Keratoconus associated with corneal stromal amyloid deposition containing TGFBIp.
OBJECTIVE
To report the identification and characterization of stromal amyloid deposits in patients with keratoconus.


METHODS
The excised corneal buttons from 2 patients diagnosed clinically with keratoconus underwent histochemical analysis with Masson trichrome, Congo red, Alcian blue, and periodic acid-Schiff stains, and immunohistochemical analysis for the transforming growth factor beta-induced gene (TGFBI) protein product (TGFBIp), prealbumin, lysozyme, and kappa and lambda light chain expression. After the collection of DNA from both patients, exons 4, 11, 12, 13 and 14 of TGFBI were amplified and sequenced to search for mutations previously associated with dystrophic corneal stromal amyloid deposition.


RESULTS
Light microscopic examination of the corneal buttons revealed stromal thinning, epithelial basement membrane abnormalities, and focal disruption of Bowman layer. Multiple stromal deposits were identified that stained red with Masson trichrome, pink with periodic acid-Schiff, and red with Congo red; the Congo red-stained deposits demonstrated birefringence and dichroism with crossed polarizing lenses. Immunohistochemical staining demonstrated reactivity of the stromal deposits with antibodies to TGFBIp but no reactivity with antibodies against prealbumin, lysozyme, or kappa and lambda light chains. Screening of TGFBI exons 4, 11, 12, 13, and 14 revealed 2 previously identified single nucleotide polymorphisms present in the heterozygous state in both individuals but no other coding region variants.


CONCLUSIONS
Two cases of keratoconus with clinically unsuspected, presumed secondary stromal amyloid deposition are described. Although TGFBIp is identified in the stromal deposits, no previously reported amyloidogenic mutations are identified in TGFBI in either affected individual, indicating a previously undescribed mechanism of stromal amyloid deposition.
Tai
Tak Yee Tania
TY
The Jules Stein Eye Institute, David Geffen School of Medicine, The University of California at Los Angeles, Los Angeles, CA 90095, USA.
Damani
Mausam R
MR
Vo
Rosalind
R
Rayner
Sylvia A
SA
Glasgow
Ben J
BJ
Hofbauer
John D
JD
Casey
Richard
R
Aldave
Anthony J
AJ
D000328:Adult; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007640:Keratoconus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013194:Staining and Labeling; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D000099222:betaIG-H3 Protein
D000682:Amyloid; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein