Immunohistochemical and ultrastructural studies on the exenterated orbital tissues of a patient with Graves' disease.

The exenterated orbital contents obtained post mortem from a 47-year-old man who had an eight-month history of treated hyperthyroidism and a two-month history of visual complaints were examined histopathologically, immunohistochemically, and by electron microscopy. All of the extraocular muscles were massively enlarged, due to early diffuse endomysial fibrosis, mucopolysaccharide deposition, and a predominantly perivascular lymphocytic and plasmacytic infiltration. Histochemical stains revealed that the intramuscular mucopolysaccharides were weakly sulfated and polycarboxylated, establishing that they were products of fibroblastic activation rather than derived from mast cells. Subsarcolemmal deposits in the myofibers were shown by electron microscopy to be collections of glycogen rosettes with intermixed lipid deposits. These inclusions were interpreted as secondary phenomena due to abnormal muscle energetics from restrictions in contractility, and not as evidence of a primary degeneration of the extraocular muscle fibers themselves. The sarcomeric organization of the striated muscle cells was undisturbed, and therefore the pathologic changes occurred int he interstitial space of the endomysium. A monoclonal antibody specific for neurofilaments (antibody 4.3 F9) revealed, in comparison with normal controls, a preferential loss of large-type axons of the proximal segment of the orbital portion of the optic nerve as well as in the intracanalicular portion. The axonal loss was associated with a mildly increased number of astrocytes as demonstrated by an antibody against glial fibrillary acidic protein. The meninges of the optic nerve, the orbital fat, and the tendons of the extraocular muscles were uninflamed. The foregoing findings are compatible with a compressive optic neuropathy mediated by the massively swollen extraocular muscles impinging upon the optic nerve at the orbital apex.