Progression of Diabetic Capillary Occlusion: A Model.

An explanatory computational model is developed of the contiguous areas of retinal capillary loss which play a large role in diabetic maculapathy and diabetic retinal neovascularization. Strictly random leukocyte mediated capillary occlusion cannot explain the occurrence of large contiguous areas of retinal ischemia. Therefore occlusion of an individual capillary must increase the probability of occlusion of surrounding capillaries. A retinal perifoveal vascular sector as well as a peripheral retinal capillary network and a deleted hexagonal capillary network are modelled using Compucell3D. The perifoveal modelling produces a pattern of spreading capillary loss with associated macular edema. In the peripheral network, spreading ischemia results from the progressive loss of the ladder capillaries which connect peripheral arterioles and venules. System blood flow was elevated in the macular model before a later reduction in flow in cases with progression of capillary occlusions. Simulations differing only in initial vascular network structures but with identical dynamics for oxygen, growth factors and vascular occlusions, replicate key clinical observations of ischemia and macular edema in the posterior pole and ischemia in the retinal periphery. The simulation results also seem consistent with quantitative data on macular blood flow and qualitative data on venous oxygenation. One computational model applied to distinct capillary networks in different retinal regions yielded results comparable to clinical observations in those regions.

A Computational Model of Peripheral Photocoagulation for the Prevention of Progressive Diabetic Capillary Occlusion.

We developed a computational model of the propagation of retinal ischemia in diabetic retinopathy and analyzed the consequences of various patterns and sizes of burns in peripheral retinal photocoagulation. The model addresses retinal ischemia as a phenomenon of adverse local feedback in which once a capillary is occluded there is an elevated probability of occlusion of adjacent capillaries resulting in enlarging areas of retinal ischemia as is commonly seen clinically. Retinal burns of different sizes and patterns, treated as local oxygen sources, are predicted to have different effects on the propagation of retinal ischemia. The patterns of retinal burns are optimized with regard to minimization of the sum of the photocoagulated retina and computer predicted ischemic retina. Our simulations show that certain patterns of retinal burns are effective at preventing the spatial spread of ischemia by creating oxygenated boundaries across which the ischemia does not propagate. This model makes no statement about current PRP treatment of avascular peripheral retina and notes that the usual spot sizes used in PRP will not prevent ischemic propagation in still vascularized retinal areas. The model seems to show that a properly patterned laser treatment of still vascularized peripheral retina may be able to prevent or at least constrain the propagation of diabetic retinal ischemia in those retinal areas with intact capillaries.