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Noh et al., Osaka and Tokyo, Japan, reported that pupilsize (PS)
is large, pupillary unrest (PU) is decreased, and accomodation amplitude
(AC) is low in hyperthyroid Graves' disease, suggesting sympathetic overactivity.
They examined these parameters before treatment and after ATD when patients
were at least three months euthyroid. They found that PS, PU and AC became
normal after treatment only in those patients without lid-retraction. When
lid-retraction was present, the abnormalities continued after the euthyroid
state was reached, indicating continued sympathetic overactivity. A very
active area of research with regard to OGD is that of the possible involvement
of the thyrotropin receptor (TSH-R) being expressed in non-thyroidal tissues
like extraocular muscle or fat, thereby acting as an autoantigen. Endo,
Yamanashi, Japan, not only isolated TSH-R mRNA in rat adipose tissue, but
by transcribing this into cDNA and transfection into CHO-K1 cells, found
that this TSH-R was functioning normally. They suggest therefore that TSH-R
may be expressed in retro-orbital fat and may act as an autoantigen playing
a role in the development of OGD.
Tallstedt, Stockholm, Sweden, not only found TSH-R expression in orbital fat, but also in extraocular muscle from patients with Graves' ophthalmopathy and from normals. Not only is the TSH-R antigen considered to be important in the development of OGD, but also another protein i.e. a 64 kDa eye muscle antigen (64 kDa-EMA). Boucher, Montreal, Canada, studied the relationship between autoantibodies against 64 kDa-EMA and the severity of eye disease in 38 patients (Hashimoto and Graves) with OGD. It appeared that there was a positive correlation between 64 kDa-EMA antibody titers and transversal diameter of extraocular eye muscles, but not with clinical activity score or proptosis. It is concluded that the titers of antibodies only reflect early eye muscle abnormalities. Kiljanski, Pittsburgh, PA, USA, studied T-lymphocyte reactivity to a recombinant 64kDa-EMA and found no reactivity using peripheral blood lymphocytes from patients with OGD, neither with lymphocytes from other groups of patients with autoimmune thyroid disease without OGD, non-autoimmune thyroid disorders and healthy subjects. However, they stated to have more promising results using a full-length 64kDa-EMA. A similar study was reported by Kendler, Vancouver, Canada, who exposed peripheral blood lymphocytes from 9 patients with active OGD and from 9 healthy controls to cultures of human fetal skeletal muscle and extraocular muscle. They found significantly higher stimulation of lymphocytes taken from most OGD patients when exposed to extraocular muscle cells but not with skeletal muscle cells, suggesting a role of extraocular muscular antigens in development of OGD. Wall, from the same group, found reactivity to 64kDa-EMA protein in 8 out of 12 patients with OGD, in 3 out of 8 patients with Graves' disease without OGD, in 1 out of 9 patients with Hashimoto without OGD, and in 1 out of 11 in normal sera. They confirmed that this 64kDa-EMA is only expressed in extraocular muscle membranes, but not in other skeletal muscles. They hypothesize that reactivity of sera against this protein can be used to screen patients before onset of OGD. Wang, Albany, NY, USA, reported changes in morphology (characterized by development of prominent cellular processes and a stellate appearance) when orbital fibroblasts from patients with Graves' disease were treated with prostaglandins. They did not find similar changes using dermal fibroblasts. The relevance of their studies is related to the fact that fibroblasts and prostaglandins are thought to play a role in the development of OGD. (Comment: No control studies were reported using orbital fibroblasts from patients without OGD and it was also not indicated if the dermal fibroblasts were from controls or from patients with OGD.) |
