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.

Postoperative Visual Loss: A Report of One Patient With Unilateral Blindness After Orthognathic Surgery.

INTRODUCTION: Blindness after orthognathic surgery may be the result of the surgical procedure itself or the consequence of factors induced by general anesthesia. However, the exact mechanism between is not known. The purpose of this article is to present a case of a postoperative visual loss after orthognathic surgery under general anesthesia concluding with a brief literature review about this topic. REPORT OF CASE: We report the case of a patient who suffered unilateral blindness with homolateral frontal paresthesia after orthognathic procedure in 2 steps. He presented intraoperative bradycardia with a potential undiagnosed hypertension, associated with significant blood loss and volume resuscitation by colloids and cristalloids.Postoperative examination concluded to posterior ischemic optic neuropathy. DISCUSSION AND CONCLUSION: By a systematic literature review, we discuss about surgical and anesthesic causes of postoperative visual loss, and particularly pathophysiology mechanism of posterior ischemic optic neuropathy. Some predisposition and risk factors have been identified and need to be taken into account.

[PSYCHOGENIC FACTORS IN THE PATHOGENESIS OF ANTERIOR ISCHEMIC OPTIC NEUROPATHY (REVIEW)].

The purpose of this systematic review is to describe the influence of psychogenic factors on the pathogenesis and course of anterior ischemic optic neuropathy (AION). Analysis of randomized clinical trials published in the journal indexed in PubMed in the period from 1978 to 2016, devoted to the study of the influence of various factors on the epidemiology, pathogenesis and course of AION. The review of the literature presents basic information on the psychogenic factors that affect the course of AION and the areas of clinical application of the data under study. Physiological and pathological ways of influence of psychogenic factors on regulation of angiogenesis are considered. The main properties of the disturbance of retinal microcirculation, the role in the regulation of the vascular bed in the norm and under the influence of psychogenic factors in patients with AION are described.

Nonarteritic Anterior Ischemic Optic Neuropathy Induced Retinal Folds and Deformations.

Purpose: We hypothesized that the edema/swelling in the retina due to acute nonarteritic anterior ischemic optic neuropathy (NAION) can induce retinal folds (RF). We determined the pattern and frequency of folds in NAION at presentation and in follow-up, and the relationship between folds and a number of functional and structural parameters over time. Methods: We prospectively studied eyes with acute NAION by spectral-domain optic coherence tomography (SD-OCT). We used transaxial and en face views to evaluate the presence of peripapillary fluid (PPF), peripapillary wrinkles (PPW), RF, choroidal folds (CF), creases, macular edema, and vitreous traction on the optic disc. Retinal deformations were correlated with the retinal nerve fiber layer (RNFL) thickness, logMAR visual acuity (VA) and mean deviation (MD). Results: At presentation, 60 eyes had mean RNFL = 224 ± 75 µm, no vitreous traction, and similar VA and MD regardless of the retinal deformation or macular edema. There was PPF in 73%, PPW in 57%, RF in 38%, creases in 20%, and macular edema in 18% of eyes, and no CF. Eyes with retinal deformations had significantly greater RNFL thickness (P< 0.026). At 1 to 2 months, 49 eyes had reduction of the RNFL (112 ± 40 µm, P = 0.001) and unchanged VA and MD that did not correlate with fewer eyes having PPF (15%, P = 0.001), PPW (10%, P = 0.001), RF (10%, P = 0.001), creases (17%), and macular edema (0%, P = 0.007). Conclusions: RF in NAION reflect stresses and strains due to extracellular fluid without increased pressure in the retrolaminar tissue and subarachnoid space, seen with papilledema. In NAION, the deformations and their resolution do not correlate with vision loss.

Bilateral ocular ischemia-induced blindness as a presenting manifestation of Takayasu arteritis: a case report.

BACKGROUND: Takayasu arteritis is a granulomatous panarteritis that predominantly affects the aorta and its major branches. The initial manifestations of this large-vessel vasculitis are usually nonspecific; however, as the disease progresses, typical symptoms of arterial occlusion, aneurysmal formation, and vascular pain become evident. Ischemic ocular complications of Takayasu arteritis which could lead to complete loss of vision are not uncommon and depend on the obliterated portion(s) of carotid(s), the intensity and rate of progression of ocular vascular insufficiency, and sufficiency of the collateral blood supply to the eye. CASE PRESENTATION: A 24-year-old woman of African descent with prior normal vision was referred to us with a 3-year history of gradual decline in visual acuity in both eyes and unintentional weight loss (17 kg) within the past 1 year. A physical examination revealed feeble brachial and radial arterial pulses on her left side. She had sinus tachycardia (136 beats/minute) and her blood pressure was 85/59 mmHg on her left and 134/82 mmHg on her right side. Bilateral microaneurysms, dot and blot hemorrhages, and multiple ischemic areas of retina together with neovascularization in her right eye were noted during a funduscopic examination. Computed tomography angiography of her thoracic and abdominal aorta revealed irregular narrowing with variable degrees of stenosis, tapering, and corrugated appearance. CONCLUSIONS: Despite its rarity, Takayasu arteritis significantly impairs a patient's quality of life and has a life-threatening potential. Early initiation of appropriate therapy could delay disease progression and reduce the associated complications.

Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy.

Purpose: The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION). Methods: The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects. Results: Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group. Conclusions: The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.

Imaging of macrophage dynamics with optical coherence tomography in anterior ischemic optic neuropathy.

Anterior ischemic optic neuropathy (AION) is a relatively common cause of visual loss and results from hypoperfusion of the small arteries of the anterior portion of the optic nerve. AION is the leading cause of sudden optic nerve related vision loss with approximately 10 cases per 100'000 in the population over 50 years. To date there is no established treatment for AION and therefore a better understanding of the events occurring at the level of the optic nerve head (ONH) would be important to design future therapeutic strategies. The optical properties of the eye allow imaging of the optic nerve in vivo, which is a part of the CNS, during ischemia. Experimentally laser induced optic neuropathy (eLiON) displays similar anatomical features as anterior ischemic optic neuropathy in humans. After laser induced optic neuropathy we show that hyperreflective dots in optical coherence tomography correspond to mononuclear cells in histology. Using fluorescence-activated flow cytometry (FACS) we found these cells to peak one week after eLiON. These observations were translated to OCT findings in patients with AION, where similar dynamics of hyperreflective dots at the ONH were identified. Our data suggests that activated macrophages can be identified as hyperreflective dots in OCT.

Pathology of Ischemic Optic Neuropathy.

Ischemic optic neuropathy (ION) describes a state of hypoxic injury of the optic nerve. Clinically, ION is divided into anterior and posterior forms defined by the presence or absence of optic disc swelling, respectively. It is further classified as arteritic when secondary to vasculitis, and nonarteritic when not. The site of vascular occlusion for anterior ION from giant cell arteritis is the short posterior ciliary arteries, but mechanical vascular obstruction does not play a role in most nonarteritic cases. Histologically, ION is characterized by axon and glial necrosis, edema, and a sparse mononuclear response. Like other ischemic injuries, the morphologic alternations in the nerve are time dependent. A variant of ION called cavernous degeneration (of Schnabel) features large cystic spaces filled with mucin. Several conditions can histologically mimic cavernous degeneration of the optic nerve. The scarcity of cases of ION examined histologically has contributed to an incomplete understanding of its pathogenesis.

Anterior ischemic optic neuropathy and hematologic malignancy: a systematic review of case reports and case series.

OBJECTIVE: Demographic and clinical characteristics associated with nonarteritic anterior ischemic optic neuropathy (NAION) are well described. Patients with hematologic neoplasms may share some of these characteristics, and it may be useful clinically to better understand this set of patients. Our objective is to review systematically the characteristics of patients with both hematologic malignancies and NAION. DESIGN: Systematic review. PARTICIPANTS: Patients with NAION diagnosis related in time to a hematologic neoplasm. METHODS: Data sources for the study included MEDLINE, Web of Science, LILACS, SciELO, and OpenGrey. The study eligibility criteria included case reports and case series. RESULTS: We found 261 records, with 15 studies included plus our case report. A total of 19 patients (8 female) with mean age of 54.6 years (range, 12-87) were analyzed: 37% (7) non-Hodgkin lymphoma; 26% (5) myeloproliferative neoplasms; 21% (4) myelodysplasia; 16% (3) leukemias. The limitations included verification bias, inability to test statistical association between NAION and hematologic neoplasms, the small number of cases, and confounding factors related to medical history and specific interventions in each case limited the robustness of our conclusions. CONCLUSIONS: Our results identified the characteristics of patients with NAION and hematologic neoplasms related in time. Additional observational studies may enlighten the importance of looking for evidence of an occult neoplastic disorder in patients presenting with NAION. A prompt diagnosis would be of invaluable significance for the best management, in terms of follow-up and therapeutics.

Perioperative Vision Loss in Spine Surgery and Other Orthopaedic Procedures.

Perioperative vision loss is a rare complication of orthopaedic surgery and has been documented after spine, knee, hip, and shoulder procedures. It is associated with several ophthalmologic diagnoses, most commonly ischemic optic neuropathy. Although the pathophysiology remains unclear, current evidence suggests that systemic hemodynamic compromise and altered balance of intraocular perfusion contribute to the development of ischemic optic neuropathy. Although vision recovery has been reported, the prognosis of perioperative vision loss is poor, and no proven effective treatment is available. Perioperative vision loss is unpredictable and can occur in healthy patients. Associated risk factors include pediatric or elderly age, male sex, obesity, anemia, hypotension or hypertension, perioperative blood loss, prolonged surgical time, and prone positioning. Preventive strategies include avoiding direct pressure to the eye, elevating the head, optimizing perioperative hemodynamic status, and minimizing surgical time with staged surgical procedures as appropriate.

[ORIGINAL PERFORMANCE OF THE INTEGRATED CIRCUITS NEUROPROTECTIVE LECHNIYA ANTERIOR ISCHEMIC OPTIC NEUROPATHY DEPENDING ON BLOOD PRESSURE].

Anterior ischemic optic neuropathy (AION) is one of the main reasons of vision disorders among middle-aged and elderly people. During the examination of patients with AION, we were interested by the fact of low efficiency of the standard treatment course. Moreover, over 60% of such patients underwent the development of AION on the other eye during 1 year after the beginning of the disease. The purpose of the given study is the development of efficient and original neuroprotection treatment scheme for AION, depending on the arterial pressure rate. We examined 58 patients (65 eyes) with AION, depending on the arterial pressure rate. The patients were divided into two clinical groups. For the first group of 38 patients (38 eyes), we used the original AION treatment scheme developed by us. The group was divided into 3 subgroups, depending on their arterial pressure rate: patients with normal ap., patients with hypertension of I-II stages and patients with hypotension. For the control group, the standard treatment scheme was used. The results received allow us to make a conclusion that the original treatment scheme, developed by us, is more efficient, and it can be recommended as a neuroprotection treatment scheme for AION among the patients with arterial hypertension of I-II stages.

Effect of Head Position on Intraocular Pressure During Lumbar Spine Fusion: A Randomized, Prospective Study.

BACKGROUND: Ischemic optic neuropathy resulting in visual loss is a rare but devastating complication of spine surgery. Elevated intraocular pressure (IOP) results in decreased perfusion and possibly ischemic optic neuropathy. We performed a randomized, prospective trial to evaluate the effect of head positioning on IOP during lumbar spine fusion. METHODS: The study included fifty-two patients treated at one institution. Inclusion criteria were a lumbar spine fusion and an age of eighteen to eighty years. Exclusion criteria were a diagnosis of tumor, infection, or traumatic injury or a history of eye disease, ocular surgery, cervical spine surgery, chronic neck pain, or cervical stenosis. The control group underwent the surgery with the head in neutral and the face parallel to the level operating room table whereas, in the experimental group, the neck was extended so that the face had a 10° angle of inclination in relation to the table. IOP measurements were recorded along with the corresponding blood pressure and PCO2 values at the same time points. The primary outcome measure was the change in intraocular pressure (ΔIOP, defined as the maximum IOP minus the initial IOP). RESULTS: Analysis of covariance (ANCOVA) was used for categorical risk factors, and regression analysis was used for continuous risk factors. The mean ΔIOP, corrected for duration of surgery, was significantly (p = 0.0074) lower in the group treated with the head elevated than it was in the group treated with the head in neutral (difference between the two groups, 4.53 mm Hg [95% confidence interval, 1.29 to 7.79 mm Hg]). No patient sustained visual loss or any cervical-spine-related complications. CONCLUSIONS: Head elevation for adult lumbar spine fusion performed with the patient prone resulted in significantly lower IOP measurements than those seen when the operation was done with the patient's head in neutral. As lower IOP correlates with increased optic nerve perfusion, this intervention could mitigate the risk of perioperative blindness after spine surgery done with the patient prone.

Giant cell arteritis: a closer look at its ophthalmological manifestations.

Giant cell arteritis with ocular involvement is an ocular emergency. Arteritic anterior ischaemic optic neuropathy (AAION) is the most common ophthalmological manifestation associated with this disease. Visual loss is usually permanent with rare cases showing visual recovery. Visual improvement, if it occurs, is generally limited, and the visual field defects are persistent and severe. The main goal of AAION treatment is the preservation of vision in the fellow eye. In patients with neurophthalmological manifestations, high-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter. We present a case of AAION and severe vision loss where significant visual recovery was seen after treatment.

Study of perfusion changes in the optic disc of patients with fibromyalgia syndrome using new colorimetric analysis software.

PURPOSE: We measured the amount of hemoglobin at the optic nerve head of fibromyalgia (FM) patients using new colorimetric analysis software. We also investigated whether perfusion defects of the optic nerve head in patients with FM lead to tissue atrophy and corresponding retinal nerve fiber layer (RNFL) thinning measured by optical coherence tomography (OCT). METHODS: We recruited for this cross-sectional study 118 FM patients and 76 sex- and age-matched healthy controls. All subjects underwent a complete neuro-ophthalmologic examination, which also included visual field testing using the Spark strategy in an Easyfield perimeter, and OCT examinations using the Spectralis. One photograph of the optic disc was obtained using a Cirrus™ Photo 800 multi-modality imager. We analyzed fundus photographs using Laguna ONhE software, a new method that allows hemoglobin levels to be measured at the optic nerve head. We compared hemoglobin percentages in different sectors of the nerve head and RNFL thicknesses between the two groups. RESULTS: Mean hemoglobin percentages and hemoglobin content in all optic nerve head sectors calculated by the Laguna ONhE program were significantly lower in FM patients than in healthy controls, and the main differences were detected in the outer ring, which corresponds with the neuroretinal rim. However, only the differences in the superotemporal RNFL were statistically significant. Correlations between the RNFL thickness and the percentage of hemoglobin in the different sectors were weak. CONCLUSION: Optic disc perfusion was decreased in patients with FM, especially within the neuroretinal rim, without clear involvement in the RNFL.

Progesterone treatment in two rat models of ocular ischemia.

PURPOSE: To determine whether the neurosteroid progesterone, shown to have protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, is also protective in ocular ischemia animal models. METHODS: Progesterone treatment was tested in two ocular ischemia models in rats: a rodent anterior ischemic optic neuropathy (rAION) model, which induces permanent monocular optic nerve stroke, and the middle cerebral artery occlusion (MCAO) model, which causes transient ischemia in both the retina and brain due to an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. Visual function and retinal histology were assessed to determine whether progesterone attenuated retinal injury in these models. Additionally, behavioral testing and 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining in brains were used to compare progesterone's neuroprotective effects in both retina and brain using the MCAO model. RESULTS: Progesterone treatment showed no effect on visual evoked potential (VEP) reduction and retinal ganglion cell loss in the permanent rAION model. In the transient MCAO model, progesterone treatment reduced (1) electroretinogram (ERG) deficits, (2) MCAO-induced upregulation of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), and (3) retinal ganglion cell loss. As expected, progesterone treatment also had significant protective effects in behavioral tests and a reduction in infarct size in the brain. CONCLUSIONS: Progesterone treatment showed protective effects in the retina following MCAO but not rAION injury, which may result from mechanistic differences with injury type and the therapeutic action of progesterone.

Postoperative visual loss in orthopedic spine surgery in the prone position: a case report.

Postoperative visual loss is rare but a devastating postoperative complication. It is a multifactorial etiology. The practice advisory for perioperative visual loss associated with spine surgery reported by the American Society of Anesthesiologists task force on perioperative visual loss was developed from several case reports and case series. We reported a new case of postoperative visual loss diagnosed as ischemic optic neuropathy after undergoing a spine surgery in prone position. This case should be added to the overall incidence of postoperative visual loss. The possible risk factors were categorized in order to identify the POVL-susceptible patients. The pathophysiology of ischemic optic neuropathy was briefly reviewed.