Acta ophthalmologica. Supplement最新文献

The aim of the present thesis was to develop, refine, and assess experimental models for the study of proliferative vitreo-retinal disorders. An intravitreal injection of a colloidal solution of microparticles was used in the primate eye to produce pathologic changes including intraocular cell invasion, cell proliferation, neovascularization, collagen synthesis, and tractional retinal detachment. In a separate primate model for laser-induced subretinal neovascularization, the origin and the occurrence of macrophages was evaluated. Examinations were performed using ophthalmoscopy, slit-lamp microscopy, light microscopy, and transmission electron microscopy. Cell cultures were employed to study the effects of vitreous humor and macrophages on the proliferation of cultured retinal pigment epithelial (RPE) cells and cultured fibroblasts using a Coulter counter. Morphologic changes were documented by phase micrography. A quantitative estimation of the extracellular matrix deposition of fibrous proteins by macrophage-modulated RPE cells as well as by vitreous-modulated RPE cells was done using enzymatic digestion and radioactive labeling techniques. A qualitative analysis of the types of collagen that was deposited in the extracellular matrices by vitreous modulated cultures was also made using indirect immunofluorescence. Using a newly developed RPE cell specific monoclonal antibody, the avidin-biotin-peroxidase labeling technique was finally employed to test the phenotypic epitope expression of macrophage-modulated and non-modulated RPE cells. A new experimental in vivo model for pathologic changes that characterize proliferative vitreo-retinal disorders was developed in the primate eye. In the model for laser-induced subretinal neovascularization, macrophages were shown to be principally recruited from the systemic circulation. Using cell cultures, it was found that both macrophage-conditioned medium and vitreous humor, separately or combined, exert mitogenic effects on RPE cells and fibroblasts. The combined effect of the two stimuli was additive, but not synergistic, on both cell lines. When incubated with macrophage-conditioned culture medium or vitreous humor, RPE cells exhibited a metaplastic transformation towards fusiform, spindle-shaped cells that were morphologically indistinguishable from fibroblasts. The extracellular matrices of RPE cells modulated by macrophage-conditioned medium also appeared converted to a more striated pattern as compared to non-modulated controls. The metaplastic transformation of cultured RPE cells reverted when experimental stimuli, macrophage-conditioned medium or vitreous humor, were withdrawn. A new in vitro method for evaluating fibrous protein deposition in the extracellular matrix by RPE cells was also described. RPE cells, that were modulated by macrophage-conditioned medium or vitreous humor, deposited less fibrous proteins per cell.(ABSTRACT TRUNCATED AT 400 WORDS)

The thesis presents a technique designed to allow a comparison of retinal function as assessed by computerized perimetry with retinal morphology as seen on photographs of the ocular fundus, including results from the practical application of this technique in the study of diabetic retinopathy. The basis of the technique is an optical algorithm that allows angular distances in the visual field to be transformed to match linear distances on fundus photographs and fluorescein angiograms. The visual field data is superimposed onto the corresponding retinal morphology on the photograph on the basis of two points of reference. The fixation point in the visual field is superimposed onto the foveola on the photograph of the ocular fundus, and the blind spot in the visual field is superimposed onto the optic disc on the photograph. In the practical application of this technique for the study of diabetic retinopathy, visual field scotomata were found corresponding to areas displaying signs of retinal vascular impairment in the form of vascular occlusion, while no relation was found between visual field scotomata and breakdown of the blood-retina barrier as studied on fluorescein angiograms. Furthermore, visual field scotomata were found to correspond to areas peripheral from retinal neovascularizations, a finding supporting the hypothesis that the neovascularizations develop because of stimulation from vasogenic factors released from ischaemic and hypoxic retinal tissue. Visual field scotomata were also found in relation to retinal cotton wool spots. These scotomata were localized, and not accurately extended, which could be expected if the retinal nerve fiber layer had been damaged. Finally, some visual field scotomata could not be related to any visible funduscopic or angiographical morphology. It is concluded that pathological changes in the inner retinal vascular supply may lead to impairment of visual function in diabetic retinopathy, but that also other mechanisms not manifested in a morphologically visible way, are involved. A further investigation of the pathophysiology leading to visual impairment in diabetes mellitus should focus on these unknown factors. A possible approach could be the development of new techniques for studying pathophysiological mechanisms in specific retinal layers, and especially the layers supplied by the external vascular supply to the retina from the choroidal circulation.

Visual field abnormality is an important diagnostic sign in glaucoma. Therefore, the presence or absence of visual field loss most often strongly influences diagnostic and therapeutic decisions in glaucoma management. Interpretation of visual field results is often difficult, however. Physiological variability of perimetric sensitivity values contributes to these difficulties. It has been our aim to develop improved computer-assisted methods for the recognition of early glaucomatous field loss. Our approach has therefore been to design techniques that are highly sensitive to small but significant departures from normality. We have investigated normal physiological variability in perimetric results and combined the obtained knowledge with pathophysiological models which are sensitive to the spatial patterns of field loss commonly seen in glaucoma. Thus, we have devised probability scores in order to take the complex physiological variability into account, and developed a hemifield analysis and an arcuate cluster analysis based on the normal anatomy of the retinal nerve fibre layer. A fundamental approach in the collection of normative data and the selection of glaucoma cases used in this project has been to select subjects using non-perimetric criteria (except for the removal of large field defects). Our objective here was to reduce bias from pre-conceived ideas of visual fields. This approach was used for (1) empirical studies on physiological variability, (2) development of analysis methods, and (3) evaluation of such methods. Glaucoma patients were selected based on evaluations of optic disc appearance. Normal subjects were never eliminated on the basis of perimetric results alone. The new methods developed in these studies have significantly improved discrimination between normal and glaucomatous field results, as compared with previously available techniques. Our results indicated that the usage of probability scores was the main source of this improvement, and that the location of observed field abnormalities and spatial modelling were other important factors. Candidate methods which did not properly combine spatial and normative analyses resulted in false positive defects in the mid-periphery and/or underestimated paracentral glaucomatous field defects. Similar approaches based on classification of visual field results in terms of significances, and on recognition of specific spatial patterns of field loss could be used for other groups of diseases having visual field abnormality as an important diagnostic sign.(ABSTRACT TRUNCATED AT 400 WORDS)

Secondary cataract formation is the most common postoperative complication following cataract surgery. To study different methods preventing the secondary cataract formation a relevant animal model is required. An in vivo rabbit model for studies on the prevention of secondary cataract formation is presented. The lens nucleus and cortex were removed by phacoemulsification, and two months later the growth of the secondary cataract was estimated by scoring on a scale from 0-4, both central and peripheral, and by measuring the wet mass of the dissected secondary cataract. The model seems to be a relevant way to study different concepts for the prevention of secondary cataract formation.

From a therapeutic and pathological point of view, it is important to classify types of cataract and to identify their stages. However, accepted criteria for quantitative diagnosis have not been established. On the other hand, based on the experience from tissue characterization applied to other clinical fields, the attenuation characteristics of the lens are expected to change according to the stage of disease and the type of cataract. In this study from echo signals we tried to measure the attenuation coefficient of the lens with the purpose of quantitatively diagnosing the cataract, and at an early stage. It is shown that the attenuation of the cataractous lens is larger than that of the normal lens and its value depends on the type of the cataract, an indication of the possibility of using tissue characterization in the evaluation of cataract.

The approximately 6-7 layers of closestpacked photoreceptor cell bodies in the outer nuclear layer of the human retina are interpreted as hexagonal multilayer phase or three-dimensional gratings with refractive index differences between the cell nucleus and the cytoplasm. A multilayer 3D grating of this type allows incident light to be processed by Fresnel interference in the plane of focus of the geometrical-optical system of the human eye, forming triplets of chromatic interference maxima made available, at discrete concentric locations, to the outer segments of the cones and rods for further processing. Transformation of the 3D grating spacing (in the sense of a stimulus-adaptive optic) into the dimensional periodicity of the spectral stimulus which is processed with maximum amplitude in the 111 color channel gives three chromatic signals at 559/537/447 nm in the visible 'spectral window', i.e. at spectral locations which match the 3 wavelengths of (photochemically determined) maximum spectral sensitivity in photopic vision. Variation of the cell geometry in the 3D grating gives rise to the Purkinje shift with fusion of the RED-GREEN diffraction orders at 512 nm. Color proves mathematically to be the product (varied by the diffraction order triplets) of the speed of light and the three-dimensional geometry. The chemistry of the photoreceptors, i.e. the programming of the visual pigments, would consequently be based on 3D grating optics. The human eye would process trichromatic Fourier signals, not geometrical-optical images. The first stage of color vision would be based on 3D grating optics, without the involvement of neuronal networks. New interpretations ensue for color constancy, color adaptation, color visual field, inter alia. The eye, as a trichromatic Fresneloptical modulator of the information present in the amplitude, phase and frequency of the processed light, receives considerably more information on perceived objects than it passes on to the brain. Cellular 3D gratings may also be models for the interference of acoustic, chemical and other waves in cortical processing centers.

Macular recovery, recorded by nyctometry, has been studied in children and adults with IDDM. Impaired macular recovery was found only in a few eyes with normal visual acuity without visible signs of retinopathy, in more than one third of the eyes with slight background retinopathy, in the majority of eyes with advanced background retinopathy, and in all eyes with proliferative retinopathy, suggesting that severe neurosensory disturbance accompanies visible vasculopathy in the retina. A significant correlation between impairment of macular recovery and reduction of the oscillatory potentials of the electroretinogram was found in groups with slight background retinopathy, severe background retinopathy, and proliferative retinopathy, suggesting that changes in these two neurosensory variables concurrently reflect abnormalities in the inner part of the retina corresponding to second order interneuronal connections. Near-normal blood glucose control obtained by continuous subcutaneous insulin infusion (CSII) significantly enhanced both normal and impaired macular recovery. This effect was more pronounced in patients with short duration of IDDM; no effect was found by short-term treatment of a selected group of patients with long-standing metabolic dysregulation and long disease duration. Young patients with normal or slightly impaired macular recovery might possibly benefit from sustained near-normal blood glucose control. Large-scale and long-term studies are needed to confirm this assumption. In a 3-year investigation with CSII, progression into proliferative retinopathy could not be prevented in those patients initially displaying severely impaired macular recovery. However, visible retinopathy did not progress in eyes, in which improvement of within normal or slightly reduced recovery performances had been recorded 6 months in advance. It is suggested that a state of irreversibility, 'point of no return', of retinal pathology, indicated by a certain severe impairment of neurosensory function, might exist. Prospective investigations, 5 years with adults, and 6 years with children, revealed progressive decline in recovery performances during the years of observation, even in eyes with no or slight deterioration of the retinal appearance; and in some eyes retaining no or slight retinopathy, severe impairment of performance developed. Both investigations showed significant differences of initial macular performance between the groups developing proliferative retinopathy and the groups remaining non-proliferative in the periods of observation, suggesting that abnormally reduced recovery performance precede by months or a few years the development of proliferative retinopathy. The development into proliferative retinopathy is generally preceded by increasing stages of background retinopathy running parallel to increasingly reduced macular recovery. The present study has demonstrated large variances of performances both in normal and diabetic indiv