Neuroprotective Strategies for Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review.

PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is the second most common form of optic neuropathy. Most patients show no improvement over time. Until now, there is still no definitive therapy for NAION. The available literatures on the possible treatment of NAION are quite diverse and controversial. Neuroprotection strategies have been suggested as one of the potential treatments for NAION. This review aims to critically evaluate the literature on neuroprotective strategy for NAION. METHODS: This report was written in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We performed a systematic literature search in Pubmed, Science Direct, Proquest, and Cochrane databases. Only neuroprotective agents that directly work in protecting neurons were included. The outcome of interest in this review is retinal ganglion cell density and apoptosis for animal studies and retinal nerve fiber layer thickness for human studies. RESULTS: The systematic search identified 591 studies of which 24 met the eligibility criteria, including 21 animal studies and three human studies. Only a few of the studies evaluated the same treatments, showing how diverse neuroprotector treatments are currently being evaluated as NAION treatment. From 21 animal studies, 14 studies showed significantly higher retinal ganglion cell density (1.49- to 2.81-fold) with neuroprotective treatment compared to control group. Two of three human studies in this review had also found a beneficial effect of preserving retinal nerve fiber layer thickness in NAION patients. CONCLUSIONS: This review suggests the potential of neuroprotection as a viable option in the quest for an effective treatment strategy for NAION. Further studies, particularly clinical studies, are necessary to establish its efficacy in NAION patients.

Management of ocular arterial ischemic diseases: a review.

PURPOSE: To summarize the existing treatment options regarding central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), arteritic anterior ischemic optic neuropathy (AAION), non-arteritic anterior ischemic optic neuropathy (NAION), and ocular ischemic syndrome (OIS), proposing an approach to manage and treat these patients. METHODS: A systematic literature search of articles published since 1st January 2010 until 31st December 2020 was conducted using MEDLINE (PubMed), Scopus, and Web of Science. Exclusion criteria included case reports, non-English references, articles not conducted in humans, and articles not including diagnostic or therapeutic options. Further references were gathered through citation tracking, by hand search of the reference lists of included studies, as well as topic-related European society guidelines. RESULTS: Acute ocular ischemia, with consequent visual loss, has a variety of causes and clinical presentations, with prognosis depending on an accurate diagnosis and timely therapeutic implementation. Unfortunately, most of the addressed entities do not have a standardized management, especially regarding their treatment, which often lacks good quality evidence on whether it should or not be used to treat patients. CONCLUSION: Ophthalmologic signs and symptoms may be a warning sign of cardiovascular or cerebrovascular events, namely stroke. Most causes of acute ocular ischemia do not have a standardized management, especially regarding their treatment. Timely intervention is essential to improve the visual, and possibly vital, prognosis. Awareness must be raised among non-ophthalmologist clinicians that might encounter these patients. Further research should focus on assessing the benefit of the management strategies already being employed .

The Benefits and Hazards of Intravitreal Mesenchymal Stem Cell (MSC) Based-Therapies in the Experimental Ischemic Optic Neuropathy.

Mesenchymal stem cell (MSC) therapy has been investigated intensively for many years. However, there is a potential risk related to MSC applications in various cell niches. METHODS: The safety of intravitreal MSC application and the efficacy of MSC-derived conditioned medium (MDCM) were evaluated in the normal eye and the diseased eye, respectively. For safety evaluation, the fundus morphology, visual function, retinal function, and histological changes of the retina were examined. For efficacy evaluation, the MDCM was intravitreally administrated in a rodent model of anterior ischemic optic neuropathy (rAION). The visual function, retinal ganglion cell (RGC) density, and neuroinflammation were evaluated at day 28 post-optic nerve (ON) infarct. RESULTS: The fundus imaging showed that MSC transplantation induced retinal distortion and venous congestion. The visual function, retinal function, and RGC density were significantly decreased in MSC-treated eyes. MSC transplantation induced astrogliosis, microgliosis, and macrophage infiltration in the retina due to an increase in the HLA-DR-positive MSC proportion in vitreous. Treatment with the MDCM preserved the visual function and RGC density in rAION via inhibition of macrophage infiltration and RGC apoptosis. CONCLUSIONS: The vitreous induced the HLA-DR expression in the MSCs to cause retinal inflammation and retina injury. However, the MDCM provided the neuroprotective effects in rAION.

Posterior ischemic optic neuropathy following a major burn injury and review of the literature.

Posterior ischemic optic neuropathy following burns is a rare but devastating condition that can result in total bilateral visual loss. Numerous treatment modalities have been trialed, yet there is no effective therapy to delay or reverse the disease. Hence, it is imperative for burns surgeons to be aware of the potential risk factors and have a high index of suspicion right from the outset to prevent this outcome. Here, we discuss the case of a patient that developed posterior ischemic optic neuropathy subsequent to a major burn injury. We also present a literature review on optic neuropathies following burns to describe the etiology, clinical signs, and potential management.

A Promising Strategy for Non-Arteritic Anterior Ischemic Optic Neuropathy: Intravitreal Mesenchymal Stem Cell Exosome.

Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of optic nerverelated permanent visual impairment among individuals of over 50 years of age after glaucoma. Due to perplexing disorder regarding its pathogenesis, there is still no widely accepted and established treatment plan. Mesenchymal stem cells (MSCs) are one of the rare stem cell types that therapeutic agents for immunomodulation and ischemic tissue repair in clinical practice. However, there are certain disadvantages in using MSCs, such as potential tumorigenicity, need for autologous collection, and short survival time. Previous evidence suggested that MSC-exosome significantly attenuated post-ischemic neuronal damage and induced long-term neuroprotection associated with enhanced angiogenesis in MSCs. Therefore, we hypothesized that the intravitreal administration of MSC-exosome could be a potentially effective therapeutic approach for NAION by using a similar mechanism via promoting angiogenesis, neuro-regeneration, and neurological recovery, suppressing oxidative stress and reducing apoptosis, and suppressing inflammation and immunity based on its biological structure and function in NAION. Questions that need to be answered before testing clinically include dose regimen, injection frequency, the optimal duration of treatment, and duration of medication.

Diagnosis of ischemic optic neuropathy caused by dissection of the internal carotid artery: A case report.

RATIONALE: Ischemic optic neuropathy (ION), due to diseases of the arteries supplying the optic nerve, is an ischemic damage of the optic nerve. This report highlights a case with monocular decreasing visual acuity caused by dissection of the internal carotid artery (ICA), which is a relatively rare cause for ION. PATIENT CONCERNS: A 44-year-old woman presented with a decreasing visual acuity and defected visual field in the right eye for 1 week. The best corrected visual acuity (BCVA) was 20/400 in the right eye, and 20/20 in the left eye. In the right eye, the pupil showed little reaction to light with a relative afferent pupillary defect. The visual field test disclosed a defect in the inferior field connecting to the blind spot. Electroretinogram recording showed no obviously declined retinal function. No recognizable waveforms were presented in pattern visual-evoked potential (PVEP) examination, whereas the flash visual-evoked potential result revealed a delayed peak time and a reduced amplitude of P2-wave. DIAGNOSIS: The patient was diagnosed as ION with the aid of computed tomographic angiography of the brain and neck, which revealed a stenosis in the right ICA and an occlusion in the right cerebral middle artery. The stenosis was verified as dissection of the ICA by digital subtraction angiography. INTERVENTIONS: Based on the clinical findings, stent implantation inside the right ICA was performed. OUTCOMES: The ICA was recanalized soon and the BCVA of the right eye was improved to be 20/25 five months later. A second PVEP examination revealed a recognizable waveform in the right eye, although the peak time and amplitude of the P100-wave was a bit abnormal compared to that of the left eye. LESSONS: ION with the sign of decreasing monocular visual acuity could occur due to dissection of the ICA, with no obvious neurologic symptom at the beginning. The present case emphasizes the importance of suspicion of ICA problems as the underlying cause for ION, which could help to take in-time measure to save the vision and avoid further complications.

[Diagnostic work-up in central retinal artery occlusion and ischemic optic neuropathy - what is important?] / Akute okuläre Ischämien ­ was ist wichtig in der internistischen Diagnostik?

Ischemia of the retina in central retinal artery occlusion (CRAO) and of the optic nerve in ischemic optic neuropathy (ION) are common causes of irreversible vision loss in elderly patients and require a thorough diagnostic work-up. First and foremost, giant cell arteritis should be confirmed or ruled out. The further work-up of non-arteritic CRAO and non-arteritic ION (nAION) aims to determine the cardiovascular risk profile. Patients with nAION should be screened for sleep apnoea. In non-arteritic CRAO, the search for embolic sources is the most important diagnostic task. A "white spot sign" seen on transorbital ultrasound confirms the diagnosis of embolic CRAO and rules out an arteritic etiology of CRAO.

Evaluation of enhanced external counterpulsation therapy for nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: To explore the effects of enhanced external counterpulsation (EECP) and its underlying influencing factors in nonarteritic anterior ischemic optic neuropathy (NAION) patients. METHODS: Patients at Zhongshan Ophthalmic Center with recent-onset (< 8 weeks) NAION were retrospectively recruited. The patients had decided whether or not they would undergo EECP treatment, and the patients who declined were included in the control group. The effectiveness of EECP was evaluated by comparing the visual function and fellow eye involvement in patients with and without EECP treatment. RESULTS: In total, 61 patients (76 eyes) were included. Twenty-nine patients (37 eyes) underwent EECP treatment, while 32 patients (39 eyes) were included in the control group. Mean time from NAION onset to EECP initiation was 27.59 ± 16.70 days. In the EECP group, the mean EECP duration was 31.57 ± 18.45 days. EECP was well tolerated by all patients. However, there was no significant difference in visual function between the EECP and control groups. Furthermore, there was no evidence of the effectiveness of EECP in the subgroup analysis of patients with different systemic health conditions. Among the 42 patients with monocular NAION, the sequential attack rate was comparable between the EECP (27.78%) and control (25.00%) groups. CONCLUSION: This study is the first nonrandomized controlled study to evaluate the effectiveness of EECP in NAION patients. Unfortunately, we failed to demonstrate the effectiveness of EECP in NAION at the 6-month follow-up. Any further application of EECP in NAION patients should be cautious.

[Ischemic optic neuropathies]. / Neuropathies optiques ischémiques.

Ischemic optic neuropathies include any vascular disease of the optic nerve. Anterior ischemic optic neuropathies are classically distinguished from posterior ischemic optic neuropathies by the presence of optic disc edema in the former, and the absence thereof in the latter. Non-arteritic acute anterior ischemic optic neuropathy is the most common ischemic optic nerve disease. Its exact cause remains unknown. A disc at risk (small and crowded optic nerve) is a typical backdrop for the development of non-arteritic ischemic optic neuropathy. There is no curative or preventive treatment. Posterior ischemic optic neuropathy is exceedingly rare, compared to anterior ischemic optic neuropathy. It is more frequent in patients with cardiovascular risk factors or in the perioperative period. There is no treatment. In any case of ischemic optic neuropathy, an arteritic cause must be ruled out urgently through clinical and paraclinical examinations. The most frequent cause is giant-cell arteritis. In this case, emergency treatment with intravenous methylprednisolone is required in order to limit vision loss in the affected eye and to prevent vision loss in the other eye.

[Acute ischemic optic nerve disease: Pathophysiology, clinical features and management (French translation of the article)]. / Pathologies ischémiques aiguës du nerf optique : physiopathologie, atteintes cliniques et prise en charge.

Ischemic optic neuropathies are among the leading causes of severe visual acuity loss in people over 50 years of age. They constitute a set of various entities that are clinically, etiologically and therapeutically different. Anatomically, it is necessary to distinguish anterior and posterior forms. From an etiological point of view, the diagnosis of the arteritic form due to giant cell arteritis requires emergent management to prevent blindness and even death in the absence of prompt corticosteroid treatment. When this diagnosis has been ruled out with certainty, non-arteritic ischemic optic neuropathies represent a vast etiological context that in the majority of cases involves a local predisposing factor (small optic nerves, disc drusen) with a precipitating factor (severe hypotension, general anesthesia or dialysis) in a context of vascular disease (sleep apnea syndrome, hypertension, diabetes, etc.). In the absence of specific available treatment, it is the responsibility of the clinician to identify the risk factors involved, in order to reduce the risk of contralateral recurrence that may occur even several years later. Due to their complexity, these pathologies are the subject of debates regarding both the pathophysiological and therapeutic perspectives; this review aims to provide a synthesis of validated knowledge while discussing controversial data.

Acute ischemic optic nerve disease: Pathophysiology, clinical features and management.

Ischemic optic neuropathies are among the leading causes of severe visual acuity loss in people over 50 years of age. They constitute a set of various entities that are clinically, etiologically and therapeutically different. Anatomically, it is necessary to distinguish anterior and posterior forms. From an etiological point of view, the diagnosis of the arteritic form due to giant cell arteritis requires emergent management to prevent blindness and even death in the absence of prompt corticosteroid treatment. When this diagnosis has been ruled out with certainty, non-arteritic ischemic optic neuropathies represent a vast etiological context that in the majority of cases involves a local predisposing factor (small optic nerves, disc drusen) with a precipitating factor (severe hypotension, general anesthesia or dialysis) in a context of vascular disease (sleep apnea syndrome, hypertension, diabetes, etc.). In the absence of specific available treatment, it is the responsibility of the clinician to identify the risk factors involved, in order to reduce the risk of contralateral recurrence that may occur even several years later. Due to their complexity, these pathologies are the subject of debates regarding both the pathophysiological and therapeutic perspectives; this review aims to provide a synthesis of validated knowledge while discussing controversial data.

Neuro-Ophthalmologic Complications of Giant Cell Arteritis: Diagnosis and Treatment.

Giant cell arteritis (GCA) is the most common vasculitis in individuals 50 years or older, with a lifetime risk in the United States of 1% in women and 0.5% in men. It is a granulomatous disease that affects large- and medium-sized vessels, most notably the branches of the internal and external carotid arteries. GCA can cause both afferent and efferent visual manifestations, the most common being arteritic anterior ischemic optic neuropathy. Diagnosis of GCA is made using criteria developed by the American College of Rheumatology, which include clinical signs, positive biopsy, and elevated erythrocyte sedimentation rate. C-reactive protein and platelet counts may be elevated in GCA, and noninvasive imaging modalities such as Doppler ultrasound and magnetic resonance imaging are now being used to aid in diagnosis. While glucocorticoids are the mainstay of treatment for GCA, new breakthrough treatments such as tocilizumab (an anti-IL-6 receptor antibody) have shown great promise in causing disease remission and reducing the cumulative glucocorticoid dose. Emerging therapies such as abatacept and ustekinumab are still being studied and may be of use to clinicians in the future.

[Non-arteritic Anterior Ischaemic Optic Neuropathy: Pathogenesis and Therapeutic Approaches]. / Pathogenese und Therapie der nicht arteriitischen anterioren ischämischen Optikusneuropathie.

Non-arteritic anterior ischemic optic neuropathy (NAION) is an acute neurodegenerative disease with a largely elusive early pathogenesis and no specific therapy. Recent data from animal models of the disease as well as from epidemiological studies have provided new insights into the disease mechanism of NAION. On the basis of this new knowledge, a broad variety of therapeutic approaches is currently being evaluated in animal and clinical studies. This review aims to provide an overview of the pathogenesis as well as neuroprotective therapeutic concepts of recent and currently running studies.

Hyperbaric oxygen therapy for perioperative posterior ischemic optic neuropathy: a case report.

PURPOSE: To report the successful treatment of postoperative posterior ischemic optic neuropathy (PION) with hyperbaric oxygen therapy and to review the current literature on the pathogenesis and treatment of PION. OBSERVATIONS: During an angiographic procedure at a community hospital, an elderly woman had a transient drop in blood pressure after receiving an intravenous dose of hydralazine. During recovery, the patient experienced bilateral vision loss. She was transferred to our specialty referral center for treatment with hyperbaric oxygen. We followed Table 5 in the U.S. Navy Diving Manual, the protocol for decompression sickness. Our patient's vision improved markedly immediately after the first session and continued to improve throughout the course of treatment to its completion. Follow-up ophthalmology visits found the patient's vision to be close to baseline. CONCLUSIONS AND IMPORTANCE: PION is a rare condition. It has been difficult to determine a successful therapeutic approach because of the lack of large case-controlled studies. Hyperbaric oxygen has been used to treat other ischemic ophthalmic conditions, but there are only few reports of its use in patients with PION. Systemic steroids and antiplatelet therapy have also been used, with mixed success. In our patient, the combination of hyperbaric oxygen therapy and steroids was successful in restoring vision after postoperative PION.

Ischemic Optic Neuropathy.

PURPOSE OF REVIEW: Vision is often threatened or lost by acute ischemic damage to the optic nerves. Such pathology most often affects the anterior portion of the nerve and is visible on funduscopic examination. Ischemic optic neuropathy is associated with typical vascular risk factors and with one systemic disease in particular: giant cell arteritis (GCA). This article provides an overview of the three major classes of ischemic optic neuropathy, including information on risk factors, differential diagnosis, evaluation, and management. RECENT FINDINGS: Optical coherence tomography provides precise anatomic imaging in ischemic optic neuropathy, showing neural loss weeks before it is visible on examination. Refinements of optical coherence tomography reveal optic nerve microvasculature and may assist in understanding pathogenesis and verifying diagnosis. New diagnostic algorithms and cranial vascular imaging techniques help define the likelihood of GCA in patients with ischemic optic neuropathy. Finally, intraocular drug and biological agent delivery holds promise for nonarteritic ischemic optic neuropathy, whereas newer immunologic agents may provide effective steroid-sparing treatment for GCA. SUMMARY: It is essential to recognize ischemic optic neuropathy upon presentation, especially to determine the likelihood of GCA and the need for immediate steroid therapy. A broad differential diagnosis should be considered so as not to miss alternative treatable pathology, especially in cases with retrobulbar optic nerve involvement.

New concepts on acute ocular ischemia.

PURPOSE OF REVIEW: To review recent advances in the management of acute ocular ischemic events, including: transient monocular vision loss, central and branch retinal artery occlusions, and nonarteritic anterior ischemic optic neuropathy. RECENT FINDINGS: Transient monocular vision loss and acute retinal arterial occlusions require immediate diagnosis and management, with recognition of these events as transient ischemic attack or stroke equivalents, respectively. Patients should undergo an immediate stroke workup in a stroke center, similar to patients with acute cerebral ischemia. The treatment of central retinal artery occlusions remains limited despite the growing use of thrombolytic treatments. The indication for these treatments remains under debate. No quality evidence exists to support any therapy, including corticosteroids, in the treatment of nonarteritic anterior ischemic optic neuropathy. The highest priority in management is to rule-out giant cell arteritis. SUMMARY: Effective therapies for the treatment of ischemic events of the retina and optic nerve remain elusive. Clinicians should focus on the prompt recognition of these events as ocular emergencies and immediately refer patients with vascular transient visual loss and acute central and branch retinal arterial occlusions to the nearest stroke center.

Non-arteritic anterior ischemic optic neuropathy - Case report.

We present a case of Non-Arteritic Anterior Ischemic Optic Neuropathy (NA-AION) with uncertain etiology but a good recovery with a total gain of central visual acuity.

Neuropatía úptica isquémica anterior unilateral asociada con ergotismo / Anterior unilateral ischemic optic neuropathy associated to ergotism

Case report of a patient with ergotism. ergotism is a complication of acute intoxication of chronic abuse of ergot derivates. Ergot is a fungus that grows on rye and less commonly on other grases such as wheat. Ergotism is a severe reaction to ergocontaminated food (such as rye bread). Ergot refers to a group of fungi of the genus Claviceps. It is a condition that develops of longterm ingestion of ergotamines. In excess, ergotamine can cause symptos such as hallucinations, severe gastrointestinal upset, a type-of dry gangrene and a pain-ful sensation in the extremities. Our patient is presented with anterior unilateral ischemic optic neuropathy. The studies performed and the clinical evaluatiion, are presented, and the treatment the same as the follow-up, are described in the article.

[Study on electroacupuncture along the visual conductive pathway for ocular cell apoptosis in anterior ischemic optic neuropathy].

OBJECTIVE: To study the protective effect of electroacupuncture (EA) along the visual conductive pathway for the optic nerve tissue of anterior ischemic optic neuropathy (AION) in terms of the structure and apoptosis. METHODS: The AION model of right eye was established with laser in 48 New Zealand white ear rabbits. All rabbits were randomly divided into a model group, an acupuncture group and an acupuncture combined with EA group, 16 rabbits in each one. Other 16 normal left eyes were selected as a blank group. Acupuncture and EA of 30 min were used in the corresponding groups for 3 days at the right "Cuanzhu" (BL 2), "Yuyao" (EX-HN 4) and "Qiaomingxue" (Extra), once a day. There was no intervention in the model group and the blank group. The morphological structure and retinal thickness of lining of the optic nerve were detected with HE stain. The expressions of the Bcl-2 and Bax in the retina were detected with immunohistochemistry. And the concentration of tumor necrosis factor-α (TNF-α) in the retina was detected with enzyme linked immunosorbent assay (ELISA). RESULTS: In the model group, the ganglion cell layer revealed hyperplasia and disorder, and the retina ganglion cells revealed loose arrangements, thin inner nuclear layers, and reduction of cell amounts, some long parts missing cells. However, the above structural damages were much weaker in the acupuncture group and acupuncture combined with EA group. The inner layer of the retina in the model group was thinner than that in the blank group (P<0.05). That in the acupuncture combined with EA group showed significant better results than those in the acupuncture and model groups (both P<0.05), which was not statistically different from that in the normal group (P>0.05). The Bcl-2 count in the model group was lower than that in the blank group (P<0.05), and that in the acupuncture combined with EA group was better than those in the acupuncture and model groups (both P<0.05), not significantly different from that in the blank group (P>0.05). The number of Bax in the model group was higher than that in the blank group (P<0.05), and that in the acupuncture combined with EA group was lower than those in the acupuncture and model groups (both P<0.05), and was similar to that in the blank group (P>0.05). Bcl-2/Bax in the model group was lower than that in the blank group (P<0.05). The value in the acupuncture combined with EA group presented better than those in the acupuncture and model groups (both P<0.05), which had no difference from that in the blank group (P>0.05). TNF-α in the model group was higher than that in the blank group (P<0.05), and no such differences were detected between other groups and the model group (bothP>0.05). CONCLUSIONS: EA along the visual conductive pathway is protective to some extent for optic nerve tissue, which can increase the expression of Bcl-2 and reduce the expression of Bax so as to restrain ganglion cell apoptosis.

Strategies to prevent ischemic optic neuropathy following major spine surgery: A narrative review.

Postoperative vision loss following a major spine operation is a rare but life-changing event. Most of reports have been linked to ischemic optic neuropathy, and patients undergoing surgery for scoliosis correction or posterior lumbar fusion seem to be at the highest risk. Despite that some key risk factors have been identified, much of the pathophysiology still remain unknown. In fact, whereas only a minority of patients at high risk will present this complication, others with similar risk factors undergoing different procedures may not develop it at all. On the other hand, even when all preventive measures have been taken, ischemic optic neuropathy may still occur. Therefore, it is appropriate for clinicians involved in these cases to inform their patients about the existence of a small but unpredictable risk of vision loss. Since ischemic optic neuropathy is deemed to be the leading cause of vision loss in the context of major spine surgery in prone position, this review will be focused on its main aspects related to the frequency, diagnosis, predisposing factors, and prevention. Regrettably, no treatment has been proved to be effective for this condition.