Tissue analysis from two patients with premacular hole lesions.
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Biomedical subjects
Publications and source records attributed to J Sebag.
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Patients with diabetes experience vitreous degeneration, characterized by "precocious" liquefaction and posterior vitreous detachment. Biochemical studies have detected that hyperglycemia alters vitreous collagen, changes that might be responsible for the observed vitreous degeneration. This study was undertaken to identify if there are morphological changes within the vitreous of diabetic patients that are consistent with the biochemical data and to identify how these could underlie the observed clinical phenomena. Ten eyes from 5 humans (4 normals aged 6, 11, 56, 82; 1 aged 9 with type I diabetes) were obtained at autopsy. Eyes were dissected in the fresh state and studied by dark field slit microscopy without fixatives or dyes. In normals, a transition was observed from a homogeneous structure in youth to one that contained fibers in middle-age, which degenerated and were associated with significant liquefaction in old age. In the diabetic child, the vitreous structure contained prominent fibers whose appearance was similar to middle-aged normals and not the age-matched controls. This study characterizes the morphological manifestations of precocious senescence of vitreous in a patient with diabetes. The abnormal vitreous fibers are likely the result of biochemical changes in collagen that are related to hyperglycemia--a phenomenon that could be inhibited by drug therapy.
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Pneumatic retinopexy was performed using only air in an attempt to minimize vitreous disturbance and lower the incidence of postoperative proliferative vitreoretinopathy (PVR) and premacular membranes (PMM). Retinal cryopexy or laser treatment (in 2 cases) and intravitreal injection of 0.8 cc filtered air were performed on 45 rhegmatogenous retinal detachments with superior breaks and no preoperative vitreous hemorrhage or PVR. Reattachment was achieved in 39 (86.7%) eyes. The remaining 6 eyes were secondarily treated with scleral buckle surgery, which was successful in all cases. The average length of follow-up was 17.1 +/- 8.6 months, at which time visual acuity was the same or better in 44 (97.8%) eyes. In 1 case (2.2%) PVR developed, a PMM formed in 1 case (2.2%), and new or missed retinal breaks were found in 4 cases (8.8%). This technique achieves a high rate of reattachment, good visual outcome, and low incidence of PVR, PMM, and new or missed breaks, perhaps due to the short-acting, nonexpansile nature of air.
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Vitreous changes in diabetes can exacerbate proliferative diabetic retinopathy. These changes may be due to the effects of diabetes on vitreous collagen. Vitreous samples from 19 patients with proliferative diabetic retinopathy and 23 patients without diabetes were analyzed for collagen crosslinks, as well as for the early glycation products, glucitolyllysine and glucitolylhydroxylysine. Fluorometry was performed to measure advanced glycation end products. Vitreous collagen derived from diabetic patients was found to have significantly higher levels of the crosslink dihydroxylysinonorleucine (3.15 vs 1.24 mol/mol collagen, P<.01) than that of control subjects. Early glycation products were elevated in diabetic vitreous (1.65 vs 0.54 mol/mol collagen, P<.05). Levels of advanced glycation end products were 20 times higher in diabetic vitreous compared with the vitreous of controls. These diabetes-induced alterations of human vitreous may be of particular importance given the role of vitreous in proliferative diabetic retinopathy and vision loss.
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Age-related differences in vitreoretinal adhesion were investigated in 59 human eyes from donors aged from 33 weeks of gestation to 94 years with the use of dark-field and electron microscopy of whole vitreous. In all eyes from individuals aged 21 years or older, dissection of the retina off the vitreous resulted in cleavage between the vitreous cortex and the internal limiting lamina. However, in six (40%) of 15 eyes from individuals aged 20 years or younger, the internal limiting lamina remained adherent to the vitreous cortex in an area that encompassed the macula, temporal arcades, and peripapillary posterior pole. Ultrastructural studies revealed inner portions of Müller's cells that were attached to the posterior aspect of the internal limiting lamina. These results suggested that, in youth, there is adhesion between the vitreous cortex and internal limiting lamina that is stronger than Müller's cell itself and is topographically more extensive than previously thought.
A total of 30 eyes of 19 patients with type I diabetes, varying severity of retinopathy, and no posterior vitreous detachment (PVD) were studied clinically, and vitreous examination was performed by preset lens biomicroscopy. Follow-up was 4.0-7.5 years. A total of 15 eyes underwent panretinal laser photocoagulation (PRP) and 15 eyes were left untreated. The incidence of PVD was 8 of 15 353%) after PRP and 1 of 15 (7%) in untreated eyes (P less than 0.02). Minimal vitreous hemorrhage occurred in 4 of 7 treated eyes (57%) that did not develop PVD and in only 2 of 8 (25%) that did. In treated eyes with no history of vitreous hemorrhage, the incidence of PVD was 6/9 (67%); in treated eyes with minimal vitreous hemorrhage at any time, it was 2/6 (33%). In treated eyes, the presence of Diabetic Retinopathy Study (DRS) high-risk characteristics was equally frequent in eyes that developed PVD as in those that did not. These data suggest that PVD occurs following PRP, independent of the severity of diabetic retinopathy or prior vitreous hemorrhage.
Retinal blood flow and oxygen saturation were evaluated in patients with unilateral inner retinal degeneration secondary to neurogenic optic atrophy. Arteriovenous O2 saturation for temporal and nasal vascular segments of the affected eyes, evaluated by retinal vessel oximetry, was 12% +/- 9% higher than in the fellow eyes (seven patients). Blood flow in the temporal retinal arteries of the affected eyes, measured by the laser Doppler technique, was 48% +/- 20% lower than in the fellow eyes (four patients). The combination of these results indicated a 40% +/- 29% reduction in O2 delivery in the affected eyes (four patients), thereby quantifying the decrease in retinal metabolism that resulted from inner retinal degeneration.
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The laser Doppler technique was used to measure the blood flow rate in 41 major vessels in ten eyes of healthy volunteer subjects. The specific relationship between blood flow rate, F, and vessel diameter, D, was determined for both retinal arteries and retinal veins. On average, F increased with increasing D at a power of 4.1, consistent with the presence of Poiseuille flow. In six eyes of six subjects, measurements on individual vessels were combined to yield the total retinal blood flow rate. The mean and standard deviation of the total retinal blood flow was 80 +/- 12 microliter/min. The blood flow rate per unit mass of retinal tissue was calculated and found to be in good agreement with that reported for macaque monkeys. Blood flow to the temporal side of the retina was approximately three times larger than to the nasal side. There was no significant difference between blood flow to the superior and the inferior retina.
Significant alterations in vitreous structure occur with aging and disease. There is controversy as to the nature of the normal structure of the vitreous and no studies have correlated macroscopic structure with ultrastructure in the same eyes. Twenty-eight fresh, untreated human eyes were examined after removal of the sclera, choroid and retina. Dark-field slit illumination of the whole vitreous revealed the presence of macroscopic fibrous structures. The fibers had an antero-posterior orientation with anterior insertions at the vitreous base and posterior insertions in the premacular vitreous cortex. Transmission electron microscopy demonstrated the presence of collagen fibrils and no membraneous structures. Parallel collagen fibrils packed in bundles were also detected. Macroscopic vitreous fibers most likely result from alteration of the hyaluronic acid-collagen complex with aggregation of collagen fibrils into bundles as seen on electron microscopy. Identifying the mechanisms underlying this process of fiber formation could clarify the pathogenesis of vitreous liquefaction and the pathophysiology of posterior vitreous detachment.
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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.