[Therapy of advanced amoeba keratitis with keratoplasty à chaud and adjuvant cryotherapy]. / Therapie der fortgeschrittenen Amöbenkeratitis mit Keratoplastik à chaud und adjuvanter Kryoapplikation.

BACKGROUND: Since the mid-1980s acanthamoeba keratitis has been diagnosed with increasing frequency, especially in contact lens wearers. The assignment to specialized centers is often delayed many months and there is hardly any chance of controlling the disease by conservative treatment alone. In these cases, penetrating keratoplasty offers the only chance for rehabilitation. The therapeutic role of penetrating keratoplasty and supportive intraoperative cryotherapy is demonstrated by the courses of six patients with unilateral acanthamoeba keratitis. PATIENTS AND METHODS: The data of six patients aged 41.2 (22-63) years with medically uncontrollable acanthamoeba keratitis were evaluated retrospectively. The diagnosis was confirmed histologically in all cases. All patients were contact lens wearers. They underwent a total of ten keratoplasties between November 1986 and January 1995. The donors were 44.8 (23-58) years of age. The transplant diameters varied between 7.7 and 9.5 mm. The margins of the host cornea were intraoperatively frozen by a cryoprobe in three patients with a far advanced stage of corneolimbal parasitic infiltration. RESULTS: During a follow-up period of +/-10.2 (1-22) months, five of six eyes were rehabilitated with visual acuities between 0.4 and 1.0. One eye went blind after the fourth keratoplasty because of uncontrollable secondary glaucoma. After three keratoplasties with simultaneous application of cryocoagulation because of an especially high risk of persisting acanthamoeba infection, all corneae remained clear and free of recurrences. CONCLUSIONS: In advanced acanthamoeba keratitis which has not responded to conservative treatment, penetrating keratoplasty not only provides elimination of the pathogen, but also good functional results. In far advanced stages, the intraoperative application of cryocoagulation for parasite elimination in the host cornea seems to be a very effective measure against local recurrences of the infection.

Tophus-like, conglomerated, crystalline calcification of the sclera.

The clinical history and the pathohistological findings of a peculiar form of multifocal scleral calcification in 3 globes of 2 patients are described. It consisted of globular drusen of rod-like crystals, fusing into large, tophus-like conglomerates. The crystals consisted of monoclinic and triclinic calcium pyrophosphate. The deposits can be interpreted therefore as scleral pseudogout. They were combined in places with a diffuse, idiopathic inner scleral calcification. The pathogenesis of these mineralizations is unclear. No signs of a dystrophic calcification were present. One patient, suffering from Alport's syndrome, had been normocalcemic for the last 16 years after renal transplantation, and no disturbed calcium metabolism was known in the second case.

Atheromatous and atheroma-like lesions of the central retinal artery: histopathological correlations.

Arteriosclerosis is very rare in the distal central retinal artery (CRA) of aged eyes devoid of significant ocular pathology. Nevertheless, atheromatous and atheroma-like lesions are occasionally observed in routine ophthalmic pathology. We investigated the histopathologic correlations of the eyes and vessels involved. Twenty-eight globes presenting atheromatous and atheroma-like lesions (defined as accumulations of foamy macrophages in the tunica intima) in the CRA or its first-order branches were obtained from our files and studied under light microscopy. Vessels were examined for 7 histological characteristics related to atherogenesis, and the histopathological features of the involved eyes were analysed. Deposits of foamy macrophages were observed most frequently in the postlaminar CRA, followed by the intraneural and the intralaminar segment. There was a conspicuous association with glaucoma (78.6%), especially neovascular glaucoma (71.4%). The most frequently associated ocular pathologic features were optic atrophy (96.4%), atrophy of the inner retina (85.7%), cataract (64.3%), and inflammatory conditions (50%). Atheromatous and atheroma-like lesions of the CRA appear to be more common than generally reported. It is unlikely that they represent an age-related degenerative type of arteriosclerosis. They are more likely to be primarily or secondarily related to the severe ocular disease conditions with which they are found.

Dystrophic calcification of an implanted hydroxyethylmethacrylate intraocular lens.

Hydroxyethylmethacrylate is a biomaterial still under clinical trial for use in foldable intraocular lenses. We observed a patient in whom a geographic opacification developed within an implanted hydroxyethylmethacrylate lens, together with granular deposits on the posterior lens capsule and in the scar of a paracentesis. The intraocular lens and posterior lens capsule were removed because of impaired visual acuity. Light and scanning electron microscopy disclosed nodular calcifications within the intraocular lens and granular, partially crystalline, calcifications on the posterior lens capsule. Energy-dispersive x-ray analysis and x-ray diffraction showed the deposits in the intraocular lens to consist of calcium hydroxyapatite. We presume this mineralization to be dystrophic, with calcium derived from lens remnants and phosphorus possibly derived from a thymoxamine solution used briefly during the cataract operation. Our observation suggests caution in the use of phosphated solutions together with hydroxyethylmethacrylate intraocular lenses and may warrant reconsideration of the suitability of hydroxyethylmethacrylate intraocular lenses, should additional similar cases be reported.

[Granuloma annulare of the eyelid]. / Granuloma anulare des Augenlides.

BACKGROUND: Granuloma annulare is a chronic inflammatory disease of connective tissue, manifested clinically by small, firm nodules. It is observed only rarely around the eyes. PATIENTS AND METHODS: We present four patients aged 33 to 66 years with papulomatous lesions of the eyelids. The lesions were mildly or not symptomatic. Biopsies were taken. There was no association with any systemic inflammatory disease. RESULTS: Histology was characteristic for granuloma annulare in all four cases. The clinical course was benign. CONCLUSION: When faced with papulomatous lesions of the eyelids, the ophthalmologist may consider a diagnosis of granuloma annulare in patients of any age. While granuloma annulare is generally observed in young persons, one of our patients was aged 66 years.

Ocular pathology in light chain deposition disease.

Light-chain deposition disease (LCDD), a rare form of monoclonal gammopathy, is characterized by deposits of amorphous light-chain material, mainly in the kidneys but also in various other organs. Here we present the first report of a light-, electron microscopic and immunohistochemical study of the globes of a patient suffering from LCDD secondary to multiple myeloma. Massive deposits of kappa light chains similar to those typically present in the kidneys were found beneath the basement membrane of the ciliary pigment epithelium, on vessels of the ciliary body, within the collagenous zones of Bruch's membrane, and in the innermost part of the choroid. The choriocapillaris in the macular area was partly obstructed by these deposits, and an exudative retinal detachment was present. Whether this detachment was the consequence of disturbed circulation of the choriocapillaris remains speculative.

[Inflammatory cellular infiltration in scleritis]. / Das entzündliche zelluläre Infiltrat bei Skleritis.

BACKGROUND: Scleritis can be a destructive disease frequently associated with autoimmune disorders. It is believed that primary vasculitis plays an important role in its pathogenesis, but little is known about the cellular effector mechanisms. The purpose of this study was to analyze the inflammatory cellular infiltrate in scleritis. PATIENTS AND METHODS: Two enucleated eyes were studied. In one patient, enucleation was done after perforation occurred in anterior necrotizing scleritis and, in the other, after the misdiagnosis of posterior scleritis as an intraocular tumor. Morphological criteria and immunohistochemical methods were used to characterize the inflammatory cellular infiltrate. RESULTS: The cells infiltrating the scleral fibers in the enucleated eyes consisted predominantly of T cells in both cases; many of the T cells were CD4-positive. Clusters of B cells were found in perivascular areas. In circumscribed areas neutrophils, macrophages, and plasma cells were part of the scleral infiltrate. Signs of a granulomatous process with activated macrophages (epitheloid and giant cells) were present in necrotizing scleritis. Expression of major histocompatibility class II molecules (MHC II) was found on lymphocytes and rarely on macrophages. Signs of primary vasculitis were not found in any of the specimens. CONCLUSION: The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T-cell mediated (autoimmune) disorder, which has major therapeutic implications.

Ocular involvement in keratosis follicularis associated with retinitis pigmentosa. Clinicopathological case report.

In 1988, Itin et al. published the combination of keratosis follicularis (KF; Darier-White disease), an autosomal-dominantly transmitted genodermatosis, and retinitis pigmentosa (RP) in two brothers. One of these patients died unexpectedly at the age of 54 years. His eyelids and globes were histologically studied post mortem. Involvement of the eyelids has rarely been described clinically and not at all histologically. The skin and the intermarginal zone of the lids exhibited the typical changes of this cutaneous disease involving the follicles of the eyelashes. Focal keratinizations of the limbal conjunctiva, a regional increase in conjunctival goblet cells and a diffuse thickening of the basement membrane of the corneal epithelium were present. They are probably not specific for KF. The retinal findings were those of a typical late stage of RP. The combination of both genetically transmitted disorders could point to a damage in neighbouring gene loci. An abnormality of the metabolism of vitamin A was supposed to play a pathogenetic role in both diseases but remains speculative, as does a genetic linkage.

Cell death and disposal in retinoblastoma: an electron microscopic study.

BACKGROUND: Tumor necrosis and cell death are common features of retinoblastoma. In non-malignant retinal cells after ischemia, as well as in many non-retinal tumors, cell death occurs in at least two ways. We investigated whether similar patterns of cell death could be demonstrated in retinoblastoma cells. METHODS: Nine globes with retinoblastoma from eight patients were studied. Paraffin sections stained with HE or the Feulgen method were examined by light microscopy. Several samples from each tumor were selected for electron microscopic study. RESULTS: Ultrastructurally, two main types of cell death were identified. Type I was characterized by progressive lysis of the cytoplasm and karyoplasm. Nuclear chromatin either dissolved or was transformed into compact clumps becoming extracellular dense bodies. Phagocytosis of cell remnants by neighboring tumor cells, or occasional macrophages, was common. Type II was characterized by progressive condensation and shrinkage of the cytoplasm and nucleus. Type II was subdivided in two forms distinguished mainly by characteristic patchy vs crescentic chromatin condensation. Small parts of condensed cytoplasm were engulfed by neighboring tumor cells. Compact cell remnants then underwent either phagocytosis by neighboring retinoblastoma cells or progressive intercellular disaggregation. CONCLUSION: Retinoblastoma cells may undergo at least two types of cell death. Type I fits the definition of necrosis, while both forms of type II exhibited several features consistent with apoptosis. The types of cell death observed in retinoblastoma exhibited similarities to patterns observed in ischemic retina, as well as in other malignant tumors. Type II cell death (apoptosis) may play a role in limiting tumor growth.

Bubbles in the bleb--troubles in the bleb? Molteno implant and intraocular tamponade with silicone oil in an aphakic patient.

A 14-year-old aphakic girl who had had previous bilateral glaucoma surgery with a Molteno implant underwent pars plana vitrectomy and silicone-oil tamponade for proliferative-vitreoretinopathy retinal detachment in both eyes. The filtering bleb of the left eye was functional for 5 months before becoming available for histologic examination. We found numerous foreign-body granulomas coating the inner surface of the bleb, as well as intracellular and extracellular deposits of emulsified silicone oil in the wall of the bleb. In the fellow eye, the filtering bleb remained functional despite repeated vitreous surgery with silicone oil. Filtration in aphakic eyes with previous Molteno surgery and silicone-oil tamponade after vitrectomy may continue normally for a prolonged period of time, although emulsified oil droplets likely will have accumulated in the bleb and become incorporated in its fibrous capsule.

Cells perpetuating the inflammatory response in scleritis.

Scleritis can be a destructive disease frequently associated with autoimmune disorders. It is believed that primary vasculitis plays an important role in its pathogenesis, but little is known about the cellular effector mechanisms. The purpose of this study was to analyse the inflammatory cellular infiltrate in scleritis. Six episcleral biopsies and two enucleated eyes were studied. The episcleral biopsies were taken from patients with nodular scleritis. In one patient enucleation was done after perforation in anterior necrotising scleritis and, in the other after misdiagnosis of posterior scleritis as intraocular tumour. Morphological criteria and immunohistochemical methods were used to characterise the inflammatory cellular infiltrate. The inflammatory cells infiltrating the episcleral tissue were mainly T lymphocytes and macrophages. There was a predominance of CD4 positive cells, but only few lymphocytes were activated (expressed IL-2 receptor). The cells infiltrating the scleral fibres in the enucleated eyes consisted in both cases predominantly of T cells. Clusters of B cells were found in perivascular areas. In circumscribed areas neutrophils, macrophages, and plasma cells were part of the scleral infiltrate. Signs of a granulomatous process with activated macrophages (epithelioid and giant cells) were present in necrotising scleritis. Expression of major histocompatibility class II molecules (MHC II) was found on lymphocytes and rarely on macrophages. Signs of primary vasculitis were not found in any of the specimens. The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T cell mediated (autoimmune) disorder, which may have major therapeutic implications.

Primary gelatinous drop-like corneal dystrophy in a white woman. A pathologic, ultrastructural, and immunohistochemical study.

A white female with primary gelatinous drop-like corneal dystrophy (PGDD) was followed from the ages of 8 to 37 years. During this time, she underwent repeated lamellar and penetrating keratoplasties on both sides due to relapsing bilateral corneal opacifications. The diagnosis of PGDD was based on the histology of the corneal specimens obtained at 10 and 36 years of age, as well as on the characteristic clinical appearance and course. Electron microscopy showed typical amyloid fibrils. Immunohistochemical staining was mildly positive for amyloid AL (light chain), but negative for amyloid AA, AF, AB, and keratin. Thus, the precursor protein of the amyloid deposits in PGDD might derive from immunoglobulins, e.g., from the tear film. However, the precursor protein might derive from a different origin altogether. In that case, the positive staining for amyloid AL would translate nonspecific absorption of fragments of light chains.

Conjunctivalization of Meibomian glands following cryosurgery for basal cell carcinoma of the eyelid.

Cryosurgery on the eyelids destroys the cellular elements in the frozen region, but preserves the collagenous supporting structures. Cells from the neighborhood colonize this framework during wound healing. The Authors describe a peculiar change in the Meibomian glands, which obviously developed by this mechanism in a lid treated by cryotherapy for a basal cell carcinoma. The collagenous lodges of the Meibomian glands, denuded of their sebaceous cells by the therapy, were epithelialized by ingrown conjunctival epithelium. This situation seems to promote the spread of and maintain acute and chronic exogenous inflammation in the tarsal plate.

Immunopathological findings in posterior scleritis.

Posterior scleritis can present with a variety of symptoms, and its clinical diagnosis is therefore difficult. Little is known about the pathogenesis and the cellular effector mechanisms. This case report presents the immunopathological findings of posterior scleritis in the enucleated eye of a 28-year-old female with no known underlying disease. The cells infiltrating the scleral fibers consisted predominantly of T cells. Many of them were CD4 cells. Clusters of T and B cells were found in perivascular areas. No signs of primary vasculitis were seen. The cellular infiltrate in posterior scleritis shows features compatible with a T-cell-mediated (autoimmune) disorder.

[Pathology of the vitreous body. Primary aspects and principles]. / Glaskörperpathologie. Grundlagen und Prinzipien.

Due to its simple structure, the vitreous body exhibits only a limited spectrum of pathological reactions. This structure undergoes age-related changes and degeneration throughout life. Modification in the relation between collagen and hyaluronic acid causes condensation of the vitreous fibrils, forming tractus, membranellae, and strands next to formations of clefts, lacunae, and detachments. Diseases of the adjacent tissues influence these degenerations qualitatively as well as quantitatively. According to its current condition, the vitreous body can influence the course and extent of diseases of adjacent tissues, its own structures acting as barriers or guiding formations for cells and tissues or as tracting "tendons". These basic principles are illustrated with examples from the particular pathology of the vitreous.

The diameter of the ciliary sulcus: a morphometric study.

Based on a precise definition of boundaries of the ciliary sulcus, a new anatomical method was used to measure the diameter of the ciliary sulcus in postmortem eyes. In each of 41 globes, 24 different ciliary sulcus diameters were measured and were compared with the axial length, measured by ultrasonography. The mean ciliary sulcus diameter was 11.25 mm (SD = 0.38 mm). By linear regression, the axial length values were significantly correlated with ciliary sulcus diameters. In addition, our data suggest that existence of two groups of eyes differentiated exclusively by the diameter of the ciliary sulcus, independent of the axial length. We propose that the displacement of the pars plicata corporis ciliaris from the peripheral iris to the iris root during the embryonic period may be incomplete in eyes of shorter axial length. The findings of the present study may play a role in cataract surgery in which an intraocular lens is inserted into the ciliary sulcus.

Common histopathological changes in aged human orbital arteries.

The physiology of the orbital arteries supplying the eye is currently under intensive investigation. However, while the anatomical distribution of these vessels in humans is well known, their normal histology and age-related or other pathologic alterations have hardly been studied. We obtained at autopsy 10 orbits from persons aged > or = 74 years, and two orbits from a person aged 47 years. Specimens were taken from 20 locations along the orbital arteries, from the internal carotid to the globe, and studied by light microscopy. We observed the following arteriosclerotic changes, in order of decreasing frequency: intimal hyperplasia, medial atrophy, atherosclerotic fibrous plaques, and calcifications of the internal elastic lamina. As a rule, the intensity of the changes decreased from proximal to distal. This study shows that aged human orbital arteries are readily subject to degenerative changes that may play an important role in ophthalmic vascular disease.

Failure to control AIDS-related CMV-retinitis with intravenous ganciclovir.

Between January 1988 and May 1991 intravenous ganciclovir (GCV) treatment was administered to eight male AIDS-patients with unilateral cytomegalovirus (CMV)-retinitis. Despite of continuous therapy with at least the recommended dose of GCV, three patients developed slowly progressive CMV-retinitis in the fellow eye after 4 to 13 months. The progression could not be stopped by GCV and thus bilateral blindness resulted after 12 to 22 months. The number of CD4-lymphocytes in the blood was reduced in all patients, but particularly in patients with progressive disease. Treatment failure was partly related to the duration of CMV-retinitis and partly to the degree of immunodeficiency. Intravenous treatment with GCV alone can not stop the progression of CMV-retinitis in long-term survivors and in those with advanced immunodeficiency.

Distended optic nerve sheaths in Leber's hereditary optic neuropathy.

Distension of the optic nerve sheaths is a feature of Leber's hereditary optic neuropathy (LHON) that has attracted attention only recently. We followed a patient with LHON for 23 years and obtained his eyes for pathological examination after death. We report the first histologic description of distension of the optic nerve sheaths, together with typical histopathological findings of LHON. Distension of the optic nerve sheaths could not be accounted for by any etiology other than LHON, although the precise pathogenic mechanisms remain enigmatic.

[Morphologic aspects of therapy-resistant cytomegalovirus retinitis]. / Morphologische Aspekte bei therapieresistenter Cytomegalovirus-Retinitis.

Intravenous ganciclovir treatment was performed in eight male AIDS patients with primary unilateral CMV-retinitis. Three patients developed slowly progressive CMV-retinitis in the fellow eye despite adequate dose of ganciclovir. These different CMV-manifestations are shown in a sequence of fundus pictures. Three types of CMV-lesions were observed in connection with this study. Untreated central lesions showed the aspect of crumbled cheese and ketchup. Untreated lesions in the peripherie were yellowish-white, granular, "dry" and showed in most cases no haemorrhages. Lesions appearing during treatment showed initially "dry" white opaque subretinal areas, turning later on to the typical aspect of untreated lesions. The progression could not be stopped by highdose ganciclovir i.v. and thus bilateral blindness resulted after 12 to 22 months. The level of CD4-lymphocytes in the blood was diminished in all patients, but much more in patients with progressive disease.