临床研究
ENGLISH ABSTRACT
自体血清点眼对神经营养性角膜病变持续角膜上皮缺损的疗效评估
王文莹
冯珺
邓世靖
李上
张阳
接英
作者及单位信息
·
DOI: 10.3760/cma.j.cn115989-20221213-00584
Evaluation of the therapeutic effect of autologous serum on neurotrophic keratopathy with persistent corneal epithelial defect
Wang Wenying
Feng Jun
Deng Shijing
Li Shang
Zhang Yang
Jie Ying
Authors Info & Affiliations
Wang Wenying
Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing 100730, China
Feng Jun
Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing 100730, China
Deng Shijing
Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing 100730, China
Li Shang
Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing 100730, China
Zhang Yang
Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing 100730, China
Jie Ying
Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing 100730, China
·
DOI: 10.3760/cma.j.cn115989-20221213-00584
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摘要

目的评估自制自体血清滴眼液对神经营养性角膜病变(NK)持续角膜上皮缺损的治疗效果。

方法采用系列病例观察研究方法,纳入2020年1月至2021年1月于首都医科大学附属北京同仁医院诊断为NK导致的持续性角膜上皮缺损患者20例20眼,按照病变严重程度将患眼分级,采用自制自体血清滴眼液为主的综合治疗,记录角膜上皮愈合时间。采用角膜荧光素染色法标记缺损的直径和面积,10倍裂隙灯显微镜下测量治疗前及治疗后1、2、3、4、8周角膜缺损直径和面积变化;采用标准对数视力表测定患眼治疗前及治疗后1、2、4、12和24周LogMAR视力改变;采用激光扫描共聚焦显微镜和Cochet-Bonnet角膜知觉计分别检查患眼治疗前及治疗后4、12、24周角膜神经纤维分布变化及角膜知觉丝线长度。采用多重线性回归分析评估基线角膜缺损特征对上皮愈合时间的影响。

结果治疗前角膜缺损范围直径为5.00(4.00,5.75)mm,缺损面积为15.50(12.00,20.00)mm 2。伴角膜基质水肿者占45%(9/20),伴内皮皱褶者占35%(7/20)。除1例糖尿病伴葡萄膜炎患者治疗前角膜溃疡面积较大(8 mm×6 mm),自体血清滴眼液治疗2周效果不明显,联合角膜清创+羊膜移植手术覆盖缺损之后继续用自体血清滴眼液治疗外,其余19例均以自体血清滴眼液治疗为主,20例患者全部治愈。自体血清滴眼液治疗前时程为2周~3个月,平均(39.55±25.34)d。角膜上皮修复时间为12~42 d,平均(19.68±9.25)d。自体血清滴眼液使用前后各时间点角膜缺损面积和直径总体比较差异均有统计学意义( χ 2=43.130、28.265,均 P<0.001),其中治疗后不同时间点角膜上皮缺损面积和直径均小于治疗前,差异均有统计学意义(均 P<0.05)。自体血清点眼前后不同时间点LogMAR视力总体比较差异有统计学意义( χ 2=84.229, P<0.001),其中自体血清点眼1、2、4、12和24周患眼LogMAR视力均优于治疗前,差异均有统计学意义(均 P<0.05)。自体血清滴眼液使用前后各时间点角膜知觉丝线长度总体比较差异有统计学意义( χ 2=55.295, P<0.001),其中自体血清点眼4、12和24周角膜知觉丝线长度均长于治疗前,差异均有统计学意义(均 P<0.05)。治疗前角膜缺损严重程度分级对愈合时间的影响有统计学意义( β=10.55, P=0.032),角膜缺损直径和角膜缺损面积对愈合时间的影响均无统计学意义( β=-2.02, P=0.501; β=0.49, P=0.199)。

结论以自体血清滴眼液为主的治疗对NK导致的顽固角膜缺损安全有效。停止血清治疗后个别患者角膜缺损复发,再次使用后仍有效。疑难病例可联合手术治疗。

神经营养性角膜病变;持续性角膜上皮缺损;自体血清;角膜知觉
ABSTRACT

ObjectiveTo evaluate the outcomes of autologous serum eye drops on persistent corneal epithelial defect caused by neurotrophic keratopathy (NK).

MethodsAn observational case series study was performed.Twenty patients (20 eyes) diagnosed with NK and persistent corneal epithelial defect were enrolled in Beijing Tongren Hospital from January 2020 to January 2021.The affected eyes were graded according to the severity of the lesion and received individualized comprehensive treatment with domestic autologous serum eye drops as the main therapy.The healing time of the corneal epithelial defect after treatment was recorded.The diameter and area of the defect were marked by corneal fluorescein staining.Changes in the diameter and area of the defect before treatment and at 1, 2, 3, 4 and 8 weeks after treatment were observed by slit lamp microscopy at 10×.Logarithm of the minimum angle of resolution (LogMAR) visual acuity was recorded with a standard logarithmic visual chart before treatment and at 1, 2, 4, 12, and 24 weeks after treatment.Changes in corneal nerve fiber distribution and silk length of corneal perception were assessed by confocal laser scanning microscopy and Cochet-Bonnet esthesiometry, respectively, before treatment and at 4, 12, and 24 weeks after treatment.Influences of corneal defect characteristics on the healing time were analyzed by multiple linear regression analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital Affiliated to Capital Medical University (No.TRECKY2021-110). Written informed consent was obtained from each subject.

ResultsThe corneal epithelial defect was 5.00 (4.00, 5.75) mm in diameter and 15.50 (12.00, 20.00) mm 2 in area before treatment.There were 45% (9/20) with corneal stroma edema and 35% (7/20) with endothelial fold.One diabetic patient with uveitis had a corneal epithelial defect area greater than 8 mm×6 mm and accepted additional corneal clearance and amniotic membrane transplantation after 2 weeks of autologous serum eye drops application.The other 19 patients received autologous serum eye drops therapy.All eyes showed complete recovery.The pretreatment duration of autologous serum eye drops ranged from 2 weeks to 3 months, with a mean of (39.55±25.34) days.The repair time of corneal epithelium ranged from 12 to 42 days, with a mean of (19.68±9.25) days.There were statistically significant differences in corneal defect diameter and area between before and after treatment ( χ 2=43.130, 28.265; both at P<0.001). Corneal defect area and diameter decreased at various time points after treatment compared to before treatment, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in LogMAR visual acuity between before and after treatment ( χ 2=84.229, P<0.001). LogMAR visual acuity improved at 1, 2, 4, 12, and 24 weeks after treatment compared to pretreatment, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in silk length of corneal perception between before and after treatment ( χ 2=55.295, P<0.001). Silk length of corneal perception improved at 4, 12 and 24 weeks compared to pretreatment, and the differences were statistically significant (all at P<0.05). Baseline corneal defect severity grade was positively correlated with healing time ( β=10.55, P=0.032). Corneal defect diameter and area had no influence on the healing time ( β=-2.02, P=0.501; β=0.49, P=0.199).

ConclusionsAutologous serum eye drop therapy is safe and effective for persistent corneal defects caused by NK.Re-application of autologous serum eye drops is still effective in individual patients with recurrent corneal defects after discontinuation of serum treatment.It can be combined with surgery for intractable cases.

Neurotrophic keratopathy;Persistent corneal epithelial defect;Autologous serum;Corneal sensation
Jie Ying, Email: mocdef.nabuyilancgniy_eij
引用本文

王文莹,冯珺,邓世靖,等. 自体血清点眼对神经营养性角膜病变持续角膜上皮缺损的疗效评估[J]. 中华实验眼科杂志,2024,42(02):143-151.

DOI:10.3760/cma.j.cn115989-20221213-00584

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神经营养性角膜病变(neurotrophic keratopathy,NK)以角膜敏感性下降和角膜愈合不良为主要特点,患眼泪液分泌减少,角膜对各种刺激更为敏感。早期NK类似泪膜破裂时间缩短型干眼 [ 1 ],表现为表层点状角膜炎(Ⅰ期)。随病情进展,角膜上皮损害程度加重,角膜上皮屏障功能障碍,出现持续性角膜上皮缺损(persistent corneal epithelial defect,PED),伴光滑、卷曲、混浊的边缘,角膜基质受累时出现角膜水肿、条纹和Descemet膜皱褶(Ⅱ期)。暴露的角膜基质易受蛋白酶分解而引起角膜溃疡或组织溶解,导致角膜穿孔(Ⅲ期)。依据疾病分期的不同,NK的治疗包括药物疗法和手术疗法,Ⅰ期给予人工泪液、眼皮贴、泪点栓等治疗;Ⅱ期采用角膜接触镜佩戴、自体血清点眼、肉毒素上睑板上缘或提上睑肌肌腹注射、眼睑缝合治疗,必要时联合抗生素治疗;Ⅲ期采用重组人神经生长因子(nerve growth factor,NGF)滴眼液点眼、羊膜移植术、结膜瓣覆盖术、角膜移植术或神经移植术等方法治疗 [ 1 ]。NK辅助治疗包括充分的眼表组织润滑和减少角膜暴露以及其他药物和手术疗法。临床试验已证实,0.002%赛奈吉明滴眼液(意大利Milan公司)对NK治疗有效 [ 2 , 3 ],但因其价格昂贵、增加角膜敏感性以及停药后角膜瘢痕形成等限制了其在临床上的广泛应用 [ 4 , 5 ]。板层或全层角膜移植术或睑缘缝合术适用于有角膜溶解趋势、累及组织较深的角膜溃疡,但手术本身的风险以及角膜移植术后神经营养的缺乏易导致植片溶解和排斥反应 [ 6 ]。研究发现,角膜神经再生手术操作复杂,且与对侧正常眼比较,术后1年患眼角膜神经功能的修复仍不完全 [ 7 ],该治疗方法患者不易接受。此外,P物质、胸腺素β4等新的NK治疗药物尚处于实验研究阶段 [ 1 ]。自体血清与泪液的渗透压、pH值和营养成分相同,含有生长因子、蛋白酶抑制剂和维生素,有利于受损角膜上皮的修复和生长,且其中的胰岛素生长因子与P物质可协同促进角膜上皮的生长和移行,用于Ⅱ期(PED期)NK的治疗可以避免NK向Ⅲ期进展 [ 8 ],然而迄至目前相关的系统疗效和安全性研究结果仍少见。本研究拟评估自制自体血清对NK导致的顽固性角膜上皮持续缺损的疗效和安全性,为临床上相关疾病的治疗选择提供参考依据。
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接英,Email: mocdef.nabuyilancgniy_eij
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王文莹:参与选题、采集数据、分析/解释数据、起草及修改文章;冯珺:设计试验、分析/解释数据;邓世靖:数据采集、共聚焦图像分析;李上:采集数据;张阳:图像采集;接英:酝酿/设计试验、对文章知识性内容作批评性审阅及智力性修改、文章定稿

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