@article {1424799,
	title = {In Vivo Confocal Microscopy Demonstrates Increased Immune Cell Densities in Corneal Graft Rejection Correlating With Signs and Symptoms},
	journal = {Am J Ophthalmol},
	volume = {203},
	year = {2019},
	month = {2019 Jul},
	pages = {26-36},
	abstract = {PURPOSE: Diagnosis of graft rejection is based on patient symptoms and on clinical signs detected by slit-lamp biomicroscopy. This study investigated whether laser in\&nbsp;vivo confocal microscopy (IVCM) can aid in the diagnosis of corneal graft rejection by detecting cellular corneal changes that take place after transplantation. DESIGN: Prospective case-control study. SUBJECTS: 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. METHODS: 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. MAIN OUTCOME MEASUREMENTS: 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. RESULTS: The IC density was significantly different between rejected and non-rejected grafts (P\&nbsp;= 0.004) and different from that of normal controls (P\&nbsp;= 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 {\textpm} 573.74 vs. 340.61 {\textpm} 268.60 cells/mm, respectively; P\&nbsp;= 0.049) and endothelial layers (250.62 {\textpm} 267.13 vs. 103.47 {\textpm} 81.91 cells/mm, respectively; P\&nbsp;= 0.001). Patients with decreased best corrected visual acuity, Khodadoust line, and anterior chamber cells demonstrated a significant increase in total IC density (P \&lt; 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 \&lt; 0.05). Patients with ocular pain had higher IC density in the epithelial layer than those without pain (P\&nbsp;= 0.03). CONCLUSIONS: 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.},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2019.02.013},
	author = {Chirapapaisan, Chareenun and Abbouda, Alessandro and Jamali, Arsia and M{\"u}ller, Rodrigo T and Cavalcanti, Bernardo M and Colon, Clara and Witkin, Deborah and Sahin, Afsun and Dana, Reza and Cruzat, Andrea and Hamrah, Pedram}
}
