Purpose
Diagnosis of corneal graft rejection in animal models is currently based on subjective classification. The aim of this study was to correlate the degree of anterior chamber (AC) inflammation and corneal thickness evaluated by anterior segment optical tomography (ASOCT) with corneal graft rejection status using a rat penetrating keratoplasty (PK) model.
Methods
A total of 26 PK was performed using Fisher rats (allogeneic groups, n = 20) and Lewis rats (syngeneic group, n = 6) as donors and Lewis rats as recipients. All grafts were evaluated for 28 days by a scoring rejection index to assess graft opacity, edema and neovascularization using slit lamp biomicroscopy. ASOCT was performed every other day to assess the AC inflammation by quantifying the intensity of hyperreflective spots in AC and to measure the central corneal thickness. The AC inflammation was further graded from grade 0 to 3.
Results
Four of the 20 allogeneic grafts developed rejection episodes at an average of 21 ± 2.2 days. The rejected grafts had a significantly higher mean AC inflammation grade and thicker central graft thickness at 2 weeks, and had more severe AC inflammation (≥ grade 2) for a significantly longer period, as compared to the non-rejected grafts (2.05 ± 0.49 versus 0.83 ± 0.36, P <0.001; 455.25 ± 42.42 μm versus 381.47 ± 12.51 μm, P =0.047; 10.8 ± 1.0 versus 3.1 ± 1.9 days, P = 0.004, respectively; Figure 1). Eyes with ≥ grade 2 AC inflammation, or with graft thickness ≥ 400 μm at 2 weeks, were significantly associated with graft rejection (odds ratio [OR], 6.48, P = 0.002 and OR, 2.81, P = 0.006, respectively). The thickness measured by ASOCT was highly correlated with the clinical edema score (r = 0.789).
Conclusions
The use of ASOCT to evaluate AC inflammation and corneal thickness aids in the early evaluation of corneal grafts in animal models. Early increased AC inflammation was an early predictor of graft failure prior to definitive clinical evaluation.
Keywords: 551 imaging/image analysis: non-clinical