Structure, function, and age-related changes of the human vitreous.
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Biomedical subjects
Publications and source records attributed to J Sebag.
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Changes in vitreous structure that occur with aging are important in the pathogenesis of vitreous liquefaction (synchisis senilis), vitreous detachment, and retinal disease. Vitreous morphology was studied in 59 human eyes post-mortem using dark-field horizontal slit illumination of the entire dissected vitreous. In many individuals younger than 30 years, the vitreous was homogeneous in structure. Middle-aged individuals had macroscopic fibers in the central vitreous, which coursed anteroposteriorly and inserted into the vitreous base and the vitreous cortex, posteriorly. During senescence, the vitreous volume was reduced, the vitreous body was collapsed (syneresis), and the fibers were thickened, tortuous, and surrounded by liquid vitreous. This sequence of age-related changes probably results from a progressive reorganization of the hyaluronic acid and collagen molecular networks. Characterization of the molecular events underlying these changes will elucidate the mechanisms of the phenomena of synchisis, syneresis, and detachment, and may provide methods with which to prevent or induce vitreous detachment prophylactically.
Sensitized photo-induced changes of vitreous structure were investigated using both in vivo and in vitro model systems. In the former, rabbit eyes were injected with the photosensitizer riboflavin, and in the latter, calf vitreous samples were treated with riboflavin or Methylene Blue prior to irradiation with white light. The active species of oxygen, i.e. singlet oxygen, superoxide anion, hydroxyl radical and hydrogen peroxide, generated by the photodynamic action of the sensitizer, caused significant liquefaction of the calf vitreous in vitro. There was little liquefaction of the rabbit vitreous in vivo, suggesting the presence of a protective mechanism in vivo. hyaluronidase induced significantly greater liquefaction in vitro than either Methylene Blue or riboflavin. This study suggests that loss of gel vitreous structure can result from extensive depolymerization of hyaluronidase by hyaluronidase and less drastic conformation and molecular weight changes in the photosensitized reactions. Although light-induced liquefaction was less marked than enzyme-induced liquefaction, the mechanism of the former is more pertinent to age-related vitreous synchysis.
Changes that occur in the vitreous during ageing contribute to a variety of vitreo-retinal disorders. These age-related changes are rheologic, biochemical, and structural in nature. Our current knowledge of these ageing changes is reviewed. Hypotheses for the mechanisms of liquefaction (synchisis senilis) and posterior vitreous detachment are proposed.
Studies in experimental models of retinal detachment have proposed that the degree of visual recovery following retinal reattachment depends upon the extent of photoreceptor degeneration. A means of assessing this degeneration would help in establishing postoperative prognosis. S-antigen (S-Ag) is a unique retinal protein found in outer segment disc membranes and photoreceptor cells. In 36 cases of human rhegmatogenous retinal detachment, subretinal fluid (SRF) concentrations of S-Ag, measured by radioimmunoassay, ranged from 43 to 170 ng/ml (serum: 1-28 ng/ml). Analysis of variance showed a positive correlation with the duration of detachment (P less than 0.001). There was a two-fold increase in S-Ag concentrations during the first 2 weeks of detachment (P less than 0.005), with constant levels thereafter. These findings reflect progressive photoreceptor degeneration and/or ongoing synthesis of outer segment proteins in the detached retina that stop after the second week of detachment. SRF S-Ag levels may provide a prognostic indicator of visual recovery after reattachment as well as a sensitive measure of retinal metabolic activity during detachment.
Anterior optic nerve blood flow was studied in nine patients with unilateral neurogenic optic atrophy using noninvasive techniques. Disk reflectometry measurements from temporal sites demonstrated a significant reduction in the index of blood volume in atrophic optic nerves as compared with the contralateral optic nerves (P less than 0.00001). Laser Doppler measurements from the same temporal sites detected a significant reduction in the speed of blood (P less than 0.002). On average, blood volume was decreased by 49% +/- 11% and blood speed by 30% +/- 17%. Combining the results of these two techniques yielded a relative index of blood flow that showed a significant reduction in the atrophic nerves (P less than 0.0001), averaging 64% +/- 14% temporally. Nasally there was less reduction in blood flow. The results correlated well with clinical assessment of the degree of optic nerve damage (rho = 0.92, P less than 0.002). This study demonstrates that clinical neurogenic optic atrophy induces significant reductions in overall anterior optic nerve blood flow that are detected by these noninvasive techniques.
Five cases of anterior ischemic optic neuropathy secondary to biopsy-proven giant cell arteritis are presented. In each case, cupping of the optic disc, which closely resembled glaucomatous cupping, was observed in the affected eye. The presence of glaucoma was ruled out on the basis of normal intraocular pressures and normal tonographic measurements of facility of outflow. These cases indicate that arteritic ischemic optic neuropathy can result in optic disc cupping, which closely resembles glaucomatous cupping. The similarities in the appearance of cupping of these discs with that seen in eyes with glaucoma suggest that the pathogenesis of cupping in glaucoma and in arteritic ischemic optic neuropathy may share some common mechanisms.
Twenty pigmented rabbits weighing 2-3 kg were employed. Under operating microscope control, a Graefe knife was used to perform a 6-mm-long perforating incision in the central cornea. The operated eye which showed a stimulation unit at 4 ng X ml-1 on rat 3T3 cells in 10 rabbits was treated locally with sterile PBS, and on day 30 the rabbits were sacrificed and the operated eye enucleated. The central cornea was excised using a cutting template 10 X 3 mm, with the long axis perpendicular to the center of the experimental wound. The tensile strength was determined by measuring the force of rupture of the wounds using a dynamometer. The results indicate that epidermal growth factor significantly (p less than 0.001) increased corneal wound tensile strength after the first month of healing.
Anterior optic nerve blood flow was measured in 9 patients with unilateral neurogenic optic atrophy. The noninvasive techniques of reflectometry and laser Doppler detected a decrease in capillary blood flow of the affected eyes as compared with the control fellow eyes as compared with the control fellow eyes (p less than 0.002) that averaged about 64% +/- 14%. There was a good correlation between the decrease in blood flow and the clinical severity of disease (p = 0.92, p less than 0.002). These noninvasive techniques provide a sensitive, safe, and accurate evaluation of the anterior optic nerve that is useful in both clinical research and patient care.
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Three cases of transorbital penetrating trauma to the frontal lobe are reported. These cases are remarkable in that minimal ocular trauma was incurred and excellent vision was preserved. These cases underscore the importance of suspecting the possibility of intracranial injury when evaluating penetrating orbital trauma.
Adult human vitreous structure was studied by dark-field Slit Microscopy in fresh, unfixed preparations of vitreous dissected off the sclera, choroid and retina. Macroscopic fibres oriented in an antero-posterior direction were detected. These fibres inserted at the vitreous base and oriented towards the macula. Significant alterations were observed in this vitreous structure with advanced age. The role of these structures in vitreo-retinal disease is discussed.
An 8-year-old boy presented with acute proptosis of the right eye. Examination revealed 8 mm of exophthalmos, limitation of upward gaze, optic disc swelling, and normal visual acuity, but an inferonasal quadrantic visual field defect. Orbital ultrasound and computed tomographic scanning demonstrated a superotemporal tumor of the right orbit with intracranial extension. At operation, this proved to be a "reparative" giant cell granuloma. After partial resection, the remaining mass resolved spontaneously without further specific treatment. There had been no recurrence at the 1-year follow-up examination.
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This study attempts to establish whether neurogenic optic atrophy induces changes in anterior optic nerve circulation and to determine how noninvasive techniques of measuring blood flow in vivo compare to microsphere distribution. Five cats underwent unilateral optic nerve transection in the orbital apex and a sham procedure in the contralateral eye. Two to three months later, no abnormalities were detected by fluorescein angiography. Laser Doppler measurements demonstrated a 53% decrease in red blood cell speed through the capillaries of the atrophic optic nerve heads in vivo. Optic disk reflectance measurements of anterior optic nerve blood volume in vivo demonstrated a 51% decrease in the estimated blood volume of the capillaries in atrophic optic nerve heads. Flow was calculated on the basis of these noninvasive measurements and demonstrated an average decrease of 74% in optic atrophy. Histologic studies of microsphere distribution demonstrated an average decrease of 80% in flow to the anterior optic nerve in optic atrophy. These results suggest that anterior optic nerve blood flow is significantly reduced in primary neurogenic optic atrophy. This study also demonstrates that the noninvasive measurements of blood flow are substantiated by histologic evaluation of microsphere distribution.
Although it had been widely accepted that vitreous traction plays a key role in the pathogenesis of aphakic cystoid macular edema, vitreoretinal traction is not observable in many patients and other hypotheses have also been investigated. The authors review the present knowledge of the anatomy of the vitreoretinal interface and the pathologic findings in cystoid macular edema. A new hypothesis combining the effects of both traction and inflammation is proposed.
A case of pigmentary retinal degeneration causing blindness in early childhood, progressive neurosensory hearing loss, diabetes mellitus, acanthosis nigricans, hypogonadism with normal secondary sex characteristics, and kyphoscoliosis without polydactyly and with no mental retardation is reported. The results of endocrinological studies, karyotype analysis, and digital dermatoglyphics supported the clinical diagnosis of the Alström syndrome. The patient had small globes, bilateral posterior subcapsular cataracts, lacy vacuolation of the iris, ciliary process hyalinisation, unilateral asteroid hyalosis, total absence of rods and cones, intraretinal melanin pigment, retinal pigment epithelium atrophy, focal chorioretinal fusion, preretinal fibrosis, bilateral giant optic disc drusen, and optic nerve atrophy. Electron microscopy of the retina demonstrated large numbers of melanolysosomes, numerous folds of basement membrane material, disruption of Bruch's membrane, and numerous bundles of extracellular collagen fibrils in the retinal pigment epithelium.