Congenital corneal opacification in De Barsy syndrome.

A newborn male was noted to have bilateral congenital corneal opacification. Findings from examination disclosed a variety of dysmorphic features, including cutis laxa, progeroid aspect, short stature, multiple hyperextensible subluxated joints, muscular hypotonia, and hyperreflexia. Bilateral penetrating keratoplasties were performed; histopathologic examination revealed diffuse epithelial thickening, loss of the Bowman layer, and stromal attenuation with anterior stromal scarring. Special stains showed no deposition of abnormal material in the corneas. Electron microscopy demonstrated absence of Bowman layer differentiation with a paucity of collagen fibers, as well as extensive small elastic fibers in the anterior stroma. The diagnosis of De Barsy syndrome was made, a rare progeroid syndrome associated with characteristic ocular, facial, skeletal, dermatologic, and neurologic abnormalities. De Barsy syndrome should be included in the differential diagnosis of congenital corneal opacification; its distinctive clinical features enable the clinician to easily differentiate it from other causes of congenitally cloudy corneas.

Immunolocalization of beta ig-h3 protein in 5q31-linked corneal dystrophies and normal corneas.

OBJECTIVE: To characterize the relation of the beta ig-h3 protein to the diagnostic corneal deposits in the hereditary corneal dystrophies recently shown to have mutations in the beta ig-h3 gene on chromosome 5q31. METHODS: Corneas with lattice, granular, mixed granular-lattice ("Avellino"), and 2 types of Reis-Bücklers dystrophy were diagnosed by the histochemical and ultrastructural characteristics of their abnormal aggregates. Dystrophic and normal corneas were compared for immunolocalization of beta ig-h3 protein. RESULTS: In normal corneas, immunoreactivity for beta ig-h3 protein was strongest in the Bowman layer, and next strong along stromal interlamellar junctions and attachment sites of collagen to the Descemet membrane. Antibody binding was intense on all dystrophic aggregates, mimicking somewhat the normal protein distribution. Mixed granular-lattice dystrophy had the most variation in beta ig-h3-immunopositive forms. The aggregates in both the "rod-shaped" Reis-Bücklers type and the "curly fiber" Thiel-Behnke type were strongly stained for beta ig-h3 protein, consistent with mutations on the beta ig-h3 gene. CONCLUSIONS: The marked immunopositivity for beta ig-h3 protein in the abnormal deposits in these dystrophies indicates that beta ig-h3 protein is a major component. The variety and quantity of immunopositive forms suggests that they consist primarily of the mutant protein, self-polymerizing and/or incorrectly binding to other corneal components. Variability of forms may relate to both the specific mutation and regional interactions of this protein.

Potato gun ocular injury.

PURPOSE: This study aimed to identify a dangerous new weapon capable of causing damage to the ocular and periocular regions. METHODS: The authors report two patients who had penetrating ocular injury in the past year because of homemade recreational potato guns. RESULTS: In one 14-year-old boy, projectiles from the firing of a potato gun resulted in orbital and cranial injuries that were life threatening with widespread fractures, marked disruption of facial structures, a cerebrospinal fluid fistula requiring bifrontal surgical repair, and loss of one eye. In a separate accident with a different potato gun, a 14-year-old boy who was wearing glasses at the time of injury had a sight-threatening perforating corneal laceration. CONCLUSION: Practitioners must be aware of the existence of these new, homemade unregulated devices. Information about the use and construction of these guns is widespread on the Internet, but no injuries resulting from these guns currently are documented in the medical literature.

Ocular involvement in familial erythrophagocytic lymphohistiocytosis.

BACKGROUND: Familial erythrophagocytic lymphohistiocytosis (FEL), a rare, rapidly fatal childhood disorder, is characterized by intermittent fevers, hepatosplenomegaly, cytopenia, hypercytokinemia and lymphohistiocytic infiltration with erythrophagocytosis involving multiple organs. We report the clinical and histological features of two infants with FEL and emphasize the ocular findings. METHODS: Microscopic examination of formalin-fixed, paraffin-embedded autopsy material was performed. Immunohistochemical studies were performed in case 1. RESULTS: The first patient presented with clinical and laboratory features and a family history consistent with FEL, and a liver biopsy revealed a lymphohistiocytic infiltrate with erythrophagocytosis consistent with FEL. A deceased brother had been diagnosed with FEL. Autopsy showed widely disseminated lymphohistiocytic infiltrates affecting the liver, spleen, bone marrow, lungs, kidneys and brain. Histologic examination of both eyes disclosed a prominent lymphohistiocytic infiltrate of the optic nerve with destruction of nerve fiber bundles as well as milder infiltrates in the choroid, scleral canals, perineural areas in the orbit and the optic nerve head perivascularly. The second patient also had the typical clinical, laboratory and autopsy findings with similar involvement of most organs, including extensive infiltration of the spleen and bone marrow. Histologic examination of one eye revealed marked lymphohistiocytic infiltration of the entire choroid as well as milder infiltration in the trabecular meshwork, iris, ciliary body, optic nerve, meninges and around the central retinal vein in the optic nerve. CONCLUSION: The findings of this study further define the ocular pathologic features of FEL, which are a part of a generalized, multiorgan disseminated disease.

Exfoliation syndrome in a 17-year-old girl.

A 17-year-old girl with unilateral congenital glaucoma who had undergone trabeculectomy and peripheral iridectomy in infancy developed apparent exfoliation syndrome (XFS) in the eye that underwent the surgical procedures. A conjunctival biopsy was performed and the specimen was fixed in 2.5% glutaraldehyde, embedded in epoxy resin (Epon-Araldite, Electron Microscopy Sciences, Fort Washington, Pa), and processed for routine electron microscopy and immunostaining for elastin. Results of ultrastructural study showed scattered fibrillar aggregates compatible with those of XFS in an older adult, differing chiefly in sparsity of granular interfibrillar matrix. The XFS fibers were closely associated with elastic fibers and microfibrils. Elastosis of the actinic-aging type was somewhat greater than expected for age. To our knowledge, this is the youngest patient described with characteristic ocular findings of XFS to date, supporting others who have suggested an association between iris surgery in youth and early onset XFS. Electron microscopy was essential in ruling out the possibility of a clinically similar entity caused by ultrastructurally different material.

HNK-1 epitope in the lens-ciliary zonular region in normal and pseudoexfoliative eyes. Immunohistochemistry and ultrastructure.

OBJECTIVE: To determine the specific binding sites for the HNK-1 adhesion molecule epitope in the lens-ciliary zonular region in normal and pseudoexfoliative (PSX) eyes. METHODS: Normal and PSX eyes and adjacent tissues from individuals aged 10 months to 89 years were investigated for the HNK-1 epitope by immunohistochemistry and immunogold electron microscopy. RESULTS: Concentration of HNK-1 epitope was high in the anterior central lens capsule into old age, but it tapered earlier and progressively in the inner capsule and elsewhere. On zonular fibers, label was strongest at their lens and ciliary attachments and intense on related elastic microfibrils in adjacent ciliary stroma. Label was also strong on PSX fibers and above normal on PSX central capsule. In contrast, HNK-1 was absent on PSX aggregates in conjunctiva and skin and on normal elastic microfibrils in these tissues. CONCLUSIONS: The prominent HNK-1 epitope in lens capsule and zonule has age- and site-specific variations that favor adhesive roles in each. The high density of epitope on ocular PSX material suggests an aberrant increase in expression that may contribute to adhesiveness of these aggregates, HNK-1 negativity on extraocular elastic microfibrils and PSX aggregates indicates a unique difference in composition of intraocular and extraocular elastic tissue, of potential significance for ocular function in aging and lens-dislocating diseases.

Elastosis of the lamina cribrosa in pseudoexfoliation syndrome with glaucoma.

BACKGROUND: Pseudoexfoliation syndrome is characterized by the presence of glycoprotein fibers in ocular and extraocular tissues, and often is associated with glaucoma. Pseudoexfoliation material may be associated closely with elastic microfibrillar-associated glycoprotein as well as elastin. METHODS: Four optic nerve heads of two patients with pseudoexfoliation syndrome and glaucoma were examined using electron microscopy and immunogold detection of elastin. Optic nerve heads from healthy age-matched individuals and patients with primary open-angle glaucoma were used for comparisons. RESULTS: In all eyes with pseudoexfoliation and glaucoma, there was marked and widespread elastosis in the connective tissue of the lamina cribrosa. Elastotic fibers appeared as large and irregular aggregates of electron-dense material labeled with anti-elastin antibody. Abundant microfibrils were interspersed in the elastotic aggregates, whereas no typical pseudoexfoliation fibers were observed. In contrast, there were less elastotic fibers in the lamina cribrosa from patients with primary open-angle glaucoma compared with pseudoexfoliation glaucoma. Other changes of extracellular matrix were similar to those observed in primary open-angle glaucoma: decreases in collagen fiber density, presence of basement membranes not associated with cell surfaces, and abundant bundles of microfibrils not labeled with elastin antibody. The elastic fibers appeared normal in other locations within the optic nerves of patients with pseudoexfoliation glaucoma, including in the pial septa and blood vessels of the retrolaminar myelinated optic nerve. CONCLUSION: The authors' findings demonstrate marked and site-specific elastosis in the lamina cribrosa of patients with pseudoexfoliation syndrome with glaucoma, suggesting an abnormal regulation of elastin synthesis and/or degradation in the optic nerve of patients with this disease.

Burkitt lymphoma presenting as a conjunctival mass.

PURPOSE: A sporadic Burkitt lymphoma, which presented as a primary conjunctival mass, demonstrates the approach to clinical diagnosis, staging, and current management of this rapidly growing malignant tumor, as well as newer concepts of its pathogenesis. PATIENT AND METHODS: A 16-year-old girl had rapid development of a conjunctival mass 6 weeks after an infectious mononucleosis-like illness, associated with a positive monospot test. A biopsy of the tumor was immunostained for lymphocyte markers. Additional clinical workup included computed tomographic scanning, nasopharyngeal biopsy, and studies of blood, bone marrow, and spinal fluid. In situ hybridization for Epstein-Barr virus (EBV)-encoded nuclear RNA was performed on the tumor and adenoidal tissue. RESULTS: The conjunctival biopsy showed a typical Burkitt lymphoma with markers positive for predominantly B lymphocytes. Computed tomographic scans indicated residual tumor in the anterior orbit. Biopsy of thickened adenoidal tissue showed only benign lymphoid hyperplasia. Evidence of EBV infection was found in the adenoidal tissue but not in the tumor cells. The patient was treated with combined chemotherapy on a Pediatric Oncology Group Study protocol for localized non-Hodgkin lymphoma, and is disease-free 4 1/2 years after diagnosis. CONCLUSIONS: A sporadic Burkitt lymphoma arising in the conjunctiva appears to be the first reported in this site. The lymphoma responded well to chemotherapy, which is now the usual course in stage 1 disease. A direct role for EBV in the oncogenesis of this sporadic tumor, similar to that in the endemic form, could not be supported because EBV-encoded nuclear RNA was absent in the tumor cells.

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.

Pseudoexfoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome.

Evidence is increasing that pseudoexfoliative material develops in widespread areas of skin and parabulbar tissues as well as intraocularly. To determine whether this process is even more diffusely distributed, ultrastructural examination was performed on visceral and ocular tissues of a patient with long-standing glaucoma found to have bilateral ocular pseudoexfoliation at autopsy. Aggregates consistent with pseudoexfoliative material were present in the lung, heart, liver, and gallbladder, in addition to the classic intraocular sites. The aggregates were in the fibrovascular septa and stroma of these organs, most frequently adjacent to elastic and oxytalan fibers. They stained positively for elastin and human amyloid P protein, like the ocular sites, in preliminary immunologic testing. Rare atypical aggregates were seen in one of the four control patients. These findings suggest that pseudoexfoliation is a systemic process involving abnormal matrix synthesis, particularly as related to elastic tissue components.

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.

Proboscis lateralis with associated orbital cyst: detailed MR and CT imaging and correlative embryopathy.

Proboscis lateralis is a rare craniofacial malformation. We present a case in a 1-week-old male infant, describe the clinical and imaging findings, and discuss the pertinent embryology. MR and CT proved to be complementary: CT provided anatomic detail in bone, defined the nasal cavity, and aided in determining the relationship of the proboscis and orbit; MR clarified the relationship of the proboscis to the orbit and skull base, and the relationships of normal brain to the dysplastic ethmoid centers.

Characterization of an associated microfibril protein through recombinant DNA techniques.

The complete primary structure of a new extracellular protein associated with elastic fiber microfibrils was determined by recombinant DNA techniques. Antiserum to insoluble bovine ocular zonule protein was used to screen a lambda gt11 cDNA expression library constructed from whole chick embryo poly(A)+ RNA. The cDNAs encoding immunoreactive fusion polypeptides were then used to rescreen the library by plaque hybridization. Nucleotide sequencing of overlapping cDNA clones revealed an open translation reading frame of 1326 bases beginning at an initiation start sequence and ending at a stop codon. The contiguous cDNA sequence contains a 3'-untranslated region of 563 bases with a possible polyadenylation site 16 bases upstream from the poly(A) tail. Primer extension of chick aortic mRNA taken together with the sequence data, reveals a 5'-untranslated region of 95 bases extending upstream from the translation start site. Northern blot analyses indicated that the isolated cDNA hybridized with a 2.1-kilobase mRNA in preparations of whole chick embryo and chick embryonic aortic, heart, and muscle RNAs. The initial translation protein encoded by the cDNA is 53,932 kDa and possesses a hydrophilic amino acid composition with glutamic acid comprising 22% of the total amino acid residues. Antiserum was elicited to a synthetic peptide sequence (14 amino acids) encoded within the deduced protein primary structure. Western blots of extracted proteins from chick embryonic aortae cultured in the presence of beta-aminopropionitrile showed that the medium and a mild salt extract contained an immunoreactive protein possessing an apparent molecular mass of 58,000 whereas harsh denaturants extracted a 32,000-kDa protein. Pulse-chase experiments using radiolabeled lysine showed that the newly synthesized 58,000-kDa protein was chased into a 32,000-kDa protein within a 2-24-h period. Immunoelectron microscopy of tissue sections from chick aortae, bovine nuchal ligament, and human ocular zonules showed that the peptide-elicited antibody localized specifically to ultrastructurally definable microfibril structures.

Abnormal scleral collagen in nanophthalmos. An ultrastructural study.

Ten patients with bilateral nanophthalmos underwent sclerectomies for uveal effusion. Ultrastructural examination of the sclera revealed abnormal collagen in seven patients. Four showed dramatic fraying of the collagen fibrils into fine filaments 2 to 3 nm in diameter. In three of these cases and three other cases without fraying, there were foci of 10- to 35-nm small collagen fibrils, some appearing to arise by splitting of otherwise normal collagen fibrils. In areas of fraying, elastic fibers were absent. All patients had a wider range of collagen diameters than did control subjects. The youngest patient with fraying also had Hallermann-Streiff syndrome. In three patients, no collagen abnormality was found. The clinical feature correlating best with the presence of abnormal collagen was an extremely small eye, since the three patients without collagen abnormality had the largest eyes (range of anteroposterior diameters, 19.2 to 20.3 mm). Nanophthalmos appears to result from several distinct defects.

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.

Rotary shadowing of elastic system microfibrils in the ocular zonule, vitreous, and ligamentum nuchae.

Rotary shadowing of zonular fibrils in human and bovine eyes revealed a "string of beads" configuration with multiple interconnecting filaments, identical to that recently reported in fibrils of unknown type within the vitreous. These 29 nm beaded fibrils were the only macrostructures present in zonular samples, showing ultrastructural features correlating with both the macro and microperiodicity of zonular fibrils in tissues. Interbead periodicity varied from 30-57 nm and interbead filaments appeared capable of stretching even further, possibly explaining the inherent elasticity of zonular fibrils. The junctions between outer filaments and beads were fibrillin-positive. Similar beaded fibrils were found in the human and bovine anterior vitreous along with type II and IX collagen fibrils, proteoglycan filaments and other unidentified fibrils. After collagenase and elastase digestion, bovine ligamentum nuchae showed type VI collagen fibrils and clumps of beaded fibrils like those in zonule and vitreous. This distribution indicates that the beaded fibril is the microfibril which constitutes the basic unit of the elastic system.

Necrobiotic xanthogranuloma with IgA multiple myeloma: a case report and literature review.

The association between necrobiotic xanthogranuloma of the dermis and paraproteinemia and/or B-cell malignancy is best described in the ophthalmologic literature. We report a case which occurred in the eyelid and orbit of a 64 year old man that led to the diagnosis of an IgA multiple myeloma. To our knowledge, this is the first report of an IgA type paraproteinemia and IgA type multiple myeloma associated with necrobiotic xanthogranuloma.

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.

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.