Takeo Iwamoto

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.

Benign conjunctival melanocytic lesions. Clinicopathologic features.

The common acquired conjunctival nevus usually undergoes progressive maturation and only exceptionally gives rise to conjunctival melanoma. Pure junctional nevi are rare except in childhood. Histologically, however, a junctional nevus may be indistinguishable from primary acquired melanosis (PAM) with atypia, a condition of middle-aged and elderly individuals that has a tendency to evolve into melanoma. Nevi in adolescents may attract a vigorous lymphocytic response and may cause clinical and histologic confusion with other entities, particularly a regressing nodule of melanoma that occurs predominantly in adults. Rarely, congenital conjunctival nevi are identified, sometimes in patients with adjacent congenital nevi of the eyelid. A variety of unusual nevi, including balloon-cell nevi, Spitz nevi, epithelioid cell nevi, dysplastic nevi, recurrent nevi, episcleral melanosis and the nevus of Ota, blue and cellular blue nevi, melanocytoma, and composite or mixed nevi all may be identified in the conjunctiva. Concepts of histogenesis as well as the clinical, light microscopic, and ultrastructural features of these and other benign pigmentary conditions of the conjunctiva are described.

Elastodysplasia and elastodystrophy as the pathologic bases of ocular pterygia and pinguecula

Specimens of normal conjunctiva from three adult patients were examined by electron microscopy, which revealed normal elastogenesis in the substantia propria, but more prominently, in the episcleral tissues. Ultrastructural examination of eight pterygia and three pinguecula also disclosed evidence of elastogenesis, but in these lesions the morphogenetic sequence of fiber formation was distorted, and the elastic fibers were abnormal. The zone of hyalinization of the substantia propria immediately beneath the epithelium was the only site that manifested clear-cut evidence of collagen degeneration, which assumed the forms of effacement of the longitudinal periodicity of the collagen fibers, and of microfibrillar unfurling of the ends of the collagen fibers. Fibroblastic activity and elastic fiber formation were inconspicuous in this region. Beneath the hyalinized zone were collections of eosinophilic granular material. This material was shown ultrastructurally to be composed of excessive numbers of hollow-centered microfibrils (an elastic fiber precursor), with a tendency to clump centrally in the larger aggregated sheets and to acquire electron-dense inclusions. Numerous fibroblasts were found within this material. Finally, the elastotic fibers of light microscopy represented an abnormal maturational phase of elastic fiber production. These abnormal elastic fibers had microfibrils at their peripheries, but numerous electron-dense inclusions were associated with focal zones of amorphous elastin deposition. Occasionally histiocytes appeared to be engulfing these abnormal fibers. We have concluded that a large component of pinguecula and pterygia is the result of newly synthesized elastic fiber precursors and abnormal maturational forms of elastic fibers (elastodysplasia) that undergo secondary degeneration (elastodystrophy). These structures are presumed to be elaborated by actinically damaged fibroblasts of the substantia propria.

Experimental Vitreous Replacement With Perfluorotributylamine

Perfluorotributylamine, a liquid fluorochemical used in artificial blood substitution, was evaluated for potential application as a vitreous substitute having heavier density than saline. It was injected into the vitreous of 38 rabbit eyes after mechanical vitrectomy or gas compression of the vitreous with perfluoropropane. The eyes were observed for periods of up to five months. Clinically the liquid occupied the lower vitreous space but gradually dispersed into smaller fluorochemical droplets. In the upper vitreous clusters of cells appeared within three to four weeks which precipitated on the posterior lens surface and in the cortical vitreous. In eyes with experimental retinal detachment perfluorotributylamine had physical properties which provided mechanical retinal tamponade. Its interfacial tension prevented passage through iatrogenic retinal breaks. Histopathologic findings showed irregularly shaped defects in the outer segment disks as early as two days after vitreous replacement. These changes appeared to reverse if perfluorotributylamine was removed after two days. The cellular response in the vitreous consisted primarily of monocyte-derived macrophages capable of ingesting fluorochemical (foam cells).

Therapeutic Ultrasound in the Treatment of Glaucoma: I. Experimental Model

Controlled ultrasonic energy was used to treat a series of laboratory animals in which glaucoma had been induced experimentally. Insonification successfully reduced elevated intraocular pressure in the majority (86%) of test animals. Histopathologic review of globes examined at varying time intervals following treatment showed localized thinning of the sclera with intact conjunctiva, allowing filtration and focal disruption of ciliary epithelium. This technique of treating elevated intraocular pressure in a noninvasive manner offers potential for clinical application in humans.

Intraocular Injection of Lidocaine

Lidocaine was inadvertently injected intraocularly in three patients. In the one patient who had not received prior mydriatics, the drug caused immediate dilation and paralysis of the pupil and diminished visual acuity to counting fingers. Retinal function began to improve after four hours and both retinal and pupillary function recovered completely by 16 hours. A second patient also recovered completely. The third patient developed a permanent field defect. The effects of intraocular lidocaine were then studied in an animal model. Lidocaine temporarily paralyzed the pupil in mydriasis and temporarily extinguished the b-wave of the electroretinogram. Light and electron microscopy study of the retina revealed no damage beyond that at the perforation site.

The Diagnostic Value of a Ring Infiltrate in Acanthamoebic Keratitis

During the past ten years it has become increasingly apparent that acanthamoebae can directly infect the cornea, usually after trauma, associated with contaminated water or soft contact lens wear. Thirteen cases of acanthamoebic keratitis have been published. In only three of these cases was the diagnosis first made by microbiologic methods, while in the others it was made only after pathologic examination of resected corneal specimens or enucleated eyes. We report three additional cases, two of which were accurately diagnosed by corneal scrape-smears and cultures before penetrating keratoplasty was performed. The reason for the accurate laboratory diagnosis in these cases was the presence of a diagnostic paracentral annular corneal infiltrate or abscess, a feature identified in over two-thirds of the earlier cases but one which has not been adequately emphasized or pursued for its early diagnostic value. We review the other clinical and epidemiological features of this entity, microbiological diagnostic techniques, the pathologic aspects, the role of topically and systemically administered medicaments, and finally point out the almost unavoidable role of penetrating keratoplasty after the temporizing effects of medical treatments have been achieved.

Discoid Lupus Erythematosus of the Eyelids

Discoid lupus erythematosus (DLE) is a chronic skin disease that may affect the eyelids. Unless suspected, these lid lesions may resemble chronic blepharitis and persist for years. We present the clinicopathologic features of DLE from the lids of seven patients, electron microscopic features of one case, and a review of 31 previously reported cases.

A comparative ultrastructural study of the normal lacrimal gland and its epithelial tumors

Six cases of benign mixed tumor (BMT), three of malignant mixed tumor (MMT), and four of adenoid cystic carcinoma (ACC) of the lacrimal gland were studied by electron microscopy, and the results were compared with those of the normal human lacrimal gland (three specimens). In the normal gland the acini were composed of inner secretory cells with large granules and outer myoepithelial cells. The inner layer of cells comprising the ducts exhibited a few small ductal granules in the apical cytoplasm, whereas the outer basal cell layer displayed bundles of tonofilaments, except for a few cells at the transition zone between the terminal duct and the acinus, where cells with incipient focal myofilamentary differentiation were discovered. The ultrastructure of all the BMTs was similar to that of the ducts, in that the inner lumen-forming cells contained small ductal granules and the outer basal cells usually exhibited tonofilaments. Among the MMTs, one tumor showed secretory acinartype granules, a second showed both ductal and acinar secretory granules, and the third showed lipid synthesis of a sebaceous carcinoma—the feature common to all being an active secretory condition. The ACCs were composed of various combinations of three different cell types: type 1 containing either ductal-type granules (type 1A) or acinar-type granules (type 1B); type 2 featuring bundles of tonofilaments and resembling basal cells; and type 3 having features intermediate between those of basal cells and those of myoepithelial cells. The stroma of the BMTs contained many cells of epithelial origin, whereas the stroma of the ACCs was derived in part from the matrix material elaborated by the epithelial cells and initially enclosed within their cystoid or adenoid spaces. Our studies on the normal lacrimal glands and their epithelial tumors suggest a possible development of myoepithelial cells from basal cells through intermediate or transitional cells.

Opportunistic Toxoplasmic Retinochoroiditis Following Chemotherapy for Systemic Lymphoma: A Light and Electron Microscopic Study

After a prolonged period of chemotherapy for a disseminated nodular lymphoma, a 51-year-old woman developed a white lesion in the left macular region, in the absence of any overt lymphomatous disease elsewhere. The initial retinal diagnosis was nonetheless a lymphomatous infiltrate. Due to her severely immunocompromised state, the patient developed pneumonia and died. The involved left eye was examined postmortem by light and electron microscopy. The retinal lesion was discovered to be caused by infection with Toxoplasma gondii, which on postmortem evaluation was also found in the brain together with subclinical lymphomatous disease and multifocal leucoencelphalopathy. Many viable and intact cysts were observed floating within the necrotic retina as well as lodged within recognizable retinal cells. Most of the organisms were encysted bradyzoites, although a rare tachyzoite was discovered in the extracellular space. Unusual features examined ultrastructurally were a preretinal membrane formed exclusively by glial cells, residual proliferating glial cells within the retina that were frequently related to surviving capillaries, and a multilaminar spindle cell placoid proliferation of pigment epithelial cells, assuming almost pseudo-sarcomatous proportions. Banded extracellular membrane material was focally observed between the proliferating pigment epithelial cells. No neoplastic lymphoreticular cells were discovered within the choroid, but a curious feature was the production of basement membranes by the surviving choroidal melanocytes. Toxoplasmosis should therefore be considered along with fungi and viruses in the differential diagnosis of white retinal lesions appearing in immunocompromised patients.