Elastic fiber components and protease inhibitors in pinguecula.

The nature of the abnormal elastotic materials seen in pingueculae and their insensitivity to elastase are poorly understood. The authors investigated their composition by immunoelectron microscopy using antibodies to elastic fiber components, serum and tissue components known to be associated with elastosis in other sites. The abnormal elastic fibers showed labeling for elastin, microfibrillar protein, and amyloid P where these components never co-localize normally, indicating the fibers are not simply immature but aberrant in organization. There was mild positivity for the serum protease inhibitor alpha-1 antitrypsin at the edges of the abnormal elastic tissue and marked positivity for lysozyme. The more superficial region of pingueculae had similar elastic constituents but no fiber formation and a paucity of elastic microfibrils. The subepithelial dense concretions showed strong staining for lysozyme, the first component to be identified in these aggregates. Amyloid P and lysozyme are characteristic components of dermal elastosis, postulated to have an inhibitory effect on elastolytic processes, indirectly affecting the control of elastogenesis. The greater prominence of nonfiber-forming aggregates in pingueculae may be related to their marked deficiency of elastic microfibrils compared with dermal elastoses. This difference speaks for more severe actinic cellular damage in the poorly protected conjunctival tissue.

Precapsular film on the aging human lens: precursor of pseudoexfoliation?

In many older patients we observed a layer of subtle opacification on the anterior lens capsule, appearing as a ground glass film biomicroscopically. This precapsular film (PCF) could be uniform but often had radial grey lines in the mid zone, holes in the paracentral region, and was occasionally rolled up in strings. Lens capsular material obtained at cataract extraction was studied in patients with and without the film. By scanning electron microscopy the PCF appeared as a friable, incomplete fibrillar layer, with rolling of the edges suggesting loose attachment. Ultrastructurally its component fibrils were from 3-6 nm in diameter, similar to the finer fibrils in pseudoexfoliation (PSX) material. Life PSX material the layer stained positively for the elastic microfibril-associated protein, fibrillin, in a lens with radial striations. These similarities suggested that the two conditions have some relationship and that the PCF may be a precursor of PSX. Finding patches of the fibrillar network in some control patients implies that the PCF is common in patients of cataract age, though seldom detected clinically.

Pseudoexfoliative fibrillopathy in the skin of patients with 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.

Pseudoexfoliative fibrillopathy in the conjunctiva. A relation to elastic fibers and elastosis.

Pseudoexfoliative (PSX) material in the conjunctiva was found to have a close association with elements of the elastic system in 13 eyes of patients with PSX disease studied ultrastructurally. Pseudoexfoliation aggregates were rare within vascular walls but frequent in proximity to the plasmalemma of stromal fibroblasts. No amyloid was found. A striking feature was the association of PSX fibers with the elastosis seen in many of the specimens. Typical PSX fibers were present in clumps of oxytalan and around small elastic fibers. In five cases with more advanced elastosis, the aggregates of PSX fibers were larger and their usual loose fibrogranular matrix was extensively replaced by a dense elastotic one. Morphology of PSX here varied from typical to thicker, fragmented, and sometimes nondiagnostic fibers. This intermingling of PSX and elastotic materials suggested that PSX fibrillopathy is itself a type of elastosis, possibly resulting from abnormal aggregation of components related to elastic microfibrils.

Preclinical diagnosis of pseudoexfoliation syndrome.

Although the diagnosis of pseudoexfoliation syndrome (PXS) is made by observation of pseudoexfoliation material (PXM) deposited on the anterior lens capsule, there are several additional signs related to pigment dispersion that are often present both in eyes with PXS and fellow eyes in unilateral cases. On the basis of the presence of these signs, we have categorized a group of patients as "pseudoexfoliation suspects" who demonstrated no evidence of PXM on the lens capsule in either eye. As PXM has previously been identified in the conjunctiva of affected eyes as well as fellow eyes in unilateral cases, we hypothesized that it could also be present in PXS suspect eyes. Inferior bulbar conjunctival biopsies were performed on four eyes with PXS, five fellow eyes, and 23 PXS suspect eyes, and specimens were examined by transmission electron microscopy. In eight PXS suspect eyes biopsy specimens demonstrated PXM, suggesting that PXS is more prevalent and possibly responsible for a greater proportion of glaucoma than previously suspected.

Pseudoexfoliative material contains an elastic microfibrillar-associated glycoprotein.

Because of histochemical similarities, there is reason for thinking that some component or components of PSX material are also present in zonular fibers. Since the zonule is a member of the elastic microfibrillar system, PSX material on the lens capsule was tested for immunologic affinity to elastic MFP from three widely divergent sources, using an indirect immunoperoxidase electron microscopic method. Positive staining was obtained with all three antibodies on all components of lens PSX material, including the superficial aggregates, deep fibrogranular zone, and capsular inclusions. The results support our hypothesis that PSX material derives from abnormal polymerization of glycoprotein associated with the zonular-elastic microfibrillar system. Similar staining of the abnormal material within the lens capsule indicates that the lens epithelial cell is involved in processing this protein. It might be suspected that other microfibrillar-secreting cells, even beyond the present range of suspected sources, could produce similar material.

Pseudoexfoliative material and oxytalan fibers.

Pseudoexfoliative material (PSX) was found to show oxytalan staining like the ocular zonular fibers. These two fibrous proteins also shared positive reactions for disulfide and sulhydryl groups and for acidic mucosubstances, both of which have been suggested as reactive groups in the oxytalan staining reaction. The deep striated zone in the pre-equatorial lens capsule and the lens capsular inclusions shared most of these reactions, indicating that they contain some similar components. PSX material showed histochemical differences from the zonule, including evidence of less PAS-positive glycoprotein and more acidic mucosubstance. Variations in staining within the PSX excrescences indicated that they are a composite of more than one substance. PSX material appears to be a product of local basement membrane-secreting cells, representing an abnormal polymerization of glycoconjugates similar to those in elastic microfibrils.

Blue fleck corneal iridescence: an occasional feature of Cogan's microcystic corneal dystrophy.

Flecks consisting of brilliant reflective blue dots and streaks were a prominent biomicroscopical feature in three patients with Cogan's microcystic corneal dystrophy. Two patients required epithelial debridement. We used the material obtained to investigate their histology and ultrastructure. A subepithelial accumulation of basement membrane-like material composed of ultrastructurally fine granules was deposited in alternating layers of compaction and rarefaction. The layers lie mostly parallel to the anterior corneal surface, but in some places they are folded. Such foldings are possibly the sites of multilaminar reflection and constructive interference, giving rise to the blue iridescence.

A typical band-shaped calcific keratopathy with keratocyte changes.

The clinical features of a patient with atypical band keratopathy are described. Histochemical and electron probe analyses indicate that the granular deposits in Bowman's layer contain calcium and phosphate. An unusual feature in this patient was the presence of severe keratocyte degeneration; its possible role in the pathogenesis of this condition is discussed. Exfoliation of the calcified Bowman's layer appears to have been the basis for severe attacks of recurrent ocular pain.

Preinvasive carcinoma of the cornea and conjunctiva.

Greyish-white spots, varying in size, caused diagnostic problems in 2 patients with pre-invasive corneal carcinoma. Keratectomy specimens permitting light and electron microscopy indicated that the smaller spots predominating in one patient correlated with epithelial microcysts and vacuoles, while areas of parakeratosis accounted for the macroscopic white patches found in the other. A variety of ultrastructural abnormalities, including excessive basement membrane fibrillogenesis, were present in both cases.

Cataract extraction complicated by capsular glaucoma.

Synechiae involving the iris pigment epithelium and the peripheral anterior lens capsule occur in capsular glaucoma. During cataract extraction they may bring about traction on the capsule threatening its rupture. The ultrastructural basis of these adhesions is a bonding of pigment cells to capsular surface by pseudoexfoliative material.

Cogan's microcystic dystrophy of the cornea: ultrastructure and photomicroscopy.

Corneal biopsy specimens from 3 patients with Cogan's microcystic corneal dystrophy were examined by light and electron microscopy. Specimens were taken from corneas showing microcysts, geographic or map-like areas, and refractile striae. In all samples there is a bilaminate subepithelial layer of fibrogranular material, the friability of which is probably the basis for recurrent erosions in this disorder. Histochemical and ultrastructural findings provide further evidence that Cogan's dystrophy, the finger print/bleb dystrophy, and Meesmann's dystrophy should be regarded as separate entities.

Retinal hamartoma in childhood.

Characteristic clinic details of two children affected with pigment-containing tumefactions of the posterior pole are described. The lesion although provisionally regarded as hamartomatous can, as in these two patients, exhibit inflammatory signs which may suggest a reactive inflammatory pathogenesis. Most tests are non-contributory, but fluorescence angiography and electro-oculography are of value in differential diagnosis. The former investigation has indicated that the pattern and intensity of vascular leakage in the mass may change over a period of a year.

Pseudoexfoliative disease of the lens: a study in electron microscopy and histochemistry.

The anterior lens capsule in pseudoexfoliative (PE) disease has been investigated with scanning electron microscopy and transmission electron microscopy. It shows several distinct zones which correlate with those seen clinically. True exfoliation of the anterior lens capsule is shown as an integral pathologic feature of PE disease. PE fibrils are mixed with various degraded cell products, including organelles, of which uveal pigment granules are the most frequent. Sheets of degenerating iris pigment epithelium as well as individual cells are often firmly adherent to the pre-equatorial lens capsule and zonules. PE fibrils on the capsule are 35 to 40 nm in width, often showing several subunit filaments about 10 nm wide. PF filaments forming vertical bundles in the pre-equatorial capsule are 10 nm wide, but show little tendency to aggregate laterally. Histochemical and ultrastructural properties of both types of PE fibril and those of the capsular inclusion suggest that they are closely related fibrillar proteins. PE fibrils share some of the characteristics of amyloid but are not identical substances. Nevertheless, a similar mechanism of synthesis is suggested. The participation of non-lenticular sites in the formation of PE fibrils is not precluded by this hypothesis.

Bleb dystrophy of the cornea: histochemistry and ultrastructure.

Corneal epithelial biopsies from two patients affected with asymptomatic bleb dystrophy were examined by light and electron microscopy. The basis of this disorder appears to be the deposition of a neutral mucopolysaccharide-protein complex as a continuous layer between the basement membrane and Bowman's layer. This material, although homogeneous in light microscopy, has a fine granular ultrastructure. It is friable, and in view of the apparent integrity of the basement membrane/hemidesmosome system it is suggested that the recurrent epithelial erosions which can occur in this disorder result from shearing of this layer. Fissures in the bleb material contain cells which may play a role in its degradation.