Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study
3D plot of the regression-inferred CNV initiation probability (Pinit) vs. three key adhesion strengths using ten simulation replicas for each adhesion scenario in the 3D parameter space obtained by setting RRp = RRl and RBp = RBl. Red corresponds to Pinit = 1 and purple to Pinit = 0. The black region at the top-front corner indicates the locus of normal adhesion. The three isosurfaces of CNV initiation probability correspond to Pinit = 0.25 (front), 0.5 (middle) and 0.75 (back). The five adhesion parameters and their (multi)linear combinations account for 88% of the observed variance in CNV initiation probability (adjusted R2 = 0.83). Regression predicts a minimum CNV initiation probability of 0.08 for normal adhesion, much higher than observed in either our simulations or experiments. For normal RPE-POS labile adhesion, moderate impairment of either RPE-RPE (RRp = RRl) or RPE-BrM (RBp = RBl) junctional adhesion increases the CNV initiation probability to ∼50%. Severe impairment of RPE-POS increases the CNV initiation probability to ∼50% even when both RPE-RPE and RPE-BrM are normal.