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Research Papers

Effects of Age and Diabetes on Scleral Stiffness

[+] Author and Article Information
Baptiste Coudrillier

Department of Biomedical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332
e-mail: baptiste.coudrillier@bme.gatech.edu

Jacek Pijanka, Craig Boote

Structural Biophysics Group,
School of Optometry and Vision Sciences,
Cardiff University,
Cardiff CF24 4HQ, Wales, UK

Joan Jefferys, Harry A. Quigley

Glaucoma Center of Excellence,
Wilmer Ophthalmological Institute,
Johns Hopkins University School of Medicine,
Baltimore, MD 21287

Thomas Sorensen

Diamond Light Source,
Didcot,
Oxfordshire OX11 0DE, UK

Thao D. Nguyen

Department of Mechanical Engineering,
Johns Hopkins University,
Baltimore, MD 21218
e-mail: vicky.nguyen@jhu.edu

Manuscript received November 16, 2014; final manuscript received February 24, 2015; published online June 2, 2015. Assoc. Editor: Pasquale Vena.

J Biomech Eng 137(7), 071007 (Jul 01, 2015) (10 pages) Paper No: BIO-14-1565; doi: 10.1115/1.4029986 History: Received November 16, 2014; Revised February 24, 2015; Online June 02, 2015

The effects of diabetes on the collagen structure and material properties of the sclera are unknown but may be important to elucidate whether diabetes is a risk factor for major ocular diseases such as glaucoma. This study provides a quantitative assessment of the changes in scleral stiffness and collagen fiber alignment associated with diabetes. Posterior scleral shells from five diabetic donors and seven non-diabetic donors were pressurized to 30 mm Hg. Three-dimensional surface displacements were calculated during inflation testing using digital image correlation (DIC). After testing, each specimen was subjected to wide-angle X-ray scattering (WAXS) measurements of its collagen organization. Specimen-specific finite element models of the posterior scleras were generated from the experimentally measured geometry. An inverse finite element analysis was developed to determine the material properties of the specimens, i.e., matrix and fiber stiffness, by matching DIC-measured and finite element predicted displacement fields. Effects of age and diabetes on the degree of fiber alignment, matrix and collagen fiber stiffness, and mechanical anisotropy were estimated using mixed effects models accounting for spatial autocorrelation. Older age was associated with a lower degree of fiber alignment and larger matrix stiffness for both diabetic and non-diabetic scleras. However, the age-related increase in matrix stiffness was 87% larger in diabetic specimens compared to non-diabetic controls and diabetic scleras had a significantly larger matrix stiffness (p = 0.01). Older age was associated with a nearly significant increase in collagen fiber stiffness for diabetic specimens only (p = 0.06), as well as a decrease in mechanical anisotropy for non-diabetic scleras only (p = 0.04). The interaction between age and diabetes was not significant for all outcomes. This study suggests that the age-related increase in scleral stiffness is accelerated in eyes with diabetes, which may have important implications in glaucoma.

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Figures

Grahic Jump Location
Fig. 1

Schematic of the experimental apparatus used for the inflation test of the human sclera. The specimens were glued on a holder and placed on a pressure chamber. The pressure in the chamber was measured with a pressure transducer and changed by controlled-injection of PBS. During testing, the deforming scleral surface was imaged by two charge-coupled device cameras positioned 50cm above the specimen and oriented 15deg from the vertical axis on opposite sides. The white scleral surface was speckled by dispersing graphite powder through a 62 μm mesh to provide a high contrast pattern for DIC.

Grahic Jump Location
Fig. 2

(a) Angular intensity profile for a single WAXS measurement located in the peripapillary sclera. The degree of fiber alignment, which was defined as the ratio of the aligned scatter to the total scatter, was calculated for each WAXS measurement and is mapped in (b) for FC74l. Scatter intensity plots from (a) can be represented as polar plots indicating the local preferred orientation (shape of the plot) and the degree of fiber alignment and assembled into polar plots as shown in (c).

Grahic Jump Location
Fig. 3

(a) Camera view of the specimen-specific mesh used for the inverse method for the specimen FC74l. The preferred fiber direction is represented for each element. (b) Side view showing the thickness variation close to the ONH. The thickness profile was created by linearly interpolating the 16 pachymeter measurements, made at two meridional positions and eight circumferential positions. The midposterior sclera was constructed from the DIC-measured position of the surface and the thickness data. DIC-displacements were applied at the edges of the mesh as kinematic boundary conditions. The boarder between the specimen-specific region and the generic region is marked with a circle in (a) and a vertical dashed line in (b).

Grahic Jump Location
Fig. 4

We modeled a biaxial stretch tension on finite element (b), which fiber structure was described using a single WAXS measurement (a). We used specimen-specific material properties and applied averaged circumferential and meridional strains measured in 35 specimens [] as boundary conditions. A representative stretch/stress curve is represented in (c). We repeated this simulation for every WAXS measurement to map the mechanical anisotropy across the posterior sclera as shown in (d).

Grahic Jump Location
Fig. 5

Degree of fiber alignment averaged over the entire peripapillary sclera for all specimens. Age was associated with a significant decrease in mean degree of fiber alignment for non-diabetic donors. Regression lines represent the age-related variation in degree of fiber alignment within the diabetic and non-diabetic groups.

Grahic Jump Location
Fig. 6

(a) Matrix shear modulus μ, (b) fiber stiffness 4αβ plotted versus age for diabetic and non-diabetic donors. Regression lines represent the age-related variation in stiffness within the diabetic and non-diabetic groups.

Grahic Jump Location
Fig. 7

Average mechanical anisotropy in the peripapillary sclera plotted versus age for the diabetic and non-diabetic specimens. Regression lines represent the age-related variation in mechanical anisotropy within the diabetic and non-diabetic groups.

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