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J.  Sebag

    J. Sebag

    • Educated at the Bronx High School of Science, Columbia and Harvard, Dr. Sebag is considered one of the world’s leadin... moreedit
    Nonenzymatic glycation alters collagen throughout the body, resulting in the histopathology that underlies diabetic disease in several organs. In the eye such changes in vitreous collagen could contribute to the progression of... more
    Nonenzymatic glycation alters collagen throughout the body, resulting in the histopathology that underlies diabetic disease in several organs. In the eye such changes in vitreous collagen could contribute to the progression of proliferative diabetic retinopathy by inducing vitreous degeneration. In this study, near infrared Fourier-transform Raman spectroscopy was performed on vitreous obtained at surgery from diabetic patients and from non-diabetic
    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... more
    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... more
    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.
    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... more
    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.
    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... more
    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.
    ... approche de l'évaluation des données médicales est présentée. Cette approche emploie des prédicats, des indicateurs et des index de santé. La description porte sur la symptomatologie et non sur le diagnostic. L'application... more
    ... approche de l'évaluation des données médicales est présentée. Cette approche emploie des prédicats, des indicateurs et des index de santé. La description porte sur la symptomatologie et non sur le diagnostic. L'application de cette technique à l'aide à la décision, dans le ...
    ABSTRACT
    Diminished blood flow plays an important role in the progression of diabetic retinopathy. Since increased blood viscosity is a contributing factor to hypoperfusion, it was of interest to determine whether therapy intended to decrease... more
    Diminished blood flow plays an important role in the progression of diabetic retinopathy. Since increased blood viscosity is a contributing factor to hypoperfusion, it was of interest to determine whether therapy intended to decrease blood viscosity and induce vasodilation could increase blood flow in patients with diabetic retinopathy. Ten patients, 4 with nonproliferative diabetic retinopathy and 6 age-matched, nondiabetic controls, were studied by a noninvasive system to index choroidal blood flow. Pentoxifylline was administered daily at an oral dose of 400 mg tid in the diabetic patients for nine months. The control group had pulse amplitude = 2.87 +/- 0.67 mm Hg with pulsatile choroidal blood flow = 714 +/- 196 microL/minute. Reproducibility studies in the control group (6 patients measured on three separate occasions) demonstrated an intraclass correlation coefficient of reliability, r = 0.83. In the diabetic patients, pulsatile flow = 276 +/- 68 microL/minute, 61% lower than the age-matched nondiabetic subjects (P = 0.003). After nine months of pentoxifylline therapy the diabetic patients had an increase in pulsatile choroidal blood flow to 469 +/- 152 microL/minute (P < 0.002). Pentoxifylline therapy brought blood flow levels in the diabetic patients closer to those of the nondiabetic age-matched control population so that following therapy there was no statistically significant difference between the two groups although the former were still lower. The potential efficacy of pentoxifylline in improving ocular blood flow in patients with diabetic retinopathy should be tested in a large controlled clinical trial.
    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... more
    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.
    PURPOSE: Pharmacologic vitreolysis is a new approach to improve vitreo-retinal surgery. Ultimately, the development of drugs to liquefy and detach vitreous from retina should prevent disease by mitigating the contribution of vitreous to... more
    PURPOSE: Pharmacologic vitreolysis is a new approach to improve vitreo-retinal surgery. Ultimately, the development of drugs to liquefy and detach vitreous from retina should prevent disease by mitigating the contribution of vitreous to retinopathy and eliminate the need for surgery. However, the mechanism of action of pharmacologic vitreolysis remains unclear. The technique of Dynamic light scattering (DLS) was used to evaluate the effects of microplasmin by following the diffusion coefficients of spherical polystyrene nano-particles injected with microplasmin into the vitreous. METHODS: Diffusion coefficients in dissected (n=9) porcine eyes were measured in vitro. DLS was performed on all specimens at 37°C as often as every 10 minutes for up to 6 hours following injections of human recombinant microplasmin at doses ranging from 0.125 mg to 0.8 mg, with 20 nm diameter tracer nanospheres. RESULTS: DLS findings in untreated porcine vitreous were similar to the previously described findings in bovine and human vitreous, demonstrating a fast (early) component, resulting from the flexible hyaluronan molecules, and a slow (late) component, resulting form the stiff collagen molecules. Microplasmin increased porcine vitreous diffusion coefficients. A new approach was developed to use DLS measurements of vitreous diffusion coefficients to evaluate the effects of microplasmin in intact eyes. CONCLUSIONS: Pharmacologic vitreolysis with human recombinant microplasmin increases vitreous diffusion coefficients in vitro. The results of these studies indicate that this new approach using DLS to measure vitreous diffusion coefficients can be used to study the effects of pharmacologic vitreolysis using microplasmin and other agents in intact eyes and ultimately in vivo.
    ● PURPOSE: To compare the state of the posterior vit- reous in exudative age-related macular degeneration (AMD) with eyes with nonexudative AMD and controls. ● DESIGN: Prospective, observational case series. ● METHODS: B-scan... more
    ● PURPOSE: To compare the state of the posterior vit- reous in exudative age-related macular degeneration (AMD) with eyes with nonexudative AMD and controls. ● DESIGN: Prospective, observational case series. ● METHODS: B-scan ultrasonography and optical coher- ence tomography (OCT) were performed in 163 eyes from 82 subjects older than 55 years, 50 eyes with exudative AMD, 57 with nonexudative
    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... more
    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.
    The induction of retinal detachment is dependent upon several factors whose relative importance remains controversial. These factors are retinal breaks, often associated with vitreous traction, inertial forces and changes in chorioretinal... more
    The induction of retinal detachment is dependent upon several factors whose relative importance remains controversial. These factors are retinal breaks, often associated with vitreous traction, inertial forces and changes in chorioretinal adhesion. Retinal breaks may be classified as holes, tears and dialyses. The relation to the vitreous base is an important prognostic indicator. Once a retinal break has occurred, inertial forces disturb the normal vitreo-retinal association. At that point, the development of a clinical detachment also depends upon loosening of the normal chorioretinal adhesion. Myopia and aphakia are important predisposing factors. The presence of preretinal membranes is a precipitating factor for recurrent retinal detachment. The high success rate of current surgical techniques (85 per cent) is mainly related to a better understanding of the mechanisms leading to retinal detachment.
    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... more
    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.
    Pharmacologic Vitreolysis is a new therapy intended to enzymatically liquefy vitreous and separate the posterior vitreous cortex from the retina. There are presently no non- invasive methods with which to quantify vitreous liquefaction.... more
    Pharmacologic Vitreolysis is a new therapy intended to enzymatically liquefy vitreous and separate the posterior vitreous cortex from the retina. There are presently no non- invasive methods with which to quantify vitreous liquefaction. This study evaluated non-invasive Dynamic Light Scattering (DLS) to assess vitreous liquefaction in model vitreous solutions. Vitreous of 5 bovine eyes was measured by DLS. Methodology involved the addition 50 IU/ml of hyaluronidase and 5 mg/ml of collagenase to solutions of 0.1 mg/ml of hyaluronan and collagen with polystyrene beads (30 nm diameter), respectively. Solutions were incubated at 37 degrees Celsius for 24 hours and DLS measurements were made at various time intervals. Results showed that the diffusion coefficients and particle size distributions determined from DLS measurements in the 5 bovine vitreous specimens were consistent and reproducible. Adding enzyme to the model vitreous solutions increased diffusion coefficients in the collagen as well as the HA solutions. These results suggest that DLS is a useful non-invasive method to measure diffusion coefficients in both model solutions and bovine vitreous. This approach may provide a quantitative means to assess different pharmacologic vitreolysis agents in vitro, and may also serve as a clinical tool for monitoring the effects of pharmacologic vitreolysis in vivo.
    To determine the mechanism of photoreceptor cell death after traumatic retinal detachment in humans. Clinical records from 1975 to 1993 of 75 patients, whose eyes were enucleated after traumatic retinal detachment, were reviewed for age,... more
    To determine the mechanism of photoreceptor cell death after traumatic retinal detachment in humans. Clinical records from 1975 to 1993 of 75 patients, whose eyes were enucleated after traumatic retinal detachment, were reviewed for age, sex, previous ocular or systemic medical history, interval from initial trauma to enucleation, visual acuity, and types of trauma. The patients were divided into five groups of 15 cases each, based on the interval from initial trauma to enucleation. The retinal tissue was examined for two markers of apoptosis: (1) nicked nuclear DNA in situ by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) technique and (2) apoptotic bodies by light and electron microscopy. Of the 75 cases of ruptured globe and traumatic retinal detachment that were evaluated, 19 eyes (25.3%) showed TUNEL-positive labeling of photoreceptor cells. Nicked nuclear DNA was detected in photoreceptor cells of detached retinas as early as 8 hours after trauma. The detached retinas in seven of 15 eyes enucleated within 2 days after ocular trauma showed TUNEL-positive photoreceptor nuclei. The number of cases showing TUNEL-positive photoreceptor nuclei decreased as the interval between initial trauma and enucleation increased. The TUNEL-positive photoreceptor cells could still be seen in the detached retinas of two eyes enucleated 22 days after trauma. Light microscopy disclosed condensation and fragmentation of photoreceptor nuclei in the detached retinas. Electron microscopy showed structures resembling apoptotic bodies phagocytosed by neighboring cells in the TUNEL-positive retinas. Apoptosis is an important mechanism of photoreceptor cell degeneration in the early stage after traumatic retinal detachment in humans.
    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... more
    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.
    To compare the maximum vertical fusion amplitudes in vertical directions (response pattern by respective higher eye), to investigate for possible asymmetry. Vertical fusion amplitude (VFA) was measured in one hundred normal adults with... more
    To compare the maximum vertical fusion amplitudes in vertical directions (response pattern by respective higher eye), to investigate for possible asymmetry. Vertical fusion amplitude (VFA) was measured in one hundred normal adults with normal single binocular vision using a computer based device that produced a gradually increasing, but optically distant test distance, Vertical fusion amplitudes in the vertical left- over-right (L/R, elevation of the left eye above the right eye) pattern direction were compared to the vertical fusion amplitudes in the vertical right-over-left direction pattern(R/L). The mean VFA was 4.08 +/-1.01 prism diopters, with vertical fusion amplitudes of 4.40 +/-1.44 prism diopters in the L/R direction and 3.75 +/-1.19 prism diopters in the R/L direction. There was no association between ocular dominance and the direction of greater VFA. Asymmetry in the vertical fusion response was found, with 77/100 subjects showing greater than a 10% difference between the means of the L/R and R/L measurements. The group with asymmetry had 17% greater mean VFA than the symmetric group. Normal adults frequently have asymmetric directional vertical fusion amplitudes. The asymmetry appears to be due to the contribution of the direction with the greater VFA, rather than the result of both alternatives. These results are intriguing and bear further investigation. Possible explanations my be asymmetry of orbital anatomy or functional asymmetry of either muscular or neuronal origin. They do not appear to be due to the relative ocular dominance. Inherent VFA asymmetry should therefore be considered in all forms of vergence testing in the vertical direction.
    ABSTRACT

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