Barbara W. Streeten

Pseudoexfoliative Fibrillopathy in the Skin of Patients by Ocular Pseudoexfoliation

In addition to its occurrence within the eye, pseudoexfoliative fibrillopathy has been reported in the conjunctiva and around a posterior ciliary artery. To determine whether it has a more diffuse extraocular distribution, we studied skin biopsy specimens ultrastructurally from one to three areas in 13 patients with classic pseudoexfoliation. A fibrillopathy closely resembling that in the eye was found in 11 of the 13 patients. Only one of the 13 control subjects, a 78-year-old man with advanced low-tension glaucoma, had a similar fibrillopathy. In the patients with pseudoexfoliation who were more than 70 years of age, the accompanying dermal elastosis made evaluation difficult, because the pseudoexfoliative nodules in the skin occur primarily along elastic fibers, and their morphologic characteristics appeared to be influenced by the elastotic process. These results suggest that pseudoexfoliation is a systemic process related closely to elastosis, and that further search for pseudoexfoliative fibers should be made in the elastic system of the deep tissues and internal organs.

Immunocytochemical localization of vascular endothelial growth factor in neurons and glial cells of human retina.

In order to establish the cellular and subcellular localization of the chemokine protein, vascular endothelial growth factor (VEGF) or vascular permeability factor, in adult human retina, we employed immunocytochemistry with double immunolabeling, using a primary antibody to amino acids 1-10 of VEGF, together with antibodies to vimentin (intermediate filaments, labeling Müller cells) or to neuron-specific enolase (labeling retinal neurons). In adult human retina, VEGF-like immunoreactivity (VEGF-IR) is found in Müller cell processes, where typically it is found in the cytoplasm in close association with Vimentin-labeled (VM-IR) intermediate filaments. VEGF-IR is sometimes found diffusely in Müller cell bodies and nuclei. VEGF-IR is found in all major classes of retinal neurons, as demonstrated by co-localization with neuron-specific enolase (NSE)-IR, but is especially prominent in cell bodies of amacrine cells (ACs) (including displaced ACs) and ganglion cells (GCs). Generally, VEGF-IR is more prominent in the nucleus, while NSE-IR is more prominent in the cytoplasm and neurites. In blood vessels, VEGF-IR co-localizes with VM-IR, marking blood vessel endothelial cells, whereas NSE-IR apparently marks the layer of smooth muscle cells. These cellular findings regarding the retinal localization of VEGF-IR are consistent with VEGF synthesis in and its export from retinal neurons, particularly amacrine and ganglion cells, as well as in glia, specifically Müller cells, and suggest that retinal neurons normally provide continuous trophic support for their retinal blood supply.

Association of elastin with pseudoexfoliative material: an immunoelectron microscopic study

Using immunoelectron microscopy, the presence of elastin and tropoelastin was demonstrated in pseudoexfoliative (PSX) material in all its classical sites on the lens capsule, ciliary non-pigment epithelium, iris epithelium and stroma, and conjunctiva. Some variability in binding affinity was seen in different sites, and labelling was more often on the periphery than the center of the PSX fibers. The elastin epitope on PSX material was more sensitive to processing than the remarkably stable epitope on mature elastic fibers. Since neither elastin nor a related component of PSX fibers, elastic microfibrillar protein, is a circulating protein, both are likely to be secreted by local ocular cells. Most of these local cells are not involved in elastogenesis normally, suggesting that an abnormal stimulus or defective regulation of matrix synthesis exists in this disease.

Amyloid P protein in pseudoexfoliative fibrillopathy

Amyloid P protein was demonstrated by immunostaining in all 14 samples of ocular and conjunctival pseudoexfoliative (PSX) material studied, although amyloid was not found by Congo red staining or ultrastructurally. Immunostaining of PSX aggregates for other common amyloid proteins, including amyloid A, prealbumin, and immunoglobulin light chains, was negative in most cases. In three eyes with advanced neovascular glaucoma there was irregular immunostaining of the PSX aggregates for 2-4 of these other amyloid proteins, besides diffuse staining of the iris and vitreous. Control cases of neovascular glaucoma without PSX disease showed minimal amyloid P, but similar tissue staining for prealbumin and immunoglobulin light chains, consistent with an origin from vascular leakage. The presence of amyloid P protein, a minor serum component, in PSX aggregates in all cases with or without evidence of vascular leakage, indicated a more specific association. Ultrastructural localization of the protein on the periphery of PSX fibers suggest it is not an intrinsic fiber component. Since PSX material has an immunological relation to elastic tissue, we propose that PSX fibers have peripheral binding sites for amyloid P protein, similar to those present on normal elastic fibers.

Molluscum Contagiosum of the Eyelids in Patients with Acquired Immune Deficiency Syndrome

BACKGROUND Infection with molluscum contagiosum has been reported in patients with acquired immune deficiency syndrome (AIDS). Involvement of the eyelids by molluscum in patients with AIDS has rarely been mentioned. METHODS Two patients with AIDS presented with eyelid molluscum contagiosum. Detailed examination and follow-up was performed. RESULTS One patient had noted ocular irritation with epiphora for several weeks and showed a typical viral keratoconjunctivitis in both eyes. The other patient progressed to confluent masses involving the entire lower eyelid on one side. Removal of the lesions by surgery and cryotherapy was followed by recurrences in both patients within 6 to 7 weeks, the incubation period for this viral infection. CONCLUSION Molluscum contagiosum can form confluent lesions on the eyelids in patients with AIDS, which may cause a keratoconjunctivitis. Local removal of molluscum eyelid nodules appears to be of limited long-term value in patients with T-cell immunodeficiency.

Syringocystadenoma Papilliferum of the Eyelid

Two patients presented with slowly developing papillated or hyperkeratotic lesions of their lid margins that began early in the fourth decade. Upon excision, these tumors were discovered to be examples of syringocystadenoma papilliferum, a lesion not previously well documented in the ophthalmic literature. By light microscopy, each tumor displayed surface poral openings where the epidermis underwent a transition into duct-like epithelium, which ramified as luminal channels throughout the tumor. Papillae projected into many of the duct-like spaces and were lined by columnar to multilaminar nonkeratinizing epithelium. A plasma cell-rich infiltrate was present in the connective tissue cores of the papillae. Electron microscopy performed on one of the lesions revealed that the channels were true ducts, with the innermost cells displaying microvilli, small numbers of tonofilaments, and apical junctional complexes composed of a zonula occludens and zonular adherens. These findings, coupled with the location of the tumors at the lid margin and the presence of dilated apocrine glands of Moll deep to one of the tumors, support an apocrine origin. The clinical differential diagnosis of syringocystadenoma papilliferum with respect to other more common lid tumors is discussed.

Histopathology of herpes simplex virus keratouveitis

Twenty-four eyes removed for complications of HSV keratitis were studied histopathologically. There were 20 men and 4 women with an average age of 61 years. Severe keratitis was seen in 14, moderate in 7, and mild in 3 eyes. Common features associated with severe keratitis were: acute perforation, granulomatous keratitis with giant cells in the stroma and Descemets region, stromal inflammatory cells, angle-closure, severe iridocyclitis with diffuse or focal infiltration of lymphocytes and plasma cells, low-grade vitritis, choroiditis, and/or retinal periphlebitis. Specimens with moderate to mild keratitis had a similar distribution of inflammation but a lower incidence of granulomatous keratitis.

Identification of extractable proteins from the bovine ocular zonule: Major zonular antigens of 32kD and 250kD

Using Western immunoblotting, the extractable proteins of the bovine zonular fibers were examined for reactivity with two zonular antisera known to have strong affinity for zonular fibers in tissues, in order to identify the antigenic components. The extracts were also tested with antisera to several matrix proteins that have been reported to be associated with zonular fibers. Proteins reactive with antisera to bovine serum albumin, serum immunoglobulins and fibronectin were present. No bands reactive with antisera to a-elastin, prealbumin, amyloid P component, collagen VI, lysyl oxidase or monoclonal antibody to fibrillin were demonstrated. The major nonserum protein band identified by both antisera was a 32kD polypeptide. An equally strong 250kD polypeptide was shown by the antiserum to guanidine-dithiothreitol extracted zonular fibers. Both of these proteins were PAS-positive and were demonstrated also by the antisera in extracts of bovine elastic neck ligament. Whether the two glycoproteins are related to each other, with the higher molecular weight protein either a precursor or aggregate form, is not yet clear. They appear to bear a close relationship to the elusive core microfibrillar protein.

Benign approach to a malignant orbital tumor: metastatic renal cell carcinoma

A well-circumscribed, pseudoencapsulated benign-appearing lesion in the retrobulbar orbit of a 50-year-old man was found to be a metastatic renal cell carcinoma. The patient had a nephrectomy for renal cell carcinoma 15 years before, and had developed four other isolated metastases over the preceding 8 years. He had a further distant metastasis 1 year later, but is living and well 4 years after excision of the orbital tumor. Metastatic renal cell carcinoma of the orbit may have very benign characteristics, both clinically and radiographically, and can often be managed effectively by local excision with prolonged survival.

Pseudomelanoma of the Iris in Herpes Simplex Keratoiritis

A 37-year-old white man with a long history of recurrent herpetic keratitis presented with a rapidly enlarging pigmented iris lesion. The primary diagnostic concern was that the lesion might be a malignant melanoma. A biopsy of the mass was done and proved it to be a granuloma with granulomatous arteritis and infarction of the iris. In a patient with a history of recurrent ocular inflammation, such a hypersensitivity granuloma should be considered in the differential diagnosis of iris melanoma.