1. Department of Ophthalmology
Thyroid Gland Dysfunction and Keratoconus
Zisis Gatzioufas, Berthold Seitz
Department of Ophthalmology
University of Saarland UKS, Germany
Chairman: Prof. Dr. B. Seitz
The authors have no financial interest in the subject matter of this poster

2. Introduction Thyroxine is important for collagen synthesis
Thyroid hormones are important for corneal
development (Coulombre, 1958)
Keratoconus may follow thyroidectomy (King, 1953)
Thyroxine is important for collagen synthesis
(Drozdz, 1979)
Hypothyroxinaemia may accelerate the progress
of keratoconus and cause acute hydrops
(Gatzioufas, 2008)
Ziel dieser klinischen Studie ist herauszufinden, ob eine Zusammenhang zwischen den Keratometerwerten und der Schilddrüsendysfunktion besteht.

3. Purpose
Is there an evidence-based association between keratoconus and thyroid gland dysfunction? ??
Keratoconus Thyroid gland dysfunction
Die Symptome, die er beschrieb waren, wenn er ein Objekt fixiert sehe er im Zentrum einen Schatten, der auch bei Blickbewegungen konstant bleibe.
Aim: to investigate the possible association between keratoconus and thyroid disease on a clinical and molecular level.

4. Methods Clinical study Basic research study
Study group: 154 patients with keratoconus
Endocrinological screening
Basic research study
Die Symptome, die er beschrieb waren, wenn er ein Objekt fixiert sehe er im Zentrum einen Schatten, der auch bei Blickbewegungen konstant bleibe.
Target protein: thyroxine receptor (THR)
Methods: Immunohistochemistry – Western blotting – Cell biology

5. Results - Endocrinological screening
Increased incidence of hypothyroidism in the keratoconus group compared to control group (p<0.001, t-test)
Groups
Hypothyroidism
Men (%)
Women (%)
Total (%)
Keratoconus group
5.3
23.3
13.6
Control group
1.0
3.3
1.9
General population
0.2
2.0
1.2
Die Symptome, die er beschrieb waren, wenn er ein Objekt fixiert sehe er im Zentrum einen Schatten, der auch bei Blickbewegungen konstant bleibe.
The incidence of positive antiTPOAb and/or antiTgAb was significantly increased in
patients with keratoconus (25.3%) compared to control subjects (6.4%) (p<0.001, t-test)

6. Results - Immunoassay Thyroxine concentration in tear film
Keratoconus group:
HTD-group: 11.8±6.2 nmol/l
n-HTD-group: 10.9±5.1 nmol/l
Control group: 3.0±1.7 nmol/l
Welcher Befund wurde erhoben: links sehen wir einen normalen Augenhintergrund
HTD
n-HTD C
HTD: patients with keratoconus and hypothyroidism; n-HTD: patients with keratoconus but without hypothyroidism; C: control group

7. Results - Immunohistochemistry
Dapi
Cy2
Overlay
NC THR
Both NC and KC expressed THR.
THR signal was detected in epithelium and stroma.
No signal was observed in corneal endothelium.
KC THR
KC THR
Control
NC: normal cornea; KC: keratoconus cornea; THR: thyroxine receptors

8. Results – Immunohistochemistry/Western blotting
Epithelial expression of THR in KC was comparable to that in normal cornea .
Stromal expression of THR in KC was upregulated compared to that in normal cornea.
Densitometry-analysis of Western blotting results revealed a 2-fold increase of THR in KC stroma compared to normal corneal stroma.
KC: keratoconus cornea; Normal: normal cornea; THR: thyroxine receptors

9. Results – Corneal cell culture
Monkey corneas (Macaca fascicularis) were cultivated in vitro
Corneal epithelium was separated from corneal stroma
Cells were treated with different thyroxine-concentrations (TH)
Stroma
Epithelium
Stroma+
Epithelium
+ TH
100 µg/l
+ TH
500 µg/l
+ TH
1 mg/l
no TH

10. Results – Corneal cell culture
Thyroxine stimulated the proliferation of both epithelial and stromal cells in vitro.
The stimulation rate was dosage-dependent.
A plateau of 2500 cell/mm2 was observed in epithelial cell cultures, while stromal cell cultures demonstrated a plateau of 1740 cell/mm2.
Cells/mm2
Stroma
Epithelium

11. Conclusions
The incidence of hypothyroidism is significantly increased in keratoconus.
Thyroxine concentration in tear film is significantly increased in patients with keratoconus.
Human cornea expresses thyroxine receptors (THR) in epithelium and stroma.
THR expression in corneal stroma is significantly increased in keratoconus.
Thyroxine stimulates the proliferation of epithelial and stromal corneal cells in vitro.

12. Thank you for your attention!