Corneal Diseases

角膜疾病
  • 文章类型: Journal Article
    目的:研究局部5-氟尿嘧啶(5-FU)治疗眼表鳞状细胞瘤(OSSN)的疗效和副作用。
    方法:回顾性研究100例接受5-FU治疗1周和3周治疗的患者的101只眼。
    结果:在100名患者(101只眼)中,诊断OSSN的平均年龄为49岁(中位数,52年;范围,11-87岁)。在6只(6%)眼中记录了先前的干预史。肿瘤中心包括球结膜(n=54;53%),角膜缘(n=27;27%),和角膜(n=20;20%)。局部施用5-FU的平均周期数为3(中位数,3;范围,1-8).通过局部5-FU在89只(88%)眼睛中实现了完全的肿瘤消退,平均2个周期(中位数,2;范围,1-6)的5-FU。其余12例(12%)病变接受额外治疗,包括切除活检(n=7),延长摘除(n=3),和局部干扰素α2b(n=2)用于完全控制肿瘤。在平均6个月的随访期内(中位数,5个月;范围,1-36个月)治疗后,2例(2%)患者出现肿瘤复发,7只(7%)眼睛出现副作用,包括结膜充血(n=1),泪点狭窄(n=1),无菌性角膜炎(n=4),角膜缘干细胞缺乏(n=1)。
    结论:外用5-FU是一种有效的非侵入性治疗OSSN,副作用最小。
    OBJECTIVE: To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN).
    METHODS: Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3 weeks off regimen.
    RESULTS: Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52 years; range, 11-87 years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6 months (median, 5 months; range, 1-36 months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1).
    CONCLUSIONS: Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.
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  • 文章类型: Case Reports
    目的:报告一例75岁的患者,该患者因局部使用环丙沙星而继发出现了晶体性角膜病,并进行了组织病理学验证,白内障术后无并发症。
    方法:病例报告与临床和摄影随访,以及带有上皮和晶体沉积物样本的载玻片。
    结果:药物暂停后角膜沉积消退,局部润滑剂的变化,以及随后的手术清创。组织病理学检查报告了与药物沉淀物相容的上皮细胞和嗜碱性颗粒。
    结论:晶体性角膜病变是指各种晶体沉积在角膜上皮和/或前基质中的病症。它可能有传染性,药理学原因或,在更罕见的情况下,角膜营养不良.某些因素,如先前的上皮缺损,糖尿病的全身病理学,眼科手术和先前的干眼症可能有利于环丙沙星的沉积,导致角膜病变的形成。
    OBJECTIVE: To report the case of a 75-year-old patient who presented crystalline keratopathy secondary to the use of topical ciprofloxacin with histopathological verification, after cataract surgery without complications.
    METHODS: Case report with clinical and photographic follow-up, as well as slides with samples of epithelium and crystalline deposits.
    RESULTS: Corneal deposits resolved after drug suspension, topical lubricant change, and subsequent surgical debridement. The histopathological examination reported epithelial cells and basophilic particles compatible with drug precipitates.
    CONCLUSIONS: Crystalline keratopathy is a condition in which crystals of various kinds are deposited in the corneal epithelium and/or in the anterior stroma. It may have an infectious, pharmacological cause or, in rarer cases, corneal dystrophies. Certain factors such as a previous epithelial defect, systemic pathology with diabetes mellitus, ocular surgery and previous dry eye can favor the deposition of ciprofloxacin leading to the formation of a keratopathy.
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  • 文章类型: Journal Article
    要比较球形分量的变化,有规律的散光,小切口微透镜摘除(SMILE)和跨上皮屈光性角膜切除术(TransPRK)后角膜前表面的不规则散光。56名患者接受了56只眼睛的微笑,68例患者在68只眼中接受了TransPRK。选择右眼进入该组。手术后六个月,获得了Scheimpflug图像,使用Pentacam内置软件对患者角膜前表面进行傅立叶分析。傅里叶参数包括各种测量,如曲率的最陡半径和球面分量的平均偏心率(SphRmin和SphEcc),最大偏心(MaxDec),中央和周边规则散光(中心[AstC]的规则散光和周边[AstP]的规则散光),和不规则性(Irr)。术后6个月,SphEcc显著降低(P<.001),MaxDec显著增加(P<.001),在SMILE组中,Irr增加不明显(P=0.254)。TransPRK组SphEcc显著降低(P<.001),MaxDec和Irr显著升高(P<.001)。TransPRK引起SphEcc更大的变化,MaxDec,角膜前表面的Irr高于SMILE(P<0.05)。MaxDec引起的SMILE和TransPRK变化量与高阶像差和球差变化量显著相关(P<0.05)。SMILE和TransPRK增加了角膜前表面的整体不规则散光,对于TransPRK更是如此,其中,分散度的变化与高阶像差的增加有关。
    To compare changes in the spherical component, regular astigmatism, and irregular astigmatism of the anterior surface of the cornea after small-incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (TransPRK). Fifty-six patients underwent SMILE in 56 eyes, and 68 patients underwet TransPRK in 68 eyes. The right eye was chosen to enter the group. Six months after the procedure, Scheimpflug images were acquired, and Fourier analysis of the anterior surface of patients\' corneas was performed using the Pentacam built-in software. Fourier parameters encompass various measurements such as the steepest radius of the curvature and average eccentricity of the spherical components (SphRmin and SphEcc), maximum decentration (MaxDec), central and peripheral regular astigmatism (regular astigmatism at the center [AstC] and regular astigmatism at the periphery [AstP]), and irregularity (Irr). At 6 months postoperatively, SphEcc decreased significantly (P < .001), MaxDec increased significantly (P < .001), and Irr increased insignificantly (P = .254) in the SMILE group. SphEcc decreased significantly (P < .001) and MaxDec and Irr increased significantly (P < .001) in the TransPRK group. TransPRK caused greater changes in SphEcc, MaxDec, and Irr on the anterior corneal surface than SMILE (P < .05). The amount of MaxDec-induced changes in SMILE and TransPRK was significantly correlated with the amount of higher-order aberrations and spherical aberration changes (P < .05). SMILE and TransPRK increase overall irregular astigmatism on the anterior surface of the cornea, more so with TransPRK, where changes in decentration are associated with with increased higher-order aberrations.
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  • 文章类型: Journal Article
    目的:疫苗相关角膜移植排斥反应的数据有限。我们检查了移植物排斥和疫苗接种之间的关联。
    方法:匹配的病例对照方法:我们在南加州KaiserPermanente于2008年1月1日至2022年8月8日之间使用电子健康记录来识别角膜移植受者。病例是在研究期间经历移植物排斥(结果)的移植接受者。随机选择的对照组在匹配的病例索引日期(排斥日期)时未经历角膜移植物排斥反应,与病例的比例为3:1。对于控件,索引日期是通过将匹配病例的移植和移植物排斥之间的天数添加到对照的移植日期来确定的。
    结果:该研究包括601例病例和1,803名匹配的对照(平均年龄66岁[s.d.17.0],52%女性,47%非西班牙裔白人)。23%的病例和22%的对照组在索引日期前12周内接受了≥1次疫苗接种。索引日期前12周疫苗接种的调整后优势比(aOR),病例与对照组的比较为1.17(95%CI:0.91,1.50])。1次疫苗接种的aOR为1.09[0.84,1.43],1.53[0.90,2.61]用于2次疫苗接种,≥3次疫苗接种为1.79[0.55,5.57]。mRNA疫苗的aOR为1.60(0.81,3.14),和1.19(0.80,1.78)的佐剂/高剂量疫苗。
    结论:我们发现没有证据表明疫苗接种和移植物排斥之间存在关联。我们的发现为角膜移植受者完成推荐的疫苗接种提供了支持,不会显着增加移植物排斥的风险。
    OBJECTIVE: Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination.
    METHODS: Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases\' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control\'s transplant date.
    RESULTS: The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received ≥1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for ≥3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines.
    CONCLUSIONS: We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.
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  • 文章类型: Observational Study
    背景:结构特征对先天性角膜混浊(CCO)的手术预后有影响。CCO的结构分类系统,然而,缺乏。根据超声生物显微镜(UBM)在婴儿和幼儿CCO发现的数据,这项研究提出了一个前段结构严重程度的分类系统。
    方法:医疗记录,我们回顾了2018年12月至2022年6月在大学第三医院诊断为CCO的婴幼儿的术前UBM图像和裂隙灯照片.根据UBM图像中观察到的眼前节结构特征,眼睛分类如下:U1,仅角膜不透明;U2,中央前粘连;U3,周围前粘连合并闭角;U4,无虹膜或晶状体异常。根据先前的研究,在裂隙灯照片中观察到的不透明外观和角膜血管形成密度被分配等级。还记录了血管形成的程度。分析了相应的眼内异常分类和眼表病变的严重程度。
    结果:在81只眼睛(65例患者)中,41(50.6%)为右眼,40只(49.4%)为左眼。检查时的中位年龄为6.91个月(n=81、1.00、34.00)。81只眼睛中有2只(2.5%)被归类为U1,20只(24.7%)被归类为U2,22只(27.2%)被归类为U3a,11(13.6%)为U3b,26(32.1%)为U4。双侧CCO眼有更严重的UBM分类(P=0.019),更严重的发育不全(P=0.012)和更大的闭角(P=0.009)。UBM分类更严重的眼睛具有更高的不透明度等级(P=0.003)和血管化等级(P=0.014)以及更大的血管化程度(P=0.001)。发育不全的眼睛有更高的雾霾等级(P=0.012)和更严重的血管形成(密度P=0.003;程度P=0.008),而角闭合范围与雾度(P=0.013)和血管化程度(P=0.003)有关。
    结论:这种基于UBM和裂隙灯摄影结果的CCO婴幼儿眼睛分类方法能够真实反映眼表和眼前节的异常程度,并与眼表异常的严重程度相关。该方法可能为CCO眼角膜移植术的外科手术设计和预后确定提供有意义的指导。
    BACKGROUND: The structural features have an impact on the surgical prognosis for congenital corneal opacity (CCO). The structural classification system of CCO, however, is lacking. Based on data from ultrasound biomicroscopy (UBM) findings in infants and toddlers with CCO, this research proposed a classification system for the anterior segment structure severity.
    METHODS: Medical records, preoperative UBM images and slit-lamp photographs of infants and toddlers diagnosed with CCO at University Third Hospital between December 2018 and June 2022 were reviewed. According to the anterior segment structural features observed in UBM images, eyes were classified as follows: U1, opaque cornea only; U2, central anterior synechia; U3, peripheral anterior synechia combined with angle closure; and U4, aniridia or lens anomaly. The opacity appearance and corneal vascularization density observed in slit-lamp photographs were assigned grades according to previous studies. The extent of vascularization was also recorded. The corresponding intraocular anomaly classifications and ocular surface lesion severity were analysed.
    RESULTS: Among 81 eyes (65 patients), 41 (50.6%) were right eyes, and 40 (49.4%) were left eyes. The median age at examination was 6.91 months (n = 81, 1.00, 34.00). Two (2.5%) of the 81 eyes were classified as U1, 20 (24.7%) as U2, 22 (27.2%) as U3a, 11 (13.6%) as U3b and 26 (32.1%) as U4. Bilateral CCO eyes had more severe UBM classifications (P = 0.019), more severe dysgenesis (P = 0.012) and a larger angle closure (P = 0.009). Eyes with more severe UBM classifications had higher opacity grades (P = 0.003) and vascularization grades (P = 0.014) and a larger vascularization extent (P = 0.001). Eyes with dysgenesis had higher haze grades (P = 0.012) and more severe vascularization (P = 0.003 for density; P = 0.008 for extent), while the angle closure range was related to haze grade (P = 0.013) and vascularization extent (P = 0.003).
    CONCLUSIONS: This classification method based on UBM and slit-lamp photography findings in the eyes of CCO infants and toddlers can truly reflect the degree of abnormality of the ocular surface and anterior segment and is correlated with the severity of ocular surface anomalies. This method might provide meaningful guidance for surgical procedure design and prognostic determinations for keratoplasty in CCO eyes.
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  • 文章类型: Randomized Controlled Trial
    目的:患有无法治愈的角膜疾病的患者尽管有健康的视网膜和光学通路,但仍有视觉障碍。规定低视力辅助(LVA)通过放大和对比度增强来优化剩余视力的使用,但不要充分利用病人的视觉能力,因为他们依赖于光学媒体。因此,我们研究了一种绕过眼前节的新型激光眼镜(LEW)技术.由集成相机捕获的图像使用低能量I-RGB类激光直接投影到视网膜上。患者能够观看全彩视频,实现为增强现实。我们旨在评估LEW增强角膜疾病患者视力的疗效。
    方法:前瞻性,随机化,交叉临床试验。
    方法:我们检查了21名因角膜疾病导致视力障碍(0.7logMAR或更差)的受试者(年龄25-69岁)的视网膜投影眼镜。患有影响视力的合并症的受试者,比如视网膜疾病,被排除在外。
    方法:使用ETDRS图分别进行最佳矫正(BC)和LEW,对近距(NV)和远距(DV)的视敏度进行标准化测量。除了阅读速度,在使用和不使用该设备的家庭阶段后,在初次访问和随后的两次访问中评估了与视觉相关的生活质量(QoL)和执行日常任务的能力。最后一次使用LEW6周后,进行包括SD-OCT或全场视网膜电图在内的眼科检查,并与基线进行比较,以评估装置的安全性。四名受试者参与并完成了随后的12个月随访阶段。
    方法:使用LEW改善视力。次要目标包括安全,阅读速度,日常活动中的QoL和可用性。
    结果:与BC相比,使用LEW的DV中视力障碍受试者的平均视敏度(VA)提高了0.43logMAR(p<0.0001)。使用LEW的2x放大模式导致与BC相比0.66logMAR的平均改善(p<0.0001)。在NV中,与BC相比实现了0.47logMAR的增加(p<0.0001)。虽然21名参与者中只有4名能够阅读BC,17/21能够阅读LEW。完成所有访问的17名受试者的QoL显着改善。
    结论:我们证明了视网膜投影眼镜通过直接将图像投射到完整的视网膜上,可以提高所有受试者的视力。在未来,LEW可以代表角膜疾病患者作为LVA的新供应选择。
    OBJECTIVE: Patients with incurable corneal diseases experience visual impairment (VI) despite having a healthy retina and optic pathway. Low-vision aids (LVAs) can optimize the use of remaining vision through magnification and contrast enhancement, but do not harness the full visual capacity because they rely on the optic media. Therefore, we investigated a novel laser eyewear (LEW) technology that bypasses the anterior segment of the eye. Images captured by an integrated camera are projected directly onto the retina using a low-energy laser. The patient is able to view a full-color video, realized as augmented reality. We aimed to evaluate the efficacy of the LEW to enhance the vision of individuals with corneal diseases.
    METHODS: Prospective, randomized, crossover clinical trial.
    METHODS: We examined the retinal projection glasses in 21 patients (25-69 years) with VI (0.7 logarithm of the minimum angle of resolution [logMAR] or worse) resulting from corneal diseases. Patients with comorbidities that impact vision, such as retinal disorders, were excluded.
    METHODS: Standardized measurements of visual acuity (VA) for near vision (NV) and distance vision (DV) were conducted using ETDRS charts with the respective best correction (BC) and then with LEW. In addition reading speed, vision-related quality of life (QoL) and capacity to carry out daily tasks were assessed at an initial visit and at 2 subsequent visits after a home phase with and without the device. Six weeks after last use of the LEW, an ophthalmologic examination including spectral-domain-OCT or full-field-electroretinography was conducted and compared with baseline findings to evaluate the safety of the device. Four patients participated and completed a subsequent 12-month follow-up phase.
    METHODS: Improvement of VA using the LEW. Secondary objectives included safety, reading speed, QoL, and usability in daily activities.
    RESULTS: The mean VA in patients with VI was improved by 0.43 logMAR in DV using the LEW compared with BC (P < 0.0001). Using the ×2 magnification mode of the LEW resulted in an average improvement of 0.66 logMAR compared with BC (P < 0.0001). In NV, an increase of 0.47 logMAR was achieved compared with BC (P < 0.0001). Although only 4 of 21 participants were able to read with BC, 17 of 21 participants were able to read with the LEW. Quality of life significantly improved in the 17 participants who completed all visits.
    CONCLUSIONS: We demonstrated that the retinal projection glasses resulted in enhanced VA for all participants by directly projecting images onto the intact retina. In future, the LEW could represent a new option as an LVA for patients with corneal diseases. No pathological alterations were observed in the safety assessments.
    BACKGROUND: The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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  • 文章类型: Clinical Trial Protocol
    目的:角膜失明是全球第三大最常见的失明原因。角膜内皮损伤是角膜移植的主要适应症,通常通过板层内皮角膜移植术进行。有两种常规的手术技术:超薄脱粒自动内皮角膜移植术(UT-DSAEK)和脱粒膜内皮角膜移植术(DMEK)。这项研究的目的是比较这两种技术。
    方法:该试验比较了UT-DSAEK和DMEK在临床和患者报告的结果方面,平行,多中心,随机对照试验,1:1分配,11个手术中心的220名参与者的样本量.主要结果是12个月时最佳矫正视力的变化。次要结果包括矫正视力和未矫正视力,折射,高视力比例,生活质量(EQ-5D-5L和VFQ25),3、6和12个月随访时的内皮细胞计数和角膜厚度。不良事件也将在术后12个月进行比较。
    背景:该方案由11个参与中心的伦理委员会审查,申办中心发布最终批准。结果将在临床会议上传播,由患者合作伙伴团体和同行评审期刊中的开放访问。
    两者,审判管理小组和审判指导委员会,与包括外科医生在内的所有利益相关者的代表一起安装,角膜银行家,患者和外部专家。
    背景:NCT05436665。
    Corneal blindness is the third most frequent cause of blindness globally. Damage to the corneal endothelium is a leading indication for corneal transplantation, which is typically performed by lamellar endothelial keratoplasty. There are two conventional surgical techniques: Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK). The purpose of this study is to compare both techniques.
    The trial compares UT-DSAEK and DMEK in terms of clinical and patient reported outcomes using a pragmatic, parallel, multicentric, randomised controlled trial with 1:1 allocation with a sample size of 220 participants across 11 surgical centres. The primary outcome is the change in best-corrected visual acuity at 12 months. Secondary outcomes include corrected and uncorrected vision, refraction, proportion of high vision, quality of life (EQ-5D-5L and VFQ25), endothelial cell counts and corneal thickness at 3, 6 and 12 months follow-up appointments. Adverse events will also be compared 12 months postoperatively.
    The protocol was reviewed by ethical committees of 11 participating centres with the sponsor centre issuing the final definitive approval. The results will be disseminated at clinical conferences, by patient partner groups and open access in peer-reviewed journals.
    Both, trial management group and trial steering committee, are installed with representatives of all stakeholders involved including surgeons, corneal bankers, patients and external experts.
    NCT05436665.
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  • 文章类型: Randomized Controlled Trial
    目的:为了研究散光矫正的效果,旋转稳定性,两种不同触觉型复曲面人工晶状体的相关因素。
    方法:前瞻性,随机化,对照试验。术前角膜散光>1D的白内障患者随机植入C环触觉复曲面IOL(AcrySof复曲面IOL)(A组)或平板触觉复曲面IOL(ATTORBI709MIOL)(B组)。残余散光,人工晶状体旋转,术后3个月测定并比较两组患者的视觉质量。
    结果:本研究纳入了79只眼,A组40只眼,B组39只眼,术前视力差异无统计学意义,眼内压,并发现了两组之间的眼科生物学参数。两组术后3个月残余散光比较,差异无统计学意义(P>0.05)。A组旋转度3.85±2.92°,B组旋转角度为2.33±2.31°,两组间人工晶状体旋转差异有统计学意义(P<0.05)。在探索两种不同触觉类型的复曲面人工晶状体的旋转相关因素时,C环触觉复曲面人工晶状体植入后的旋转与眼轴长度(Pearsonr=0.522,P=0.01)和角膜白白距离(Pearson相关分析r=0.356,P=0.024)呈正相关。
    结论:两种不同触觉类型的复曲面人工晶状体可有效矫正规则角膜散光,并在术后提供良好的旋转稳定性。但是平板触觉复曲面IOL的稳定性优于C环触觉复曲面IOL。C环触觉复曲面人工晶状体的旋转稳定性通常与眼轴长度和角膜白间距离有关。
    OBJECTIVE: To study the effect of astigmatism correction, rotational stability, and related factors of two different haptic type toric intraocular lenses.
    METHODS: A prospective, randomized, controlled trial. Cataract patients with preoperative corneal astigmatism of > 1 D were randomly implanted with C-loop haptic toric IOL (AcrySof-toric IOL) (group A) or plate-haptic toric IOL (AT TORBI 709 M IOL) (group B). The residual astigmatism, intraocular lens rotation, and visual quality were determined and compared between the two groups at 3 months after surgery.
    RESULTS: Seventy-nine eyes were included in this study, including 40 eyes in the group A and 39 eyes in the group B. No significant difference in preoperative visual acuity, intraocular pressure, and ophthalmic biological parameters was found between the two groups. There was no significant difference in residual astigmatism between the two groups at 3 months after surgery (P > 0.05). The rotation degree in the group A was 3.85 ± 2.92°, the rotation degree in the group B was 2.33 ± 2.31°, and a significant difference in intraocular lens rotation was identified between the two groups (P < 0.05). Upon exploring the rotation-related factors of the two different haptic type toric intraocular lenses, the rotation after implanting C-loop haptic toric IOL was positively correlated with axial length (Pearson r = 0.522, P = 0.01) and corneal white-to-white distance (Pearson correlation analysis r = 0.356, P = 0.024).
    CONCLUSIONS: The two different haptic type toric intraocular lenses effectively corrected regular corneal astigmatism and provided a good rotational stability after surgery. But the stability of plate-haptic toric IOL was better than that of C-loop haptic toric IOL. The rotational stability of C-loop haptic toric IOL was often related to axial length and corneal white-to-white distance.
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  • 文章类型: Clinical Trial, Phase I
    Tusamitamabravtansine是一种抗体-药物缀合物,靶向癌胚抗原相关细胞粘附分子5(CEACAM5)并递送细胞毒性类美登素有效载荷。在I期剂量递增研究中,最大耐受剂量(MTD)为每2周100mg/m2(Q2W).在这里,我们报告两个替代时间表的结果。
    成年人年龄≥18岁(范围,34-73)伴有局部晚期/转移性实体瘤(N=43;结肠/直肠,29;胃,7;胰腺,4;其他,3)表达/可能表达CEACAM5接受静脉内Tusamitamabravtansine120-170mg/m2[负荷剂量(LD)],然后100毫克/平方米Q2W(Q2W-LD,n=28),或120-190mg/m2固定剂量[每3周(Q3W),n=15]。主要终点是第1-2周期(Q2W-LD)和第1周期(Q3W)的剂量限制性毒性(DLTs)。
    在9例患者中的2例(2级角膜病变;2级角膜炎)在Q2W-LD中观察到170mg/m2的可逆性DLT,在3例患者中的2例(2级角膜病变;3级转氨酶升高)在Q3W中观察到190mg/m2的可逆性DLT。Q2W-LD中的19例(67.9%)患者和Q3W中的13例(86.7%)患者经历了治疗相关的不良事件(AE);43例患者中有3例因AE而停止治疗。最常见的不良事件是虚弱,肠胃不适,角膜病变,角膜炎,和周围感觉神经病变。在这个小小的,大量预处理的人群,没有观察到确认的反应;然而,在Q2W-LD中有35.7%的患者病情稳定,在Q3W中有40.0%的患者病情稳定。
    Tusamitamabravtansine在两种替代给药方案下都具有良好的安全性;MTD为170mg/m2(LD),随后为100mg/m2Q2W,和170mg/m2Q3W作为固定剂量。(NCT02187848)。
    这项I期剂量递增研究的集体结果将为进一步研究具有CEACAM5表达的实体瘤患者的tusamitamabravtansine提供信息,包括非小细胞肺癌患者。
    Tusamitamab ravtansine is an antibody-drug conjugate that targets carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and delivers a cytotoxic maytansinoid payload. In a phase I dose-escalation study, the maximum tolerated dose (MTD) was 100 mg/m2 every 2 weeks (Q2W). Here we report results for two alternative schedules.
    Adults ages ≥18 years (range, 34-73) with locally advanced/metastatic solid tumors (N = 43; colon/rectum, 29; stomach, 7; pancreas, 4; other, 3) expressing/likely to express CEACAM5 received intravenous tusamitamab ravtansine 120-170 mg/m2 [loading dose (LD)], then 100 mg/m2 Q2W (Q2W-LD, n = 28), or 120-190 mg/m2 fixed dose [every 3 weeks (Q3W), n = 15]. The primary endpoint was dose-limiting toxicities (DLTs) during cycles 1-2 (Q2W-LD) and cycle 1 (Q3W).
    Reversible DLTs were observed in 2 of 9 patients (grade 2 keratopathy; grade 2 keratitis) with 170 mg/m2 in Q2W-LD and in 2 of 3 patients (grade 2 keratopathy; grade 3 transaminase elevation) with 190 mg/m2 in Q3W. Nineteen (67.9%) patients in Q2W-LD and 13 (86.7%) patients in Q3W experienced treatment-related adverse events (AE); 3 of 43 patients discontinued treatment because of AEs. The most common AEs were asthenia, gastrointestinal complaints, keratopathy, keratitis, and peripheral sensory neuropathy. In this small, heavily pretreated population, no confirmed responses were observed; however, stable disease occurred in 35.7% of patients in Q2W-LD and 40.0% of patients in Q3W.
    Tusamitamab ravtansine had a favorable safety profile with both alternative administration schedules; MTDs were 170 mg/m2 (LD) followed by 100 mg/m2 Q2W, and 170 mg/m2 Q3W as a fixed dose. (NCT02187848).
    The collective results of this phase I dose-escalation study will inform further studies of tusamitamab ravtansine in patients with solid tumors with CEACAM5 expression, including patients with non-small cell lung cancer.
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  • 文章类型: Observational Study
    背景:比较虹膜角膜内皮(ICE)综合征患者角膜内皮移植术(EK)与穿透性角膜移植术(PK)的移植物存活率,并确定与移植物存活率相关的眼部特征。
    方法:观察性,prospective,队列研究。通过澳大利亚角膜移植登记处确定了1985年至2020年之间进行的总共30806例首次移植,并包括在此观察中。前瞻性队列研究。共有196只眼接受了ICE综合征的原发性角膜移植。进行Kaplan-Meier移植物存活图和卡方检验以确定EK和PK的移植物存活率。还记录并分析了眼内压(IOP)升高的病史。将患有ICE综合征的眼睛的移植物存活率与其他适应症的移植物存活率进行比较。
    结果:在2005年至2020年期间,ICE综合征的移植物增加到所有病例的0.8%,而在1985年至2004年期间为0.5%(χ2=9.35,p=0.002)。从2010年开始,EK超过PK成为首选的接枝类型。患有ICE综合征的眼睛的原发性移植物的存活率低于其他适应症(log-rank=56.62,p<0.001)。PK后移植物存活率高于Descemet剥离(自动)内皮角膜移植术(DS(A)EK)(log-rank=10.56,p=0.001)。与有报告的IOP升高史的那些相比,在没有IOP升高史的眼睛中移植物存活率更高(log-rank=13.06,p<0.001)。
    结论:ICE综合征对移植物存活预后不良。DS(A)EK的预后比PK差。IOP升高的病史与较高的移植物失败风险相关。
    To compare graft survival of endothelial keratoplasty (EK) versus penetrating keratoplasty (PK) in patients with iridocorneal endothelial (ICE) syndrome and identify ocular features associated with graft survival.
    Observational, prospective, cohort study. A total of 30 806 first grafts performed between 1985 and 2020 were identified through the Australian Corneal Graft Registry and included in this observational, prospective cohort study. A total of 196 eyes underwent a primary corneal graft for ICE syndrome. Kaplan-Meier graft survival plots and Chi-squared tests were performed to identify graft survival rates for EK and PK. A history of raised intraocular pressure (IOP) was also recorded and analysed. Graft survival of eyes with ICE syndrome were compared to that of other indications.
    Grafts performed for ICE syndrome increased to 0.8% of all cases during the 2005 to 2020 period compared with 0.5% between 1985 to 2004 (χ2 =9.35, p = 0.002). From 2010, EK surpassed PK as the preferred graft type. Survival of primary grafts in eyes with ICE syndrome was lower than for other indications (log-rank = 56.62, p < 0.001). Graft survival was higher following PK than Descemet stripping (automated) endothelial keratoplasty (DS(A)EK) (log-rank = 10.56, p = 0.001). Graft survival was higher in eyes without a history of raised IOP compared to those with a reported history of raised IOP (log-rank = 13.06, p < 0.001).
    ICE syndrome carries a poor prognosis for graft survival. DS(A)EK had a poorer prognosis than PK. A history of raised IOP is associated with higher risk of graft failure.
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