A common experimental technique for viewing in vivo angiogenesis utilises tumours implanted into a test animal cornea. The cornea is avascular but the tumour promotes vascularisation from the limbus and the new blood vessels can be readily observed through the transparent cornea. Many of the early mathematical models for tumour angiogenesis used this scenario as their experimental template and as such assumed that there is a large gap, of the order of 2 mm, between the tumour and neighbouring vasculature at the onset of angiogenesis. In this work we consider whether the assumption that there is a significant gap between the tumour and neighbouring vasculature is unique to intra-cornea tumour implants, or whether this characterises avascular tumour growth more generally. To do this we utilise a simple scaling argument, derive a multi-compartment model for tumour growth, and consider in vivo images. This analysis demonstrates that the corneal implant experiments and the corresponding mathematical models cannot be applied to a clinical setting.

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Assessment of ocular irritation potential is an international regulatory requirement in the safety evaluation of industrial and consumer products. None in vitro ocular irritation assays are capable of fully categorizing chemicals as stand-alone. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI consortium assessed the reliability of eight in vitro test methods and computational models as well as established a tiered-testing strategy. One of the selected assays was Bovine Corneal Opacity and Permeability (BCOP). In this project, the same corneas were used for measurement of opacity using the OP-KIT, the Laser Light-Based Opacitometer (LLBO) and for histopathological analysis. The results show that the accuracy of the BCOP OP-KIT in identifying Cat 1 chemicals was 73.8% while the accuracy was 86.3% for No Cat chemicals. BCOP OP-KIT false negative results were often related to an in vivo classification driven by conjunctival effects only. For the BCOP LLBO, the accuracy in identifying Cat 1 chemicals was 74.4% versus 88.8% for No Cat chemicals. The BCOP LLBO seems very promising for the identification of No Cat liquids but less so for the identification of solids. Histopathology as an additional endpoint to the BCOP test method does not reduce the false negative rate substantially for in vivo Cat 1 chemicals.

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