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。
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.
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版权归中华医学会所有。
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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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