The cornea demonstrates considerable stiffening with age with the behavior closely fitting an exponential power function typical of collagenous tissue. The increase in stiffness could be related to the additional age-related nonenzymatic cross-linking affecting the stromal collagen fibrils.

The purpose of this study was to determine the true intraocular pressure and modulus of elasticity of the human cornea in vivo. The cornea was modeled as a shell, and the equations for the deformations of a shell due to applanating and intraocular pressures were combined to model the behavior of the cornea during applanation tonometry. At certain corneal dimensions called the calibration dimensions, the applanating and intraocular pressures are considered to be equal. This relationship was used to determine the modulus of elasticity of the cornea and the relationship between the applanating and intraocular pressures. The true intraocular pressure (IOPT) was found to be related to Goldmann's applanating pressure (IOPG) as IOPT = IOPG/K, where K is a correction factor. For the calibration corneal thickness of 0.52 mm, the modulus of elasticity E in MPa of the human cornea was found to be related to the true intraocular pressure IOPT in mmHg as E = 0.02291OPT. The generalization of the Imbert-Fick law that takes into account the effect of corneal dimensions and stiffness was found to be given by IOPT = 73.5W/(K A), where W is the applanating weight in gf (gram force) and A is the applanated area in mm2. The calculated true intraocular pressure and modulus of elasticity were found to agree with published experimental results. The mathematical model developed may therefore be used to improve results from applanation tonometry and to estimate the mechanical property of the cornea in vivo.

ABSTRACT.Purpose: To investigate the expression of proteases, proteolytic activity and cytokines in the tear film of people with keratoconus. Methods: Basal tears from people with keratoconus, from individuals who had undergone corneal collagen cross-linking for the treatment of keratoconus, and from normal controls were collected using a capillary tube. Corneal curvature of each subject was mapped. The total protein in tears was estimated. Levels and activity of proteases in the tears were analysed using specific antibody arrays and activity assays. Results: The total tear protein level was significantly reduced in keratoconus (4.1 ± 0.9 mg ⁄ ml) compared with normals (6.7 ± 1.4 mg ⁄ ml) (p < 0.0001) or subjects who had undergone corneal collagen cross-linking (5.7 ± 2.3 mg ⁄ ml) (p < 0.005). Significantly (p < 0.05) increased tear expression of matrix metalloproteinases (MMP) -1, -3, -7, -13, interleukins (IL) -4, -5, -6, -8 and tumour necrosis factor (TNF) -a, -b were evident in keratoconus. Tear IL-6 was the only cytokine significantly (p < 0.05) increased in tears of keratoconus subjects compared with the collagen cross-linked group. No significant difference in tear proteases were observed between the normal and the cross-linked groups, although the expression of TNF-a was significantly (p < 0.05) increased in the cross-linked group compared with the controls. Elevated gelatinolytic (87.5 ± 33.6 versus 45.8 ± 24.6 FIU, p < 0.0001) and collagenolytic (6.1 ± 3.2 versus 3.6 ± 2.0 FIU, p < 0.05) activities were observed in tears from keratoconus compared with normal subjects. The activity of tear gelatinases (69.6 ± 22.2 FIU) and collagenases (5.7 ± 3.3 FIU) in the collagen cross-linked group was not significantly different compared with either keratoconus or normals. Conclusion: Tears of people with keratoconus had 1.9 times higher levels of proteolytic activity and over expression of several MMPs and cytokines compared with tears from controls. Further investigations are required to study the possible implications of these changes and whether they can be used to monitor disease progression or determine the success of corneal collagen cross-linking.

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Background: Proteases, protease activity and inflammatory molecules in tears have been found to be relevant in the pathogenesis of keratoconus. We sought to determine the influence of eye rubbing on protease expression, protease activity and concentration of inflammatory molecules in tears. Methods: Basal tears were collected from normal volunteers before and after 60 seconds of experimental eye rubbing. The total amount of matrix metalloproteinase (MMP)-13 and inflammatory molecules interleukin (IL)-6 and tumour necrosis factor (TNF)-a in the tear samples were measured using specific enzyme-linked immunosorbent assays (ELISA). Tear collagenase activity was investigated using a specific activity assay. Results: The concentrations of MMP-13 (51.9 Ϯ 34.3 versus 63 Ϯ 36.8 pg/ml, p = 0.006), IL-6 (1.24 Ϯ 0.98 versus 2.02 Ϯ 1.52 pg/ml, p = 0.004) and TNF-a (1.16 Ϯ 0.74 versus 1.44 Ϯ 0.66 pg/ml, p = 0.003) were significantly increased in normal subjects after eye rubbing. The experimental eye rub did not alter significantly the collagenase activity (5.02 Ϯ 3 versus 7.50 Ϯ 3.90 fluorescent intensity units, p = 0.14) of tears. Conclusion: Eye rubbing for 60 seconds increased the level of tear MMP-13, IL-6 and TNF-a in normal study subjects. This increase in protease, protease activity and inflammatory mediators in tears after eye rubbing may be exacerbated even further during persistent and forceful eye rubbing seen in people with keratoconus and this in turn may contribute to the progression of the disease.