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. 2009 Aug;127(8):1029-35.
doi: 10.1001/archophthalmol.2009.184.

Histopathologic and immunohistochemical studies of keratoglobus

Beeran Meghpara  1 , Hiroshi Nakamura, Geeta K Vemuganti, Somasheila I Murthy, Joel Sugar, Beatrice Y J T Yue, Deepak P Edward
Affiliations

Histopathologic and immunohistochemical studies of keratoglobus

Beeran Meghpara et al. Arch Ophthalmol. 2009 Aug.

Abstract

Objective: To examine histopathologic and immunohistochemical features of human corneal buttons from patients who developed keratoglobus.

Methods: Nine corneal buttons were obtained during penetrating keratoplasty from patients with keratoglobus. Histologic features were examined using hematoxylin-eosin-stained sections. Immunohistochemical staining for alpha1-proteinase inhibitor, Sp1, and matrix metalloproteinases 1, 2, and 3 was performed, with 2 normal and 2 corneal sections with keratoconus as controls.

Results: Hematoxylin-eosin staining revealed diffuse stromal thinning and focal disruptions in Bowman's layer in all keratoglobus specimens. Similar abnormal immunostaining results for alpha1-proteinase inhibitor and Sp1 were detected in keratoglobus and keratoconus at their respective active disease sites. Immunostaining for matrix metalloproteinases 1, 2, and 3 was significantly more intense in corneas with keratoglobus than in normal controls. Matrix metalloproteinase staining intensity was especially prominent in areas where the underlying Bowman's layer was disrupted.

Conclusions: Histological features in our keratoglobus specimens are consistent with previous reports. The similarities in immunohistochemical labeling between keratoglobus and keratoconus suggest that these entities may share common mechanisms that are involved in stromal thinning.

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Figures

Figure 1
Figure 1
Clinical photographs of keratoglobus. A, Profile examination image showing globular corneal protrusion (patient 4). B, Slitlamp image showing limbus-to-limbus corneal thinning (patient 3). C, Diffuse illumination showing corneal neovascularization (patient 5, arrow).
Figure 2
Figure 2
Histopathologic analysis of keratoglobus cases. There is diffuse corneal thinning in all cases (hematoxylin-eosin, original magnification ×63).
Figure 3
Figure 3
Histopathologic analysis of keratoglobus cases at high magnification. Peripheral cornea of patient 2 (A) and central cornea of patient 3 (B) showing disruption of Bowman's layer and subepithelial scars (arrows). C, Peripheral cornea of patient 4 showing disruption of Descemet's membrane (double arrows). D, Central cornea of patient 9 showing a disrupted and thickened Descemet's membrane (double arrows). E, Peripheral cornea of patient 3 showing absence of Bowman's layer. F, Central cornea of patient 2 showing epithelial hyperplasia, with Bowman's layer replaced by a collagenous scar (arrowheads encircling scar) and neovascularization (asterisk) (hematoxylin-eosin). Scale bars equal 50 μm for all.
Figure 4
Figure 4
Immunostaining results for α1-proteinase inhibitor (α1-PI) and Sp1. There is intense staining of α1-PI in the epithelium of the normal control. By comparison, epithelial staining in both corneas with keratoglobus and the cornea with keratoconus is markedly reduced (chromogen 3,3-diaminobenzidine tetrahydrochloride). The intensity of Sp1 nuclear staining is much lower in the epithelium of the normal control compared with that in keratoglobus and keratoconus (chromogen Fast Red TR/Naphthol AS-MX phosphate staining). The abnormal staining patterns in the keratoglobus corneas were more prominently observed in the mid-peripheral than the central cornea for both α1-PI and Sp1. Scale bars equal 50 μm for all.
Figure 5
Figure 5
Immunostaining results for the matrix metalloproteinases (MMPs). The underlying Bowman's layer in keratoglobus, while present, was markedly attenuated compared with that in normal controls. Note the increased staining intensity for all MMPs in the corneas with keratoglobus and MMP-1 in the cornea with keratoconus. By comparison, epithelial staining in the normal controls is nearly absent. Staining within the corneas with keratoglobus is the strongest where the Bowman's membrane is disrupted (chromogen 3,3-diaminobenzidine tetrahydrochloride). Scale bars equal 50 μm for all.
Figure 6
Figure 6
Epithelial staining intensity for α1-proteinase inhibitor and Sp1 in normal controls, corneas with keratoglobus, and corneas with keratoconus in the central and mid-peripheral areas. Error bars indicate standard error of the mean.
Figure 7
Figure 7
Epithelial staining intensity for matrix metalloproteinases (MMPs) in normal controls, corneas with keratoglobus and an underlying Bowman's layer, corneas with a keratoglobus with disrupted Bowman's layer, and central cornea with keratoconus. Error bars indicate standard error of the mean.
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