Protecting Prostate Cancer Classification From Rectal Artifacts via Targeted Adversarial Training.

Magnetic resonance imaging (MRI)-based deep neural networks (DNN) have been widely developed to perform prostate cancer (PCa) classification. However, in real-world clinical situations, prostate MRIs can be easily impacted by rectal artifacts, which have been found to lead to incorrect PCa classification. Existing DNN-based methods typically do not consider the interference of rectal artifacts on PCa classification, and do not design specific strategy to address this problem. In this study, we proposed a novel Targeted adversarial training with Proprietary Adversarial Samples (TPAS) strategy to defend the PCa classification model against the influence of rectal artifacts. Specifically, based on clinical prior knowledge, we generated proprietary adversarial samples with rectal artifact-pattern adversarial noise, which can severely mislead PCa classification models optimized by the ordinary training strategy. We then jointly exploited the generated proprietary adversarial samples and original samples to train the models. To demonstrate the effectiveness of our strategy, we conducted analytical experiments on multiple PCa classification models. Compared with ordinary training strategy, TPAS can effectively improve the single- and multi-parametric PCa classification at patient, slice and lesion level, and bring substantial gains to recent advanced models. In conclusion, TPAS strategy can be identified as a valuable way to mitigate the influence of rectal artifacts on deep learning models for PCa classification.

Sparse Dynamic Volume TransUNet with multi-level edge fusion for brain tumor segmentation.

3D MRI Brain Tumor Segmentation is of great significance in clinical diagnosis and treatment. Accurate segmentation results are critical for localization and spatial distribution of brain tumors using 3D MRI. However, most existing methods mainly focus on extracting global semantic features from the spatial and depth dimensions of a 3D volume, while ignoring voxel information, inter-layer connections, and detailed features. A 3D brain tumor segmentation network SDV-TUNet (Sparse Dynamic Volume TransUNet) based on an encoder-decoder architecture is proposed to achieve accurate segmentation by effectively combining voxel information, inter-layer feature connections, and intra-axis information. Volumetric data is fed into a 3D network consisting of extended depth modeling for dense prediction by using two modules: sparse dynamic (SD) encoder-decoder module and multi-level edge feature fusion (MEFF) module. The SD encoder-decoder module is utilized to extract global spatial semantic features for brain tumor segmentation, which employs multi-head self-attention and sparse dynamic adaptive fusion in a 3D extended shifted window strategy. In the encoding stage, dynamic perception of regional connections and multi-axis information interactions are realized through local tight correlations and long-range sparse correlations. The MEFF module achieves the fusion of multi-level local edge information in a layer-by-layer incremental manner and connects the fusion to the decoder module through skip connections to enhance the propagation ability of spatial edge information. The proposed method is applied to the BraTS2020 and BraTS2021 benchmarks, and the experimental results show its superior performance compared with state-of-the-art brain tumor segmentation methods. The source codes of the proposed method are available at https://github.com/SunMengw/SDV-TUNet.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Macrophage-induced integrin signaling promotes Schlemm's canal formation to prevent intraocular hypertension and glaucomatous optic neuropathy.

Schlemm's canal (SC) functions to maintain proper intraocular pressure (IOP) by draining aqueous humor and has emerged as a promising therapeutic target for glaucoma, the second-leading cause of irreversible blindness worldwide. However, our current understanding of the mechanisms governing SC development and functionality remains limited. Here, we show that vitronectin (VTN) produced by limbal macrophages promotes SC formation and prevents intraocular hypertension by activating integrin αvß3 signaling. Genetic inactivation of this signaling system inhibited the phosphorylation of AKT and FOXO1 and reduced ß-catenin activity and FOXC2 expression, thereby causing impaired Prox1 expression and deteriorated SC morphogenesis. This ultimately led to increased IOP and glaucomatous optic neuropathy. Intriguingly, we found that aged SC displayed downregulated integrin ß3 in association with dampened Prox1 expression. Conversely, FOXO1 inhibition rejuvenated the aged SC by inducing Prox1 expression and SC regrowth, highlighting a possible strategy by targeting VTN/integrin αvß3 signaling to improve SC functionality.

A self-supervised network-based smoke removal and depth estimation for monocular endoscopic videos.

In minimally invasive surgery videos, label-free monocular laparoscopic depth estimation is challenging due to smoke. For this reason, we propose a self-supervised collaborative network-based depth estimation method with smoke-removal for monocular endoscopic video, which is decomposed into two steps of smoke-removal and depth estimation. In the first step, we develop a de-endoscopic smoke for cyclic GAN (DS-cGAN) to mitigate the smoke components at different concentrations. The designed generator network comprises sharpened guide encoding module (SGEM), residual dense bottleneck module (RDBM) and refined upsampling convolution module (RUCM), which restores more detailed organ edges and tissue structures. In the second step, high resolution residual U-Net (HRR-UNet) consisting of a DepthNet and two PoseNets is designed to improve the depth estimation accuracy, and adjacent frames are used for camera self-motion estimation. In particular, the proposed method requires neither manual labeling nor patient computed tomography scans during the training and inference phases. Experimental studies on the laparoscopic data set of the Hamlyn Centre show that our method can effectively achieve accurate depth information after net smoking in real surgical scenes while preserving the blood vessels, contours and textures of the surgical site. The experimental results demonstrate that the proposed method outperforms existing state-of-the-art methods in effectiveness and achieves a frame rate of 94.45fps in real time, making it a promising clinical application.

Influence of Goniotomy Size on Treatment Safety and Efficacy for Primary Open-Angle Glaucoma: A Multicenter Study.

PURPOSE: To compare the efficacy and safety of 120-, 240-, and 360-degree goniotomy (GT) with or without phacoemulsification with intraocular lens implantation (PEI) for patients with primary open-angle glaucoma (POAG). DESIGN: Multicenter, retrospective, comparative, nonrandomized interventional study. METHODS: Patients diagnosed with POAG who underwent GT with or without PEI were included, and divided into 6 groups: 1) standalone 120-degree GT (120GT); 2) standalone 240-degree GT (240GT); 3) standalone 360-degree GT (360GT); 4) PEI + 120GT; 5) PEI + 240GT; and 6) PEI + 360GT. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. Success was defined as a postoperative IOP within the range of 6 to 18 mm Hg and a 20% reduction from baseline without further glaucoma surgery. Complete success and qualified success were defined as the above without and with ocular hypotensive medications, respectively. RESULTS: Three hundred eight eyes of 231 patients were included with a mean follow-up of 14.4 ± 8.6 months (6.0-48.0 months). There were no significant differences in the reductions in IOP and number of medications and cumulative survival probability for complete and qualified success rates among the 3 groups of standalone GT and PEI + GT. The 360GT group had the highest proportion of hyphema with or without PEI. CONCLUSIONS: 120GT, 240GT, and 360GT with or without PEI showed similar efficacy in reducing IOP and medications used in POAG. 360GT with or without PEI was more likely to cause hyphema compared with 120GT or 240GT. 120GT with or without PEI was sufficient for treating POAG with or without cataract..

Noncontact Conjunctiva: A Better Mitomycin C Application Site for Trabeculectomy.

INTRODUCTION: Bleb scarring is the most important complication of trabeculectomy. Changing the application position of mitomycin C (MMC) during trabeculectomy might affect the surgery outcome. Our aim is to compare the effectiveness and safety of intraocular pressure (IOP) lowering in two different application sites of mitomycin in trabeculectomy. METHODS: This retrospective trial compared the surgical outcomes of 177 eyes that underwent trabeculectomy with adjunctive mitomycin C. In 70 eyes, an MMC-soaked sponge was applied under the scleral flap without touching Tenon's capsule. In 107 eyes, an MMC-soaked sponge was applied under the scleral flap covered by Tenon's capsule. Outcome measures were the IOP, best-corrected visual acuity (BCVA), success rates, and incidence of complications. RESULTS: Within both groups, a highly significant IOP reduction was seen during follow-up. The effectiveness in reducing IOP and the change in best-corrected visual acuity (BCVA) were similar between the two groups. Thin-walled blebs and postoperative hypotony were seen more often when MMC-soaked sponges were applied under the scleral flap covered by Tenon's capsule (P = 0.008 and P = 0.012, respectively). There was no significant difference in BCVA or other complications in either group. CONCLUSION: Since the effectiveness of IOP reduction was similar between both groups and with a low incidence of thin-walled blebs and hypotony, the subscleral application without touching Tenon's capsule seems to be the safer application site of MMC during trabeculectomy.

One-Year Results of a Multicenter Study: Intraocular Pressure-Lowering Effect of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Cases of Advanced Primary Angle-Closure Glaucoma With Cataract.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of the combination of phacoemulsification with intraocular lens implantation (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes of advanced primary angle-closure glaucoma (PACG) with cataract. DESIGN: Multicenter observational study. METHODS: We enrolled 83 eyes of 83 patients with advanced PACG who received combined PEI+GSL+GT at 8 ophthalmic institutes. Each patient was assessed before treatment and at 1, 7 days, 1, 3, 6, and 12 months postsurgery. The criteria for complete success were IOP within 6 to 18 mm Hg and at least 20% of reduction in IOP from baseline without ocular hypotensive medications or reoperation. The definition of qualified success was similar to that of complete success, except for the need for ocular hypotensive medications. The potential prognostic factors for surgical success were investigated using a multivariate logistic model. RESULTS: All participants completed 1 year of follow-up. Complete and qualified success were achieved in 74 (89.1%) and 79 (95.2%) of 83 eyes, respectively. The mean preoperative and postsurgical IOPs were 27.4±7.3 and 14.2±2.6 mm Hg, respectively. Participants used an average of 2.0 and 0.3 types of ocular hypotensive medications before and after surgery, respectively. The chief complications included hyphema (n=9), IOP spike (n=9), and corneal edema (n=8). None of the eyes required reoperation or developed vision-threatening complications. Multivariate analysis showed that older age was associated with a higher probability of complete success (odds ratio=1.13; 95% CI: 1.02-1.25; P=0.020). CONCLUSIONS: The 1-year results of combination of PEI+GSL+GT in treating advanced PACG cases with cataract appear to be safe and effective. Further large-scale multination and multicenter studies are warranted.

Targeting VEGF-A/VEGFR2 Y949 Signaling-Mediated Vascular Permeability Alleviates Hypoxic Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear. METHODS: VEGF-A/VEGFR2 signal activation and VEGFR2 Y949-dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 (Vefgr2Y949F) and mice with conditional endothelial deletion of Vegfr2 after chronic hypoxia exposure. RESULTS: We show that PH leads to excessive pulmonary vascular leak in both patients and hypoxic mice, and this is because of an overactivated VEGF-A/VEGFR2 Y949 signaling axis. In the context of hypoxic PH, activation of Yes1 and c-Src and subsequent VE-cadherin phosphorylation in endothelial cells are involved in VEGFR2 Y949-induced vascular permeability. Abolishing VEGFR2 Y949 signaling by Vefgr2Y949F point mutation was sufficient to prevent pulmonary vascular permeability and inhibit macrophage infiltration and Rac1 activation in smooth muscle cells under hypoxia exposure, thereby leading to alleviated PH manifestations, including muscularization of distal pulmonary arterioles, elevated right ventricle systolic pressure, and right ventricular hypertrophy. It is important that we found that VEGFR2 Y949 signaling in myeloid cells including macrophages was trivial and dispensable for hypoxia-induced vascular abnormalities and PH. In contrast with selective blockage of VEGFR2 Y949 signaling, disruption of the entire VEGFR2 signaling by conditional endothelial deletion of Vegfr2 promotes the development of PH. CONCLUSIONS: Our results support the notion that VEGF-A/VEGFR2 Y949-dependent vascular permeability is an important determinant in the pathogenesis of PH and might serve as an attractive therapeutic target pathway for this disease.

Efficacy and safety of trabeculectomy versus peripheral iridectomy plus goniotomy in advanced primary angle-closure glaucoma: study protocol for a multicentre, non-inferiority, randomised controlled trial (the TVG study).

INTRODUCTION: Primary angle-closure glaucoma (PACG) is a major subtype of glaucoma that accounts for most bilateral glaucoma-related blindness globally. Filtering surgery is a conventional strategy for PACG, yet it has a long learning curve and undesirable disastrous complications. Minimally invasive glaucoma surgery (MIGS) plays an increasing role in the management of glaucoma due to its safer and faster recovery profile; cataract surgery-based MIGS is the most commonly performed such procedure in PACG. However, for patients with a transparent lens or no indications for cataract extraction, incorporation of MIGS into PACG treatment has not yet been reported. Therefore, this multicentre, non-inferiority, randomised controlled clinical trial aims to compare the efficacy and safety of trabeculectomy versus peripheral iridectomy plus an ab interno goniotomy in advanced PACG with no or mild cataracts. METHODS AND ANALYSIS: This non-inferiority, multicentre, randomised controlled trial will be conducted at seven ophthalmic departments and institutes across China. Eighty-eight patients with no or mild cataracts and advanced PACG will be enrolled and randomised to undergo trabeculectomy or peripheral iridectomy plus ab interno goniotomy. Enrolled patients will undergo comprehensive ophthalmic examinations before and after surgery. The primary outcome is intraocular pressure (IOP) at 12 months postoperatively. The secondary outcomes are cumulative success rate of surgery, surgery-related complications and number of IOP-lowering medications. Participants will be followed up for 36 months postoperatively. ETHICS AND DISSEMINATION: The study protocol was approved by the ethical committees of the Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ191) and of all subcentres. All participants will be required to provide written informed consent. The results will be published in peer-reviewed journals and disseminated in international academic meetings. TRIAL REGISTRATION NUMBER: NCT05163951.

Efficacy and safety of phacotrabeculectomy versus phacogoniotomy in advanced primary angle-closure glaucoma: study protocol for a multicentre non-inferiority randomised controlled trial (PVP Study).

INTRODUCTION: Primary angle-closure glaucoma (PACG) has a high prevalence and blinding rate across Asia. The first-line treatment of PACG is surgery, and phacotrabeculectomy remains the mainstream surgery for advanced PACG. However, it may cause vision-threatening complications with long learning curve. Minimally invasive glaucoma surgery has been gradually used in PACG combined with cataract surgery and achieved efficacy without excessive injury, of which goniotomy is the most commonly performed. Therefore, this study aimed to conduct a multicentre, non-inferiority randomised controlled clinical trial to compare the efficacy and safety of phacotrabeculectomy versus phacogoniotomy in advanced PACG. METHODS AND ANALYSIS: This is a non-inferiority multicentre randomised controlled trial and will be conducted at eight ophthalmic departments and institutes in China. 124 patients with advanced PACG will be enrolled and randomised to undergo phacotrabeculectomy or phacogoniotomy. Comprehensive ophthalmic examinations will be performed before and after the surgery. The primary outcome is the change of intraocular pressure at 12 months after surgery compared with the baseline intraocular pressure. An extended follow-up period of 36 months will be required. Cumulative success rate of surgery, intraoperative and postoperative complications, and number of anti-glaucomatous medications will also be compared between the groups as secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethical committee of Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ090) and all subcentres. All the participants will be required to provide written informed consent. The results will be disseminated through scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04878458.

Ultrasound Biomicroscopy Might Predict the Outcome of Phacoemulsification-Visco Dissection in Medically Controlled Primary Angle-Closure Glaucoma Eye With Extensive Peripheral Anterior Synechia.

Objective: The treatment procedures of primary angle-closure glaucoma (PACG) with extensive peripheral anterior synechia (PAS) is a subject of debate. This study is to investigate the clinical features of phacoemulsification (Phaco)-visco dissection in medically controlled PACG patients with PAS > 180° and evaluate the predictability of Ultrasound Biomicroscopy (UBM) parameters on postoperative intraocular pressure (IOP). Methods: 48 eyes (48 patients) with acute angle-closure glaucoma (AACG) and 30 eyes (30 patients) with chronic angle-closure glaucoma (CACG) were prospectively included. All patients underwent phaco-viscogoniolysis and foldable lens implantation and were followed for 1 year after surgery. We analyzed preoperative and postoperative IOP, the numbers of anti-glaucoma medicine, the visual field value, the extent of PAS, and UBM parameters alterations, and evaluated the correlation between preoperative UBM parameters and one-year postoperative IOP. Results: IOP reduced significantly from 16.24 ± 4.33 to 14.49 ± 3.69 mmHg in AACG group and from 16.16 ± 3.69 mmHg to 14.31 ± 4.12 mmHg in CACG group, and PAS decreased significantly from 270 ± 60.33 to 171 ± 56.44° in AACG group and from 285 ± 70.46 to 168 ± 61.32° in CACG group, and the number of anti-glaucoma drugs decreased significantly in both groups. Several UBM parameters, including anterior chamber depth, trabecular iris angle, and peripheral iris thickness 500 increased while iris convex reduced considerably in the two groups, and angle opening distance 500 and trabecular-meshwork ciliary process angle increased significantly only in AACG group. One-year postoperative IOP correlated with preoperative angle opening distance 500 and trabecular iris angle negatively and iris convex positively. Conclusion: Phaco-visco dissection can effectively reduce IOP, the numbers of glaucomatous medications, and PAS in medically controlled PACG patients with extensive PAS. UBM parameters might be valuable for analyzing postoperative anterior segment structure and predicting postoperative IOP of Phaco-visco dissection in PACG patients with extensive PAS.

A Comparison of Subconjunctival Wound Healing between Different Methods of Dissecting Subconjunctival Tissues.

OBJECTIVE: To compare different methods for dissecting subconjunctival tissues by developing subconjunctival wound healing models. METHODS: New Zealand white rabbits were separated into 3 groups based on the method by which the rabbit subconjunctival wound healing model was generated: subconjunctival tissues were dissected episclerally (EPI) or subepithelially (SUB), with a corresponding blank control (CON). All the cases in the experimental groups were surgically prepared with conjunctival flaps, and they were sacrificed on the third postoperative day. At the surgical sites, the protein levels of hypoxia-inducible factor-1 (HIF-1)-α, vascular endothelial growth factor (VEGF)-A, and matrix metalloproteinase (MMP)-2 were detected by Western blot, morphological vascularity was measured by Adobe Photoshop, and subconjunctival fibrosis was assessed by histology. RESULTS: Compared with the CON group, both the EPI and SUB groups showed significantly upregulated protein levels of HIF-1α, VEGF-A, and MMP-2. In addition, the protein levels of HIF-1α, VEGF-A, and MMP-2 were higher in the EPI group than in the SUB group. Morphological vascularity was significantly elevated in the EPI group compared with the SUB and CON groups. Collagen content was markedly increased in the EPI group compared with the SUB and CON groups. CONCLUSIONS: Dissecting subconjunctival tissues subepithelially inhibits subconjunctival fibrosis, which may be instructive in tenonectomy in filtration surgery.

Illness uncertainty, anxiety and depression in Chinese patients with glaucoma or cataract.

This study evaluated illness uncertainty, anxiety and depression among glaucoma patients and cataract patients in China. 263 patients with primary glaucoma and 100 patients with age-related cataract were recruited sequentially from Zhongshan Ophthalmic Center between October 2013 and March 2016. All the participants completed questionnaires for socio-demographic information, Mishel Uncertainty in Illness Scale (MUIS) and Hospital Anxiety and Depression Scale (HADS). 25 of the 263 glaucoma patients and 21 of the100 cataract patients finished two copies of the same questionnaires before and after surgery. Statistics were analyzed using SPSS17.0 software. We observed that glaucoma patients had higher MUIS and HADS score than did cataract patients. Multivariate logistic regression analysis indicated risk factors for illness uncertainty, anxiety and depression for glaucoma patients were high HADS score, poor visual acuity (VA) in the better eye and education level respectively. Risk factors for the same parameters of cataract patients were high HADS-A score, poor VA in the better eye and high illness uncertainty respectively. Scores of MUIS and HADS both decreased after surgery, but the change in HADS score among glaucoma patients was not significant. Clinical workers should take these factors into account to improve therapy, especially for glaucoma patients who undergo surgery.

Prox1-GFP/Flt1-DsRed transgenic mice: an animal model for simultaneous live imaging of angiogenesis and lymphangiogenesis.

The roles of angiogenesis in development, health, and disease have been studied extensively; however, the studies related to lymphatic system are limited due to the difficulty in observing colorless lymphatic vessels. But recently, with the improved technique, the relative importance of the lymphatic system is just being revealed. We bred transgenic mice in which lymphatic endothelial cells express GFP (Prox1-GFP) with mice in which vascular endothelial cells express DsRed (Flt1-DsRed) to generate Prox1-GFP/Flt1-DsRed (PGFD) mice. The inherent fluorescence of blood and lymphatic vessels allows for direct visualization of blood and lymphatic vessels in various organs via confocal and two-photon microscopy and the formation, branching, and regression of both vessel types in the same live mouse cornea throughout an experimental time course. PGFD mice were bred with CDh5CreERT2 and VEGFR2lox knockout mice to examine specific knockouts. These studies showed a novel role for vascular endothelial cell VEGFR2 in regulating VEGFC-induced corneal lymphangiogenesis. Conditional deletion of vascular endothelial VEGFR2 abolished VEGFA- and VEGFC-induced corneal lymphangiogenesis. These results demonstrate the potential use of the PGFD mouse as a powerful animal model for studying angiogenesis and lymphangiogenesis.

Ex-PRESS implantation versus trabeculectomy in Chinese patients with POAG: fellow eye pilot study.

AIM: To compare the outcomes of Ex-PRESS implantation in one eye versus trabeculectomy with mitomycin C in the fellow eye in Chinese patients with primary open-angle glaucoma (POAG). METHODS: This was a prospective, non-randomized comparative study. Forty-eight eyes of 24 patients with bilateral POAG necessitating surgery were included and underwent Ex-PRESS implantation under the scleral flap in one eye and trabeculectomy in the other eye according to patients' choice. Primary outcome measures included mean intraocular pressure (IOP) and success rate. Secondary outcome measures were aqueous flare, postoperative medication use, visual acuity, and incidence of complications. RESULTS: All 24 patients finished a 1-year follow-up. Both groups maintained significant reductions in IOP after surgery throughout the follow-up period. At any point in time, the IOP of the two groups did not differ significantly. The Kaplan-Meier survival curve analysis showed no significant differences in success between the two groups (P=0.289). The mean number of anti-glaucoma medicines and visual acuity in both groups were not significantly different. Eyes with Ex-PRESS implantation had lower aqueous flare values on days 1 and 3 (both P<0.05). Instances of early postoperative hypotony and choroidal effusion were significantly fewer in frequency after Ex-PRESS implantation under the scleral flap compared with those after trabeculectomy (P<0.001). CONCLUSION: Ex-PRESS is comparable to trabeculectomy in terms of IOP, success rate, number of glaucoma medications used, and visual acuity. However, Ex-PRESS resulted in fewer cases of inflammation and a lower rate of complications.

Limited versus total epithelial debridement ocular surface injury: Live fluorescence imaging of hemangiogenesis and lymphangiogenesis in Prox1-GFP/Flk1::Myr-mCherry mice.

BACKGROUND: Immunohistochemical staining experiments have shown that both hemangiogenesis and lymphangiogenesis occur following severe corneal and conjunctival injury and that the neovascularization of the cornea often has severe visual consequences. To better understand how hemangiogenesis and lymphangiogenesis are induced by different degrees of ocular injury, we investigated patterns of injury-induced corneal neovascularization in live Prox1-GFP/Flk1::myr-mCherry mice, in which blood and lymphatic vessels can be imaged simultaneously in vivo. METHODS: The eyes of Prox1-GFP/Flk1::myr-mCherry mice were injured according to four models based on epithelial debridement of the: A) central cornea (a 1.5-mm-diameter circle of tissue over the corneal apex), B) total cornea, C) bulbar conjunctiva, and D) cornea+bulbar conjunctiva. Corneal blood and lymphatic vessels were imaged on days 0, 3, 7, and 10 post-injury, and the percentages of the cornea containing blood and lymphatic vessels were calculated. RESULTS: Neither central corneal nor bulbar conjunctival debridement resulted in significant vessel growth in the mouse cornea, whereas total corneal and corneal+bulbar conjunctival debridement did. On day 10 in the central cornea, total cornea, bulbar conjunctiva, and corneal+bulbar conjunctival epithelial debridement models, the percentage of the corneal surface that was occupied by blood vessels (hemangiogenesis) was 1.9±0.8%, 7.14±2.4%, 2.29±1%, and 15.05±2.14%, respectively, and the percentage of the corneal surface that was occupied by lymphatic vessels (lymphangiogenesis) was 2.45±1.51%, 4.85±0.95%, 2.95±1.27%, and 4.15±3.85%, respectively. CONCLUSIONS: Substantial corneal debridement was required to induce corneal neovascularization in the mouse cornea, and the corneal epithelium may therefore be partially responsible for maintaining corneal avascularity. GENERAL SIGNIFICANCE: Our study demonstrates that GFP/Flk1::myr-mCherry mice are a useful model for studying coordinated hemangiogenic and lymphangiogenic responses.

Aqueous humor concentration of VEGF and retinal oxygen saturation after unilateral acute primary angle closure.

PURPOSE: To measure the levels of vascular endothelial growth factor (VEGF) in aqueous humor in patients with unilateral acute primary angle closure (APAC) and retinal oxygen saturation (SO2 ) after trabeculectomy. METHODS: Twelve patients, with unilateral trabeculectomy-required APAC, were recruited as the study group. Aqueous humor samples were collected prospectively for every subject. VEGF concentrations were analysed via enzyme-linked immunosorbent assay (ELISA), and retinal SO2 was measured using oximeter (Reykjavik, Iceland) at 1 month after trabeculectomy. RESULTS: In the APAC eyes, the mean aqueous humor concentration of VEGF was 388.4 ± 260.1 pg/ml and positively correlated with preoperative intraocular pressure (ρ = 0.658, p = 0.020). In the normal controls, the mean SO2 levels in the larger arterioles and venules were 93.0 ± 5.9% and 59.5 ± 5.4% and the arteriovenous [A-V] difference was 33.5 ± 6.3%. In the study group, the arteriolar SO2 at 1 month after surgery (97.6 ± 19.4%, p = 0.147) did not differ significantly from the values in the control group. However, the mean venular SO2 was significantly lower than the control eyes (50.0 ± 9.1% versus 59.5 ± 5.4%, p = 0.004), and a remarkable increased A-V difference (47.6 ± 22.7% versus 33.5 ± 6.3%) was found in the APAC eyes (p = 0.037). CONCLUSIONS: Lower venular SO2 and increased A-V difference existed in the APAC eyes after surgery, and it is possible that the saturation was even lower during the attack. Together with the elevated VEGF concentrations in aqueous humor, these provided indirect evidence that ocular hypoxia was constantly present during APAC attack.

Vascular Endothelial Growth Factor is Increased in Aqueous Humor of Acute Primary Angle-Closure Eyes.

PURPOSE: To measure and compare the levels of vascular endothelial growth factor (VEGF) in the aqueous humor of patients with acute primary angle closure (APAC), primary angle-closure glaucoma (PACG), and normal cataract (controls). METHODS: Aqueous humor samples were prospectively collected from 38 APAC eyes, 36 PACG eyes, and 25 nonglaucomatous cataract control eyes. The levels of aqueous humor VEGF were measured using enzyme-linked immunoassays. The clinical characteristics of participants were also collected for correlation analysis. RESULTS: VEGF was detected in aqueous humor samples of 35 of 38 APAC patients (mean±SE of the mean, 935±258 pg/mL), 30 of 36 PACG patients (165±37.5 pg/mL), and 16 of 25 cataract controls (69.5±13.5 pg/mL). The mean concentration of VEGF in APAC eyes was 13.5 and 5.7 times higher than that in controls and PACG eyes, respectively, and these differences were statistically significant (both P<0.0167). In the correlation analysis that included all participants, the aqueous humor VEGF level was found to correlate negatively with axial length (ρ=-0.342, P=0.001), and positively with intraocular pressure (ρ=0.434, P<0.001). CONCLUSIONS: VEGF was significantly increased in aqueous humor of APAC eyes. An increase in aqueous humor VEGF may be the result of the characteristic ocular ischemia and hypoxia observed in APAC eyes as a consequence of sudden excessive increases in intraocular pressure during the acute episode.

Chemokine (C-C motif) ligand 2 and chemokine (C-C motif) ligand 7 in angle-closure glaucoma.

PURPOSE: To compare the concentrations of chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-C motif) ligand 7 (CCL7) in aqueous humour of eyes with acute primary angle-closure (APAC), primary angle-closure glaucoma (PACG) or with age-related cataract. METHODS: The prospective investigation included a study group of 56 patients (24 patients with APAC; 32 patients with PACG) undergoing glaucoma surgery and a control group of 21 patients undergoing routine cataract surgery. The interval between glaucoma attack and trabeculectomy was 19.4 ± 9.8 days. RESULTS: The concentrations of CCL2 (3037 ± 501 versus 1127 ± 141 pg/ml; p = 0.003) and CCL7 (10.5 ± 2.4 versus 2.8 ± 0.4 pg/ml; p < 0.001) were significantly higher in the APAC group than in the PACG group, while the concentrations of both cytokines did not differ significantly between the PACG group and the control group (CCL2: 1190 ± 98 pg/ml; p = 0.10; CCL7: 2.0 ± 0.6; p = 0.18). The concentrations of both cytokines were significantly and inversely correlated with the interval between the acute angle-closure attack and surgery (CCL2: p = 0.02; ρ = -0.48; CCL7: p = 0.04; ρ = -0.42). Higher CCL2 concentrations were associated with higher prevalence of surgical failure (28.6% versus 7.1%; p = 0.036). CONCLUSIONS: Concentrations of CCL2 and CCL7 as major inflammatory cytokines with potential influence on the risk of filtering surgery failure were significantly elevated after an acute glaucoma attack and decreased with longer interval to the attack. Trabeculectomy may have a lower risk of failure if performed later than earlier after an acute glaucoma attack, with lower CCL2 concentrations associated with better surgical outcome.