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Kevin Lai, Jason Reidy, Benjamin Bert, Tatyana Milman; Spheroidal degeneration in H626R TGFBI corneal stromal dystrophy: clinical, genetic, histopathologic, immunohistochemical, and ultrastructural analysis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1845.
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To describe the clinical, imaging, histopathologic, immunohistochemical, and ultrastructural characteristics of coexistent amyloid and spheroidal degeneration-type deposits in a family with Histidine-626-Argenine Transforming Growth Factor Beta Inducible Gene (H626R TGFBI) corneal stromal dystrophy.
Retrospective clinical-pathologic and genetic analysis of one family with H626R lattice dystrophy.
The disease showed autosomal dominant inheritance pattern by pedigree analysis. The affected individuals presented in 4th or 5th decades with progressive visual impairment and recurrent erosions. Ophthalmic examination of the 3 affected family members revealed asymmetric, thick, branching lattice-like deposits, associated with corneal haze. Sequencing of the TFGBI gene revealed a high-penetrance disease causing sequence variation (H626R CAT>CGT heterozygous). Optical coherence tomography demonstrated fusiform, poorly demarcated, hyper-echoic stromal deposits, consistent with amyloid, with focal hypo-echoic central region. Histologic evaluation of the corneal buttons from the 2 affected family members showed stromal fusiform Periodic acid-Schiff (PAS)-positive, Congo red-positive, birefringent, and keratoepithelin antibody-immunoreactive deposits, consistent with TGFBI amyloid. Few amyloid deposits contained a central nidus of spheroidal degeneration-type material. This material demonstrated autofluorescence, stained with elastic and Masson-trichrome stains, did not stain with PAS or Congo red stains, was non-birefringent, and did not immunoreact with keratoepithelin antibodies. Transmission electron microscopy confirmed the presence of peripheral amyloid fibrils with central electrodense, homogeneous, discrete spheroidal degeneration-type deposits.
Presence of spheroidal degeneration-type deposits in a subset of affected patients, the variability in presentation within an individual and between the family members, the predominant anterior corneal stromal location and the non-immunoreactivity of deposits for keratoepithelin suggest that these deposits are degenerative in nature. The deposits may arise from ultraviolet light-altered proteins diffused from the limbus, which form a nidus for mutant keratoepithelin deposition in patients with the late onset H626R lattice dystrophy variant.
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