Fourier-domain optical coherence tomography-guided phototherapeutic keratectomy for the treatment of anterior corneal scarring

AIM:To evaluate the safety,visual and anatomic outcomes of fourier-domain optical coherence tomography(FD-OCT)-guided excimer laser phototherapeutic keratectomy(PTK)combined with photorefractive keratectomy(PRK)surgery in treating anterior corneal scarring.METHODS:Clinical data of 23 eyes of 21 patients with anterior corneal scarring underwent FD-OCT-guided PTK and PRK from Dec.2014 to Jul.2016 were reviewed.Patients were assessed for preoperative and postoperative uncorrected visual acuity(UCVA),best spectacle-corrected visual acuity(BSCVA),contrast sensitivity(CS),FD-OCT,corneal topography and colour figures of anterior segments.RESULTS:The preoperative corneal pathologic conditions included viral keratitis(7 patients,7 eyes),band keratopathy(2 patients,4 eyes),corneal dystrophy(4 patients,4 eyes),traumatic corneal disease(2 patients,2 eyes)and corneal chemical injury(6 patients,6 eyes).Mean follow-up time was 10.65(range,3-19)mo.UCVA(in IogMAR)improved from a mean of 0.79(95%Cl,0.28­1.29)preoperatively to a mean of 0.45(95%Cl,0.29-0.62)postoperatively(P=0.021).BSCVA(in IogMAR)improved from 0.57(95%Cl,0.27-0.88)preoperatively to a mean of 0.28(95%Cl,0.15-0.41)postoperatively(P=0.001).Corneal topographic indices postoperatively showed significant improvement in corneal cylinder(P=0.009),the surface regularity index(P=0.007)and surface asymmetry index(P=0.00).Postoperative spherical equivalent averaged-0.53 diopters(-1.49 to 0.42).No complications were associated with the treatment.CONCLUSION:FD-OCT-guided PTK combined with PRK is safe and effective for the treatment of anterior corneal scarring by eliminating or reducing corneal opacities.

Evaluation of traumatic retinopathy with ultra-wide field imaging under corneal scar or fixed small pupil

AIM： To evaluate the value of ultra-wide field（UWF） imaging in the management of traumatic retinopathy under the condition of corneal scar or fixed small pupil after complicated ocular trauma. METHODS： Twenty-eight patients（28 eyes） with complicated ocular trauma were enrolled in the study from June 2016 to May 2017, including 19 males and 9 females with age ranged from 11 to 64（43.42±12.62）y. All patients were treated with secondary vitrectomy after emergency operation for wound repair of open ocular trauma. Direct ophthalmoscopy and 45-degree fundus photography were taken at each time point of follow up for comparison of findings with UWF images. Routine eye examination including visual acuity, intraocular pressure, slit lamp examination were performed and analyzed as well.RESULTS： Among the 28 traumatized eyes, the positive rate for identification of traumatic retinopathed was 32.1%（9 cases）, 14.9%（5 cases）, and 85.7%（24 cases） with direct ophthalmoscopy, 45-degree fundus photography, and UWF imaging, respectively. The detective rate of UWF imaging under the condition of corneal scar or fixed small pupil was statistically greater than that of 45-degree fundus photography and direct ophthalmoscopy（Bonferroni correction, P〈0.001）. UWF image was obtained in 19 eyes with opaque corneal scar, otherwise their fundus could not be seen by conventional methods. The additional findings of traumatic retinopathies by UWF imaging included periretinal membranes or pre-retinal proliferating strip, retinal holes, hemorrhage in the vitreous or sub-retinal space.CONCLUSION： UWF imaging is superior to traditional fundus photography in the evaluation of traumatic retinopathies under the condition of corneal scar or fixed small pupil after complicated ocular trauma.

Reduction of corneal scarring in rabbits by targeting the TGFB1 pathway with a triple siRNA combination

Purpose: The transforming growth factor beta1 (TGFB1) pathway has been linked to fibrosis in several tissues including skin, liver, kidney and the cornea. In this study, a RNA interference-based approach using siRNAs targeting three critical scarring genes, TGFB1, TGFB receptor 2 (TGFBR2) and connective tissue growth factor (CTGF), was tested for effects on reducing alpha smooth muscle actin (SMA) and corneal scarring (haze) in excimer laser ablated rabbit corneas. Methods: Levels of TGFB1 and CTGF mRNAs were measured using qRT-PCR in the epithelial and endothelial cell layers of normal and excimer ablated rabbit corneas at 30 minutes, 1 day and 2 days after ablation. Two different scarring models were utilized to assess the effects of the triple siRNA combination on corneal scarring. In the first model, rabbit corneas were unevenly ablated creating a mesh pattern then treated immediately with the triple siRNA combination. After 1 day the ablated areas of corneas were collected and levels of mRNAs for TGFB1, TGFBR2 and CTGF were measured. After 14 days, levels of mRNA for SMA were measured and SMA protein immunolocalized in frozen sections. In the second model, rabbit corneas were uniformly ablated to a depth of 155 microns followed by three daily doses of the triple combination of siRNA. After 14 days, corneas were photographed and images were analyzed using Image J software to assess corneal scarring. Corneas were also analyzed for levels of SMA mRNA. Results: In both unwounded and wounded corneas, levels of TGFB1 and CTGF mRNA were always significantly higher in endothelial cells than in epithelial cells (10 to 30 fold). Thirty minutes after injury, levels of both TGFB1 and CTGF mRNAs increased approximately 20-fold in both epithelial and endothelial cells, and further increased approximately 60-fold in 2 days. In the first therapeutic experiment with a single siRNA dose, two of three rabbits showed substantial reductions of all three target genes after 1 day with a maximum knock down of 80% of TGFb 1, 50% reduction of TGFBR2 and 40% reduction of CTGF mRNA levels and reduced SMA mRNA at day 14. In the second therapeutic experiment with multiple doses of siRNA treatment, both rabbits showed a ~22% reduction in scar formation at day 14 as calculated by image analysis. There was also a corresponding 70% and 60% reduction of SMA RNA expression. Conclusion: These results demonstrate that both TGFB1 and CTGF dramatically increase in rabbit corneal epithelial and endothelial cells after injury. Treatment of excimer ablated rabbit corneas with a triple combination of siRNAs effectively reduced levels of the target genes and SMA, leading to reduced corneal scarring at 14 days, suggesting that this triple siRNA combination may be an effective new approach to reducing scarring in cornea and other tissues.

Treatment of anterior corneal scarring,following DSAEK graft failure,with combined graft exchange and phototherapeutic keratectomy

Background:To present a method,alternative to penetrating keratoplasty,for the restoration of impaired corneal clarity with anterior stromal scarring following long-standing corneal graft failure.Case presentation:A 48-year old female who had previously underwent Descemet stripping automated endothelial keratoplasty(DSAEK)for the treatment of pseudophakic bullous keratopathy,presented with longstanding corneal oedema and anterior corneal scarring.A significant improvement in corrected distance visual acuity was demonstrated,as corneal clarity was restored following graft exchange and phototherapeutic keratectomy(PTK).Conclusions:The combination of corneal graft exchange and phototherapeutic keratectomy may represent an effective therapeutic option for long-standing corneal oedema with concomitant anterior corneal scarring after failure of a DSAEK graft.

Research progress on animal models of corneal epithelial-stromal injury

A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithelialstromal defects.Currently,the etiology and pathogenesis of these defects remain inadequately understood,necessitating further investigation through experimental research.Various modeling methods exist both domestically and internationally,each with distinct adaptive conditions,advantages,and disadvantages.This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury,including mechanical modeling,chemical alkali burns,post-refractive surgery infections,and genetic engineering.The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.

羊膜匀浆提取液对大鼠碱烧伤后角膜瘢痕形成的抑制作用

目的观察大鼠角膜碱烧伤使用羊膜匀浆提取液(extraction of amniotic membrane,EAM)后角膜瘢痕的变化,探讨羊膜匀浆提取液应用于角膜碱烧伤的临床价值及作氉用机理。方法取SD大鼠40只随机分为EAM组(20只)和对照组(20只),所有大鼠通过1 mol·L-1的NaOH溶液建立右眼角膜碱烧伤模型。EAM组行EAM滴眼,每天4次,对照组用PBS缓冲液滴眼。通过裂隙灯显微镜下观察大鼠角膜透明性,角膜共聚焦显微镜动态观察大鼠角膜超微结构的变化,计算肌成纤维细胞的数量。结果碱烧伤后28 d,EAM组的角膜透明度评分明显好于对照组,两组分别为2.36±0.81和3.36±1.12(P<0.01)。碱烧伤后第9天、第11天、第14天EAM组肌成纤维细胞密度均小于对照组,各时间点EAM组、对照组分别为(201±39)个·mm-2、(291±48)个·mm-2,(248±84)个·mm-2、(349±105)个·mm-2,(108±57)个·mm-2、(175±62)个·mm-2,两组之间差异均有统计学意义(均为P<0.01)。结论新鲜EAM可以有效抑制碱烧伤后肌成纤维细胞的激活和增殖,减少角膜瘢痕的形成。

TGF-β在角膜瘢痕形成及无瘢痕愈合中的作用

转化生长因子β(transforming growth factor-β,TGF-β)是一种多功能的细胞因子。体外和多种动物模型中研究已证实在角膜TGF-β是主要参与角膜损伤后启动瘢痕化的重要生长因子。近年来针对TGF-β抗瘢痕化研究已取得一些进展。本文综述了TGF-β分子结构、生物学功能,角膜损伤修复中瘢痕形成过程中基质细胞在TGF-β调控下的变化及TGF-β治疗角膜瘢痕的进展。

真菌性角膜溃疡的综合治疗及临床转归

目的:探讨综合疗法治疗真菌性角膜溃疡的效果及临床转归。方法:在我院接受治疗的真菌性角膜溃疡患者共159例159眼,采取10项综合措施治疗,随访3mo以上,观察溃疡愈合情况及最终视力。结果:真菌性角膜溃疡平均住院时间12.11±5.13d,治愈148例148眼,治愈率93.1%,好转8例(5.0%),无效3例(1.9%)。最终视力≥0.3占56.0%(89/159)。最终视力≥0.1者占85.5%(136/159),在148例治愈患者中占91.9%(136/148)。结论:采取综合疗法治疗真菌性角膜溃疡有较高的治愈率,视力恢复良好。

117例穿透性角膜移植患者的病因分析

目的总结2002年12月～2004年4月在我院接受穿透性角膜移植手术患者的流行病学资料,并将其与国外类似报道比较。方法对相应的临床资料做回顾性分析。结果在上述时间内共进行117例穿透性角膜移植。其中男性82例,女性35例。平均年龄45.5±18.7岁(8～75岁)。角膜移植的病因按病例数由多至少依次为角膜炎后角膜白斑,计38例(33.48%),其中,尤以病毒性角膜炎为主。外伤后角膜疤痕及大泡性角膜病变占第二位,各17例(14.53%),随后为移植片排斥、真菌性角膜溃疡、圆锥角膜、角膜营养不良、以及原因不明的角膜白斑。圆锥角膜组的平均年龄为21.83±8.3岁(15～33岁),较平均年龄小(P<0.01)。而大泡性角膜病变组的平均年龄为60±16.65岁(25～84岁),较平均年龄大(P<0.01)。结论与发达国家不同,角膜炎后角膜白斑,外伤后角膜疤痕,大泡性角膜病变依次是角膜移植最常见的原因。

飞秒激光辅助穿透性角膜移植术的早期临床研究

目的:评价应用飞秒激光辅助穿透性角膜移植术(FSPKP)的早期疗效及安全性。方法:回顾性分析46例48眼FS-PKP术病例。术前最佳矫正视力为2.35±1.01(标准对数视力表),角膜病变累及全层,包括圆锥角膜、白斑、外伤性瘢痕等。采用飞秒激光制作不同直径和边缘形状的全层角膜植片与对应植床,进行角膜移植术,术后治疗与常规穿透性角膜移植术(传统PKP)相同。评价指标包括术前及术后1,6,10mo的裸眼视力(UCVA)、最佳矫正视力(BCVA)、角膜散光(CA)值、手术并发症。将同期完成的43例44眼传统PKP病例作为对照组。两组数据采用统计软件SPSS 18.0成组设计的两样本均数比较和χ2检验。结果:所有手术均顺利完成,术后视力均有不同程度的提高;在与传统PKP的比较中,两种术式的术后UCVA在术后1mo时分别是3.48±0.43和2.97±1.14,有显著的统计学差异(P=0.009);术后3mo时UCVA分别是3.86±0.25和3.74±0.73,术后6mo时分别是4.04±0.23和3.98±0.29,均无统计学差异(P=0.146,P=0.56);FSPKP组术后1mo BCVA优于传统PKP手术组,差异有显著统计学意义(P=0.002),而术后6,10mo,两组的BCVA比较无统计学差异(P6mo=0.132,P10mo=0.47);但在术后散光、高眼压、切口裂开等方面FS-PKP组的发生率明显低于传统PKP组,有统计学差异(P<0.05)。结论:与传统的穿透性角膜移植相比,飞秒激光辅助的穿透性角膜移植术后早期的视力恢复快,角膜散光值和并发症的发生率显著降低,体现了这一新技术的临床优越性。

飞秒激光辅助的大气泡法全板层角膜移植治疗圆锥角膜及角膜瘢痕临床疗效观察

目的观察飞秒激光辅助的大气泡全板层角膜移植术治疗圆锥角膜及角膜瘢痕临床效果。方法系列病例研究。20例(23只眼)患者(圆锥角膜22只眼,角膜瘢痕1只眼)采用飞秒激光辅助的大气泡法全板层角膜移植手术。供体及受体角膜均采用500-kHz VisuMax飞秒激光进行垂直边切,平均随访时间为(53.6±5.5)个月(47~61个月)。结果术中大气泡成功形成及后弹力层清晰暴露的成功率为91.3%(21/23)。术后裸眼视力、最佳矫正视力、角膜曲率、角膜散光及角膜厚度均有改善,与术前相比差异显著(P<0.05)。结论飞秒激光辅助的大气泡法全板层角膜移植对于圆锥角膜和角膜瘢痕患者具有良好的临床效果及安全性。

多层羊膜填塞治疗微小角膜溃疡穿孔

目的观察多层羊膜填塞治疗微小角膜溃疡穿孔的临床效果,了解其有效性、安全性和局限性。方法对12例12眼角膜溃疡继发微小穿孔(穿孔直径0.5～3.0 mm)患者采用多层羊膜填塞治疗。其中细菌性6例、病毒性2例、真菌性4例。清除溃疡处坏死组织,用多层羊膜填塞穿孔,其表层羊膜间断或连续缝合固定于浅层角膜上,单层羊膜再次覆盖于整个角膜表面,连续或间断缝合固定于角巩缘。术后继续使用药物治疗原发病。随访6～24个月。观察患眼溃疡愈合、前房形成、角膜厚度及并发症等。结果术后第1天,患眼前房均形成,穿孔区密闭良好,炎症控制。术后40～60 d,溃疡瘢痕愈合,溃疡表面完全被角膜上皮覆盖,角膜厚度基本正常,视力均有不同程度提高,随访期间前房稳定,未出现溃疡复发及严重并发症。结论羊膜填塞治疗微小角膜溃疡穿孔安全有效。但溃疡以瘢痕愈合。

20(R)-人参皂苷Rg3抗角膜瘢痕机制研究

目的:研究不同浓度的20(R)-人参皂苷Rg3(GRg3)对兔角膜成纤维细胞增殖和转化生长因子-β1(TGF-β1)表达的影响,探讨GRg3抑制角膜瘢痕增生的机制。方法:直接选用大白兔获取兔角膜成纤维细胞后进行原代培养,采用甲基噻唑基四唑(MTT)比色法观察不同浓度(10 mg·L^(-1),20 mg·L^(-1),50 mg·L^(-1),100 mg·L^(-1),150 mg·L^(-1),200 mg·L^(-1))GRg3对兔角膜成纤维细胞增殖作用的影响。应用反转录-PCR(RT-PCR)技术研究不同浓度GRg3对培养的兔角膜成纤维细胞TGF-β1m RNA表达的影响。结果:MTT法检测结果:与对照组比较,当GRg3浓度达到20 mg·L^(-1)及以上时,兔角膜成纤维细胞增殖均显著受抑制。当GRg 3浓度达到50 mg·L^(-1)及以上时,GRg3对兔角膜成纤维细胞TGF-β1 mRNA表达具有抑制作用。结论:GRg3具有抑制体外培养的兔角膜成纤维细胞增殖的作用,并随着GRg3浓度的增加,其抑制作用增强。随培养时间的延长,GRg3抑制作用增强。GRg3对兔角膜成纤维细胞TGF-β1mRNA表达具有抑制作用。

显微板层角膜移植术后形态学改变及对角膜透明度的影响

目的了解显微板层角膜移植术后的组织学改变及对角膜透明度的影响。方法利用光镜、电镜和分光光度计观察了显微板层角膜移植术后不同时间角膜基质的组织学变化、透光率和吸光度,对比观察了显微角膜切削刀和准分子激光切削的角膜剖面形态。结果准分子激光切削的角膜表面有许多变性胶原碎屑。显微角膜切开刀切削的角膜表面光滑,术后1个月,光镜下无明显的瘢痕,透射电镜仅见2～3个角膜板层厚度的界面瘢痕,其下3～4个板层内的角膜细胞有较多伪足,但无炎性细胞浸润。术后1,3个月角膜的透光率和吸光度与未手术角膜比较无显著性差异。结论显微板层角膜移植术后界面瘢痕轻微,不影响角膜透明度。

妊娠晚期子宫破裂的原因分析和预防

目的探讨妊娠晚期子宫破裂的原因,针对病因积极预防,减少母儿不良结局。方法回顾性分析6例妊娠晚期子宫破裂患者的临床资料,包括年龄、孕产次、孕周、既往手术史、临床表现及阳性体征、子宫破裂部位、破裂长度、确诊手段、子宫破裂类型、手术方式、出血量、是否输血、新生儿体重、新生儿Apgar评分、新生儿结局、孕妇结局。结果所有患者均有子宫既往手术史,其中3例有腹腔镜下宫角妊娠治疗史;1例因人工流产手术后行经腹子宫穿孔修补术;1例因既往剖宫产术中出血多行子宫捆绑手术;1例由于子宫肌瘤行子宫肌瘤消融术。6例子宫破裂均发生在孕晚期,5例有腹痛,2例有胎心缓慢,1例无明显临床症状。3例破裂部位在右侧宫角;1例在宫底完全破裂;1例在子宫宫体右侧壁处;另外1例是左侧宫角处。6例均行剖宫产+子宫破裂修补术,5例为子宫完全性破裂,1例为子宫不完全性破裂。其中4例未输血,2例输血。6例产妇经及时手术治疗,术后恢复好,顺利出院,产后42 d随访均无异常。6例胎儿均活产。结论子宫破裂是妊娠期的严重并发症,严重威胁母儿生命,对于存在明确相关病史,尤其子宫手术史,要提高警惕,以及有可疑子宫破裂的患者应加强监测,及早识别,及时挽救母儿生命安全。

外伤角膜瘢痕无晶状体眼戴角膜接触镜后的角膜地形图改变

目的探讨外伤性角膜瘢痕无晶状体限戴硬性透气性接触镜前、后角膜表面的改变。方法对戴该镜者17限及对照组（不戴镜）12眼，在戴镜前后进行角膜地形图检测。结果戴镜后平均8．4月，角膜散光减少（P＜0.01），角膜表面变得比较规则（P＜0．05），角膜表面的屈光度有变得相对比较平均的趋势。结论戴硬性透气性角膜接触镜能使角膜瘢痕所致角膜散光减少，角膜表面变得较为规则。

退翳眼膏治疗角膜瘢痕的临床研究

对角膜瘢痕患者随机分退翳眼膏组与消朦眼膏 组对照治疗 ,观察视力及角膜瘢痕变化 ,分别治疗 78例 90只眼和 74例 87只眼 ,治疗 3个疗程后 ,两种药物均有效 ,有效率分别为 90 .0 0 %和 78.10 % ,经卡方检验 ,χ2=4.6 6 ,P<0 .0 5 ,差异有显著性意义。

深板层角膜移植修复瘢痕期圆锥角膜

背景:深板层角膜移植治疗圆锥角膜可显著提高视力,且并发症少,排斥反应率低,但对于瘢痕期圆锥角膜仍以部分穿透性角膜移植为主。目的:评价深板层角膜移植治疗瘢痕期圆锥角膜的临床疗效。方法:58例Ⅲ期、Ⅳ期有角膜瘢痕患者分为角膜浅基质层有角膜瘢痕形成患者37例(浅瘢痕组),角膜深基质层或全层有角膜瘢痕形成患者21例(深瘢痕组)。58例患者行深板层角膜移植,移植后随访12个月,比较移植前后视力变化。结果与结论:所有患者角膜移植后裸眼视力与移植前比较均有明显提高。58只眼角膜植片均透明,其中1只眼角膜移植后2个月发生上皮型排斥反应,经药物治疗后恢复透明。深瘢痕组2例角膜移植后出现眩光,改做部分穿透性角膜移植。角膜移植后1年浅瘢痕组与深瘢痕组视力相比差异无显著性意义。提示深板层角膜移植治疗瘢痕期圆锥角膜可显著提高视力,且并发症少,排斥率低,是一种安全有效,长期疗效稳定的治疗方法,尤其对于大基底的圆锥角膜应作为首选方案。

转化生长因子-β促角膜基质瘢痕形成的分子机制

转化生长因子-β（TGF-β）对角膜基质瘢痕形成具有极其重要的生物学效应,而且是导致细胞外基质（ECM）异常沉积及胶原纤维结构异常的关键调控因子.TGF-β是一个由多种细胞分泌、具有多效性的细胞因子家族,必须激活才具备效应.TGF-β主要通过与相关受体结合后激活Smads信号通路才能发挥作用.TGF-β可刺激胶原及蛋白多糖的合成和分泌,引起ECM合成与降解失调.TGF-β通过上调结缔组织生长因子（CTGF）、下调硫酸角质素蛋白聚糖（KSPGs）及调节基质金属蛋白酶（MMPs）从而抑制ECM降解.近年来,TGF-β因其广泛的生物学作用而成为抗瘢痕形成的研究热点.就TGF-β的生物学特征、TGF-β受体（TGFF-βR）、Smads信号通路及TGF-β促角膜基质瘢痕的分子机制进行综述.

多西环素对角膜瘢痕形成的影响

目的:研究多西环素对角膜瘢痕形成的影响。方法:(1)体外实验:收集人眼角膜基质分离并培养,使用免疫荧光双染鉴定所提取到的细胞为人角膜细胞。多西环素组在传代培养后加入重组人转化生长因子-β1(TGF-β1)诱导人角膜细胞分化成角膜肌成纤维细胞,培养2 h后加入浓度为20 ng/mL的多西环素溶液,另设不加入任何药物的对照组和只加入TGF-β1的模型组,放入培养箱继续培养48 h。蛋白免疫印迹(Western blotting)检测CollagenⅠ和Fibronectin蛋白表达;实时荧光定量PCR(RT-qPCR)法检测CollagenⅠ和Fibronectin mRNA相对表达量。(2)体内实验:采用36只雌性SD大鼠构建角膜碱烧伤模型,随机分为对照组和多西环素组,每组18只。采用体视显微镜观察大鼠角膜恢复情况并在第3、第7、第14天进行角膜混浊度评分,角膜取材后做HE染色观察大鼠角膜组织结构变化。结果:模型组细胞Fibronectin、CollagenⅠmRNA和蛋白相对表达量均较对照组升高(均P<0.05),多西环素组细胞Fibronectin、CollagenⅠmRNA和蛋白相对表达量均较模型组降低(均P<0.05)。与对照组相比,大鼠角膜碱烧伤后第7、第14天,多西环素组大鼠角膜混浊度评分更低(P<0.05);HE染色图片,各个时间点多西环素组大鼠角膜基质结构更规整,第7天多西环素组上皮修复更佳、炎症细胞浸润更少。结论:多西环素可以抑制人角膜细胞分化为肌成纤维细胞,促进大鼠角膜碱烧伤后角膜愈合,减轻角膜瘢痕。