OBJECTIVE: To understand factors affecting visual prognosis and the number of intravitreal antivascular endothelial growth factor (anti-VEGF) injections needed to stabilize wet age-related macular degeneration (AMD).
METHODS: In this retrospective cohort, 119 treatment-naïve wet AMD patients were followed for two years. In patients with bilateral disease, the eye with worse best-corrected visual acuity (BCVA) or that received more intravitreal injections was recruited as the study eye. In all visits, BCVA was recorded, ophthalmological examination was performed including macular optical coherence tomography imaging. Twenty health status/lifestyle questions were asked to the patients via phone as potential risk factors. All patients received 3 loading doses of intravitreal bevacizumab injections and received repeat injections of aflibercept or ranibizumab when the eye had a new, active neovascular lesion.
RESULTS: Patients who took regular micronutrition had similar visual outcome and injection numbers compared to the ones who did not. Patients with bilateral disease needed less intravitreal injections compared to unilateral AMD patients (p = 0.016) and women on hormone replacement therapy (HRT) required less injections compared to the women who were not (p = 0.024). Female patients had a mean gain of 2.7 letters while male patients lost 3.8 letters (p = 0.038). Wet AMD started at an earlier age in smokers (p = 0.002). Patients with a better education level presented earlier with better BCVA (p = 0.037).
CONCLUSIONS: HRT and anti-VEGF injections to the fellow eye improved the prognosis of wet AMD, while male patients had slightly worse prognosis. Estrogen\'s protective effects and potential contribution in wet AMD needs further attention. Retrospectively registered: 2020/0622.

UNASSIGNED: The purpose of this study was to analyze optical coherence tomography (OCT) images of generative adversarial networks (GANs) for the prediction of diabetic macular edema after long-term treatment.
UNASSIGNED: Diabetic macular edema (DME) eyes (n = 327) underwent anti-vascular endothelial growth factor (VEGF) treatments every 4 weeks for 52 weeks from a randomized controlled trial (CRTH258B2305, KINGFISHER) were included. OCT B-scan images through the foveal center at weeks 0, 4, 12, and 52, fundus photography, and retinal thickness (RT) maps were collected. GAN models were trained to generate probable OCT images after treatment. Input for each model were comprised of either the baseline B-scan alone or combined with additional OCT, thickness map, or fundus images. Generated OCT B-scan images were compared with real week 52 images.
UNASSIGNED: For 30 test images, 28, 29, 15, and 30 gradable OCT images were generated by CycleGAN, UNIT, Pix2PixHD, and RegGAN, respectively. In comparison with the real week 52, these GAN models showed positive predictive value (PPV), sensitivity, specificity, and kappa for residual fluid ranging from 0.500 to 0.889, 0.455 to 1.000, 0.357 to 0.857, and 0.537 to 0.929, respectively. For hard exudate (HE), they were ranging from 0.500 to 1.000, 0.545 to 0.900, 0.600 to 1.000, and 0.642 to 0.894, respectively. Models trained with week 4 and 12 B-scans as additional inputs to the baseline B-scan showed improved performance.
UNASSIGNED: GAN models could predict residual fluid and HE after long-term anti-VEGF treatment of DME.
UNASSIGNED: The implementation of this tool may help identify potential nonresponders after long-term treatment, thereby facilitating management planning for these eyes.

Malignant melanoma presents a formidable challenge due to its aggressive metastatic behavior and limited response to current treatments. To address this, our study delves into the impact of anlotinib on angiogenesis and vasculogenic mimicry using malignant melanoma cells and human umbilical vein endothelial cells. Evaluating tubular structure formation, cell proliferation, migration, invasion, and key signaling molecules in angiogenesis, we demonstrated that anlotinib exerts a dose-dependent inhibition on tubular structures and effectively suppresses cell growth and invasion in both cell types. Furthermore, in a mouse xenograft model, anlotinib treatment resulted in reduced tumor growth and vascular density. Notably, the downregulation of VEGFR-2, FGFR-1, PDGFR-β, and PI3K underscored the multitargeted antitumor activity of anlotinib. Our findings emphasize the therapeutic potential of anlotinib in targeting angiogenesis and vasculogenic mimicry, contributing to the development of novel strategies for combating malignant melanoma.

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher\'s exact test and group t-test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (P>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)μm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)μm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P>0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P>0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P<0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm2, significantly different from that in the combination therapy group [(0.34±0.16) mm2] at 12 months (P<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.
目的： 探讨阈值下微脉冲激光（SMPL）联合雷珠单克隆抗体治疗糖尿病性黄斑水肿（DME）的有效性、安全性及特点。 方法： 前瞻性随机对照研究。连续收集2020年1月至2022年12月在北京医院眼科确诊为DME的患者，使用随机数字表按照1∶1比例随机分为SMPL联合雷珠单克隆抗体治疗组（联合组）和单纯雷珠单克隆抗体治疗组（单纯组）。记录并比较两组治疗前（基线）和治疗6和12个月随访时的最佳矫正视力（BCVA）、黄斑中心凹视网膜厚度（CMT）以及相干光层析血管成像术参数，包括浅层毛细血管丛血管密度（SCP-VD）、深层毛细血管丛血管密度（DCP-VD）、黄斑中心凹无血管区（FAZ）面积、视盘旁血管密度（P-VD）；治疗前和治疗12个月随访时的荧光素眼底血管造影术（FFA）检查结果，治疗12个月随访时玻璃体腔注射药物次数、SMPL治疗次数和不良反应。采用Fisher精确概率法和成组t检验进行统计学分析。 结果： 共纳入符合标准DME患者72例（72只眼），年龄为（61.1±8.2）岁；联合组36例（36只眼），男性19例（19只眼），女性17例（17只眼）；单纯组36例（36只眼），男性17例（17只眼），女性19例（19只眼），两组基线特征比较差异均无统计学意义（均P>0.05）。治疗6和12个月随访时，两组BCVA均明显改善［联合组提升至（58.5±12.9）和（58.2±12.2）个早期治疗糖尿病视网膜病变研究（ETDRS）字母；单纯组提升至（63.3±13.1）和（63.8±12.5）个ETDRS字母］；CMT均显著下降［联合组降低至（451.0±185.5）和（380.4±159.3）μm；单纯组降低至（387.5±135.5）和（372.8±146.1）μm］，差异均有统计学意义（均P<0.05），但是组间比较的差异均无统计学意义（均P>0.05）。治疗12个月随访时，单纯组（42.6%±5.9%）和联合组（42.2%±5.5%）SCP-VD与基线比较的差异和组间比较的差异均无统计学意义（均P>0.05）；联合组DCP-VD增加至47.5%±5.6%，与单纯组比较（43.4%±5.1%）的差异有统计学意义（P<0.05）；单纯组FAZ面积缩小至（0.32±0.13）mm2，联合组FAZ面积缩小至（0.34±0.16）mm2，两组比较差异有统计学意义（P<0.05）；眼内注射药物次数单纯组为（7.3±2.5）次，联合组为3次。两组随访期间FFA检查无明显变化，全身或局部无严重不良反应发生。 结论： SMPL联合雷珠单克隆抗体注射治疗DME患者有效且安全；与单纯雷珠单克隆抗体注射治疗比较，可减少眼内注射药物次数，并改善深层毛细血管丛的血流灌注，改善黄斑缺血。.

Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients\' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.
呼吸道乳头状瘤是呼吸道较常见的良性肿瘤，少数可发生恶变。该病起病隐匿，缺乏特异性临床表现，其表现与肿瘤生长方式、部位、大小密切相关，可有喉、气管、支气管、肺实质等多个部位受累，引起咳嗽、声音嘶哑、发音困难，严重者可致呼吸道梗阻。目前，呼吸道乳头状瘤的治疗缺乏规范统一的标准，且尚无治愈该病的有效方法，手术是减轻患者症状、预防气道梗阻的主要治疗方式。然而呼吸道乳头状瘤复发率高，患者往往需要经历多次手术治疗，频繁的手术降低患者的生活质量，增加患者的疾病负担与经济负担。贝伐珠单抗作为血管内皮生长因子结合抗体抑制剂，是一种有希望的辅助治疗方式，在减轻症状、减少手术频率方面表现出较好的潜力。本文主要对贝伐珠单抗治疗呼吸道乳头状瘤的有效性及安全性进行综述，并探讨全身性应用和病灶内注射贝伐珠单抗治疗呼吸道乳头状瘤的差异及疗效。.

Objectives: To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication. Methods: A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed. Results: Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients (P=0.007), which was related to tumor site (P=0.032), tumor size (P=0.029) and TP53 wild-type (P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb (P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions: PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.
目的： 探索PIK3CA在结直肠癌中的突变情况，分析PIK3CA与结直肠癌患者临床病理特征的关系，评估PIK3CA在指导临床治疗及预后评估中的价值。 方法： 收集山西省肿瘤医院2018—2021年病理确诊为结直肠癌的石蜡样本128例，从中提取DNA，采用二代测序方法检测PIK3CA突变，回顾性分析其与结直肠癌患者临床病理特征的关系以及对预后的影响。 结果： 128例结直肠癌样本中，男性75例，女性53例；患者年龄为32~86岁，中位年龄为61.5岁；PIK3CA突变的有27例（21.09%）。PIK3CA突变的结直肠癌易发生在男性患者（P=0.007），与肿瘤部位（P=0.032）、肿瘤大小（P=0.029）和TP53野生型（P=0.001）相关，且PIK3CA常见位点突变多出现在肿瘤突变负荷≥10 Muts/Mb的肿瘤中（P=0.031）。生存分析显示，PIK3CA突变对患者的生存预后无显著影响，但该类患者术后加用靶向抗血管生成药物治疗效果较差。 结论： PIK3CA突变是结直肠癌中较为常见的突变，在结直肠癌的发生发展过程中起到了重要作用。PIK3CA突变可能会导致结直肠癌抗血管生成药物的耐药性产生，但其对患者生存预后的影响还有待进一步研究。.

OBJECTIVE: To compare the results of intravitreal bevacizumab (IVB) monotherapy and combined intravitreal bevacizumab and laser photocoagulation (LPC) therapies applied in the same session to patients with aggressive retinopathy of prematurity (A-ROP) in our clinic.
METHODS: The study included 67 eyes of 37 patients diagnosed with A-ROP and treated. Forty-nine eyes treated with anti-vascular endothelial growth factor agent injection monotherapy for A-ROP treatment were included in the first group. The second group consisted of 18 eyes that received injection therapy and LPC treatment. The clinical findings of the two groups were investigated, and their treatment results were compared.
RESULTS: Recurrence was observed in 19 of the 49 (38%) eyes in the first group, but there was no recurrence in any of the cases in the second group. While only IVB was applied to eight cases with recurrence, the combination of LPC and IVB treatment was applied to 11 cases. A second recurrence was detected in two of the eight cases that had received IVB monotherapy as a treatment for recurrence and in three of the 11 cases that had received LPC and IVB. The treatment outcomes of the two groups did not statistically significantly differ (P = 0.181).
CONCLUSIONS: We consider that the combined simultaneous LPC and IVB treatment we applied in A-ROP cases is an effective approach, particularly for cases where there are concerns about the patient\'s ability to attend follow-up appointments.

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OBJECTIVE: This study sought to provide an overview of the current research and further analyze publication trends in the field of vascular endothelial growth factor (VEGF) and anti-VEGF treatment for neovascular age-related macular degeneration (NVAMD).
METHODS: We downloaded all related publications from 2001 to 2020 from the Web of Science Core Collection and conducted a bibliometric analysis using the bibiometrix package in R programming software.
RESULTS: A total of 3717 publications were included in the analysis. The USA contributed the largest number of publications (1443), and achieved the highest number of citations (74,946) and H-index value (28). Johns Hopkins University, USA, was the top institution with the most publications, and Peter A. Campochiaro was the most productive professor at The Wilmer Eye Institute, USA. 9.60% of the total publications were from the Journal of Retinal and Vitreous Diseases. Trend analysis demonstrated that anti-VEGF therapy was introduced in early 2000 after steroids, and the last 2 decades have witnessed the blossom of several anti-VEGF agents. \"Treat-and-extend\" and \"resistance\" were two popular trend topics in recent years.
CONCLUSIONS: The USA occupies a dominant position in the research field of VEGF and anti-VEGF treatments in NVAMD. Steroid administration, photodynamic therapy, and anti-VEGF therapy have been pivotal advances in the treatment of NVAMD patients over the past 2 decades. Limited acting period and resistance are potential investigation directions in future studies.