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Rafael Grytz, Ian A. Sigal, Jeffrey W. Ruberti, J. Crawford Downs; Lamina Cribrosa Thickening In Early Glaucoma Is Predicted by a Biomechanically-Driven Growth and Remodeling Approach. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4810.
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© ARVO (1962-2015); The Authors (2016-present)
Recent evidence suggests that the lamina cribrosa (LC) remodels into a thicker, more posterior structure that incorporates more connective tissue during the earliest stages of experimental glaucoma. We present a numerical growth and remodeling (G&R) formulation based on collagen fibril strain to explore a potential multi-scale mechanism of these structural changes.
We hypothesize that the mechanical strain experienced by the collagen fibrils and cells in the LC stimulates the G&R response at elevated IOP. The G&R algorithm controls collagen fibril synthesis/degradation and adapts the residual strains between collagen fibrils and the surrounding tissue to achieve biomechanical homeostasis. The G&R algorithm was applied to a generic finite element model of the human optic nerve head with uniform initial collagen content throughout the tissues within the neural canal, and allowed to achieve homeostasis at normal (15 mmHg) and elevated IOPs (25 mmHg).
At normal IOP, the G&R algorithm created a LC-like structure that spanned the scleral canal. At elevated IOP, the simulation remodeled the LC as follows to maintain the hypothesized homeostatic state: (i) 38% increase in collagen fibrils; (ii) up to 2% increase in local residual strain; (iii) 20% increase in LC volume; (iv) 40% increase in LC thickness; (v) inward migration of the anterior LC surface and (vi) outward migration of the posterior LC surface that resulted in further insertion of the LC into the pia mater.
The G&R algorithm confirmed the biomechanical necessity of a LC at normal IOP. The numerical results suggest that IOP elevation leads to LC thickening due to an increase in collagen fibril mass, which is in good agreement with experimental observations in early glaucoma monkey eyes. This is the first study to demonstrate that a biomechanically-driven G&R mechanism can lead to the LC thickening and migration seen in early glaucoma.
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