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Nancy J. Newman - One of the best experts on this subject based on the ideXlab platform.
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postoperative Ischemic Optic Neuropathy
Spine, 2010Co-Authors: Lorri A Lee, Nancy J. Newman, Ted A Wagner, Joseph R Dettori, Nathan J DettoriAbstract:Study Design. Systematic literature review. Objective. To determine if there are predictors or preventative measures for postoperative Ischemic Optic Neuropathy (ION) associated with spine surgery. Summary of Background Data. Postoperative ION is a devastating complication that is most common after cardiac and spinal fusion surgery. Identifying patient or perioperative predictors for postoperative ION could lead to therapeutic modifications designed to minimize its occurrence. Methods. A systematic literature review was conducted in MEDLINE, EMBASE, and the Cochrane Collaboration Library for literature published in English from 1990 through 2008 reporting on ION following spine surgery. References from review articles of ION were used, but articles without original material were excluded. Data on study design, patient demographics, and perioperative characteristics were collected and analyzed. Two independent reviewers assessed the strength of literature using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria assessing quality, quantity, and consistency of results. Disagreements were resolved by consensus. Results. Nineteen of 360 articles on postoperative ION after spine surgery met inclusion/exclusion criteria. The quality of evidence was very low as the majority of articles were case reports. The majority of ION patients were men between 30 and 69 years, undergoing spinal fusion surgery with an operative duration greater than 5 hours and an estimated blood loss greater than 1 L. Confounding factors and lack of a denominator from the case reports and case series precluded identification of risk factors with even a modest level of evidence. Conclusion. Postoperative ION after spinal surgery is a rare event, which may be associated with prone position surgery of more than 5 hours surgical duration and blood loss of more than 1 L. Informing patients of this remote risk should be considered during preoperative counseling. The quality of evidence for preventative measures for postoperative ION after spinal fusion surgery is very low, but it has been proposed that efforts aimed at reducing the duration or severity of venous congestion in the head may be beneficial.
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treatment of nonarteritic anterior Ischemic Optic Neuropathy
Survey of Ophthalmology, 2010Co-Authors: Nancy J. Newman, Edward J Atkins, Beau B Bruce, Valerie BiousseAbstract:Nonarteritic anterior Ischemic Optic Neuropathy (NAION) is the most common clinical presentation of acute Ischemic damage to the Optic nerve. Most treatments proposed for NAION are empirical and include a wide range of agents presumed to act on thrombosis, on the blood vessels, or on the disk edema itself. Others are presumed to have a neuroprotective effect. Although there have been multiple therapies attempted, most have not been adequately studied, and animal models of NAION have only recently emerged. The Ischemic Optic Neuropathy Decompression Trial, the only class I large multicenter prospective treatment trial for nonarteritic anterior Ischemic Optic Neuropathy, found no benefit from surgical intervention. One recent large, nonrandomized controlled study suggested that oral steroids might be helpful for acute NAION. Others recently proposed interventions are intravitreal injections of steroids or anti-vascular endothelial growth factor (anti-VEGF) agents. There are no class I studies showing benefit from either medical or surgical treatments. Most of the literature on the treatment of NAION consists of retrospective or prospective case series and anecdotal case reports. Similarly, therapies aimed at secondary prevention of fellow eye involvement in NAION remain of unproven benefit.
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Ischemic Optic Neuropathy following spine surgery
American Journal of Ophthalmology, 2005Co-Authors: Nancy J. Newman, Suzan J Song, Susan Ksiazek, Steven RothAbstract:Visual loss after monocular surgery is rare, but devastating. The most common cause of perioperative visual loss (POVL) is Ischemic Optic Neuropathy (ION). Increasing numbers of cases of ION are being reported after spine surgery, but the etiology of postoperative ION remains poorly understood. The growing concern about POVL has led neuroanesthesiologists to establish the ASA Postoperative Visual Loss Registry. This article summarized our current knowledge on this topic. The authors reviewed the literature and selected case reports of ION, specifically those reported after spine surgery performed with the patient in the prone position. Most of the cases involved posterior ION (PION, n = 17), and the remainder anterior (AION, n = 5). Most patients had no or few preoperative vascular disease risk factors. All except one PION and 2 of 5 AION cases reported symptom onset within the first 24 hours after surgery. Visual loss was frequently bilateral (40% of AION, 47% of PION cases). Mean operative time exceeded 450 minutes. The lowest average intraoperative mean arterial blood pressure was 64 mm Hg and the mean lowest intraoperative hematocrit was 27%. The average blood loss was 1.7 L for AION and 5 L for PION patients. PION patients received an average of 8 L of crystalloid solution and 2.2 L of colloid intraoperatively. This compilation of case reports suggests that a combination of prolonged surgery in the prone position, decreased ocular perfusion pressure, blood loss and anemia/hemodilution, and infusion of large quantities of intravenous fluids are some of the potential factors involved in the etiology of postoperative ION. However, levels of blood pressure and anemia intraoperatively were frequently at levels considered acceptable in anesthesia practice. The etiology of postoperative ION remains incompletely understood. Potential strategies to avoid this complication are discussed. —Valerie Biousse.
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Ischemic Optic Neuropathy following spine surgery
Journal of Neurosurgical Anesthesiology, 2005Co-Authors: Nancy J. Newman, Suzan J Song, Susan Ksiazek, Steven RothAbstract:Perioperative visual loss (POVL) is a devastating injury that has been reported infrequently after nonocular surgery. The most common cause of POVL is Ischemic Optic Neuropathy (ION). Increasing numbers of cases of ION are being reported after spine surgery, but the etiology of postoperative ION remains poorly understood. After a MEDLINE search of the literature, we reviewed published case reports of ION, specifically those reported after spine surgery performed with the patient in the prone position. Most of the cases involved posterior ION (PION, n = 17), and the remainder anterior (AION, n = 5). Most patients had no or few preoperative vascular disease risk factors. All except one PION and 2 of 5 AION cases reported symptom onset within the first 24 hours after surgery. Visual loss was frequently bilateral (40% of AION, 47% of PION cases). Mean operative time exceeded 450 minutes. The lowest average intraoperative mean arterial blood pressure was 64 mm Hg and the mean lowest intraoperative hematocrit was 27%. The average blood loss was 1.7 L for AION and 5 L for PION patients. PION patients received an average of 8 L of crystalloid solution and 2.2 L of colloid intraoperatively. This compilation of case reports suggests that a combination of prolonged surgery in the prone position, decreased ocular perfusion pressure, blood loss and anemia/hemodilution, and infusion of large quantities of intravenous fluids are some of the potential factors involved in the etiology of postoperative ION. However, levels of blood pressure and anemia intraoperatively were frequently at levels considered acceptable in anesthesia practice. The etiology of postoperative ION remains incompletely understood. Potential strategies to avoid this complication are discussed.
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clinical spectrum of posterior Ischemic Optic Neuropathy
American Journal of Ophthalmology, 2001Co-Authors: Srinivas R Sadda, Nancy J. Newman, Neil R Miller, Valerie Biousse, Michelle Nee, Anthony C KouzisAbstract:Abstract PURPOSE : To describe the systemic and visual characteristics and prognosis in patients with posterior Ischemic Optic Neuropathy (PION). DESIGN : Observational case series. METHODS : Retrospective chart review in a multicenter setting. Seventy-two patients (98 eyes) with a clinical diagnosis of PION. Co-morbid systemic diseases and visual function were recorded at both initial presentation and after mean visual follow-up of 4.1 years and systemic follow-up of 5.4 years. RESULTS : PION occurred in three main settings: in the perioperative period following a variety of surgical procedures (28 patients), associated with giant cell (temporal) arteritis (6 patients), and associated with nonarteritic systemic vascular disease (38 patients). Patients with perioperative and arteritic PION were more likely to have severe, bilateral visual loss that did not improve. Among eyes with nonarteritic PION, 34% experienced improvement in vision, 28% remained stable, and 38% worsened. Among patients with nonarteritic PION, carotid artery disease and a history of stroke (with or without carotid artery disease) were both associated with a statistically significant increased risk of poor final visual outcome. CONCLUSIONS : There are three distinct subtypes of PION: perioperative, arteritic, and nonarteritic. Patients with PION that is unassociated with surgery should undergo an evaluation for systemic vascular diseases, including giant cell arteritis, that may or may not be apparent at the time of vision loss. The visual prognosis for patients with perioperative or arteritic PION is poor, whereas that for nonarteritic PION is similar to that for patients with nonarteritic AION.
Steven L Bernstein - One of the best experts on this subject based on the ideXlab platform.
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dendrimers target the Ischemic lesion in rodent and primate models of nonarteritic anterior Ischemic Optic Neuropathy
PLOS ONE, 2016Co-Authors: Yan Guo, Neil R Miller, Mary A Johnson, Zara Mehrabian, Manoj K Mishra, Rangaramanujam M Kannan, Steven L BernsteinAbstract:Introduction Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the Optic nerve (ON) Ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior Ischemic Optic Neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment.
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axonal degeneration regeneration and ganglion cell death in a rodent model of anterior Ischemic Optic Neuropathy raion
Experimental Eye Research, 2010Co-Authors: C Zhang, Bernard J Slater, Neil R Miller, Steven L BernsteinAbstract:Using laser-induced photoactivation of intravenously administered rose Bengal in rats, we generated an Ischemic infarction of the intrascleral portion of the Optic nerve (ON) comparable to that which occurs in humans to investigate Optic nerve axon degenerative events following Optic nerve infarct and the potential for axon re-growth. Animals were euthanized at different times post infarct. Axon degeneration was evaluated with SMI312 immunolabeling, and GAP-43 immunostaining was used to identify axon regeneration. Terminal dUTP nick end labeling (TUNEL) was used to evaluate retinal ganglion cell (RGC) death. There was significant axon structural disruptinot ion at the anterior intrascleral portion of the ON by 3d post-infarct, extending to the posterior ON by 7d post-stroke. Destruction of normal axon structure and massive loss of axon fibers occurred by 2 weeks. GAP-43 immunoreactivity occurred in the anterior ON by 7d post-infarct, lasting 3-4 weeks, without extension past the primary Ischemic lesion. TUNEL-positive cells in the RGC layer appeared by 7d post-insult. These results indicate that following induction of Ischemic Optic Neuropathy, significant axon damage occurs by 3d post-infarct, with later neuronal death. Post-stroke adult rat retinal ganglion cells attempt to regenerate their axons, but this effort is restricted to the unmyelinated region of the anterior ON. These responses are important in understanding pathologic process that underlies human non-arteritic anterior Ischemic Optic Neuropathy (NAION) and may guide both the appropriate treatment of NAION and the window of opportunity for such treatment.
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a primate model of nonarteritic anterior Ischemic Optic Neuropathy
Investigative Ophthalmology & Visual Science, 2008Co-Authors: Celia S Chen, Bernard J Slater, Neil R Miller, Mary A Johnson, Robert A Flower, Steven L BernsteinAbstract:The Optic nerve (ON) is a central nervous system (CNS) tract composed of retinal ganglion cell (RGC) axons that synapse in the lateral geniculate nuclei. Nonarteritic anterior Ischemic Optic Neuropathy (NAION) is an isolated infarct of the anterior ON.1 Although incidence figures are not available for most countries, the incidence of NAION in the United States is 3 to 10 per 100,000 per year2,3 and 6 per 100,000 per year in mainland China.4 No effective clinical treatments exist, largely because little is known about its pathophysiology, and there are few histopathologic studies of the acute5 or chronic6 condition. Previous models of nonhuman primate ON stroke have been produced by surgical ablation of major arteries supplying the ON and posterior portions of the globe,7 generating a model that more closely approximates arteritic anterior Ischemic Optic Neuropathy (AAION), in part because ablation of these vessels also causes retinal and choroidal infarction. The AAION model thus is physiologically and therapeutically distinct from NAION. We have established a rodent model of NAION (rAION),8,9 using a novel thromboembolic mechanism to affect preferentially the small vessels on the Optic disc. Considerable structural and physiological differences exist between rodent and primate ON, however. First, the primate ON is highly structured, possessing a distinct, well-formed barrier within the anterior ON, the lamina cribrosa, which in rodents is present but extremely attenuated. Second, the rodent ON vascular circulation is distinct from that of primates. Third, the rodent immune response is considerably different from that of primates. Fourth, there are significant differences in the time-associated responses to CNS infarcts in primates and rodents. Fifth, the primate retina contains a highly specialized retinal region, the macula, with a high density of RGCs.10–12 These biological differences between the two mammalian families make it difficult to identify accurately the clinically relevant targets for treatment and to predict treatment responses and timing for NAION in humans and for human white-matter infarcts in general. Although ex vivo isolated ON preparations are used to study white-matter ischemia13–15 and to evaluate CNS axon regeneration,16 such preparations cannot be used to analyze effectively the long-term effects such as ischemia-associated inflammation.17 Thus, we generated a nonhuman primate model that clinically, electrophysiologically, and angiographically closely resembles human NAION (pNAION) so that we could characterize the various ON-associated mechanistic, cellular, and immune-related changes associated with this condition in living primates.
Steven Roth - One of the best experts on this subject based on the ideXlab platform.
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Update on Perioperative Ischemic Optic Neuropathy Associated With Non-ophthalmic Surgery
Frontiers Media S.A., 2018Co-Authors: Steven Roth, Heather E. MossAbstract:Perioperative visual loss (POVL) is a rare, serious complication of non-ophthalmic surgeries. Ischemic Optic Neuropathy (ION), and retinal arterial occlusion (RAO) are the main causes (1, 2). Less frequent are cortical blindness (3), acute glaucoma (4), and choroidal and vitreous hemorrhage (5). ION is the most common cause for which the neurologist or neuro-ophthalmologist is consulted as it is associated either with a normal ophthalmic exam (posterior ION, PION), or less often, with Optic nerve (ON) head swelling (anterior ION, AION). The presumed cause is impaired blood supply to the Optic nerve (Figure 1). The most common surgical procedures complicated by ION are cardiac surgery and spinal fusion. Retrospective studies, surveys, and case reports are the basis of most knowledge regarding peri-operative ION (poION), with cohort and case-control studies helping to identify candidate risk factors (6, 7). Animal models have provided insight regarding mechanisms (8). This mini-review is an update on the latest advancements regarding poION in non-ophthalmic surgeries in epidemiological, clinical, and animal studies
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Ischemic Optic Neuropathy in Cardiac Surgery: Incidence and Risk Factors in the United States from the National Inpatient Sample 1998 to 2013.
Anesthesiology, 2017Co-Authors: Daniel S. Rubin, Monica M. Matsumoto, Heather E. Moss, Charlotte E. Joslin, Avery Tung, Steven RothAbstract:Background Ischemic Optic Neuropathy is the most common form of perioperative visual loss, with highest incidence in cardiac and spinal fusion surgery. To date, potential risk factors have been identified in cardiac surgery by only small, single-institution studies. To determine the preoperative risk factors for Ischemic Optic Neuropathy, the authors used the National Inpatient Sample, a database of inpatient discharges for nonfederal hospitals in the United States. Methods Adults aged 18 yr or older admitted for coronary artery bypass grafting, heart valve repair or replacement surgery, or left ventricular assist device insertion in National Inpatient Sample from 1998 to 2013 were included. Risk of Ischemic Optic Neuropathy was evaluated by multivariable logistic regression. Results A total of 5,559,395 discharges met inclusion criteria with 794 (0.014%) cases of Ischemic Optic Neuropathy. The average yearly incidence was 1.43 of 10,000 cardiac procedures, with no change during the study period (P = 0.57). Conditions increasing risk were carotid artery stenosis (odds ratio, 2.70), stroke (odds ratio, 3.43), diabetic retinopathy (odds ratio, 3.83), hypertensive retinopathy (odds ratio, 30.09), macular degeneration (odds ratio, 4.50), glaucoma (odds ratio, 2.68), and cataract (odds ratio, 5.62). Female sex (odds ratio, 0.59) and uncomplicated diabetes mellitus type 2 (odds ratio, 0.51) decreased risk. Conclusions The incidence of Ischemic Optic Neuropathy in cardiac surgery did not change during the study period. Development of Ischemic Optic Neuropathy after cardiac surgery is associated with carotid artery stenosis, stroke, and degenerative eye conditions.
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perioperative visual loss in spine fusion surgery Ischemic Optic Neuropathy in the united states from 1998 to 2012 in the nationwide inpatient sample
Survey of Anesthesiology, 2017Co-Authors: Daniel S. Rubin, Heather E. Moss, Charlotte E. Joslin, Lorri A Lee, Isaac Parakati, Steven RothAbstract:Background:Perioperative Ischemic Optic Neuropathy (ION) causes visual loss in spinal fusion. Previous case–control studies are limited by study size and lack of a random sample. The purpose of this study was to study trends in ION incidence in spinal fusion and risk factors in a large nationwide ad
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Ischemic Optic Neuropathy following spine surgery
American Journal of Ophthalmology, 2005Co-Authors: Nancy J. Newman, Suzan J Song, Susan Ksiazek, Steven RothAbstract:Visual loss after monocular surgery is rare, but devastating. The most common cause of perioperative visual loss (POVL) is Ischemic Optic Neuropathy (ION). Increasing numbers of cases of ION are being reported after spine surgery, but the etiology of postoperative ION remains poorly understood. The growing concern about POVL has led neuroanesthesiologists to establish the ASA Postoperative Visual Loss Registry. This article summarized our current knowledge on this topic. The authors reviewed the literature and selected case reports of ION, specifically those reported after spine surgery performed with the patient in the prone position. Most of the cases involved posterior ION (PION, n = 17), and the remainder anterior (AION, n = 5). Most patients had no or few preoperative vascular disease risk factors. All except one PION and 2 of 5 AION cases reported symptom onset within the first 24 hours after surgery. Visual loss was frequently bilateral (40% of AION, 47% of PION cases). Mean operative time exceeded 450 minutes. The lowest average intraoperative mean arterial blood pressure was 64 mm Hg and the mean lowest intraoperative hematocrit was 27%. The average blood loss was 1.7 L for AION and 5 L for PION patients. PION patients received an average of 8 L of crystalloid solution and 2.2 L of colloid intraoperatively. This compilation of case reports suggests that a combination of prolonged surgery in the prone position, decreased ocular perfusion pressure, blood loss and anemia/hemodilution, and infusion of large quantities of intravenous fluids are some of the potential factors involved in the etiology of postoperative ION. However, levels of blood pressure and anemia intraoperatively were frequently at levels considered acceptable in anesthesia practice. The etiology of postoperative ION remains incompletely understood. Potential strategies to avoid this complication are discussed. —Valerie Biousse.
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Ischemic Optic Neuropathy following spine surgery
Journal of Neurosurgical Anesthesiology, 2005Co-Authors: Nancy J. Newman, Suzan J Song, Susan Ksiazek, Steven RothAbstract:Perioperative visual loss (POVL) is a devastating injury that has been reported infrequently after nonocular surgery. The most common cause of POVL is Ischemic Optic Neuropathy (ION). Increasing numbers of cases of ION are being reported after spine surgery, but the etiology of postoperative ION remains poorly understood. After a MEDLINE search of the literature, we reviewed published case reports of ION, specifically those reported after spine surgery performed with the patient in the prone position. Most of the cases involved posterior ION (PION, n = 17), and the remainder anterior (AION, n = 5). Most patients had no or few preoperative vascular disease risk factors. All except one PION and 2 of 5 AION cases reported symptom onset within the first 24 hours after surgery. Visual loss was frequently bilateral (40% of AION, 47% of PION cases). Mean operative time exceeded 450 minutes. The lowest average intraoperative mean arterial blood pressure was 64 mm Hg and the mean lowest intraoperative hematocrit was 27%. The average blood loss was 1.7 L for AION and 5 L for PION patients. PION patients received an average of 8 L of crystalloid solution and 2.2 L of colloid intraoperatively. This compilation of case reports suggests that a combination of prolonged surgery in the prone position, decreased ocular perfusion pressure, blood loss and anemia/hemodilution, and infusion of large quantities of intravenous fluids are some of the potential factors involved in the etiology of postoperative ION. However, levels of blood pressure and anemia intraoperatively were frequently at levels considered acceptable in anesthesia practice. The etiology of postoperative ION remains incompletely understood. Potential strategies to avoid this complication are discussed.
Rod Foroozan - One of the best experts on this subject based on the ideXlab platform.
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perioperative posterior Ischemic Optic Neuropathy review of the literature
American Journal of Ophthalmology, 2005Co-Authors: Lawrence M Buono, Rod ForoozanAbstract:Posteriorc Ischemic Optic Neuropathy (PION) is an uncommon cause of perioperative visual loss which is usually devastating. This thorough review summarizes most cases published in the English literature. Perioperative PION has been most frequently reported after spinal surgery and radical neck dissection. The visual loss typically presents immediately after recovery from anesthesia, although it may be delayed by several days. Visual loss is often bilateral and profound with count fingers vision or worse. The examination findings are consistent with an Optic Neuropathy; however, the funduscopic examination is initially normal. The cause is unknown, although patient-specific susceptibility to perioperative hemodynamic derangements is likely. No treatment has proven to be effective. The prognosis for visual recovery is generally poor. — Valerie Biousse.
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perioperative posterior Ischemic Optic Neuropathy review of the literature
Survey of Ophthalmology, 2005Co-Authors: Lawrence M Buono, Rod ForoozanAbstract:Posterior Ischemic Optic Neuropathy (PION) is an uncommon cause of perioperative visual loss. Perioperative PION has been most frequently reported after spinal surgery and radical neck dissection. The visual loss typically presents immediately after recovery from anesthesia, although it may be delayed by several days. Visual loss is often bilateral and profound with count fingers vision or worse. The examination findings are consistent with an Optic Neuropathy; however the funduscopic examination is initially normal. The cause is unknown, although patient-specific susceptibility to perioperative hemodynamic derangements is likely. No treatment has proven to be effective. The prognosis for visual recovery is generally poor.
Neil R Miller - One of the best experts on this subject based on the ideXlab platform.
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dendrimers target the Ischemic lesion in rodent and primate models of nonarteritic anterior Ischemic Optic Neuropathy
PLOS ONE, 2016Co-Authors: Yan Guo, Neil R Miller, Mary A Johnson, Zara Mehrabian, Manoj K Mishra, Rangaramanujam M Kannan, Steven L BernsteinAbstract:Introduction Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the Optic nerve (ON) Ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior Ischemic Optic Neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment.
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axonal degeneration regeneration and ganglion cell death in a rodent model of anterior Ischemic Optic Neuropathy raion
Experimental Eye Research, 2010Co-Authors: C Zhang, Bernard J Slater, Neil R Miller, Steven L BernsteinAbstract:Using laser-induced photoactivation of intravenously administered rose Bengal in rats, we generated an Ischemic infarction of the intrascleral portion of the Optic nerve (ON) comparable to that which occurs in humans to investigate Optic nerve axon degenerative events following Optic nerve infarct and the potential for axon re-growth. Animals were euthanized at different times post infarct. Axon degeneration was evaluated with SMI312 immunolabeling, and GAP-43 immunostaining was used to identify axon regeneration. Terminal dUTP nick end labeling (TUNEL) was used to evaluate retinal ganglion cell (RGC) death. There was significant axon structural disruptinot ion at the anterior intrascleral portion of the ON by 3d post-infarct, extending to the posterior ON by 7d post-stroke. Destruction of normal axon structure and massive loss of axon fibers occurred by 2 weeks. GAP-43 immunoreactivity occurred in the anterior ON by 7d post-infarct, lasting 3-4 weeks, without extension past the primary Ischemic lesion. TUNEL-positive cells in the RGC layer appeared by 7d post-insult. These results indicate that following induction of Ischemic Optic Neuropathy, significant axon damage occurs by 3d post-infarct, with later neuronal death. Post-stroke adult rat retinal ganglion cells attempt to regenerate their axons, but this effort is restricted to the unmyelinated region of the anterior ON. These responses are important in understanding pathologic process that underlies human non-arteritic anterior Ischemic Optic Neuropathy (NAION) and may guide both the appropriate treatment of NAION and the window of opportunity for such treatment.
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a primate model of nonarteritic anterior Ischemic Optic Neuropathy
Investigative Ophthalmology & Visual Science, 2008Co-Authors: Celia S Chen, Bernard J Slater, Neil R Miller, Mary A Johnson, Robert A Flower, Steven L BernsteinAbstract:The Optic nerve (ON) is a central nervous system (CNS) tract composed of retinal ganglion cell (RGC) axons that synapse in the lateral geniculate nuclei. Nonarteritic anterior Ischemic Optic Neuropathy (NAION) is an isolated infarct of the anterior ON.1 Although incidence figures are not available for most countries, the incidence of NAION in the United States is 3 to 10 per 100,000 per year2,3 and 6 per 100,000 per year in mainland China.4 No effective clinical treatments exist, largely because little is known about its pathophysiology, and there are few histopathologic studies of the acute5 or chronic6 condition. Previous models of nonhuman primate ON stroke have been produced by surgical ablation of major arteries supplying the ON and posterior portions of the globe,7 generating a model that more closely approximates arteritic anterior Ischemic Optic Neuropathy (AAION), in part because ablation of these vessels also causes retinal and choroidal infarction. The AAION model thus is physiologically and therapeutically distinct from NAION. We have established a rodent model of NAION (rAION),8,9 using a novel thromboembolic mechanism to affect preferentially the small vessels on the Optic disc. Considerable structural and physiological differences exist between rodent and primate ON, however. First, the primate ON is highly structured, possessing a distinct, well-formed barrier within the anterior ON, the lamina cribrosa, which in rodents is present but extremely attenuated. Second, the rodent ON vascular circulation is distinct from that of primates. Third, the rodent immune response is considerably different from that of primates. Fourth, there are significant differences in the time-associated responses to CNS infarcts in primates and rodents. Fifth, the primate retina contains a highly specialized retinal region, the macula, with a high density of RGCs.10–12 These biological differences between the two mammalian families make it difficult to identify accurately the clinically relevant targets for treatment and to predict treatment responses and timing for NAION in humans and for human white-matter infarcts in general. Although ex vivo isolated ON preparations are used to study white-matter ischemia13–15 and to evaluate CNS axon regeneration,16 such preparations cannot be used to analyze effectively the long-term effects such as ischemia-associated inflammation.17 Thus, we generated a nonhuman primate model that clinically, electrophysiologically, and angiographically closely resembles human NAION (pNAION) so that we could characterize the various ON-associated mechanistic, cellular, and immune-related changes associated with this condition in living primates.
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clinical spectrum of posterior Ischemic Optic Neuropathy
American Journal of Ophthalmology, 2001Co-Authors: Srinivas R Sadda, Nancy J. Newman, Neil R Miller, Valerie Biousse, Michelle Nee, Anthony C KouzisAbstract:Abstract PURPOSE : To describe the systemic and visual characteristics and prognosis in patients with posterior Ischemic Optic Neuropathy (PION). DESIGN : Observational case series. METHODS : Retrospective chart review in a multicenter setting. Seventy-two patients (98 eyes) with a clinical diagnosis of PION. Co-morbid systemic diseases and visual function were recorded at both initial presentation and after mean visual follow-up of 4.1 years and systemic follow-up of 5.4 years. RESULTS : PION occurred in three main settings: in the perioperative period following a variety of surgical procedures (28 patients), associated with giant cell (temporal) arteritis (6 patients), and associated with nonarteritic systemic vascular disease (38 patients). Patients with perioperative and arteritic PION were more likely to have severe, bilateral visual loss that did not improve. Among eyes with nonarteritic PION, 34% experienced improvement in vision, 28% remained stable, and 38% worsened. Among patients with nonarteritic PION, carotid artery disease and a history of stroke (with or without carotid artery disease) were both associated with a statistically significant increased risk of poor final visual outcome. CONCLUSIONS : There are three distinct subtypes of PION: perioperative, arteritic, and nonarteritic. Patients with PION that is unassociated with surgery should undergo an evaluation for systemic vascular diseases, including giant cell arteritis, that may or may not be apparent at the time of vision loss. The visual prognosis for patients with perioperative or arteritic PION is poor, whereas that for nonarteritic PION is similar to that for patients with nonarteritic AION.
