Retinopathy in diabetic hypertensive monkeys: a pathologic study.

BACKGROUND: No satisfactory primate model of diabetic retinopathy has been produced. The clinical picture of microangiopathic retinopathy in diabetic hypertensive monkeys has been previously reported. The present study describes the pathologic findings of these animals. METHODS: Eleven eyes of six monkeys (five rhesus, one cynomolgus) were studied. Diabetes mellitus was either spontaneous or induced by streptozocin; mild arterial hypertension was either spontaneous or induced by fludrocortisone acetate. In two monkeys, the horseradish peroxidase tracer technique was employed. Trypsin flat preparations of the nasal retinal vasculature were prepared. The material was studied by light and electron microscopy. RESULTS: We divided the development of the microangiopathic retinopathy into three stages. In the early stage, background retinopathy was characterized by microvascular abnormalities and capillary dropout. Massive vascular leakage, intraretinal exudates and hemorrhage, cystoid degeneration, and cotton-wool spots were features of an exudative retinopathy in the second stage. In the final stage, chronic ischemic retinopathy was characterized by vascular occlusions and areas of retinal atrophy. CONCLUSION: Microangiopathic retinopathy in diabetic monkeys with mild hypertension presented many features of human diabetic and hypertensive retinopathy, except vitreous neovascularization.

Genetic heterogeneity in autosomal dominant pattern dystrophy of the retina.

PURPOSE: Mutations in the retinal degeneration slow (RDS)/peripherin gene have been shown to be associated with pattern dystrophy of the retina (PDR) and other retinal dystrophies. The aim of our study was to confirm or exclude the RDS locus and the rhodopsin (RHO) locus as the disease causing locus in a large Swiss family affected with pattern dystrophy of the retina. MATERIALS AND METHODS: A Swiss family with 14 members across 3 generations affected with PDR was examined. Eleven living family members were investigated using 6 markers surrounding the RDS and RHO loci. RESULTS: Linkage to two possible candidate genes, the RDS gene on chromosome 6p and the rhodopsin gene on chromosome 3q, could be excluded. CONCLUSIONS: The family provides evidence for genetic heterogeneity of PDR and is in agreement with heterogeneity in other retinal dystrophies. Further investigations are in progress to map the gene causing PDR in this family.

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.

Necrosis and apoptosis in neuroretina and pigment epithelium after diffuse photodynamic action in rats: a light and electron microscopic study.

Cell death in the rat retina has been shown to occur mainly along two distinct pathways after pressure-induced ischemia. The authors conducted a qualitative investigation to determine whether similar types of cell death could be identified after diffuse photodynamic injury and photothrombosis. After i.v. injection of rose bengal (40 mg/kg), the eyes of 21 albino rats were exposed to light for durations ranging from 2 to 15 minutes, at a light intensity of 15-17,000 ft-cd, with interposition of a Kodak Wratten gelatin filter #15. Survival times ranged from 15 minutes to 6 days. The specimens were studied by light and electron microscopy. We identified two types of retinal cell death in the neuroretina and in the retinal pigment epithelium (RPE). Type I cell death was consistent with necrosis, and type-II cell death showed many features of apoptosis. These observations may not be exhaustive. The patterns of retinal cell death in this model appeared to be identical with those found after pressure-induced ischemia. The morphology of apoptosis of the RPE is hitherto undescribed. This study corroborates the concept of a limited number of types of cell death in the retina after exposure to noxious stimuli of various kinds.

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.

beta-Galactosidase transgene expression in transplanted rabbit retinal pigment epithelial cells in vivo.

BACKGROUND: Intraocular transplantation of genetically modified cells that release a particular substance could have a major impact on the treatment of various ocular diseases. We studied the expression of the reporter gene beta-galactosidase (lacZ) in transplanted retinal pigment epithelial (RPE) cells in vivo. METHODS: RPE cells from pigmented rabbits were transduced with the beta-galactosidase gene in a retroviral vector. Cells were then assayed for gene expression and transplanted subretinally into the eyes of New Zealand White rabbits. RPE cells that were transduced with a similar vector without the beta-galactosidase gene were used as controls. Rabbits were killed on days 1, 7, and 21 and the eyes processed for transmission electron microscopy RESULTS: Neomycin-resistant rabbit RPE cells that showed beta-galactosidase activity were generated within 2-5 weeks. After transplantation, viable RPE cells that expressed the transgene and that phagocytosed rod outer segments were observed on days 1, 7, and 21 CONCLUSIONS: The results show that generation of genetically modified RPE cells is feasible and that the transplanted cells remain viable and continue to express the transgene in the subretinal space of the host animal for at least 21 days. Transplantation of such genetically modified RPE cells could provide a new tool for studying retinal diseases and, potentially, for correcting metabolic abnormalities in retinal degenerations and dystrophies.

Age-dependent phenotypic expression of a pattern dystrophy of the retina.

We studied a family with pattern dystrophy of the retina (PDR) in order to elucidate the clinical course of the disorder, relations between the different forms, and the mode of inheritance. Thirty-nine family members, representing three generations, underwent a thorough ophthalmological examination, with fluorescein angiography whenever a macular abnormality was suspected. Of family members over the age of 32 years, 46.7% showed signs of PDR. We classified the clinical forms of PDR in this family into four types: minimal lesion, pseudovitelliform type, butterfly-spider type, and late-stage lesion. These forms were predominant in the order cited in age groups 31-40 years, 41-50, 51-60, and > 60 years. Significant visual loss occurred only after the age of 50 years, when 8 of 14 eyes had visual acuity of less than 20/25. Inheritance was autosomal dominant. PDR presented different clinical forms in members of this family, and in successive age classes patterns of increasing severity prevailed. Thus, the different phenotypic forms apparently represent transient stages related to the age of the patient.

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.

[Arteriosclerosis of the orbital arteries]. / Arteriosklerose in Orbitalarterien.

BACKGROUND: The anatomy of the orbital arteries is well known, and their physiology is under intensive investigation. Their age-related or other pathologic alterations, however, are still largely unknown. METHOD: We obtained at autopsy 16 orbits from 8 persons aged > 70 years, and 4 orbits from 2 persons between 40 and 50 years. Specimens were taken from 20 locations along the orbital arteries, from the internal carotid to the globe, and studied by light microscopy. RESULTS: 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. The frequency and severity generally decreased with smaller arterial caliber. CONCLUSION: Arteriosclerosis was ubiquitous in persons > 70 years of age. Degenerative changes in aged human orbital arteries may play an important role in ophthalmic vascular diseases.

[Irreversible cataract as a possible side effect of isoretinoin]. / Irreversible Katarakt als mögliche Nebenwirkung von Isoretinoin.

BACKGROUND: Isoretinoin, a drug used in the treatment of severe cystic acne, is known for its numerous adverse ocular side effects, among others. Generally these side effects are benign in nature and reversible on cessation of drug therapy, as for instance transient acute myopia. However, two cases of irreversible cataract possibly related to isotretinoin have been described up till now. PATIENT: We examined a 37-year-old woman with acute unilateral cataract that occurred after a treatment with isotretinoin for four months, terminated a few days previously. A clear etiological relation could not be established. CONCLUSION: The time relation, the acute onset and the absence of other factors nevertheless suggest an influence of isotretinoin therapy to the occurrence of the cataract.

[Pseudallescheria boydii fungal endophthalmitis. 6 years after trabeculectomy]. / Pseudallescheria-boydii-Pilzendophthalmitis. 6 Jahre nach Trabekulektomie.

A case is reported of a 67-year-old female patient, in whom a fungal endophthalmitis occurred 6 years after trabeculectomy. Pseudallescheria Boydii was isolated. This organism is a rare cause of infection. In the literature only 14 cases of keratitis and 8 cases of endophthalmitis have been reported. Miconazole is the therapy of choice. However in 55% of the published cases, (as in the one reported here), an exenteration or enucleation of the affected bulbus was necessary.

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.

Injuries induced by diffuse photodynamic action in retina and choroid of albino rats. Morphologic study of an experimental model.

BACKGROUND: The morphologic changes of the retina, choroid, and respective vasculatures in an experimental model of diffuse photothrombosis and photodynamic injury were studied. METHODS: After intravenous injection of rose bengal (40 mg/kg), eyes of 21 albino rats were exposed to a light intensity of 15-17,000 ft-cd for 2 to 15 minutes. Survival times ranged from 15 minutes to 6 days. The specimens were studied by light and electron microscopy. RESULTS: Photothrombosis of retinal and choroidal vessels was variable in extension and duration. Vascular lesions included vacuolation and sloughing off of endothelium, and necrosis and apoptosis of pericytes and smooth muscle cells. Retinal and choroidal injuries exhibited considerable regional and structural differences, such as predominance in the outer versus inner retina, or focal versus diffuse injury. CONCLUSION: Damage produced by this model was irregular in extent and character, due to several hard-to-control parameters. It was presumably due not only to ischemia but also to free radical chain reactions initiated by photodynamic action. This model may not be suitable for rapid quantitative assessment of ischemic retinal injury, but it provides opportunities for the investigation of pathophysiologic mechanisms.

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.

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.