Ocular Surface Imaging Center, Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Center for Translational Ocular Immunology, and Cornea Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Am J Ophthalmol. 2019 Jul;203:26-36. doi: 10.1016/j.ajo.2019.02.013. Epub 2019 Feb 18.
Diagnosis of graft rejection is based on patient symptoms and on clinical signs detected by slit-lamp biomicroscopy. This study investigated whether laser in vivo confocal microscopy (IVCM) can aid in the diagnosis of corneal graft rejection by detecting cellular corneal changes that take place after transplantation.
Prospective case-control study.
Thirty-eight eyes of 38 patients with penetrating keratoplasty (15 eyes with corneal graft rejection, 23 eyes without rejection) and 9 age-matched normal controls.
Laser IVCM was performed in the corneal grafts centrally. The density of immune cells (IC) was assessed for epithelial, sub-epithelial, stromal, and endothelial layers by 2 masked observers. IC density was compared among different groups and correlated to clinical signs and symptoms of corneal graft rejection.
Outcome measurement was the IC density in the corneal layers and its associations with the presence of clinical signs and symptoms of corneal graft rejection.
The IC density was significantly different between rejected and non-rejected grafts (P = 0.004) and different from that of normal controls (P = 0.001). Among corneal layers, IC density was significantly higher in rejected grafts than in non-rejected grafts in only the sub-basal (611.54 ± 573.74 vs. 340.61 ± 268.60 cells/mm, respectively; P = 0.049) and endothelial layers (250.62 ± 267.13 vs. 103.47 ± 81.91 cells/mm, respectively; P = 0.001). Patients with decreased best corrected visual acuity, Khodadoust line, and anterior chamber cells demonstrated a significant increase in total IC density (P < 0.05), whereas patients with symptoms of irritation, light sensitivity, and pain revealed a specific increase in IC density in the sub-basal layer (P < 0.05). Patients with ocular pain had higher IC density in the epithelial layer than those without pain (P = 0.03).
Patients with corneal graft rejection demonstrate a significant increase in corneal immune cells, particularly, in the sub-basal and endothelial layers compared to patients with non-rejected grafts and controls. Although symptoms associated with endothelial rejection demonstrate a general increase in IC, pain, irritation, and light sensitivity are associated with increased IC in the sub-basal layer. Assessment of patients with corneal graft rejection by IVCM may serve as an adjunctive tool in the diagnosis and management of corneal graft rejection.
移植物排斥反应的诊断基于患者症状和裂隙灯生物显微镜检测到的临床体征。本研究通过检测移植后发生的细胞性角膜变化，探讨激光共聚焦显微镜（IVCM）是否有助于诊断角膜移植排斥反应。
前瞻性病例对照研究。
38 只眼（38 例）穿透性角膜移植患者（15 只眼发生角膜移植排斥反应，23 只眼无排斥反应）和 9 名年龄匹配的正常对照者。
对角膜移植中央进行激光 IVCM。两名盲法观察者评估上皮、上皮下、基质和内皮层的免疫细胞（IC）密度。比较不同组之间的 IC 密度，并与角膜移植排斥反应的临床体征和症状相关联。
观察指标为角膜各层的 IC 密度及其与角膜移植排斥反应的临床体征和症状的关系。
排斥反应组和非排斥反应组的 IC 密度差异有统计学意义（P = 0.004），与正常对照组也有差异（P = 0.001）。在角膜各层中，仅在基底下（611.54 ± 573.74 与 340.61 ± 268.60 个细胞/mm，P = 0.049）和内皮层（250.62 ± 267.13 与 103.47 ± 81.91 个细胞/mm，P = 0.001）中，排斥反应组的 IC 密度明显高于非排斥反应组。最佳矫正视力下降、Khodadoust 线和前房细胞减少的患者总 IC 密度显著增加（P < 0.05），而有刺激、畏光和疼痛症状的患者基底下 IC 密度增加具有特异性（P < 0.05）。有眼部疼痛的患者上皮层的 IC 密度高于无疼痛的患者（P = 0.03）。
与非排斥反应移植和对照组相比，角膜移植排斥反应患者的角膜免疫细胞显著增加，尤其是基底下和内皮层。尽管与内皮排斥反应相关的症状显示 IC 普遍增加，但疼痛、刺激和畏光与基底下层 IC 增加相关。通过 IVCM 评估角膜移植排斥反应患者可能成为诊断和管理角膜移植排斥反应的辅助工具。
