical coherence tomography angiography (OCTA) images from eyes of patients with branch retinal vein occlusion (BRVO). METHODS: Macular OCTA images of 33 eyes of 33 patients with BRVO were obtained using the HS100 HR-SD-OCT system (Canon, Inc.). For each eye, five OCTA cube scans were obtained with a 3 × 3 mm scan protocol, and the data were averaged and compounded into a single high image quality cube data using built-in software. Pre- and post-averaging images were compared qualitatively and quantitatively in superficial capillary plexus (SCP) and deep capillary plexus (DCP) OCTA image slabs. RESULTS: After averaging, all OCTA images showed marked improvement in image quality with less background noise and better vessel continuity. The number of microaneurysms in both the SCP and DCP was larger in single images than in averaged images. A significant increase in the detection rate of capillary telangiectasia in the DCP was noted after image averaging. The number of eyes with disrupted foveal avascular zone (FAZ) decreased significantly after averaging (P = .0253). Five eyes (15.2%) with a disrupted FAZ on the single image showed an intact FAZ after averaging. Vessel length density (VLD) and fractal dimension (FD) significantly decreased and vessel diameter index (VDI) increased after averaging, while significant changes were not observed in vessel density (VD) in both the SCP and DCP. In the SCP, lower VD, VLD, and fractal dimension were significantly correlated with worse visual acuity. CONCLUSIONS: OCTA averaging has a significant effect on qualitative and quantitative assessments in eyes with BRVO.

DOI： 10.1007/s00417-020-04713-9

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

BACKGROUND: To investigate the effects of deep learning denoising on quantitative vascular measurements and the quality of optical coherence tomography angiography (OCTA) images. METHODS: U-Net-based deep learning denoising with an averaged OCTA data set as teacher data was used in this study. One hundred and thirteen patients with various retinal diseases were examined. An OCT HS-100 (Canon inc., Tokyo, Japan) performed a 3 × 3 mm2 superficial capillary plexus layer slab scan centered on the fovea 10 times. A single-shot image was defined as the original image and the 10-frame averaged image and denoised image generated from the original image using deep learning denoising for the analyses were obtained. The main parameters measured were the OCTA image acquisition time, contrast-to-noise ratio (CNR), peak signal-to-noise ratio (PSNR), vessel density (VD), vessel length density (VLD), vessel diameter index (VDI), and fractal dimension (FD) of the original, averaged, and denoised images. RESULTS: One hundred and twelve eyes of 108 patients were studied. Deep learning denoising removed the background noise and smoothed the rough vessel surface. The image acquisition times for the original, averaged, and denoised images were 16.6 ± 2.4, 285 ± 38, and 22.1 ± 2.4 s, respectively (P < 0.0001). The CNR and PSNR of the denoised image were significantly higher than those of the original image (P < 0.0001). There were significant differences in the VLD, VDI, and FD (P < 0.0001) after deep learning denoising. CONCLUSIONS: The deep learning denoising method achieved high speed and high quality OCTA imaging. This method may be a viable alternative to the multiple image averaging technique.

DOI： 10.3390/jcm9051322

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Medical Association (AMA)  

DOI： 10.1001/jamaophthalmol.2019.0318

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

DOI： 10.1016/j.ogla.2019.11.002

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：金原出版(株)  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Igaku-Shoin Ltd  

Background: While surgeons usually use donor sclera or half-thickness self-scleral flaps to cover glaucoma drainage implant tubes, implant exposure is not completely preventable. We report our experience of secondary glaucoma requiring glaucoma implant removal and re-installation for two implant exposures. Case: A 54-year-old man underwent 8 intraocular surgeries, including Baerveldt glaucoma implant (BGl) surgery in the inferotemporal region 1.5 years ago. He reported right-sided ocular pain when he came to our hospital. The BGI tube was retracted and exposed from the conjunctiva. The intraocular pressure (IOP) was high (30-38 mmHg) with concomitant glaucoma medication. We removed the BGI tube and performed Ahmed glaucoma valve (AGV) surgery in the superotemporal region. Eight months after surgery, the AGV plate slid forward and was exposed, and leakage of the aqueous humor was observed. We removed the AGV completely and performed AGV surgery again in the inferonasal region. The IOP is well controlled, and the implant has not been exposed for 3 months after the surgery. Conclusions: Surgeons should pay attention to implant exposure when performing glaucoma drainage implant surgery. Although implant removal is an effective procedure to treat implant exposure, strategies for treatment of subsequent IOP increase should be ascertained.

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Authorship：Lead author,　Corresponding author  

DOI： 10.1016/j.ajo.2019.05.008

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

PURPOSE: To compare the retinal area measured on a panoramic en face optical coherence tomography angiography (OCTA) image with that on an ultra-widefield fluorescein angiography (UWF FA) image. METHODS: Sixteen eyes (11 with branch retinal vein occlusion, 2 with central retinal vein occlusion, 1 with branch retinal artery occlusion, and 2 with hypertensive retinopathy) were included in this study. A panoramic en face OCTA image was created from five single non-panoramic en face OCTA 12 × 12-mm images. The panoramic OCTA image was superimposed on the corresponding UWF FA image after image registration; the total retinal area was measured using the grid displayed on the UWF FA image. The area on the UWF FA image was measured using stereographic projection software. RESULTS: The area of retina measured on a single non-panoramic 12 × 12-mm en face OCTA image, a panoramic en face OCTA image, and a UWF FA image was 152.4 ± 3.4 mm2, 369.6 ± 26.9 mm2, and 813.1 ± 24.4 mm2, respectively (P < 0.0001). The panoramic OCTA image was 2.42-fold larger than a single non-panoramic 12 × 12-mm OCTA image and 0.46-fold smaller than a UWF FA image. CONCLUSIONS: Grid-based measurements using an OCTA image superimposed on the UWF FA image enabled measurement on the panoramic en face OCTA image with minimum influence of magnification errors because of the curved surface of the retina.

DOI： 10.1007/s00417-019-04310-5

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ogla.2018.10.009

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

PURPOSE: To characterize and compare the ganglion cell complex (GCC) thickness and macula vessel density in preperimetric and early primary open-angle glaucoma (POAG) eyes. DESIGN: Cross-sectional study. METHODS: Fifty-seven healthy, 68 preperimetric, and 162 early POAG eyes enrolled in the Diagnostic Innovations in Glaucoma Study. Optical coherence tomography angiography (OCT-A)-based superficial macula vessel density and OCT-based GCC thickness were evaluated simultaneously. Percent loss from normal of GCC thickness and macula vessel density was compared. Area under the receiver operating characteristic curve was used to describe the diagnostic utility. RESULTS: Both GCC thickness and vessel density were significantly lower in preperimetric and early POAG eyes compared to healthy eyes. Compared to the preperimetric POAG group, the early POAG group showed larger GCC thickness percent loss (whole image 4.72% vs 9.86%; all P < .01) but similar vessel density percent loss (whole image 4.97% vs 6.93%; all P > .05). In preperimetric POAG, GCC thickness and vessel density percent losses were similar (all P > .1). In contrast, in early POAG, GCC thickness percent loss was larger than that of vessel density (all P ≤ .001). To discriminate preperimetric or early glaucoma eyes from healthy eyes, GCC thickness and macula vessel density showed similar diagnostic accuracy (all P > .05). CONCLUSIONS: Both GCC thinning and macula vessel density dropout were detectable in preperimetric and early POAG eyes. GCC loss was greater than macula vessel density loss in early perimetric POAG. However, OCT-A and OCT measurements showed similar efficiency to detect early glaucoma.

DOI： 10.1016/j.ajo.2018.11.012

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To investigate conjunctival and intrascleral vasculatures using anterior segment optical coherence tomography angiography (AS-OCTA) in normal eyes. DESIGN: Cross-sectional study. METHODS: AS-OCTA images of the corneal limbus were acquired circumferentially using a swept-source optical coherence tomography system in 10 eyes of 10 healthy subjects. AS-OCTA flow patterns with en face maximum projection were compared between the superficial (from the conjunctival epithelium to a depth of 200 μm) and deep (from a depth of 200 μm to 1000 μm) layers. The OCTA images were also compared with fluorescein scleral angiography and indocyanine green aqueous angiography images. Quantitative parameters (vessel density, vessel length density, vessel diameter index, and fractal dimension) were compared among different locations. RESULTS: The OCTA vessel patterns differed between the superficial and deep layers. The superficial-layer flow signals showed centrifugal patterns from the limbus, whereas the deep-layer flow signals showed segmental patterns. The OCTA en face images with whole signals had a similar appearance to the scleral angiography images, whereas those in the deep layer showed a similar appearance to the aqueous angiography images. In the superficial layer, only the vessel diameter index was significantly different among the locations (P = .003). In the deep layer, all 4 parameters differed significantly among the locations (P < .001 to P = .003). CONCLUSIONS: OCTA is a promising tool for evaluating conjunctival and intrascleral vasculatures. It may also help in understanding ocular surface blood flow relevant to vascular and ocular surface diseases, as well as aqueous humor outflow.

DOI： 10.1016/j.ajo.2018.08.009

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The purpose of this study was to investigate the lamina cribrosa (LC) microvasculature using swept-source optical coherence tomography angiography (OCTA) images that have been processed using multiple image averaging and a projection-resolved algorithm. OCTA has recently gained popularity for assessing retinal and choroidal microvasculature. However, it is not known if the LC microvasculature, which likely holds important information for further understanding of glaucoma, can be visualized with OCTA. METHODS: One normal subject and 1 glaucomatous subject were enrolled and optic disc 3×3 mm swept-source OCTA cubic images were obtained for each subject. Anterior LC slab frames were developed, and the averaged images were created using 3 frames. Images were examined both with and without removal of projection artifacts. RESULTS: The OCTA images of anterior LC slabs before projection artifact removal contained information on superficial and deep layer vessel blood flow. However, after projection artifact removal, fewer blood flow signals remained. These en face OCTA images showed flow signals on or immediately adjacent to lamina beams, but not inside lamina pores. The glaucomatous eye had a sectoral reduction in LC microvasculature blood flow that was not detected in normal eye. CONCLUSIONS: This is the first demonstration of imaging of the inner LC microvasculature, which, in agreement with previous histologic reports, was arranged in a polygonal pattern. Furthermore, glaucomatous eye had decreased flow signals in comparison with normal eye. Therefore, future imaging studies with OCTA may be helpful for identifying and better understanding LC pathologic changes associated with glaucoma.

DOI： 10.1097/IJG.0000000000001069

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DOI： 10.1038/s41598-018-35419-y

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

DOI： 10.1016/j.ogla.2018.06.001

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

Purpose: To compare the rates of visual field (VF) loss and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients with or without type 2 diabetes mellitus (DM). Design: Cohort study. Methods: A total of 197 eyes (55 eyes of 32 POAG patients with DM in POAG/DM group and 142 eyes of 111 age-matched POAG patients without DM in POAG/DM- group) were included from the Diagnostic Innovations in Glaucoma Study (DIGS). Type 2 DM participants were defined by self-report of DM history and use of antidiabetic medication. The rates of VF loss and RNFL loss were compared in POAG eyes with and without DM using univariate and multivariable mixed-effects models. Results: The median (interquartile range) follow-up was 5.7 years (4.0, 6.4). The mean rate of global RNFL loss in the POAG/DM group was 2-fold slower than in the POAG/DM- group overall (−0.40 μm/year vs −0.83 μm/year, respectively P =.01). Although a slower rate of VF mean deviation and pattern standard deviation loss was found in the POAG/DM group compared to the POAG/DM- group, the difference was not statistically significant. Conclusions: POAG patients with treated type 2 DM, who had no detectable diabetic retinopathy, had significantly slower rates of RNFL thinning compared to those without diagnosed DM.

DOI： 10.1016/j.ajo.2018.02.002

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

DOI： 10.1038/s41467-018-03649-3

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Purpose: To compare clinical outcomes between trabeculotomy ab externo (TLO) and trabecular ablation ab interno using a Trabectome (TAT) for open angle glaucoma (OAG). Study Design: Prospective and retrospective cohort study. Methods: We prospectively recruited 68 patients who underwent TAT between May 2013 and July 2015, and retrospectively recruited 59 patients who underwent TLO between April 2010 and May 2013. We included OAG patients who could be followed up for more than 12 months after surgery. Surgical outcomes were compared between groups. Kaplan-Meier analyses and Cox proportional hazards’ models were used for four sets of criteria using postoperative intraocular pressures (IOP) ≤ 18 or ≤ 16 mmHg, and/or showing ≥ 20% reduction from baseline. Results: Mean preoperative IOPs were 22.6 ± 7.4 mmHg in the TAT group and 24.3 ± 6.6 mmHg in the TLO group. Mean postoperative IOPs in the TAT group were 15.8 ± 3.6 mmHg at 12-months, and 15.7 ± 5.5 mmHg at 36-months, and 16.0 ± 3.4 mmHg at 12 months and 15.2 ± 3.8 mmHg at 36 months in the TLO group. Postoperatively, success rates at 36-months were significantly higher in the TLO group in some criteria
IOP reductions at 1- and 2- years were significantly higher in the TLO group
these differences were not significant after adjustment with other potential prognostic factors. The number of glaucoma medications were significantly higher in the TAT group, at 2-years (P OpenSPiltSPi 0.001) but not at 3-years (P = 0.22). Conclusion: Surgical successes following TLO and TAT are not significantly different 3 years postoperatively after adjustment of potential prognostic factors.

DOI： 10.1007/s10384-017-0559-0

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

DOI： 10.1007/s00417-017-3874-8

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Other Link： http://link.springer.com/content/pdf/10.1007/s00417-017-3874-8.pdf

Language：English  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

Purpose: To evaluate the association between macula vascular density assessed by optical coherence tomography angiography (OCT-A) and central visual field (VF) threshold sensitivities in healthy, glaucoma suspect, and glaucoma patients. Methods: A total of 185 eyes from 38 healthy participants, 31 glaucoma suspects, 72 mild glaucoma patients, and 44 moderate/severe glaucoma patients from the Diagnostic Innovations in Glaucoma Study who underwent OCT-A images of the macula and 10-2 VF testing were enrolled in this observational cross-sectional study. The relationship between central VF mean sensitivity (MS) and superficial macula whole-image vessel density (wiVD), and the relationship between the MS of the 4 central points of the 10-2 VF (MS4) and parafoveal vessel density (pfVD), were assessed using linear regression models. Results: Mean wiVD (52.5%, 49.8%, 49.4% and 45.2%, respectively) and mean pfVD (54.9%, 52.1%, 51.8% and 47.7%, respectively) were found to be significantly higher in healthy eyes and glaucoma suspect eyes compared with glaucoma eyes with mild and moderate/severe disease [analysis of covariance (ANCOVA) P&lt
0.001]. The univariate associations between 10-2 MS and wiVD (R 2 =26.9%) and between 10-2 MS4 and pfVD (R 2 =16.8%) were statistically significant (P&lt
0.001 for both). After adjusting for scan quality, age, sex and intraocular pressure, superficial macula wiVD and pfVD were still independently associated with central VF loss. Macula wiVD performed better [area under the receiver operator characteristic (AUROC)=0.70] than ganglion cell complex thickness (AUROC=0.50) for differentiating between glaucoma suspect and healthy eyes (P=0.010). Conclusions: Loss of OCT-A macula vessel density is associated with central 10-2 VF defects. Macula vessel density is a clinically relevant parameter that may enhance monitoring of glaucoma suspects and patients.

DOI： 10.1097/IJG.0000000000000964

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Authorship：Lead author   Language：English  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

Purpose: To evaluate strength of associations between optical coherence tomography (OCT)-angiography vessel density (VD) measurements in the macula and peripapillary region of the optic nerve head (ONH) with standard structural OCT thickness measures. Materials and Methods: This cross-sectional study included 333 eyes of 219 primary open-angle glaucoma patients, 41 glaucoma suspects, and 73 healthy participants from the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality OCT angiography images. The strength of associations between microvasculature measures in the ONH retinal nerve fiber layer (RNFL) and superficial macula layer was assessed using linear regression models. Associations between ONH and macula VD, and circumpapillary (cp) RNFL thickness and macular ganglion cell complex (mGCC) measures were also evaluated. Results: The strength (r2) of associations among VD and thickness measures of ONH and macula ranged from 14.1% to 69.4%
all were statistically significant (P&lt
0.001). The association between ONH and macula whole-image VD (r2 =41.0%) was significantly weaker than the relationship between mGCC and cpRNFL thickness (r2 =69.4%, P&lt
0.001). Although both cpRNFL and mGCC thicknesses tended to be more strongly associated with ONH VD (r2 =39.2% and 26.7%, respectively) than macula VD (r2 =27.5% and 17.7%, respectively), differences did not reach statistical significance (P=0.050 and P=0.113, respectively). Conclusions: The strength of the association of VD with cpRNFL and mGCC thicknesses varies by retinal layer. The weaker association of macula VD compared with ONH VD with tissue thickness may be due to differences in micorovasculature between the macula and ONH.

DOI： 10.1097/IJG.0000000000000862

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

Lacrimal canaliculus (LC) has a key role in tear drainage, but it is difficult to evaluate the LC in detail, using the existing examinations. In this study, our novel LC imaging technique provided the high-resolution images of LC in a non-invasive manner. Three-dimensional images of LC were acquired via the palpebral conjunctiva from 20 healthy volunteers (20 eyes) and 10 patients with various lacrimal disorders (10 eyes), using optical coherence tomography (OCT) dacryography (OCTD). The LC images showed morphological differences between the vertical and horizontal segments. The function of LC could be evaluated by measuring the intralumen signal intensity over time after instillation of a contrast agent (2% rebamipide ophthalmic suspension). OCTD clearly visualised the blind extremity of the LC in four patients with punctal obstruction, which was useful for deciding the punctal incision location. In one patient with canalicular obstruction, contrast agent successfully highlighted the LC that had become narrow toward the site of obstruction. Significant differences were not found in the function and morphology of LC between the patients with NLDO and the healthy subjects. OCTD may be a useful tool for LC imaging, because it facilitates quantitative and simultaneous evaluation of LC morphology and function.

DOI： 10.1038/s41598-018-27802-6

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

This study evaluated the morphological change in aqueous humor outflow (AHO) pathways using swept-source optical coherence tomography (SS-OCT) volumetric scans in glaucoma patients before and after glaucoma surgery. In this prospective observational case series, 15 eyes (13 patients) with glaucoma were treated with 120-degree Trabectome or 360-degree suture trabeculotomy and followed up for 3 months. B-scan images of the posttrabecular AHO pathway were reconstructed and the pathway areas were evaluated, before and after surgery. Changes in posttrabecular AHO pathway were qualitatively classified as "increased", "non-significant change", and "decreased" on reconstructed B-scan images. Quantitative measurements of the posttrabecular AHO pathway areas were performed pre- and postoperatively. Factors associated with both qualitative and quantitative changes in AHO pathway were investigated. From 30 regions (15 nasal and 15 temporal regions) in the 15 eyes, AHO pathways were analyzable in 20 regions pre- and postoperatively. Qualitative assessments of the pathway changes were "increased" in 8 regions, "non-significant change" in 9 regions, and "decreased" in 3 regions. Quantitative assessments of the average pathway area did not change significantly (from 3155±1633 pixels preoperatively to 3212±1684 pixels postoperatively, P = 0.50). All parameters relating to intraocular pressure changes or the surgical location were not associated with postoperative AHO pathway change. The intrascleral AHO pathway could be well visualized in glaucoma patients pre- and postoperatively using swept-source optical coherence tomography. However, structural changes in the AHO pathway assessed by SS-OCT were not significant after trabecular-targeted glaucoma surgery. Functional assessments of AHO are needed in future studies.

DOI： 10.1371/journal.pone.0199739

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

The incidence of high myopia is increasing worldwide with myopic maculopathy, a complication of myopia, often progressing to blindness. Our two-stage genome-wide association study of myopic maculopathy identifies a susceptibility locus at rs11873439 in an intron of CCDC102B (P = 1.77 × 10-12 and Pcorr = 1.61 × 10-10). In contrast, this SNP is not significantly associated with myopia itself. The association between rs11873439 and myopic maculopathy is further confirmed in 2317 highly myopic patients (P = 2.40 × 10-6 and Pcorr = 1.72 × 10-4). CCDC102B is strongly expressed in the retinal pigment epithelium and choroids, where atrophic changes initially occur in myopic maculopathy. The development of myopic maculopathy thus likely exhibits a unique background apart from the development of myopia itself; elucidation of the roles of CCDC102B in myopic maculopathy development may thus provide insights into preventive methods for blindness in patients with high myopia.

DOI： 10.1038/s41467-018-03649-3

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

DOI： 10.1371/journal.pone.0201729

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DOI： 10.2147/OPTH.S183689

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

Purpose: Optical coherence tomography angiography (OCT-A) is a noninvasive technology that allows visualization of retinal blood vessels. It is important to determine reproducibility of measurements as low precision can impair its diagnostic capabilities. The purpose of this study is to determine intravisit and intervisit reproducibility of optic nerve head (ONH) and macular vessel density measurements with OCT-A.
Patients and Methods: Fifteen healthy volunteers and 14 glaucoma patients completed 2 OCT-A (AngioVue; Optovue Inc.) scanning sessions on each of 2 separate days to assess intravisit and intervisit reproducibility. A series of ONH and macula scans were acquired at each session. Vessel density (%), the proportion of vessel area over the total measurement area was calculated. Reproducibility was summarized using coefficients of variation (CV) and intraclass correlation coefficients calculated from variance component models.
Results: In healthy eyes, the CV of intravisit and intervisit global vessel density measures ranged from 1.8% to 3.2% in ONH scans and 2.5% to 9.0% in macular scans. In glaucoma eyes, the CV of intravisit and intervisit global vessel density measures ranged from 2.3% to 4.1% in ONH scans and 3.2% to 7.9% in macular scans. CVs were lower for global than sectorial measures. Global OCT-A ONH intraclass correlation measurements for the retinal nerve fiber layer in healthy eyes were lower (range: 0.65 to 0.85) than in glaucoma eyes (range: 0.89 to 0.94). Scan size did not make large differences in measurement CVs.
Conclusions: Reproducibility of OCT-A ONH and macula vessel density measurements is good. Moreover, glaucoma patients have sparser vessel density with poorer reproducibility than healthy subjects.

DOI： 10.1097/IJG.0000000000000768

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

PURPOSE: To characterize the rate of macula vessel density loss in primary open-angle glaucoma (POAG), glaucoma-suspect, and healthy eyes.
DESIGN: Longitudinal, observational cohort from the Diagnostic Innovations in Glaucoma Study.
METHODS: One hundred eyes (32 POAG, 30 glaucoma-suspect, and 38 healthy) followed for at least 1 year with optical coherence tomography angiography (OCT-A) imaging on at least 2 visits were included. Vessel density was calculated in the macula superficial layer. The rate of change was compared across diagnostic groups using a multivariate linear mixed-effects model.
RESULTS: Baseline macula vessel density was highest in healthy eyes, followed by glaucoma-suspect and POAG eyes (P &lt; .01). The rate of vessel density loss was significantly different from zero in the POAG, but not in the glaucoma-suspect or healthy eyes. The mean rate of change in macula whole en face vessel density was significantly faster in glaucoma eyes (-2.23%/y) than in glaucoma-suspect (0.87%/y, P = .001) or healthy eyes (0.29%/y, P = .004). Conversely, the rate of change in ganglion cell complex (GCC) thickness was not significantly different from zero in any diagnostic group, and no significant differences in the rate of GCC change among diagnostic groups were found.
CONCLUSIONS: With a mean follow-up of less than 14 months, eyes with POAG had significantly faster loss of macula vessel density than either glaucoma suspect or healthy eyes. Serial OCT-A measurements also detected glaucomatous change in macula vessel density in eyes without evidence of change in GCC thickness. (C) 2017 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajo.2017.07.011

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

Purpose: To investigate longitudinal temporal and spatial associations between disc hemorrhage (DH) and rates of local retinal nerve fiber layer (RNFL) thinning before and after DHs.
Design: Longitudinal, observational cohort study.
Participants: Forty eyes of 37 participants (23 with glaucoma and 17 with suspect glaucoma at baseline) with DH episodes during follow-up from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study.
Methods: All subjects underwent optic disc photography annually and spectral-domain optical coherence tomography (OCT) RNFL thickness measurements every 6 months. The rates of RNFL thinning were calculated using multivariate linear mixed-effects models before and after DH.
Main Outcome Measures: Rates of global and local RNFL thinning.
Results: Thirty-six eyes of 33 participants with inferior or superior DHs were analyzed. The rates of RNFL thinning were significantly faster in DH quadrants than in non-DH quadrants after DH (-2.25 and -0.69 mu m/year; P &lt; 0.001). In the 18 eyes with intensified treatment after DH, the mean rate of RNFL thinning significantly slowed after treatment compared with before treatment in the non-DH quadrants (-2.89 and -0.31 mu m/year; P &lt; 0.001), but not in the DH quadrants (-2.64 and -2.12 mu m/year; P = 0.19). In 18 eyes with unchanged treatment, the rate of RNFL thinning in the DH quadrant was faster after DH than before DH (P = 0.008). Moreover, compared with eyes without a treatment change, intensification of glaucoma treatment after DH significantly reduced the global, non-DH quadrants, and DH quadrant rates of RNFL thinning after DH compared with before DH (global, P = 0.004; non-DH quadrant, P &lt; 0.001; DH quadrant, P = 0.005). In the multiple linear regression analysis, treatment intensification (beta, 1.007; P = 0.005), visual field mean deviation (beta, 0.066; P = 0.049), and difference in intraocular pressure before and after DH (beta, -0.176; P = 0.034) were associated significantly with the difference of global RNFL slope values before and after DH.
Conclusions: Although the rate of RNFL thinning worsened in a DH quadrant after DH, glaucoma treatment intensification may have a beneficial effect in reducing this rate of thinning. (C) 2017 by the American Academy of Ophthalmology

DOI： 10.1016/j.ophtha.2017.03.059

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Although ocular circulation at the retina and optic disc is known to be associated with the pathology of glaucoma, direct measurement of blood flow velocity has been difficult to obtain. This prospective observational study enrolled 11 consecutive patients with treatment-naive primary open-angle glaucoma (POAG) and 11 healthy subjects, and the effects of topical tafluprost treatment on ocular circulation were examined at baseline and at 1, 4, and 12 weeks after initiating treatment with topical tafluprost on POAG patients using multiple modalities, which include adaptive optics scanning laser ophthalmoscopy (AOSLO). Baseline mean intraocular pressure (IOP) was significantly higher and mean parafoveal blood flow velocity (pBFV) was significantly lower in POAG eyes than in healthy eyes. Mean IOP was significantly decreased (1 week, -19.1%; 4 weeks, -17.7%; and 12 weeks, -23.5%; all P &lt; 0.001) and mean pBFV was significantly increased from the baseline at all follow-up periods after initiating treatment (1 week, 14.9%, P = 0.007; 4 weeks, 21.3%, P &lt; 0.001; and 12 weeks, 14.3%, P = 0.002). These results reveal that tafluprost may not only lower IOP but may also improve retinal circulation in POAG eyes and AOSLO may be useful to evaluate retinal circulatory change after treatment.

DOI： 10.1038/s41598-017-05258-4

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

DOI： 10.1167/iovs.16-20797

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

Purpose: To compare hemifield differences in the vessel density of the peripapillary and macula in open-angle glaucoma eyes with visual field (VF) defect confined to one hemifield using optical coherence tomography angiography (OCT-A).
Design: Cross-sectional study.
Participants: A total of 58 eyes of 58 patients with glaucoma with VF loss confined to a single hemifield and 28 healthy eyes.
Methods: Retinal vasculature information was summarized as circumpapillary vessel density (cpVD) and perifoveal vessel density (pfVD). Circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thickness were calculated using spectral domain optical coherence tomography (SD OCT). Paired and unpaired t tests were used to evaluate differences between the perimetrically affected and intact hemiretinae and healthy hemiretinae. Linear regression analyses were performed to evaluate the associations between VF measures with vascular and structural measurements.
Main Outcome Measures: Total and hemispheric cpVD, pfVD, cpRNFL, mGCC, and mean sensitivity (MS).
Results: Mean cpVD and pfVD in the intact hemiretinae of glaucoma eyes (59.0% and 51.1%, respectively) were higher than in the affected hemiretinae (54.7% and 48.3%, respectively; P &lt; 0.001) but lower than in healthy eyes (62.4% and 53.8%, respectively; P &lt; 0.001). Similar results were noted with cpRNFL and mGCC thickness measurements (P &lt; 0.05 for both). The strongest associations between MS in the affected hemifields were found for cpVD (r = 0.707), followed by pfVD (r = 0.615), cpRNFL (r = 0.496), and mGCC (r = 0.482) in the corresponding hemiretinae (P &lt; 0.001 for all). Moreover, the correlations in the intact hemifields between MS with cpVD and pfVD were higher (r = 0.450 and 0.403) than the correlations between MS and cpRNFL and mGCC thickness measurements (r = 0.340 and 0.290; P values &lt; 0.05 for all).
Conclusions: Reduced peripapillary and macular vessel density was detectable in the perimetrically intact hemiretinae of glaucoma eyes with a single-hemifield defect. Vessel density attenuation in both affected and intact hemiretinae was associated with the extent of VF damage in the corresponding hemifields. Optical coherence tomography angiography potentially shows promise for identifying glaucomatous damage before focal VF defects are detectable. (C) 2017 by the American Academy of Ophthalmology

DOI： 10.1016/j.ophtha.2017.01.004

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

To investigate longitudinal changes in intraocular pressure (IOP), axial length (AL), and choroidal thickness (ChT) in primary open-angle glaucoma (POAG) eyes after trabeculectomy and to evaluate the parameters that might influence those changes.
In this prospective observational study, we recruited 28 patients with POAG (28 eyes) scheduled for trabeculectomy. The average macular ChTs and foveal retinal thicknesses along 6-mm segments centered on the fovea were examined preoperatively and postoperatively (at 1, 3, and 6 months) using swept-source optical coherence tomography. The IOP, AL, and mean deviation (MD) of standard automated perimetry (SAP) were also analyzed as independent variables.
Results from 16 patients were included in the final analysis. A significant increase in ChT with respect to the preoperative value was observed at every postoperative stage (1 month, P &lt; 0.001; 3 months, P &lt; 0.001; 6 months, P = 0.011), whereas the retinal thickness showed no significant change over the study period. The ChT increase and IOP reduction were sustained throughout the 6-month period without further significant changes. Stepwise multivariate analyses showed significant correlations between the percentage decrease in IOP and the percentage increase in ChT at 1 and 6 months postoperatively. The percentage increase in ChT was also significantly correlated with a better MD of the SAP at 1 month (beta = 0.01; P = 0.009).
The ChT increase following trabeculectomy was sustained at 1, 3, and 6 months postoperatively. The percentage increase in ChT was significantly correlated with the percentage change in IOP and (more weakly) with better SAP MD values.

DOI： 10.1007/s10384-016-0482-9

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

To determine the clinical characteristics and surgical outcomes of highly myopic (HM) eyes with an axial length (AL) of aeyen26.0 mm that underwent trabeculectomy with mitomycin C (MMC).
This was a retrospective study of 63 eyes of 54 patients with primary open-angle glaucoma that underwent trabeculectomy with MMC. The characteristics and surgical outcomes of 19 HM eyes were compared with those of 44 non-HM eyes. Surgical success was defined as an high intraocular pressure (IOP) of aecurrency sign21 mmHg (criterion A), aecurrency sign18 mmHg (criterion B), or aecurrency sign15 mmHg (criterion C), with a lower IOP cutoff of 6 mmHg and a &gt; 20 % reduction regardless of the use of antiglaucoma medication. Cox regression analyses were performed to evaluate the effect of each pretreatment and surgical factor on the success rate.
Patients with HM eyes were significantly younger than those with non-HM eyes (mean age 64.1 +/- 9.9 vs. 69.1 +/- 9.5 years; P &lt; 0.05). The 3-year qualified success rates for HM eyes and non-HM eyes did not differ significantly for the three criteria. Younger age [hazard ratio (HR) for a 1-year increase 0.93, P &lt; 0.005], preoperative pseudophakia (HR 3.88, P &lt; 0.005), and shorter AL (HR for a 1-mm increase 0.72, P &lt; 0.05) were found to be significant risk factors for trabeculectomy failure based on an IOP of aecurrency sign15 mmHg (criterion C). Age and pseudophakia also had significant effects on trabeculectomy failure based on criteria A and B, and the AL had a significant influence based on criterion A.
In our patient cohort a longer AL was not a risk factor for trabeculectomy failure, but it may be a success factor for trabeculectomy with MMC.

DOI： 10.1007/s10384-016-0468-7

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

PURPOSE: To investigate photoreceptor changes in eyes with glaucoma.
DESIGN: Cross-sectional study.
METHODS: The study included 35 eyes of 35 patients with primary open-angle glaucoma who had suffered parafoveal visual field loss at least 3 years previously, as well as 21 eyes of 21 normal subjects. Eyes with an axial length &gt;= 26.0 mm were excluded. All subjects underwent a full ophthalmologic examination, including spectral domain optical coherence tomography (SDOCT) and prototype adaptive-optics scanning laser ophthalmoscopy (AO-SLO) imaging.
RESULTS: As determined using AO-SLO, eyes with glaucoma did not differ significantly from normal eyes in terms of either cone density (26 468 3392 cones/m(2) vs 26 147 +/- 2700 cones/m(2), respectively; P = .77; measured 0.5 mm from the foveal center) or cone spatial organization (ratio of hexagonal Voronoi domain: 43.7% +/- 4.4% vs 44.3% +/- 4.9%; P = .76; measured 0.5 mm from the foveal center). Furthermore, SDOCT showed that the 2 groups did not differ significantly in terms of the photoreceptor-related layer thickness, and that the photoreceptor ellipsoid zone band was continuous in all normal and glaucoma eyes. In glaucoma eyes with vertically asymmetric severity, the more affected side did not significantly differ from the less affected side in terms of cone density, cone spatial organization, or photoreceptor-related layer thickness. In 8 eyes (22.9%) with glaucoma, dark, partition-like areas surrounded the cones on the AO-SLO.
CONCLUSIONS: Both AO-SLO and SDOCT showed cone integrity in eyes with glaucoma, even in areas with visual field and nerve fiber loss. In AO-SLO, microcystic lesions in the inner nuclear layer may influence images of the cone mosaic. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajo.2016.08.021

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc  

Purpose To investigate the effects of intraocular pressure (IOP) reduction on the eyeball shape in highly myopic eyes with high IOP. Methods This study included patients with an axial length ≥26.5 mm and high IOP ≥22 mmHg after receiving maximum medication, with successful trabeculectomy by a single surgeon, and who underwent swept-source optical coherence tomography (SS-OCT) examinations on preoperative and postoperative ≥3 months periods. Eight eyes of 7 patients were included in the analysis. The morphological changes in the eyeball that occurred pre- and post-operation were analyzed from the SS-OCT images. Results In 6 out of 8 examined eyes, the following apparent morphological changes in the posterior pole and/or peripapillary sclera were postoperatively detected on SS-OCT images: peripapillary scleral shrinkage, decrease in the lamina cribrosa depth, flattening of the peripapillary scleral insertion into the optic disc, decrease in the angle of the scleral protrusion temporal to the optic disc, and inhomogeneous change in scleral curvature of the posterior pole. Conclusions and importance We found that the shape of some eyes with high myopia and high IOP changed owing to the decrease in IOP. Eyeball deformities may be affected by high IOP, and IOP reduction might reduce scleral deformation in highly myopic eyes with high IOP.

DOI： 10.1016/j.ajoc.2016.06.006

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

PURPOSE: To investigate microcirculation of peripapillary retina and optic disc in eyes with primary open angle glaucoma (POAG) and hemifield visual field (VF) defects.
DESIGN: Prospective observational case series with normal comparison group.
METHODS: Sixty eyes with POAG (41 with superior and 19 with inferior hemifield VF defects) and 21 normal eyes were included in this study. Optical coherence tomography (OCT) angiography was used to acquire 3 x 3-mm optic disc cubes, and circumpapillary retinal nerve fiber layer thickness was also measured using OCT. Vessel densities in the peripapillary superficial retina and whole-signal-mode optic disc were individually analyzed based on the sectorial division.
RESULTS: The peripapillary vessel densities were significantly reduced at the corresponding location of the VF defects in both non-highly myopic (P &lt; .001, P = .006) and highly myopic glaucomatous eyes (P &lt; .001, P = .005) compared with the normal eyes. Vessel densities of the optic discs were significantly reduced at locations corresponding to the VF defects in eyes without high myopia but with inferior hemifield VF defects (P = .006), but not in the other eyes. The vessel densities in the peripapillary retina were significantly associated with visual field total deviation values at their corresponding sides. The choroidal microvascular reduction in the peripapillary area extended to the alpha-peripapillary atrophy (PPA) as well as beta-PPA zones.
CONCLUSIONS: Microvascular reduction was associated with VF defects in a region-specific manner: significantly and partially in the peripapillary retina and optic disc, respectively. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajo.2016.06.009

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

DOI： 10.1167/iovs.15-18798

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

Purpose: To investigate the effects of the axial length (AL)-related ocular magnification on the thickness of the macular ganglion cell complex (mGCC), and the diagnostic accuracy of the built-in normative database of the spectral-domain optical coherence tomographic (SD-OCT) instrument for early glaucoma detection.
Methods: This retrospective study included 41 eyes with early primary open-angle glaucoma and 36 normal eyes. The mGCC thickness within a 20-degree circle, equivalent to a 6 mm diameter in the Gullstrand model eye, was measured in the SD-OCT images. The magnification effect was corrected using Bennett formula, and the mGCC thickness within the actual 6 mm diameter circle was determined.
Results: In normal eyes, the inferior corrected mGCC was significantly correlated with the AL (beta = - 0.40, P = 0.028), but correction for the magnification reduced the correlation. In 38 nonhighly myopic eyes, the sensitivity and specificity of the SD-OCT's significance maps for distinguishing early glaucoma were 95.0% and 94.4% when using either the uncorrected or the corrected mGCC. In 39 highly myopic eyes, the diagnostic accuracy was lower when using the uncorrected mGCC thickness (sensitivity was 95.2% and specificity was 44.4%), and was not improved when using the corrected mGCC (81.0% and 61.1%, respectively).
Conclusions: The inferior mGCC was thinner in eyes with longer AL. The accuracy of the diagnosis with the SD-OCT built-in normative database for early glaucoma was not improved significantly by the correction of the AL-associated magnification in highly myopic eyes. Evaluation of highly myopic eyes with the nonhighly myopic normative database can lead to misdiagnosis.

DOI： 10.1097/IJG.0000000000000330

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER MEDICAL ASSOC  

IMPORTANCE Although trabeculotomy is a glaucoma surgical procedure for modest intraocular pressure (IOP) reduction, some eyes exhibit very low IOP during the early postoperative period. To our knowledge, the reason and its effect have not been investigated.
OBJECTIVES To investigate ciliochoroidal detachment (CCD) immediately after ab interno trabeculotomy and evaluate its effect on IOP immediately after surgery.
DESIGN, SETTING, AND PARTICIPANTS This prospective, observational, case series was conducted at Kyoto University Hospital, Kyoto, Japan. Patients with open-angle glaucoma who underwent ab interno trabeculotomy using a microsurgical device by a single surgeon between July 1, 2014, and May 31, 2015, were included. Thirty-seven consecutive patients were enrolled, 33 of whom were included in the analysis. The dates of the analysis were August 1 to August 15, 2015.
INTERVENTION Imaging of CCD using anterior-segment optical coherence tomography (AS-OCT).
MAIN OUTCOMES AND MEASURES The incidence of CCD immediately after ab interno trabeculotomy and its effect on IOP in the early postoperative period.
RESULTS The study cohort comprised 33 patients. Their mean (SD) age was 69.4 (13.2) years, and 19 (58%) were male. At postoperative day 3, CCD was detected in 14 of 33 eyes (42%) (CCD group) using AS-OCT. The CCD group had shorter axial length (mean [SD], 23.66 [1.67] vs 25.16 [1.59] mm) and thinner central corneal thickness (mean [SD], 505.9 [35.8] vs 533.9 [39.1] mu m) than the non-CCD group. Only 5 eyes had CCD at postoperative day 10, and 4 of these eyes had CCD at 1 month after surgery. The postoperative IOPs at all follow-up periods were lower in the CCD group than in the non-CCD group, but the difference in the postoperative IOPs between the groups decreased as time passed. The mean (SD) IOPs for the CCD group vs the non-CCD group were 9.1 (3.0) vs 14.2 (5.8) mmHg at day 1, 8.4 (2.4) vs 13.4 (5.0) mmHg at day 3, 11.0 (3.0) vs 15.5 (6.3) mmHg at day 10, 13.4 (2.4) vs 15.5 (3.3) mm Hg at 1 month, and 13.9 (3.4) vs 15.5 (4.0) mmHg at 3 months. In several eyes in the CCD group, the AS-OCT images revealed a connection between the CCD and the anterior chamber via the trabeculotomy site.
CONCLUSIONS AND RELEVANCE Ciliochoroidal detachment after ab interno trabeculotomy was not rare and was associated with low IOP immediately after surgery. Postoperative CCD may be partially attributed to the transient increase in uveoscleral aqueous outflow via the trabeculotomy site.

DOI： 10.1001/jamaophthalmol.2015.5765

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

Purpose: To investigate the relationship between the microstructure of beta-zone peripapillary atrophy (PPA) and the subsequent visual field (VF) progression in eyes with primary open-angle glaucoma (POAG), including highly myopic eyes.
Design: Retrospective cohort study.
Participants: A total of 129 patients with POAG who had been followed up for a minimum of 2 years and had undergone at least 5 reliable standard automated perimetry tests after spectral-domain (SD) optical coherence tomography (OCT) examination.
Methods: beta-Zone PPA was evaluated from 3 SD OCT scans centered on the optic disc. Upper and lower scans were defined as scans at 30 degrees above and below the horizontal scan, respectively. From 3 scans of each eye, b-zone PPA was classified as PPA(+BM) or PPA(-BM) on the basis of the presence or absence of Bruch's membrane (BM), respectively. Eyes were classified into 3 groups according to the horizontal scan images: group A (only PPA(+BM)), group B (both PPA(-BM) and PPA(-BM)), and group C (only PPA(-BM)). Factors associated with the subsequent mean deviation (MD) slope after OCT examination were analyzed, and the hemifield total deviation (TD) slope was assessed in eyes with unilateral hemifield VF defects in the corresponding direction.
Main Outcome Measures: Subsequent MD slope after OCT examination.
Results: The VF progression in group A was faster than in group C (P = 0.004). A larger PPA(+BM) width was associated with a faster MD slope in all eyes (P &lt; 0.001) and highly myopic eyes (P &lt; 0.001) and with a faster TD slope in eyes with superior or inferior hemifield VF defects in the corresponding direction (P = 0.002 and P = 0.035, respectively). A larger PPA-BM was correlated with a slower MD slope in all eyes (P = 0.030 and P = 0.034) but not in highly myopic eyes.
Conclusions: There were significant differences in VF progression according to the microstructure of the b-zone PPA in eyes with POAG. The PPA(+BM) width may be an important risk factor for VF progression in POAG, including high myopia, and the PPA-BM width may have a protective effect for VF progression in this subtype of POAG. (C) 2016 by the American Academy of Ophthalmology.

DOI： 10.1016/j.ophtha.2015.10.061

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER MEDICAL ASSOC  

DOI： 10.1001/jamaophthalmol.2015.3674

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

To investigate the dissociation of the Bruch's membrane opening (BMO) from the scleral canal opening (SO) of the optic disc.
In this prospective, cross-sectional, observational study, 101 eyes from 101 patients or suspected subjects of primary open angle glaucoma were included. Enhanced depth imaging spectral domain optical coherence tomography images along the long axis of the optic disc were used to visualize better the deep structures around the optic disc on both the temporal and nasal sides. The distances between the BMO and SO were measured at the temporal and nasal sides of the optic disc, and their correlations with age, axial length, intraocular pressure, disc size, disc ovality index, disc torsion degree, and visual field mean deviation were investigated.
The temporal and nasal distances of BMO from SO correlated significantly with each other (R = 0.632, P &lt; 0.0001). By multiple linear regression analysis, significant correlations were found for disc ovality index (temporal: beta = -0.691, P &lt; 0.0001; nasal: beta = -0.420, P &lt; 0.0001) and axial length (temporal: beta = 0.224, P = 0.002; nasal: beta = 0.310, P = 0.001). The other factors did not show any significant correlation.
Locations of the SO at not only the temporal, but also the nasal side of the optic disc are nasally shifted from the BMO with optic disc tilting and axial length elongation in glaucomatous eyes, and are significantly correlated to each other. The nasal shift of the deep structures of the optic disc should be considered especially when assessing myopic eyes with optic disc tilt.

DOI： 10.1007/s00417-015-3210-0

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

DOI： 10.3109/13816810.2015.1020559

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

PURPOSE. We compared longitudinal changes in functional and structural measures in eyes with glaucomatous optic neuropathy.
METHODS. Circumpapillary retinal nerve fiber layer thickness (cpRNFL) and macular ganglion cell complex thickness (mGCC) were measured using spectral-domain optical coherence tomography (SD-OCT; RTVue). The Spectralis HRA+OCT instrument also was used to measure cpRNFL, and Heidelberg retina tomography II (HRT) and standard automated perimetry (SAP) were performed. Assessments were performed every 3 months over several years. Linear mixed modeling was used to evaluate the rate of change in each measure.
RESULTS. Totals of 1406 RTVue, 1366 Spectralis, 1245 HRT, and 1392 SAP measurements were analyzed. Average baseline SAP mean deviation (MD) was -6.24 +/- 5.46 dB. Linear mixed modeling revealed that SAP MD changed by -0.23 dB/y (95% confidence interval [CI], -0.34 to -0.12 dB/y). Significant negative trends also were detected in cpRNFL (RTVue, -0.41 mu m/y [95% CI, -0.67 to -0.16 mu m/y]; Spectralis, -1.36 mu m/y [95% CI, -1.65 to -1.07 mu m/y]; and mGCC (RTVue, -0.47 mu m/y [95% CI, -0.64 to -0.30 mu m/y]). Disc rim area remained constant over time (HRT, -0.01 mm(2)/y [95% CI, -0.03 to 0.01 mm(2)/y]). The SAP MD, RTVue mGCC, and Spectralis cpRNFL showed the fastest changes in the inferior retina (superior visual field), while RTVue cpRNFL changed the fastest in the superior retina.
CONCLUSIONS. Functional (SAP) and structural (SD-OCT) testing can detect longitudinal changes of glaucomatous optic neuropathy, but in different ways.

DOI： 10.1167/iovs.15-16704

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

We aimed to determine the sensitivity and specificity of the normative database of non-myopic and highly myopic eyes of the macular ganglion cell complex (mGCC) thickness embedded in the NIDEK RS-3000 spectral-domain optical coherence tomography (SD-OCT) for detecting early glaucoma in highly myopic eyes.
Forty-seven highly myopic eyes (axial length a parts per thousand yen26.0 mm) of 47 subjects were studied. The SD-OCT images were used to determine the mGCC thickness within a 9-mm diameter circle centered on the fovea. The sensitivity and specificity of the non-myopic database were compared to that of the highly myopic database for distinguishing the early glaucomatous eyes from the non-glaucomatous eyes. The mGCC scans were classified as abnormal if at least one of the eight sectors of the significance map was &lt; 1 % of the normative thickness.
Twenty-one eyes were diagnosed to be non-glaucomatous and 26 eyes to have early glaucoma. . The average mGCC thickness was significantly thinner (80.9 +/- 8.5 mu m) in the early glaucoma group than in the non-glaucomatous group (91.2 +/- 7.5 mu m; p &lt; 1 x 10(-4)). The sensitivity was 96.2 % and specificity was 47.6 % when the non-myopic database was used, and the sensitivity was 92.3 % and the specificity was 90.5 % when the highly myopic database was used. The difference in the specificity was significant (p &lt; 0.01).
The significantly higher specificity of the myopic normative database for detecting early glaucoma in highly myopic eyes will lead to fewer false positive diagnoses. The database obtained from highly myopic eyes should be used when evaluating the mGCC thickness of highly myopic eyes.

DOI： 10.1007/s00417-015-3026-y

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Dove Medical Press Ltd  

Glaucoma drainage device implantation is efficacious for the treatment of pediatric glaucoma patients when multiple angle surgeries fail. However, tube touching of the corneal endothelium is one of the major postoperative complications to deal with. A 15-month-old male patient with Wilms’ tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome was diagnosed with bilateral developmental glaucoma. He underwent Baerveldt glaucoma implant (BGI) surgeries in both eyes after multiple failed trabeculotomies. The tube in his right eye was touching the cornea 15 months after BGI surgery. To avoid corneal endothelium damage, BGI tube repositioning with scleral fixation was performed without serious complications. The bilateral BGI surgeries achieved successful intraocular pressure reduction for over 2 years and tube repositioning with scleral fixation of BGI tube was successful for BGI tube malposition. Although careful attention to intraocular pressure and tube malposition is essential after glaucoma drainage device implantation, especially in pediatric cases, BGI surgery is effective in the management of developmental glaucoma following unsuccessful angle surgeries.

DOI： 10.2147/OPTH.S80444

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

Objective
To examine microcystic inner nuclear layer (INL) changes in glaucomatous eyes and to determine associated factors.
Design
Retrospective, cross-sectional, observational study.
Methods
Two hundred seventeen eyes of 133 patients with primary open angle glaucoma (POAG), 41 eyes of 32 patients with preperimetric glaucoma and 181 normal eyes of 117 subjects were ultimately included. Microcystic INL lesions were examined with infrared fundus images and with 19 vertical spectral domain optical coherence tomography (SD-OCT) images in the macular area.
Results
Microcystic INL changes were observed in 6.0% of eyes with POAG, but none of the normal eyes or eyes with preperimetric glaucoma showed microcystic INL changes. The proportion of eyes with advanced glaucoma was significantly larger (P = 0.013) in eyes with microcystic lesions than without. The visual field mean deviation (MD) slope was also significantly worse (P = 0.027) in eyes with microcystic lesions. No significant differences were observed in age, sex, refraction, axial length, intraocular pressure, or MD value between eyes with and without microcystic INL lesions. In several cases, microcystic INL lesions occurred along with glaucomatous visual field progression. The retinal nerve fiber layer (RNFL) thickness (P = 0.013) and ganglion cell layer (GCL) + inner plexiform layer thickness (P = 0.023) were significantly lower in areas with microcystic lesions than without. The INL was also significantly thicker (P = 0.002) in areas with microcystic lesions.
Conclusions
Microcystic INL lesions in glaucomatous eyes are closely associated with RNFL and GCL thinning and correlated with worse MD slope. These INL lesions may indicate focal and progressive damage in glaucoma.

DOI： 10.1371/journal.pone.0130175

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

Purpose: To determine the association between reflectivity levels in foveal cystoid spaces on optical coherence tomography images and the course of the logarithm of the minimum angle of resolution (logMAR) after triamcinolone acetonide treatment for diabetic macular edema.
Methods: We retrospectively reviewed 58 consecutive eyes treated with an intravitreal or sub-Tenon's injection of triamcinolone acetonide for diabetic macular edema. The foveal cystoid spaces within central 1 mm were circumscribed, followed by measurement of optical coherence tomography reflectivity. The correlation between the reflectivity and visual outcome was investigated.
Results: The optical coherence tomography reflectivity levels in foveal cystoid spaces increased at 1 month after treatment, but not at 3 months or 6 months. The preoperative reflectivity levels were correlated negatively with logMAR changes from 1 month to 6 months and from 3 months to 6 months but not with logMAR at individual time points compared with the preoperative logMAR. The changes in foveal thickness from 1 month to 6 months were correlated negatively with the baseline reflectivity and positively with logMAR changes from 1 month to 6 months and from 3 months to 6 months.
Conclusion: Lower optical coherence tomography reflectivity in foveal cystoid spaces was associated with the rebound in macular thickening and visual deterioration after triamcinolone acetonide treatment for diabetic macular edema.

DOI： 10.1097/IAE.0000000000000282

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

PURPOSE: To determine if asymmetry in thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer, ganglion cell complex, and total retina between upper and lower macula halves can predict glaucoma.
DESIGN: Retrospective case-control series.
METHODS: One hundred twenty-two eyes of 122 patients (30 normal eyes and 30 preperimetric, 31 early, and 31 advanced glaucoma eyes) were studied. The RNFL, ganglion cell layer, ganglion cell complex, and total retina were segmented and measured on 10 vertical B-scans over a 30 x 15 degree macular area. The equation asymmetry index = vertical bar log(10) (lower hemiretinal thickness/upper hemiretinal thickness)vertical bar was used to calculate asymmetry indices for 8 pairs of upper and lower 0.5-mm segments equidistant from the fovea on each scan. Areas under the receiver operating characteristic curve (AROCs) for mean thickness and mean asymmetry index of 10 B-scans were compared.
RESULTS: The overlap in values for normal and glaucomatous eyes was minimal for the ganglion cell layer asymmetry index. Thickness parameters decreased with the severity of glaucoma, whereas asymmetry indices did not. AROCs for thickness measurements tended to increase with increasing glaucoma severity (preperimetric, 0.746-0.808; early, 0.842-0.940; advanced, 0.943-0.995), whereas AROCs for asymmetry indices did not have distinct ranges according to glaucoma severity (advanced, 0.819-0.996; early, 0.861-0.998; preperimetric, 0.773-0.994). The AROC for the ganglion cell layer asymmetry index remained almost perfect regardless of glaucoma severity (0.994-0.998).
CONCLUSIONS: Macular retinal layer thickness asymmetry indices, particularly for the ganglion cell layer, show promise as early indicators of glaucomatous retinal damage. (C) 2014 by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajo.2014.08.040

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

Purpose: To investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia.
Methods: A total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure beta-peripapillary atrophy (PPA) lengths with and without Bruch's membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well.
Results: LC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P &lt; 0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P &lt; 0.001), and larger vertical/horizontal tilt angles (vertical, P &lt; 0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P &lt; 0.001) and vertical tilt angle (P &lt; 0.001) were identified as significant.
Conclusions: The presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.

DOI： 10.1371/journal.pone.0115313

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

Objectives: To compare the optic nerve head (ONH) structure between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to determine whether selected ONH quantitative parameters effectively discriminate between GON and CON, especially CON cases presenting with a glaucoma-like disc.
Methods: We prospectively assessed 34 patients with CON, 34 age-matched patients with moderate or severe GON, and 34 age-matched healthy control subjects. The quantitative parameters of ONH structure were compared using the Heidelberg Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an enhanced depth imaging method.
Results: The mean and maximum cup depths of CON were significantly smaller than those with GON (P&lt;0.001 and P&lt;0.001, respectively). The distance between Bruch's membrane opening and anterior surface of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller than that of glaucoma but was similar to that of the healthy group (P, 0.001 and P = 0.47, respectively). Based on Moorfields regression analysis of the glaucoma classification of HRT2, 15 eyes with CON were classified with a glaucoma-like disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma-like disc and cases of GON (P = 0.16), but the BMO-anterior LC and mean and maximum cup depths of CON cases with a glaucoma-like disc were smaller than those in GON (P = 0.005, P = 0.003, and P = 0.001, respectively).
Conclusions: Measurements of the cup depths and the LC depth had good ability to differentiate between CON with a glaucoma-like disc and glaucoma. There was no laminar remodeling detected by laminar surface position in the patients with CON compared to those with GON.

DOI： 10.1371/journal.pone.0112403

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ PUBLISHING GROUP  

The lamina cribrosa (LC) is believed to be the site of injury to retinal ganglion cell axons in glaucoma. The ability to visualise this structure has the potential to help increase our understanding of the disease and be useful in the early detection of glaucoma. While for many years the research on the LC was essentially dependent on histology and modelling, a number of recent advances in optical coherence tomography (OCT) have dramatically improved the ability to visualise the LC, such that it is now possible to image the LC in vivo in humans and animals. In this review, we highlight recent advances in OCT imaging of the LC, in the technology, processing and analysis, and discuss the impact that these will have on the ability to diagnose and monitor glaucoma, as well as to expand our understanding of its pathophysiology. With this manuscript, we aspire to share our excitement on the achievements and potential of recent developments as well as advise caution regarding the challenges that remain before imaging of the LC and optic nerve can be used routinely in clinical practice.

DOI： 10.1136/bjophthalmol-2013-304751

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

Purpose: To investigate the correlation between visual outcomes and preoperative hyperreflective foci in the outer retinal layers seen on spectral domain optical coherence tomography images in eyes that underwent vitrectomy for diabetic macular edema.
Methods: We retrospectively reviewed 32 consecutive eyes that underwent vitrectomy for diabetic macular edema. Ten eyes had accumulated or many hyperreflective foci in the outer retinal layers preoperatively; 22 eyes did not have the pathology. The logarithm of the minimum angle of resolution and the junction between inner and outer segments were studied in the groups.
Results: Logarithm of the minimum angle of resolution was significantly better in eyes without hyperreflective foci than in those with hyperreflective foci at 3 months and 6 months, and the last visit (P = 0.029, 0.010, and &lt;0.001, respectively) compared with no differences at the baseline. Visual improvement was greater in eyes with no hyperreflective foci at the same time points. Seven eyes with hyperreflective foci had no junction between inner and outer segments at the final visit, whereas only 4 eyes with no foci had no junction between inner and outer segments (P = 0.004). However, the foveal thickness did not differ between the groups at any time.
Conclusion: Preoperative hyperreflective foci in the outer retinal layers detected by spectral domain optical coherence tomography might predict the photoreceptor damage and a poorer prognosis after vitrectomy for diabetic macular edema.

DOI： 10.1097/IAE.0000000000000005

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

Purpose: To study the relationship between retinal vessel diameter and qualitative and quantitative evaluations on spectral-domain optical coherence tomography in patients with diabetic macular edema.
Methods: One hundred and eight consecutive eyes of 80 patients, with clinically significant macular edema underwent optical coherence tomography and color fundus photography. The authors evaluated the retinal thickness of the Early Treatment Diabetic Retinopathy Study grid and foveal pathomorphologies including cystoid macular edema and serous retinal detachment on the optical coherence tomography images. The diameters of the superotemporal or inferotemporal retinal vessels originating from the optic disk were measured using a computer-assisted technique.
Results: The mean diameters of the superotemporal and inferotemporal venules were larger in eyes with diabetic macular edema than in healthy eyes. The mean diameter of the temporal venules but not the arterioles was associated with perifoveal thickening in the inferior subfield in eyes with diabetic macular edema (P = 0.014). Although the retinal thickening in the central subfield was not correlated with the diameters of the retinal vessels, eyes with foveal serous retinal detachment had larger mean diameters of superotemporal and inferotemporal venules than those without serous retinal detachment (P &lt; 0.001).
Conclusion: The mean diameters of the superotemporal and inferotemporal venules were significantly associated with foveal serous retinal detachment in diabetic macular edema.

DOI： 10.1097/IAE.0b013e3182a48732

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

To describe, in glaucomatous patients, spectral-domain optical coherence tomography (SD-OCT) results predictive of paracentral visual field (VF) defects present on standard automated perimetry (SAP) 10-2, but not on SAP 24-2.
The SAP 10-2 test was repeated 3 times to determine whether paracentral VF defects were present. Spectralis (TM) HRA + OCT was used to obtain speckle-noise-reduced macular B-scans. The macular scan protocol consisted of 19 vertical cross-sectional scan lines centered on the fovea (30A degrees A xA 15A degrees volume scan), each of which was the average of 50 scans. A 3D OCT-2000 was also used to determine macular layer thicknesses and to detect abnormally thin regions (below the 1 % confidence interval of the normative data).
We identified 3 cases in which paracentral VF defects were detected on SAP 10-2, but not on SAP 24-2. Paracentral VF defects were detected on all of the SAP 10-2 tests repeated 3 times, and included absolute scotoma in 2 of the 3 SAP 10-2 results. Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) damage was diminished on SD-OCT macular images; 2 patients had RNFL and GCL thinning within and central to the parafoveal region, where the GCL is generally thickest in healthy eyes, and 1 patient had evident RNFL and GCL thinning in the papillomacular bundle.
Macular SD-OCT scans may be useful in deciding whether SAP 10-2 should be performed.

DOI： 10.1007/s10384-013-0298-9

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PURPOSE: To characterize preperimetric retinal nerve fiber layer (RNFL) defects on speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT), and to determine whether detection of preperimetric RNFL defects can be improved by speckle noise reduction. PATIENTS AND METHODS: Thirty-two eyes of 32 patients with preperimetric glaucoma and 30 normal eyes of 30 volunteers underwent complete ophthalmic examinations and scanning by speckle noise-reduced SD-OCT (Spectralis), single-scan SD-OCT (RTVue-100), and single-scan time-domain (Stratus) OCT. RESULTS: All 40 RNFL defects identified by photography had angular widths <30 degrees and no disruption of RNFL reflectivity on Spectralis. Circumpapillary RNFL (cpRNFL) boundaries were accurately determined by Spectralis for 38 (95.0%) of the 40 defects, by RTVue-100 for 25 (62.5%), and by Stratus OCT for 23 (57.5%). Sensitivity for the detection of RNFL defects (cpRNFL thinning to <1% of normal for an age-matched database) was 15% for Stratus, 42.5% for RTVue, and 47.5% for Spectralis on sector maps and significantly higher for SD-OCT on temporal-superior-nasal-inferior-temporal (TSNIT) thickness graphs: RTVue-100 (57.5%; P=0.031) and Spectralis (90.0%; P=0.0001). On the basis of TSNIT thickness graphs, sensitivity for the detection of RNFL defects was significantly higher for Spectralis compared with RTVue-100 (P=0.001) and Stratus (P=0.0005). Spectralis TSNIT graphs were more sensitive (P=0.001) for glaucoma detection without significant reduction (P=0.125) in specificity compared with Spectralis sector maps. CONCLUSIONS: Our results suggest that accurate measurement of cpRNFL thickness by speckle noise-reduced SD-OCT and a comparison of the results with normative database using TSNIT graphs are required to improve the sensitivity for detecting preperimetric RNFL defects.

DOI： 10.1097/IJG.0b013e3182707456

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

PURPOSE. To visualize changes in deep optic nerve head (ONH) structures following glaucoma surgery using (3-dimensional [3D]) swept-source optical coherence tomography (SS-OCT) and to determine the clinical and structural factors associated with postoperative lamina cribrosa (LC) and prelaminar neural tissue (PLT) changes.
METHODS. In this prospective observational case series, SS-OCT thin-sliced datasets of the ONH covering a 3- x 3-mm area comprised of 256 B-scans (interval between scans = similar to 12 mu m) were obtained before and 3 months after the surgery and evaluated in 73 eyes of 73 patients with glaucoma. Bruch's membrane opening (BMO) and anterior LC boundary were manually delineated by two methods; one in every four B-scans (64 B-scans per eye) and 15 equally spaced horizontal B-scans in BMO area, excluding both ends (interval between scans = 96-120 mu m). After former delineation, the point with maximum LC depth among 64 B-scans was automatically calculated, and LC depth and PLT thickness were averaged among 5 points adding 4 points 100 mu m apart from this point vertically and horizontally. Associations between the percent change in LC depth and other clinical and structural parameters were tested for statistical analysis.
RESULTS. Lamina cribrosa depth and axial length significantly decreased and PLT thickness significantly increased after surgery. The percent change of maximum LC depth correlated significantly with the percent change of IOP (P = 0.008), baseline LC depth (P = 0.032), and visual field mean deviation (P = 0.035; at the point with maximum LC depth), while the percent change of axial length correlated with IOP reduction (P = 0.002) but not with visual field mean deviation.
CONCLUSIONS. Swept-source optical coherence tomography enables 3D analysis of deep ONH structures, and the change in LC depth after glaucoma surgery have association with IOP change and the severity of glaucomatous optic neuropathy.

DOI： 10.1167/iovs.13-11897

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Dove Medical Press  

Malignant glaucoma, which is characterized by a shallow or flat anterior chamber with high intraocular pressure, can usually be resolved by pars plana vitrectomy with anterior hyaloidectomy. We describe two cases in which malignant glaucoma was refractory to conventional treatment and complete vitrectomy. Case one an 88-year-old woman with pseudoexfoliation glaucoma underwent trabeculotomy and subsequently developed malignant glaucoma. Four months after transient recovery by pars plana vitrectomy, the malignant glaucoma recurred. She underwent peripheral iridectomy and local zonulectomy with successful control of her intraocular pressure. In case two, an 85-year-old man had a history of pseudoexfoliation glaucoma. Seven months after phacoemulsification and intraocular lens implantation, he developed malignant glaucoma that was refractory to pars plana vitrectomy. He underwent peripheral iridectomy, goniosynechialysis and trabectome surgery resulting in the successful control of his intraocular pressure. In rare cases of malignant glaucoma refractive to vitrectomy, peripheral iridectomy with or without local zonulectomy is a reasonable and minimally invasive surgical procedure. © 2014 Arora et al.

DOI： 10.2147/OPTH.S60704

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

PURPOSE: To evaluate the predictive ability of macular parameters defined in the significance map created using spectral-domain optical coherence tomography (SDOCT) for paracentral visual field defects in early glaucoma.
DESIGN: Prospective comparative study.
METHODS: We studied 78 early-glaucomatous eyes of 78 patients, who underwent SD-OCT and standard automated perimetry 10-2. Macular layer parameters included the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) + inner plexiform layer (IPL), and RNFL + GCL + IPL. The minimal distance between the area with abnormal (P &lt; 1%) thickness and foveal center was defined as the shortest distance. A wider area of an abnormally thinned ( &lt; 1%) region, within either an inferior or a superior hemicircle with a diameter of 6 mm centered at the fovea, was defined as the macular abnormal area. A circumpapillary RNFL parameter was defined in its 36 sectors. Areas under the receiver operating characteristic curves (ROCs) were calculated to discriminate between eyes with (n = 39) and without (n = 39) paracentral visual field defects in the central 5 degrees.
RESULTS: Measurement reproducibility was almost perfect in the macular parameters at P &lt; 1% (intraclass correlation, 0.907-0.942). Areas under the ROC were significantly higher (P &lt; 0.01) in the macular parameters (0.870-0.930), including the shortest distance of GCL + IPL/RNFL + GCL + IPL, and the macular abnormal area of RNFL/GCL + IPL/RNFL + GCL + IPL than in the circumpapillary RNFL parameter (0.676). When specificity was fixed at 90%, the shortest distance of GCL + IPL (area under the ROC = 0.874) and the macular abnormal area of RNFL (area under the ROC = 0.894) showed sensitivities greater than 50%.
CONCLUSIONS: Macular structural parameters defined on an SD-OCT significance map may be potentially useful predictors of the presence of paracentral scotoma. ((C) 2013 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2013.06.029

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Purpose: To determine how evaluations of macular structures on spectral-domain optical coherence tomography compare with those of the optic disc and circumpapillary retinal nerve fiber layer (RNFL) in discriminating between highly myopic eyes with and without glaucoma. Design: Retrospective, comparative study. Methods: The appearances of ganglion cell layer and RNFL on Spectralis macular scans (Heidelberg Engineering) and optic disc on photographs were evaluated by 2 observers. The receiver operating characteristic regression was conducted for macular ganglion cell complex and circumpapillary RNFL measurements on RTVue-100 (Optovue). Results: Ninety highly myopic eyes (-6.0 to -15.0 diopters
mean deviation [MD], -5.6 ± 5.1 dB) and 91 non-highly myopic eyes (1.0 to -5.5 diopters
MD, -4.9 ± 5.7 dB) were enrolled. In highly myopic eyes (&lt
-6 diopters), the Cohen κ for qualitative decisions by observers was 0.363 for photographs and 0.946 for Spectralis macular scans, and observers' evaluations of Spectralis macular scans were more accurate (94.5% and 94.5%, respectively
P &lt
.0001) than their evaluations of photographs (71.4% and 80.2%, respectively). In the receiver operating characteristic regression analyses assessing the influences of age, sex, MD, and axial length, the better MD (P =.002 to.016) and longer axial length (P =.031 to.041) were associated significantly with diagnostic performances for all or some spectral-domain optical coherence tomography parameters. The receiver operating characteristic curves of average macular ganglion cell complex and circumpapillary RNFL thicknesses were comparable at low MD. Conclusions: In high myopes, observers' assessments of the spectral-domain optical coherence tomography macular scans may agree better and be more accurate than observers' optic disc assessments. Glaucoma diagnostic performance of the macular ganglion cell complex may be less affected by axial length compared with that of circumpapillary RNFL. © 2013 by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajo.2013.04.028

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PURPOSE. To visualize lamina cribrosa defects using three-dimensional (3D) swept-source optical coherence tomography (SS-OCT), and to determine the factors associated with this feature. METHODS. All subjects were examined using an SS-OCT prototype system, which uses a tunable laser as a light source, operated at 100,000 Hz A-scan repetition rate in the 1050-nm wavelength. A 3D raster scan protocol consisting of 256 × 256 A-scans was acquired over a square area of 3 mm × 3 mm centered on the optic disc. En face sectioned volume and serial en face images and orthogonal (horizontal and vertical) serial B-scans were evaluated. RESULTS. A total of 182 eyes of 111 patients with glaucoma and 29 healthy eyes of 26 subjects were included. Twenty full-thickness focal lamina cribrosa defects were found in 12 (6.6%) of 182 eyes with glaucoma, whereas no lamina defects were found in healthy eyes. Nine eyes (75.0%) showed 15 full-thickness lamina cribrosa defects near the margin of the lamina cribrosa, and 3 eyes showed 4 lamina defects at the margin, as if detached from the sclera. Focal lamina cribrosa defects corresponded with neuroretinal rim thinning, concurrent or previous disc hemorrhages, abnormal circumpapillary retinal nerve fiber layer thickness, and visual field defects. The presence of lamina cribrosa defects was significantly associated with longer axial length and disc hemorrhages (P 1/4 0.033 and 0.024, respectively). CONCLUSIONS. 3D SS-OCT imaging allows visualization of the lamina cribrosa defects, which may be more prevalent in eyes with longer axial length and related to disc hemorrhages. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

DOI： 10.1167/iovs.13-11677

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

PURPOSE: To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO).
DESIGN: Prospective cross-sectional study.
METHODS: Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system.
RESULTS: The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P &lt; .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P &lt; .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017).
CONCLUSIONS: AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. (Am J Ophthalmol 2013;155: 870-881. (C) 2013 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2012.11.016

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

PURPOSE: To study peripapillary morphologic changes in highly myopic eyes using swept-source optical coherence tomography at a longer wavelength.
DESIGN: Prospective cross-sectional study.
METHODS: Peripapillary regions of 196 eyes of 107 patients with high myopia (refractive error, &lt; -8.0 diopters or axial length, &gt; 26.0 mm) were analyzed quantitatively and qualitatively with an swept-source optical coherence tomography prototype system that uses a tunable laser light source operated at a 100,000-Hz A-scan repetition rate in the 1-mu m wavelength region. The visual field was evaluated by standard automated perimetry. Area of peripapillary atrophy p and presence of scleral protrusion temporal to the optic disc were assessed.
RESULTS: Peripapillary atrophy 3 area, but not disc area, was significantly larger in eyes with visual field defect (3.16 +/- 2.70 mm(2); range, 0.00 to 12.85 mm(2)) than those without visual field defect (2.31 +/- 2.83 mm(2); range, 0.00 to 17.70 mm(2)). Temporal scleral protrusion was detected by color stereo disc photography in 22 (19.5%) of 113 eyes with visual field defect and in 4 (4.8%) of 83 eyes without visual field defect. Scleral bending demonstrated a wide range of angles (mean, 31.0 +/- 21.1 degrees; range, 2 to 80 degrees). The angle of scleral bending, but not the distances from scleral bend to disc margin or foveal center, correlated significantly with retinal nerve fiber layer thickness above the bend (r = -0.557, P = .007) and visual field defect severity (r = -0.445, P = .038).
CONCLUSIONS: Swept-source optical coherence tomography visualizes peripapillary deep structures in high myopia. Some cases of high myopia may be affected by direct scleral compression or stretching at the peripapillary region. (Am J Ophthalmol 2013;155: 927-936. (C) 2013 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2012.12.014

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

To determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG).
Twenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100. SAP and FDT indices, HRT parameters, and circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were correlated using Pearson's test. Areas under the receiver operating characteristic curves (AUROCs) and sensitivity/specificity based on each parameter's definition of abnormalities were compared between parameters.
Significant differences were found in FDT-MD, FDT-PSD, SAP-PSD, cpRNFL, and mGCC parameters (p &lt; 0.001-0.015), but not in SAP-MD or HRT parameters, between PPG and control groups. Significant correlations were not found between visual field indices and structural parameters, except between FDT-MD and HRT rim area (r = 0.450, p = 0.021) and between FDT-PSD and temporal cpRNFL thickness (r = 0.402, p = 0.021). AUROCs for cpRNFL (p = 0.0047-0.033) and mGCC (p = 0.0082-0.049) parameters were significantly better than those of HRT parameters, whereas significant differences were not found between FDT indices and cpRNFL or mGCC parameters or between cpRNFL and mGCC parameters. Adding average cpRNFL or mGCC thickness to FDT-MD significantly increased sensitivity compared to single parameters (p = 0.016-0.031).
Structural and functional parameters were poorly correlated but complementary for glaucoma detection in PPG. Combining these parameters may improve PPG diagnosis.

DOI： 10.1007/s00417-012-2076-7

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

PURPOSE. To test the glaucoma-discriminating ability of a new method for detecting local ganglion cell loss using spectral-domain optical coherence tomography (OCT).
METHODS. This study included 58 glaucomatous and 48 healthy eyes from Japanese subjects. Combined thickness of the ganglion cell layer and inner plexus layer (GCIPL) was measured on a macular cube scan in Cirrus HD-OCT. Average GCIPL thickness within a macular elliptical annulus and minimum GCIPL thickness on 360 spokes extending from the inner to the outer radius of the elliptical annulus were calculated. Area under the receiver operating characteristic curve (AROC) to discriminate between healthy eyes and early (mean deviation [MD], &gt;=-6 dB)/advanced (MD, &lt;-6 dB) glaucomatous were compared between parameters.
RESULTS. Forty-three were normal-tension glaucoma, and 15 were high-tension glaucoma. The mean minimum GCIPL thickness was 77.0 mu m in healthy eyes and 60.6 mu m in glaucomatous eyes (P &lt; 0.001). For the intersession repeatability, the coefficients of variation for average GCIPL and minimum GCIPL were 0.98 and 1.85 in glaucomatous eyes, and 0.89 and 1.85 in healthy eyes, respectively. Minimum GCIPL thickness AROC (0.896) was significantly higher (P = 0.0062) than average GCIPL thickness (0.821) for early glaucoma, whereas minimum GCIPL AROC (0.991) was comparable (P = 0.103) to average GCIPL (0.964) for advanced glaucoma. The minimum GCIPL thickness AROC was comparable (P = 0.861) to average circumpapillary retinal nerve fiber layer (cpRNFL) thickness (0.890) for early glaucoma.
CONCLUSIONS. In Japanese patients with 74.1% of normal-tension glaucoma, the minimum GCIPL on spokes may be useful for detecting early glaucoma. (Invest Ophthalmol Vis Sci. 2012; 53:6904-6913) DOI:10.1167/iovs.12-10210

DOI： 10.1167/iovs.12-10210

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

PURPOSE. To measure the inner and outer retinal thicknesses on spectral-domain optical coherence tomography (SD-OCT) and evaluate their association with logMAR after vitrectomy for diabetic macular edema (DME).
METHODS. In this retrospective case series, there were 55 consecutive eyes with DME for which vitrectomy was performed. The total retinal thickness, the inner thickness (from the innermost of the retina to the inner nuclear layer), and the outer thickness (from the outer plexiform layer to the retinal pigment epithelium) in the parafoveal subfields were measured manually, and the association with logMAR was evaluated.
RESULTS. The total retinal thicknesses in the central, nasal, and inferior subfields were significantly (r = 0.37, P = 0.005; r = 0.29, P = 0.032; r = 0.33, P = 0.015, respectively) associated with the baseline logMAR; no subfield thickness was correlated with the logMAR at the final visit. However, segmentational analysis showed that the outer retinal thickness of the temporal subfield was associated with disruption of the junction between the inner and outer segments at the fovea (P = 0.021 and P = 0.005) and negatively correlated with the logMAR (r = -0.37, P = 0.006 and r = -0.28, P = 0.042) at the 6-month and final visit. The inner thickness of the nasal subfield did not change after vitrectomy compared with the other subfields and the outer thickness of all subfields in the parafoveal area; the baseline nasal total thickness was correlated most significantly with the logMAR (r = 0.40, P = 0.002 and r = 0.37, P = 0.006) at the 6-month and final visits.
CONCLUSIONS. Segmentational analysis provided useful information for considering the prognosis and pathogenesis after vitrectomy for DME. (Invest Ophthalmol Vis Sci. 2012;53:6668-6674) DOI:10.1167/iovs.12-9934

DOI： 10.1167/iovs.12-9934

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

PURPOSE. To compare the retinal nerve fiber layer (RNFL) defects in early glaucomatous eyes between highly and non-highly myopic eyes.
METHODS. Sixty-one highly myopic eyes (&lt; -6.0 diopters [D]) of 61 patients and 55 non-highly myopic eyes of 55 patients with early visual field (VF) defects were studied. The angular locations and widths of the RNFL defects were measured from red-free fundus photographs. The RNFL defect closest to the fovea was designated the "nearest RNFL defect" of each hemisphere.
RESULTS. In total, 131 RNFL defects were found in highly myopic eyes and 82 in non-highly myopic eyes. Twenty-seven (44.3%) of the 61 highly myopic eyes, but only 8 (14.5%) of the 55 non-highly myopic eyes had their nearest RNFL defects between 0 degrees and 10 degrees (P &lt; 0.001). Although the frequencies of paracentral scotomas were comparable between the two groups, the rate of inferotemporal paracentral scotomas was significantly higher in the high myopia group (P = 0.02). The numbers of nearest RNFL defects in the superior hemisphere or extending over both hemispheres were significantly higher in the high-myopia group. Multiple logistic regression analyses showed that high myopia and the nearest RNFL defect involving the papillomacular bundle were significantly associated with paracentral scotomas (odds ratio [OR]: 4.78, P &lt; 0.05, and OR: 5.31, P &lt; 0.001, respectively). High myopia was significantly associated with the nearest RNFL defect involving the papillomacular bundle (OR: 2.95, P &lt; 0.05).
CONCLUSIONS. These findings suggest that highly myopic eyes are more susceptible to papillomacular bundle damage in early glaucoma. (Invest Ophthalmol Vis Sci. 2012;53:6472-6478) DOI:10.1167/iovs.12-10319

DOI： 10.1167/iovs.12-10319

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

PURPOSE. To determine whether measurement of ganglion cell complex (GCC) thickness over a wide area (8-mm diameter) can improve the glaucoma-discriminating ability of spectral-domain optical coherence tomography (SD-OCT) compared to that in the standard macular area (6-mm diameter).
METHODS. Ninety-three subjects were enrolled, including 46 healthy eyes of 46 volunteers and 47 eyes of 47 glaucoma patients (23 eyes with preperimetric glaucoma [PPG] and 24 eyes with early glaucoma [EG]). All patients underwent SD-OCT raster scanning over a 9 mmx9 mm square area centered on the fovea. Areas under the receiver operating characteristic curves (AROCs) were compared between wide sector (1-8-mm ring) and standard-size sector (1-6-mm ring) charts.
RESULTS. AROCs for average GCC thickness in the wide chart were significantly greater than those of the standard chart in eyes with PPG (0.928 vs. 0.891; P = 0.038), EG (0.912 vs. 0.861; P = 0.003), and both (0.920 vs. 0.876; P = 0.004). Overall, the AROCs of regional GCC thicknesses were nearly comparable between the middle ring (4-6 mm) and outer ring (6-8 mm). Coefficients of variation were 0.68% and 0.97% in the standard and wide sector charts, respectively, in eyes with PPG, and 0.45% and 0.72% in the standard and wide sector charts, respectively, in eyes with EG.
CONCLUSIONS. Addition of the GCC thickness outside the macula to the standard macular GCC thickness significantly increased the glaucoma-discriminating ability of SD-OCT. (Invest Ophthalmol Vis Sci. 2012;53:4805-4812) DOI: 10.1167/iovs.12-9870

DOI： 10.1167/iovs.12-9870

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PURPOSE. To visualize and assess the surface-level pores of the lamina cribrosa in patients with glaucoma by using a prototype adaptive optics scanning laser ophthalmoscopy (AOSLO) system.
METHODS. The numbers of laminar pores were compared between color disc photography, scanning laser ophthalmoscopy (SLO) without AO, and AOSLO. The pore area and elongation index were examined for correlation with ocular parameters such as the mean deviation, disc area, cup/disc ratio, disc ovality index, intraocular pressure (IOP), and axial length in the AOSLO images.
RESULTS. The 40 eyes (20 normal and 20 glaucomatous) of 40 subjects were enrolled. The AOSLO provided laminar pore images of better quality than other imaging methods, and the number of visible pores was significantly greater in the AOSLO images than in the other imaging methods (the color disc photographs [P &lt; 0.001] and SLO without AO images [P &lt; 0.001]) when compared for 26 subjects. When compared for 40 subjects using AOSLO, the pore area was significantly larger in glaucomatous subjects than in normal subjects (P = 0.031), but elongation index was not. The pore area correlated significantly with the axial length (P = 0.008) in normal subjects, with the untreated IOPs (P = 0.002) in the glaucomatous subjects, and with the axial length (P = 0.001) and cup/disc ratio (P = 0.012) in the total subjects. Via multiple regression analysis, significant correlations with pore area were found for axial length in the normal (beta = 0.684, P = 0.001) and total subjects (beta = 0.496, P &lt; 0.001) and untreated IOP in the glaucomatous (beta = 0.506, P = 0.023) and total subjects (beta = 0.331, P = 0.014).
CONCLUSIONS. AOSLO is a useful imaging technology for assessing laminar pore morphology. The laminar pore area may be affected by axial length and IOP. (Invest Ophthalmol Vis Sci. 2012;53:4111-4119) DOI:10.1167/iovs.11-7536

DOI： 10.1167/iovs.11-7536

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Objective: To study the characteristics of the reflectivity of the cystoid spaces and serous retinal detachment (SRD) on spectral-domain optical coherence tomography (SD-OCT) and the correlation with fluorescein findings in diabetic macular edema (DME).
Design: Retrospective, observational, cross-sectional study.
Participants: Consecutive 134 eyes of 114 patients with clinically significant macular edema for whom SD-OCT and fluorescein angiography (FA) were performed on the same day.
Methods: Fluorescein angiography using Heidelberg Retina Angiograph 2 (Heidelberg Engineering, Heidelberg, Germany) and OCT images using Spectralis OCT (Heidelberg Engineering) were obtained. The reflectivity of the cystoid spaces and SRD on the OCT images was evaluated qualitatively and quantitatively and compared with the fluorescein pooling intensity on FA images.
Main Outcome Measures: The relationship between the fluorescein pooling and the reflectivity characteristics of the cystoid spaces on SD-OCT images.
Results: A total of 141 cystoid spaces in 101 eyes were delineated on OCT images, and 138 spaces (97.9%) had fluorescein pooling. Fifty-five cystoid spaces (39.9%) with marked fluorescein pooling intensity had lower reflectivity on OCT images than those with modest pooling (12.1 +/- 10.4 vs. 22.0 +/- 15.4, P &lt; 0.001). The heterogeneity of the reflectivity of the cystoid spaces on the OCT images was associated significantly (P &lt; 0.001) with modest fluorescein pooling. The hyperreflective foci in the cystoid spaces were correlated significantly with modest fluorescein pooling and higher or heterogeneous reflectivity on OCT images (P &lt; 0.001, P &lt; 0.001, and P = 0.005, respectively). In addition, the cystoid spaces with microaneurysms had higher or heterogeneous reflectivity on OCT images more frequently than those without microaneurysms (P &lt; 0.001 and P = 0.019, respectively). The reflectivity levels in the SRD were significantly (P = 0.005) lower than in the cystoid spaces, and only 1 eye (3.3%) had heterogeneous reflectivity on OCT images.
Conclusions: The results provided a novel interpretation of fluorescein pooling and OCT characteristics of cystoid spaces and SRD in DME and suggested several mechanisms by which the blood-retinal barrier is disrupted and concomitant edematous changes develop.

DOI： 10.1016/j.ophtha.2011.10.030

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Purpose: To describe a patient with intrachoroidal cavitation in the normal eye that caused self-limiting recurrent macular detachment and retinoschisis. Case Report: An 80-year-old female patient with intrachoroidal cavitation in the normal eye presented with macular detachment and retinoschisis after cataract surgery. These were treated with intravitreal bevacizumab and then absorbed within 9 months. One year after cataract surgery, the patient presented with macular detachment and retinoschisis in the same eye again. These were absorbed within 4 months without treatment. Conclusion: This case suggests that similar cases of cystoid macular edema after cataract surgery can occur, and that intrachoroidal cavitation is observed not only in eyes with pathologic myopia but also in normal eyes with peripapillary atrophy
intrachoroidal cavitation can cause macular detachment and retinoschisis. Copyright © 2012 S. Karger AG, Basel.

DOI： 10.1159/000339292

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PURPOSE: To determine if hyperreflective foci in the outer retina are associated with photoreceptor integrity and the logarithm of minimal angle of resolution (logMAR) visual acuity (VA) in patients with diabetic macular edema (DME).
DESIGN: Retrospective, observational, cross-sectional study.
METHODS: Patients (n = 76; 108 eyes) with clinically relevant macular edema and no serous retinal detachment were analyzed retrospectively. Spectral-domain optical coherence tomography (SD-OCT) images were obtained for all patients. We investigated the relationship between the hyperreflective foci in the outer retinal layers of the external limiting membrane (ELM) at the fovea and the photoreceptor integrity and VA.
RESULTS: SD-OCT showed that 58 eyes (53.7%) had hyperreflective foci in the outer retinal layers, and 107 eyes (99.1%) had hyperreflective foci in the inner retinal layers. The logMAR VA was significantly (P &lt; .0001) worse in eyes with hyperreflective foci in the outer retinal layers than in eyes without them (0.463 +/- 0.382 vs 0.127 +/- 0.206, respectively). Disruption of the ELM line on OCT was significantly (P &lt; .0001, for both comparisons) associated with both hyperreflective foci in the outer retinal layers and poor logMAR VA. Disruption of the junction of the inner and outer segment line (IS/OS) also was related to hyperreflective foci in the outer retinal layers and poor logMAR VA (P &lt; .0001 for both comparisons).
CONCLUSIONS: The presence of hyperreflective foci in the outer retina is closely associated with a disrupted ELM and IS/OS line on SD-OCT images and decreased VA in DME. (Am J Ophthalmol 2012;153:710-717. (C) 2012 by Elsevier Inc. All rights reserved.)

DOI： 10.1016/j.ajo.2011.08.041

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

PURPOSE. To investigate the relationship between the cystoid spaces in the outer plexiform layer (OPL) and the characteristics of the photoreceptors beneath the cystoid spaces in patients with diabetic macular edema (DME).
METHODS. In this observational cross-sectional study, 123 eyes of 96 consecutive patients with clinically significant macular edema were retrospectively reviewed. The characteristics of the photoreceptors on optical coherence tomography (OCT) images represented by the external limiting membrane (ELM) and the junction between inner and outer segments (IS/OS), and their association with the overlying cystoid spaces were investigated.
RESULTS. The areas beneath the cystoid spaces in the OPL had a longer transverse length of disrupted or faint IS/OS and disrupted ELM lines than those without cystoid spaces (P &lt; 0.001, P &lt; 0.001, and P = 0.009). The IS/OS lines beneath the cystoid spaces had higher reflectivity than those in areas without cystoid spaces (P &lt; 0.001). Enlarged cystoid spaces extending from the inner nuclear layer to the OPL were associated with disrupted IS/OS or ELM but not faint IS/OS (P &lt; 0.001, P &lt; 0.001, and P = 0.467). The transverse length of disrupted IS/OS at the fovea was correlated with the logarithm of the minimum angle of resolution (logMAR) more than the association between foveal thickness and logMAR (r = 0.49, P &lt; 0.001 vs. r = 0.28, P = 0.002). The ELM descended to the RPE more frequently in eyes with single-lobulated fluorescein pooling in the foveal avascular zone than those with multilobulated pooling (P &lt; 0.001).
CONCLUSIONS. OCT showed that the cystoid spaces in the OPL were accompanied by photoreceptor damage beneath the cystoid spaces in DME. (Invest Ophthalmol Vis Sci. 2012;53:1506-1511) DOI:10.1167/iovs.11-9231

DOI： 10.1167/iovs.11-9231

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Other Link： http://search.jamas.or.jp/link/ui/2013034423

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PURPOSE. To evaluate peripapillary atrophy beta (PPA-beta) characteristics in highly myopic eyes, using simultaneous confocal scanning laser ophthalmoscopy (cSLO) and enhanced spectraldomain optical coherence tomography (SD-OCT).
METHODS. The authors retrospectively analyzed 61 highly myopic (&gt;= -6.0D) eyes without myopic retinopathy. cSLO fundus images were used to measure the distances from the foveal center to the temporal and nasal margins of the PPA-beta zone; horizontal cross-sectional SD-OCT images, to determine the position where the inner plexiform layer (IPL) terminates within the PPA-beta zone; and A-mode ultrasonography, to measure axial length.
RESULTS. The distance from the foveal center to the PPA-beta zone temporal margin (2.68-4.39 mm) correlated with the circumferential extent of PPA-beta (P &lt; 0.001, r = -0.49). The distance from the foveal center to the nasal margin (3.41-5.60 mm) correlated with the ovality index of the optic disc (P &lt; 0.001, r = -0.51) and with the axial length (P &lt; 0.05, r = 0.26). PPA-beta zone width (0.20 -2.05 mm) correlated with the circumferential extent of PPA-beta (P &lt; 0.001, r = 0.42), ovality index of the optic disc (P &lt; 0.001, r = -0.68), and axial length (P &lt; 0.05, r = 0.32). The IPL termination within the PPA-beta zone was significantly closer to the optic disc when the circumferential extent of PPA-beta was large (P &lt; 0.01, r = 0.36).
CONCLUSIONS. Interindividual variations in biometric features of PPA-beta in highly myopic eyes showed different associations with axial length, degree of disc ovality, and circumferential extent of PPA-beta. (Invest Ophthalmol Vis Sci. 2011; 52: 6706-6713) DOI: 10.1167/iovs.11-7580

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Language：Japanese   Publisher：眼科臨床紀要会  

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：SPRINGER TOKYO  

DOI： 10.1007/s10384-009-0747-7

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Purpose: To determine the cause and prognosis of neurologically isolated third, fourth, or sixth cranial nerve dysfunction in cases of oculomotor palsy, and to determine the best imaging methods to make a correct diagnosis.
Methods: The medical records of 221 consecutive patients with oculomotor palsy caused by neurologically isolated cranial nerve dysfunction were reviewed. There were 63 cases of third, 41 of fourth, and 117 of sixth cranial nerve dysfunction. The patients were examined at the Neuro-ophthalmology Clinic of Kyoto University Hospital between 1993 and 2001.
Results: Vascular disorders accounted for 34.9% of the third nerve dysfunction, and 90% of these recovered completely in 6 months. Ninety percent of the patients with an isolated third nerve dysfunction that was caused by an aneurysm also had anisocoria, and 68% of the patients with a third nerve dysfunction caused by a vascular disorder had anisocoria. In all of the vascular cases with anisocoria, the difference in the pupillary diameter was &lt; 1.0 mm. The presence of ptosis did not play an important role in making a diagnosis of third nerve dysfunction. Ninety percent of the patients with fourth nerve dysfunction and 60% of the patients with sixth nerve dysfunction recovered within 9 months.
Conclusions: The age of the patient, signs of an improvement, and associated alterations are important diagnostic markers to determine the best type of imaging methods for evaluating neurologically isolated third, fourth, and sixth cranial nerve dysfunction.

DOI： 10.1007/s10384-007-0489-3

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

Regeneration in the mammalian CNS is severely limited. Unlike in the chick, current models hold that retinal neurons are never regenerated. Previously we demonstrated that, in the adult mammalian retina, Muller glia dedifferentiate and produce retinal cells, including photoreceptors, after acute neurotoxic injury in vivo. However, the number of newly generated retinal neurons is very limited. Here we demonstrate that Wnt (wingless-type MMTV integration site family)/beta-catenin signaling promotes proliferation of Muller glia-derived retinal progenitors and neural regeneration after damage or during degeneration. Wnt3a treatment increases proliferation of dedifferentiated Muller glia &gt; 20-fold in the photoreceptor-damaged retina. Supplementation with retinoic acid or valproic acid induces differentiation of these cells primarily into Crx ( cone rod homeobox)- positive and rhodopsin-positive photoreceptors. Notably, injury induces nuclear accumulation of beta-catenin, cyclin D1 upregulation, and Wnt/beta-catenin reporter activity. Activation of Wnt signaling by glycogen synthase kinase-3 beta inhibitors promotes retinal regeneration, and, conversely, inhibition of the signaling attenuates regeneration. This Wnt3a-mediated regeneration of retinal cells also occurs in rd mice, a model of retinal degeneration. These results provide evidence that Wnt/beta-catenin signaling contributes to CNS regeneration in the adult mammal.

DOI： 10.1523/JNEUROSCI.4193-06.2007

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DOI： 10.1016/j.neures.2007.06.327

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

PURPOSE. The purpose of this study was to investigate the effects of various genes related to photoreceptor development on rodent and primate iris cells and the potential of iris cells as donor cells for retinal transplantation.
METHODS. Adult rat and monkey iris tissue were cultured in serum-free medium containing basic fibroblast growth factor. Gene deliveries of Crx, Nrl, NeuroD and some combinations (Crx-Nrl, Crx-NeuroD) were performed with recombinant retrovirus. Immunocytochemistry, Western blot analysis, RT-PCR, and intracellular recording were used to examine the expression of photoreceptor-specific phenotypes in the iris-derived cells after gene transfer,. Coculture of the iris-derived cells with embryonic retinal explant was conducted, to investigate the potential integration of these cells in coculture conditions.
RESULTS. Misexpression of Crx induced adult rat iris cells to express several photoreceptor-specific antigens and transcripts, such as rhodopsin, recoverin, cGMP-gated channel, arrestin, interphotoreceptor retinal-binding protein, rhodopsin kinase, and NeuroD. In primates, a combination of Crx and NeuroD was needed to induce monkey iris - derived cells to adopt photoreceptor-specific phenotypes. Furthermore, the photoreceptor-like cells derived from both rat- and primate-iris tissues showed rod photoreceptor-specific electrophysiological response to light stimuli after Crx and Crx-NeuroD gene transfer, respectively. The results further showed that iris-derived cells integrated in the developing host retina in coculture conditions.
CONCLUSIONS. Adult iris-derived cultured cells of both rodents and primates expressed photoreceptor-specific phenotypes by inductions of transcription factors. These iris-derived photoreceptor-like cells have electrophysiological characteristics of rod photoreceptors. Furthermore, they can integrate in the developing retina under coculture conditions.

DOI： 10.1167/iovs.04-1112

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While a number of retinal transplantation studies using various types of donor cells have been performed thus far, our study focused on iris tissue as a donor cell source. This is because donor cells from iris pigment epithelium have the following characteristics: (1) they are embryonically related to the neural retina
(2) autologous iris tissue can be obtained via a surgical approach
and (3) they can be cultured to increase the number of donor cells and establish photoreceptor-like cells from iris-derived cells by means of the appropriate gene transfer. Although the potential of iris-derived cells has been indicated, there remain many issues to be investigated.

DOI： 10.1080/08820530590921855

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

PURPOSE. It remains unclear which gene induction effectively generates photoreceptor-specific phenotypes from nonretinal tissues. The purpose of this study was to determine whether Crx and Otx2-homeobox genes related to photoreceptor development-can induce the generation of these phenotypes in cells derived from adult ciliary and iris tissue and in mesencephalon-derived neural stem cells.
METHODS. Crx and Otx2 were transferred into adult rat ciliary- and embryonic mesencephalon-derived neurospheres and adult rat iris-derived cells with the aid of a recombinant retrovirus. The presence of photoreceptor-specific phenotypes was confirmed by immunocytochemistry and Western blot analysis.
RESULTS. More than 90% of the Crx- and Otx2-transfected ciliary- and iris-derived cells exhibited rod opsin immunoreactivity, whereas few of the similarly transfected mesencephalon-derived neural stem cells expressed rod opsin. At least two additional key components of the phototransduction cascade, recoverin and Gpartial derivativet1, were expressed by Crx- and Otx2-transfected iris-derived cells.
CONCLUSIONS. Crx and Otx2 effectively induced the generation of photoreceptor-specific phenotypes from ciliary- and iris-derived cells. That both Crx and Otx2 induced phenotype generation in cells derived from iris or ciliary tissue may suggest an approach to photoreceptor cell preparation for retinal transplantation.

DOI： 10.1167/iovs.04-0697

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATL ACAD SCIENCES  

It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Muller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Muller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.

DOI： 10.1073/pnas.0402129101

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Retinal precursor cells give rise to six types of neurons and one type of glial cell during development, and this process is controlled by multiple basic helix-loop-helix ( bHLH) genes. However, the precise mechanism for specification of retinal neuronal subtypes, particularly horizontal neurons and photoreceptors, remains to be determined. Here, we examined retinas with three different combinations of triple bHLH gene mutations. In retinas lacking the bHLH genes Ngn2, Math3, and NeuroD, horizontal neurons as well as other neurons such as bipolar cells were severely decreased in number. In the retina lacking the bHLH genes Mash1, Ngn2, and Math3, horizontal and other neurons were severely decreased, whereas ganglion cells were increased. In the retina lacking the bHLH genes Mash1, Math3, and NeuroD, photoreceptors were severely decreased, whereas ganglion cells were increased. In all cases, glial cells were increased. The increase and decrease of these cells were the result of cell fate changes and cell death and seem to be partly attributable to the remaining bHLH gene expression, which also changes because of triple bHLH gene mutations. These results indicate that multiple bHLH genes cross-regulate each other, cooperatively specify neuronal subtypes, and regulate neuronal survival in the developing retina.

DOI： 10.1074/jbc.M400871200

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

One of the major roles of brain-derived neurotrophic factor (BDNF) is to promote the differentiation and support the survival of neurons in the central nervous system. The objective of the present study was to evaluate the effect of BDNF on the fate of adult rat hippocampus-derived neural stem cells (AHPCs) transplanted into the developing rat retina. Immunohistochemical analysis showed a significant increase in the ratio of grafted AHPCs stained for MAP2ab (P &lt; 0.05) and a marked decrease in the ratio of nestin-positive grafted cells in the slow-releasing BDNF group compared with the control group. The respective changes in the ratios of MAP5 and GFAP-positive grafted cells were comparable for the two groups. The results reported here suggest a potentially beneficial role for extended delivery of BDNF in the differentiation of grafted neural stem cells, which may lead to a novel modification of stem cell transplantation. (C) 2003 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2003.08.076

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

Embryonic retina is one of the possible cell sources that will repair degenerated retina such as retinitis pigmentosa. Retinal progenitor cells isolated from embryonic rats could be cultured and expanded in serum free medium with both epidermal growth factor and basic fibroblast growth factor. We analyzed the properties of two different retinal progenitor cells in terms of culture periods. Retinal progenitor cells from embryonic retina could be expanded keeping immature cell properties and had the ability to migrate into degenerated adult retina from subretinal space after transplantation. They differentiated into neurons and glias, even into photoreceptor cells both in vitro and in vivo. However, they appeared to lose their tissue specificity after a long-term culture. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(03)00177-0

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.11477/mf.1410906908

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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：Japanese   Publisher：(株)メディカルレビュー社  

＜文献概要＞緑内障診療の救急医療として最初に想起される場面としては,緑内障の急性発作や眼圧スパイクが挙げられる.そして術後合併症のなかでも濾過胞感染,過剰濾過による前房消失なども深刻な状況であり,眼虚血症候群のような血管新生緑内障もいまだ失明の大きな要因となっている.これらの深刻な疾患からいかにして患者の視機能を守るかは,緑内障診療における重要課題である.今回は,迅速な診断と適切な治療が求められる緑内障の救急医療の現状,課題についてエキスパートの先生方にお話しいただいた.

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J03471&link_issn=&doc_id=20231102250003&doc_link_id=10.34449%2FJ0024.01.66_0015-0023&url=https%3A%2F%2Fdoi.org%2F10.34449%2FJ0024.01.66_0015-0023&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞目的 広義原発開放隅角緑内障(広義POAG)で通院,加療中の患者にアイフレイルチェックリストについて回答していただき,緑内障重症度とチェックリストの関係性および緑内障患者で該当しやすい項目に関して検討した。対象と方法 対象は40歳以上の手術治療,レーザー治療の既往がない広義POAG患者97名(平均年齢58±9.3歳,男性51名,女性46名)である。アイフレイルチェックリストにおいて,2項目以上該当した割合と項目別の該当数を検討した。またHumphrey視野(HFA)24-2 MD値-6dBで早期例と中期以降例の2群に分けて比較した。結果 2項目以上該当したのは97例中79例(81.4%)で,早期では33例中26例(78.8%),中期以降では64例中53例(82.8%)であった(P=0.783)。平均該当項目数は3.4±2.0個で,該当項目数とBetter eyeのHFA 24-2 MD値-3.74±4.86dB(P=0.028),Worse eyeの24-2 MD値-9.32±6.32dB(P=0.016),Worse eyeの10-2 MD値-8.31±6.73dB(P=0.047)とそれぞれで弱い相関を認めた。該当率が高かった項目は「目が疲れやすくなった(59.8%)」「夕方になると見えにくくなることがある(46.4%)」「新聞や本を長時間見ることが少なくなった(47.4%)」「眼鏡をかけてもよく見えないと感じることが多くなった(47.4%)」「まぶしく感じやすい(42.3%)」であった。また「新聞や本を長時間見ることが少なくなった」が早期30.3%に対して中期以降56.3%(P=0.019),「段差や階段が危ないと感じたことがある」が早期12.1%に対して中期以降40.6%(P=0.005)と有意に増加していた。該当項目がなかった7例中6例はBetter eyeの24-2・10-2 MD値ともに-2dB以上であった。結論 アイフレイルチェックリストは緑内障の検出に有用である可能性がある。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00293&link_issn=&doc_id=20230622030013&doc_link_id=10.18888%2Fga.0000003160&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fga.0000003160&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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

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Language：Japanese   Publisher：(株)全日本病院出版会  

Minimally(micro-)invasive glaucoma surgery(MIGS)は結膜切開を施行しない,あるいは極わずかな結膜切開で行う低侵襲緑内障手術である.いくつかの異なるタイプの手術が含まれるが,現在日本で行われているMIGSはほぼすべて線維柱帯をターゲットとした流出路再建術である.日本では以前から強結膜を切開して行う眼外アプローチの線維柱帯切開術が成人の開放隅角緑内障に対して一般的に行われていた.線維柱帯をターゲットとするMIGSの手術効果や適応は概ねこれと同じと考えられ,MIGSにおける結膜切開を必要としないメリットは大きい.日本でもMIGSは急速に普及しており,今後は濾過手術タイプのMIGSも登場してくる.今後も適切な症例に適切な術式を選択できるように尽力していく必要がある.(著者抄録)

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞◆近視性変化によるストレスは乳頭内や乳頭周囲にさまざまな構造変化を生じる。◆OCTによって病的近視の病態理解が急速に進んできた。◆病的近視で生じる構造変化はしばしば視野障害の原因になる。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01537&link_issn=&doc_id=20220831030007&doc_link_id=10.11477%2Fmf.1410214493&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410214493&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   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：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：Japanese   Publisher：(株)メディカル葵出版  

目的:角膜移植・濾過手術後の唯一眼に眼内炎を発症した症例を報告する。症例:58歳、男性、両眼角膜変性症に対して全層角膜移植術の既往があり16年前に両眼続発緑内障に対して濾過手術を施行されていた。X年末より感冒症状があり翌年1月2日に右眼霧視の増悪を自覚し京都大学医学部附属病院眼科を受診した。右眼視力は手動弁、左眼は光覚なし、右眼眼圧10mmHg、耳上側に無血管性の濾過胞とその周囲に強い結膜充血を認め、著明な角膜混濁のため前房内や眼底は透見不能だった。濾過胞感染と診断し、抗菌薬治療を開始するも超音波検査で硝子体混濁症が増悪したため1月4日・9日に内視鏡併用硝子体手術を施行した。内視鏡下では虹彩の表面と網膜前面に多量のフィブリンを認めた。術後眼内炎は鎮静を得られ術後3ヵ月時には右眼矯正視力は0.08に改善した。結論:本症例では角膜混濁のために感染の波及範囲を把握することに難渋したが、眼内内視鏡併用硝子体手術により眼内炎の鎮静を得られた。(著者抄録)

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Language：Japanese   Publisher：(公社)日本眼科医会  

緑内障診療にOCTが必要不可欠な存在となって久しい。特に前視野緑内障や初期緑内障症例ではOCTによる評価が極めて重要な位置づけとなる。乳頭周囲網膜神経線維層解析と黄斑部内層解析が主たるOCT撮影法であるが、他にも様々な撮影法が存在する。症例に応じた撮影法の使い分けが望ましい。緑内障の診断のみならず、進行評価をOCTで行うことも現在では一般的となっている。緑内障診療でOCTを活用するうえで知っておくべきことについて整理してみた。(著者抄録)

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Language：Japanese   Publisher：(株)先端医学社  

近年、MIGS(minimally invasive glaucoma surgery)の普及により房水主流出路の機能評価が注目されている。前眼部OCTA(optical coherence tomography angiography)の深層画像はおもに強膜内の血流構造を描出し、房水主流出路の一部を可視化できる。MIGS術前に撮影された前眼部OCTA深層画像の血管密度が低い症例は手術効果が高い可能性がある。(著者抄録)

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

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Language：Japanese   Publisher：(株)先端医学社  

近年、MIGS(minimally invasive glaucoma surgery)の普及により房水主流出路の機能評価が注目されている。前眼部OCTA(optical coherence tomography angiography)の深層画像はおもに強膜内の血流構造を描出し、房水主流出路の一部を可視化できる。MIGS術前に撮影された前眼部OCTA深層画像の血管密度が低い症例は手術効果が高い可能性がある。(著者抄録)

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

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Language：Japanese   Publisher：眼科臨床紀要会  

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

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

課題に対する本計画の論点は,「光干渉断層血管撮影(OCT-A)はフルオレセイン蛍光眼底造影検査(FA)の代わりになり得る検査なのか?」である.侵襲的な眼科検査とは,痛み・接触・羞明を伴うもの,造影剤を使用するもの,時間がかかるもの,生検であり,これらを軽減できる検査方法の改良や代替検査の開発は検査の低侵襲化といえる.また検査精度の向上は疾病の早期発見を可能にし,結果的に治療の低侵襲化につながる.なかでも,FAは頻度は少ないが重篤な合併症を引き起こす可能性のある比較的侵襲性の高い検査であり,検査時間が長く,散瞳に伴う羞明や末梢静脈路の確保に関連した痛みも伴う.しかしながら,多くの眼底疾患の診断や治療に欠かせない検査であり,代替検査の開発・普及は眼科診療の発展に大きく貢献できると期待される.OCT-Aは,造影剤を使用せずに高いコントラストで網膜血管像を描出することができる機器であり,比較的低侵襲なFAの代替検査として注目されているが,市販機が登場して5年以上が経った現在でもFAの代わりとして単純に置き換えることは不可能である.読影方法や治療方針の決定,効果判定を行う所見の取り方に関する科学的根拠も,半世紀以上の歴史を経て確立されたFAと比較して極端に少なく,またそもそも臨床機器として未熟である.画質が不安定であり,定量のしやすさとは裏腹に定量の不安定さが存在することは臨床機器としては致命的な欠点である.我々は,OCT-AがFAの代替検査として成熟するために,今後成長が必要な項目を明らかにし,OCT-Aの臨床機器としての完成度を高めることを計画した.I.OCT-Aにおける血管描出能の基礎的な検討 OCT-Aにおける血管の描出方法はFAとはまったく異なる.理論的な部分は理解できても,画像処理により抽出された血流信号が実際の網膜微小循環の動態とどのような対応をしているのかを直接観察した報告はなく,未知である.今後の成長を眺めれば,なぜ映り,なぜ映らないのかを網膜微小循環を直接可視化した状態で検証することは,まさに永くブラックボックスであった領域を照らすことであり,避けては通れない.補償光学走査レーザー検眼鏡を用いて血球の動きを可視化し,血球密度や流れる血球の種類がOCT-Aの描出能に与える影響について,細胞レベルで検証した.II.高画質化に関する検討 Volume scanから再構成するOCT-Aはその画質の安定化が大きな課題の一つである.加算平均,人工知能(AI)を用いた高画質化や,それが定量評価に与える影響について検討した.III.広画角化に関する検討 OCT-Aの画角の狭さは当初より問題であった.近年では画角が広くなりつつあるが,一方で画角と画質はトレードオフの関係にあり,単純な広画角化が画質の低下につながることもクローズアップされてきている.現状,OCT-Aが眼底のどれほどの範囲を撮影することができ,それが臨床的にどの程度有用であるかを調査した.IV.FAを超えるOCT-Aの機能に関する検討 FAの代替検査として期待される一方で,FA検査では得難い情報が得られるのはOCT-Aの大きな強みであり,OCT-Aが注目される大きな理由となっている.前眼部OCT-A,脈絡毛細血管板の可視化と定量評価について検討した.(著者抄録)

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Language：Japanese   Publisher：(株)メディカルレビュー社  

＜文献概要＞緑内障手術には濾過手術と流出路再建術があり,近年より簡便で安全性の高いMIGS(minimally invasive glaucoma surgery)が広く普及している.わが国では特に流出路再建系のMIGSが主流であるが,これは房水流出抵抗の主座である線維柱帯を切開・切除することで眼圧を下降させることを目的とする.しかし,上強膜静脈圧などのシュレム管以降に存在する房水流出抵抗が高いような一部の症例では十分な眼圧下降効果が得られないことが考えられ,シュレム管以降の房水流出機能の評価の重要性が高まっている.そのような状況のなかで,光干渉断層計(optical coherence tomography:OCT)が実臨床に用いられるようになって20年以上経過した現在,比較的新しい技術である前眼部光干渉断層血管撮影(OCT angiography:OCTA)を用いた深層(強膜内)画像で,房水流出路の一部を可視化できる可能性が報告され,注目されている.本稿では,前眼部OCTAを用いて緑内障の何がわかるようになってきているのかについて既報の情報を整理しつつ,主に房水主流出路に関連すると考えられる前眼部OCTA深層(強膜内)画像とMIGSの手術成績の関係を検討した我々の研究について紹介する.

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J03471&link_issn=&doc_id=20220418260001&doc_link_id=10.34449%2FJ0024.01.63_0001-0007&url=https%3A%2F%2Fdoi.org%2F10.34449%2FJ0024.01.63_0001-0007&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   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：医歯薬出版(株)  

近視は緑内障発症の危険因子であるが、近視性の変化と緑内障性の変化は多くの共通項を含んでおり、厳密に両者を分離することは容易ではない。緑内障による視神経障害は篩状板で生じるとされ、眼圧上昇は篩状板の後方変位とともに網膜神経節細胞の軸索障害を引き起こす。一方で、緑内障を合併した強度近視眼のなかには眼球(強膜)の変形程度と視神経障害の程度が相関するような一群も存在し、眼圧下降治療によって篩状板の位置変化ではなく強膜変形の改善を認める症例も存在する。病的近視を含めた強度近視における視神経障害は篩状板以外の部位でも生じうると考えられるが、眼圧下降治療がどの程度有効かは明らかになっていない。眼圧下降治療が有効な病的近視眼を判別できれば病的近視による失明を抑制できるかもしれない。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00060&link_issn=&doc_id=20211011020007&doc_link_id=%2Faa7ayuma%2F2021%2F027902%2F008%2F0141b0145%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2021%2F027902%2F008%2F0141b0145%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

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：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞OCT-angiography(OCTA)はOCT(光干渉断層計)を用いて血流分布を三次元的に評価する技術であり,2006年にMakitaらによってはじめて報告された。同一部位を時間差で複数回撮影したOCT画像から,組織内を血球が移動する際に生じるOCT信号の位相変化や強度変化を検出することで血流分布を描出する。血管病変や循環動態を評価するための検査であった従来のフルオレセイン(FA)造影検査と比べると,非侵襲的に,三次元情報から任意の深さの情報を抜き出すことができる点が,OCTAの大きな利点である。

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Language：Japanese   Publisher：(株)メディカ出版  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J06107&link_issn=&doc_id=20210518350009&doc_link_id=issn%3D2187-2422%26volume%3D10%26issue%3D3%26spage%3D315&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D2187-2422%26volume%3D10%26issue%3D3%26spage%3D315&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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

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

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

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

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

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

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

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

背景:Sturge-Weber症候群では脈絡膜血管腫と緑内障を高率に併発する.合併した脈絡膜血管腫に伴う滲出性網膜剥離には放射線外照射治療が奏功したが,緑内障には流出路再建術が無効で,緑内障チューブシャント手術を要した1例を経験したので報告する.症例:7歳2ヵ月女児.顔面に血管腫を認め,Sturge-Weber症候群の診断であった.右眼に脈絡膜血管腫による滲出性網膜剥離を認め,総線量21Gyの放射線外照射治療を行い,3ヵ月後には網膜下液は完全に消失し,治療後2年以上再発はなかった.緑内障に対しては点眼治療を継続していたが,高眼圧ならびに視神経乳頭rimと光干渉断層計(OCT)における網膜神経線維層の菲薄化が進行したため流出路再建術としてsuture trabeculotomyを行った.術後2日目から進行性の前房出血と高眼圧を生じたため前房洗浄を施行した.前房出血が改善した後も高眼圧が持続したため緑内障チューブシャント手術を行い,眼圧の正常化を得た.結論:Sturge-Weber症候群では脈絡膜血管腫と緑内障に対する継続的な経過観察と適切な治療が重要である.緑内障については,発症時期が遅い場合は特に流出路再建術が無効である可能性を念頭に置いて対処する必要がある.(著者抄録)

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Language：Japanese   Publisher：眼科臨床紀要会  

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Language：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：(株)メディカル葵出版  

前眼部OCT angiography(OCTA)によって結膜強膜の血流が可視化され、強膜内静脈叢から上強膜静脈にかけての房水流出路も観察できる。結膜濾過胞では外観からはわからない濾過胞内部の血流が観察でき、虹彩においては虹彩新生血管の変化をとらえることも可能である。(著者抄録)

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

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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   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：Japanese   Publisher：(公社)日本眼科医会  

緑内障症例における実際のOCTAとOCTの画像を供覧し、緑内障の診察において注目すべきOCTAのポイントについて整理した。現在の緑内障診療においては、診断や進行判定の中心は視野検査とOCT検査である。OCTAは、緑内障の進行に伴う網膜表層の血流低下を捉えることができるだけでなく、OCTAで検出される血流低下はその後の緑内障の進行にも影響する可能性がある。また、緑内障の進行をOCTよりも捉えやすいケースもあるようである。OCTAには緑内障診療の質向上に欠かせない検査として今後普及するポテンシャルがある。(著者抄録)

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

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

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

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞●緑内障診療の基本OCTはcpRNFL解析と黄斑部網膜内層解析である。●OCT加算平均縦スキャンも緑内障診断に有用である。●実際の緑内障診療におけるOCTAの有用性はいまだ定まっていない。

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＜文献概要＞背景:緑内障インプラント手術では通常,保存強膜などのパッチ材料や自己強膜半層弁でチューブを被覆することでチューブの眼外への露出を予防するが,それでも術後合併症でインプラント露出を生じることがある。インプラント露出を繰り返し,インプラント摘出と再留置術による治療を施行した1例を経験したので報告する。症例:54歳,男性。右眼の網膜剥離および続発緑内障に対して計8回の内眼手術既往があった。右眼の眼圧上昇と眼痛に対する治療目的で当科を紹介され受診した。1年半前に耳下象限に留置された右眼バルベルト緑内障インプラント(BGI)のチューブが結膜から露出し,チューブは後退し,先端は眼内から脱出していた。右眼圧は30〜38mmHgと高値であった。BGIチューブ切除と耳上象限へのアーメド緑内障バルブ(AGV)手術を施行し,右眼圧下降と眼痛の消失を得られた。その8ヵ月後,耳上象限のAGVプレートが前方へと移動しプレートの一部が結膜から露出し,露出部から房水漏出を認め,耳上象限のAGV摘出術と鼻下象限へのAGV手術を施行した。術後3ヵ月の現在,眼圧コントロールが得られており,インプラント再露出はない。結論:緑内障インプラント手術の合併症として,インプラント露出には注意が必要である。インプラント露出に対してインプラント除去術は有効な治療法であるが,除去後の眼圧上昇への対策が必要である。

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眼底写真からさまざまな情報が得られるが、それだけでは得られない情報もたくさんある。緑内障診療はOCTの登場により大きな変革を遂げた。それは眼底写真ではわからない網膜神経線維層や網膜神経節細胞層の実際の厚みをOCTによって計測できるようになったためであり、いまでは診断のみならず進行判定にまで利用することが可能である。OCTAは現段階では緑内障診療に不可欠な存在ではないが、今後新たな変革をもたらす可能性を秘めている。多種多様な画像検査機器が存在するが、ここではOCTとOCTAの画像を中心に緑内障眼の何が見えるのかを供覧したい。(著者抄録)

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DOI： 10.1016/j.ophtha.2017.10.013

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DOI： 10.1016/j.ajo.2016.08.018

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緑内障における網膜神経節細胞の軸索障害は篩状板で生じるとされる。緑内障眼では篩状板に部分的な欠損がまれならず生じている。乳頭出血既往眼に多くみられ、乳頭出血の出現に伴って篩状板欠損は出現あるいは拡大する。また、網膜神経線維の障害との関係も強く、緑内障進行の危険因子とされる。緑内障の診療において注目すべき所見の一つである。(著者抄録)

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1990年代の中頃からの神経幹細胞,胚性幹細胞(ES細胞),人工多能性幹細胞(iPS細胞)と続く基礎科学の進歩を受けて,最近では,中枢神経を含めさまざまな組織の細胞移植による治療(再生医療)が将来医療の大きな流れになると考えられている.著者らは実用化研究を経て,2014年,iPS細胞由来網膜色素上皮(RPE)細胞シートを滲出型加齢黄斑変性患者1例目に移植した.加齢黄斑変性というRPEの老化によって引き起こされる疾患を患者本人の若返った正常な組織で置き換えることは根本治療につながると考える.初めてのiPS細胞由来細胞を用いた臨床研究であるので主要評価項目は安全性であり,手術1年後に副次評価項目である効果とともに判定する.移植する細胞シートはさまざまな検査や免疫不全マウスを用いて繰り返し行った造腫瘍性試験で安全性が確認されており,細胞の純度,染色体,遺伝子の解析などを検討して安全を確保しているが,実際の安全性を確認することが目的であった.これをスタートとして再生医療を将来の標準治療とするためには,費用と効果などを考え戦略を練る必要がある.自家RPE細胞シートは科学的には最も良い細胞材料であるものの,作製コストが莫大であり手術法の難易度が高いという問題がある.広く使える治療とするためには,京都大学山中伸弥教授が計画しているhuman leukocyte antigen(HLA)6座ホモのiPS細胞ストックを用いて,HLAが部分的にマッチした患者への他家移植を標準治療として進めていくことが考えられる.対象疾患や病期によっても必要な細胞の剤形は異なるとも考えられるので,再生医療はこれまでの薬剤治療とはまったく異なる道筋で治療を完成させていくことになろう.また,視細胞の変性に対してはiPS細胞由来の視細胞をマウスモデルに移植して動物でのproof of concept(POC)がほぼ得られ,視細胞移植についても最短で臨床試験を開始したいと考え準備をしている.さらに,現在,視細胞移植の材料は杆体細胞と錐体細胞の混合シートであるものの錐体細胞の割合は低いので,錐体細胞の率を高めた移植材料も必要となる.視細胞移植で効果が出れば中枢神経の神経回路網再構築の最初の例であり,RPE細胞のシートや浮遊液,脈絡膜血管の治療と合わせて,さまざまな網膜変性疾患の治療法が広がることと考えられる.(著者抄録)

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トラベクトーム手術は結膜切開せずに、直視下で短時間にSchlemm管内壁を焼灼切除できる術式である。重篤な合併症はほとんどないのが利点であるが、術後の前房出血や一過性高眼圧には十分な理解と注意が必要である。(著者抄録)

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Ahmed glaucoma valve(AGV)とBaerveldt glaucoma implant(BGI)はロングチューブタイプの2大緑内障インプラントであり、それらの多施設ランダム比較試験であるAhmed Baerveldt comparison(ABC)StudyとAhmed versus Baerveldt(AVB)Studyの3年経過の結果を整理した。AGVとBGIの成績は目標眼圧21mmHg以下なら同等、それ以下を目標眼圧とするならBGIのほうが分がある。BGIのほうが低い眼圧値を狙えて点眼も少なくてすむ反面、低眼圧に起因する合併症や再手術が多い。それぞれの利点欠点を理解したうえで、個々の症例に最適な術式選択を行いたい。(著者抄録)

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濾過手術による眼圧下降は視神経乳頭にさまざまな変化をもたらす。小児においては視神経乳頭陥凹やrimの改善、乳頭の縮小化、変形、ときに乳頭周囲網脈絡膜萎縮(parapapillary atrophy:PPA)の大きさも変わる。一方で、成人の場合、通常はその変化は非常に小さい。しかし、近年の光干渉断層計(optical coherence tomography:OCT)の進歩によりその微細な変化が捉えられるようになり、成人でも想像以上に乳頭変化が生じていることがわかってきた。緑内障眼で後方に変位している篩状板は緑内障手術後に前方に移動し、菲薄化した前篩状組織は肥厚する。眼圧による視神経乳頭への機械的ストレスの変化を垣間見ることができる。(著者抄録)

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平成24年4月から難治緑内障に対するglaucoma drainage devices(GDD)を用いた緑内障チューブシャント手術がわが国でも保険適用となり、バルベルト緑内障インプラントが難治症例に対して使用されてきている。国内での手術成績の報告は乏しいが、米国では以前から各種のチューブシャント手術が積極的に行われており、その有用性に関する報告が数多くある。その一方で、GDDを用いることで生じうる特有の合併症もあるため、施行する際には十分な理解と注意が必要である。(著者抄録)

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Language：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：金原出版(株)  

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CiNii Article

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Other Link： http://search.jamas.or.jp/link/ui/2011281845

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