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.

mTOR regulates neuroprotective effect of immunized CD4+Foxp3+ T cells in optic nerve ischemia.

The therapeutic potential of targeting CD4+Foxp3+ regulatory T cells (Tregs) remains controversial under the condition of neuroinflammation. This study aims to explore the neuroprotective role of Tregs in optic nerve ischemia (ONI) and evaluate the therapeutic strategy of Tregs transfer with a focus on targeting the mammalian target of rapamycin (mTOR) pathway. Intraocular pressure was transiently increased in adult C57BL/6 mice to induce ONI. Mucosal tolerance of myelin basic protein (MBP) markedly increased retinal ganglion cell (RGC) survival after ONI through enhanced Tregs suppression. mTOR inhibition significantly promoted the frequency of MBP-immunized Tregs in vitro with increased production of anti-inflammatory cytokines. Transient rapamycin treatment highly promoted the immunosuppressive capacity of Tregs and inhibited retinal inflammation in ONI animals. Intravenous infusion of MBP-immunized Tregs, instead of regular Tregs, beneficially modulated immune activities of host retinal CD11b+ cells and CD4+ effector T cells, leading to significant improvement of RGC survival. Importantly, rapamycin treatment further enhanced the neuroprotective effect of Tregs transfer. Taken together, these findings reveal a fine regulation of mTOR signaling on immunized Tregs after acute retinal injury. Adoptive transfer with targeting-mTOR strategy markedly improves neuronal recovery after ONI, supporting the therapeutic potentials of Tregs in acute and chronic neurological disorder.

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.

[Bilateral amaurosis after spinal trauma]. / Beidseitige Amaurose nach Wirbelsäulentrauma.

This article presents the case of a 72-year-old male patient who suffered severe trauma of the spinal column. The patient developed persistent, bilateral, complete blindness after prolonged emergency neurosurgical treatment in a prone position. A bilateral surgical posterior ischemic optic neuropathy (PION) was diagnosed, which is a rare but severe complication of prolonged non-ocular surgery with circulatory stress. The massive, mostly bilateral, irreversible visual loss up to complete blindness leads to severe and permanent impairment of affected patients.

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.

Patient positioning and prevention of injuries in patients undergoing laparoscopic and robot-assisted urologic procedures.

Positioning injuries in the perioperative period are one of the inherent risks of surgery, but particularly in robot-assisted urologic surgery, and can result in often unrecognized morbidity. Injuries such as upper or lower extremity peripheral neuropathies occur via neural mechanisms and injuries such as compartment syndrome, rhabdomyolysis, ischemic optic neuropathy, and acute arterial occlusion occur via vascular mechanisms. The risk of injury may be exacerbated by operative and patient-related risk factors. Patient-related risk factors include ASA class and BMI, while surgery-related risk factors include physical orientation of the patient and operative length. These injuries can be prevented or reduced by joint effort of the surgeon, anesthesiologist, and operating room staff.

Obstructive sleep apnea and nonarteritic anterior ischemic optic neuropathy: evidence for an association.

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most prevalent optic nerve disorder among patients over 50 years of age, characterized by sudden onset, painless visual loss, with an accompanying relative afferent pupillary defect and optic disc edema. Although the pathophysiology of NAION has not been fully elucidated, several risk factors have been considered, including advanced age, systemic hypertension, diabetes mellitus, and certain optic disc morphologies. An association between obstructive sleep apnea (OSA) and NAION has also been recognized. One prospective cohort study indicated that the relative risk of OSA among patients with NAION was 4.9; a later retrospective cohort study demonstrated that patients with OSA not treated with continuous positive airway pressure (CPAP) had a 16% increased hazard of developing NAION compared to patients without OSA.The following review will discuss the most recent understanding of the relationship between OSA and NAION, with implications for further research and prevention strategies.

Protection of mouse retinal ganglion cell axons and soma from glaucomatous and ischemic injury by cytoplasmic overexpression of Nmnat1.

PURPOSE: The Wlds mutation affords protection of retinal ganglion cell (RGC) axons in retinal ischemia and in inducible and hereditary preclinical models of glaucoma. We undertook the present study to determine whether the Nmnat1 portion of the chimeric protein provides axonal and somatic protection of RGCs in models of ischemia and glaucoma, particularly when localized to nonnuclear regions of the cell. METHODS: The survival and integrity of RGC axons and soma from transgenic mice with confirmed cytoplasmic overexpression of Nmnat1 in retina and optic nerve (cytNmnat1-Tg mice) were examined in the retina and postlaminar optic nerve 4 days following acute retinal ischemia, and 3 weeks following the chronic elevation of intraocular pressure. RESULTS: Ischemia- and glaucoma-induced disruptions of proximal segments of RGC axons that comprise the nerve fiber layer in wild-type mice were both robustly abrogated in cytNmnat1-Tg mice. More distal portions of RGC axons within the optic nerve were also protected from glaucomatous disruption in the transgenic mice. In both disease models, Nmnat1 overexpression in extranuclear locations significantly enhanced the survival of RGC soma. CONCLUSIONS: Overexpression of Nmnat1 in the cytoplasm and axons of RGCs robustly protected against both ischemic and glaucomatous loss of RGC axonal integrity, as well as loss of RGC soma. These findings reflect the more pan-cellular protection of CNS neurons that is realized by cytoplasmic Nmnat1 expression, and thus provide a therapeutic strategy for protecting against retinal neurodegeneration, and perhaps other CNS neurodegenerative diseases as well.

[Bilateral anterior ischemic optic neuropathy following EHEC sepsis and hemolytic-uremic syndrome]. / Bilaterale anteriore ischämische Optikusneuropathie nach EHEC-Sepsis und hämolytisch-urämischem Syndrom.

After emerging from a coma caused by enterohemorrhagic Escherichia coli (EHEC) sepsis with severe neurological and renal involvement a 53-year-old female patient complained of blurred vision. Due to hemolytic-uremic syndrome (HUS) the patient also suffered from dialysis-dependent acute kidney failure. Horizontal visual field defects of the lower hemifield and corresponding segmental optic disc pallor were found in both eyes. Bilateral anterior ischemic optic neuropathy (AION) was diagnosed presumably caused by high volume shifting and hypotonia due to sepsis and dialysis. The literature revealed that bilateral AION is often seen after complex surgical procedures or in patients with severe metabolic disorders. This ophthalmologic complication should always be taken into consideration because of the serious permanent visual damage.

Case of ischemic optic neuropathy developed eleven days after an aortic arch replacement.

We present a case of ischemic optic neuropathy (ION) developed 11 days after an aortic arch replacement in a 59 year-old male who had a history of untreated hypertension. Thoracic CT revealed severe stenosis of the right common carotid artery with poor blood flow. Aortic clamping time was 96 minutes, and selective cerebral perfusion time was 48 minutes. The lowest hemoglobin concentration of venous blood during cardiopulmonary bypass was 8.1 g/dl and the lowest arterial pressure was 60 mmHg. Due to pulmonary congestion, artificial ventilation was required until 11 post-surgical days. After removal of ventilator, the patient's consciousness was clear with no motor paralyses evident. However, the patient complained of blurred vision on that day. Bilateral papillae of the optic fund were pale. Atrophy of the papillae was also noted. Visual evoked potential was bilaterally flat suggesting bilateral optic nerve disturbance. The diagnosis of ION was made by ophthalmologist and neurologists. We speculated that low hemoglobin level during cardiopulmonary bypass was not the sole etiology of ION. Untreated hypertension, low blood flow through internal carotid artery and prolonged mechanical ventilation were also deteriorating factors of ION in this patient. We should be alert to prevent ION in such a complicated case.

Ischemic optic neuropathy: are we any further?

PURPOSE OF REVIEW: Postoperative vision loss (POVL) as related to spinal surgery and the prone position has garnered increasing attention in the US over the last 15 years, resulting in an increase of litigations submitted to the legal system. It might be associated with the development of new surgical techniques involving complex instrumentation of the spine. By 2000, the magnitude of this problem was such that the American Society of Anesthesiologists developed a Postoperative Visual Loss Registry in an effort to better understand and evaluate this devastating operative complication. RECENT FINDINGS: The cause of ischemic optic neuropathy (ION) as the most complex entity of POVL is still unclear. Retrospective studies show that although it can strike patients of any age, there is an increased incidence in patients less than 18 and more than 65 years of age. Significant risk factors include male sex, anemia, surgery lasting over 6 h, and intraoperative hypotension. Profound anatomical knowledge and new animal studies have helped to define possible mechanisms underlying ION. SUMMARY: ION is still poorly understood and risk factors remain speculative. Given that there is no known treatment, increased understanding should help to prevent this postoperative complication.

Possible neuroprotective effect of brimonidine in a mouse model of ischaemic optic neuropathy.

PURPOSE: To investigate the neuroprotective effect of brimonidine following induction of ischaemic optic neuropathy in rodents (rAION). METHODS: Mice were treated with an intraperitoneal injection of brimonidine 48, 24 or 0 h before rAION induction or eye drops for 5 days after rAION induction. Retinal ganglion cell (RGC) loss and expression of genes involved in the angiogenesis (vascular endothelial growth factor [VEGF], pigment epithelium-derived factor [PEDF], The epidermal growth factor homology domains-2 [Tie-2]), ischaemia (haem oxygense-1 [HO-1], hypoxia-inducible factor 1alpha[HIF-1alpha], endothelial nitric oxide synthase [eNOS]) and oxidative stress (superoxide dismutase-1 [SOD-1], glutathione peroxidase-1 [GPX-1]) response to ischaemic damage were compared with sham or rAION-untreated mice. RESULTS: No RGC loss was detected in the brimonidine-treated mice. Effect of post-rAION eye drops: day 1--no decrease in retinal mRNA levels of angiogenesis-related genes, increase in ischaemia- and oxidative stress-related genes except HIF-1alpha; day 3--baseline or higher levels of oxidative and ischaemia-related genes except HIF-1alpha, increase in VEGF, decrease in PEDF; day 21--no change in angiogenesis-related genes. Effect of pre-rAION injection: baseline levels of angiogenesis-related genes with all injection schedules; increase in ischaemia-related genes with 48-h and 0-h pretreatment; decrease in HO-1 and eNOS with 24-h pretreatment; increase in oxidative-related genes except GPX-1. In optic nerve tissue, HO-1, HIF-1alpha and SOD-1 decreased on day 1 after topical administration and were still below baseline on day 3. CONCLUSIONS: The increase in HO-1 associated with rAION is mitigated with brimonidine treatment, especially when administered intraperitoneally. Topical brimonidine apparently reduces VEGF, Tie-2, HIF-1alpha and GPX-1 expression on day 21. These results agree with published data and may have therapeutic implications for patients diagnosed with AION in the acute phase.

Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review.

OBJECTIVE: To review the available evidence for the neuroprotective qualities of brimonidine tartrate in optic nerve and retinal injury. METHODS: References for this study were obtained by running a search of the PubMed database using keywords brimonidine, neuroprotection, ischemic optic neuropathy, and alpha2-adrenergic agonists. References focusing on ocular hypertension were excluded. RESULTS: Forty-eight articles addressing 1 of 4 criteria for neuroprotection were included. The literature confirms that brimonidine therapy meets the first 3 criteria for neuroprotection: receptors on its target tissues, adequate penetration into the vitreous and retina at pharmacologic levels, and induction of intracellular changes that enhance neuronal resistance to insults or interrupt apoptosis in animal models. Brimonidine did not meet the final neuroprotective criterion of success in humans. CONCLUSIONS: Experimental evidence has demonstrated that brimonidine is a potential neuroprotective agent. However, to date, clinical trials have failed to translate into similar efficacy in humans.

Effect of unoprostone on topographic and blood flow changes in the ischemic optic nerve head of rabbits.

OBJECTIVE: To determine whether subconjunctival injection of unoprostone isopropyl alters changes in the topography and blood flow of the optic disc induced by endothelin 1 (ET-1) in rabbits. METHODS: From April 1, 2005, to April 28, 2006, we injected ET-1 (20 pmol) intravitreally into rabbits twice per week for 4 weeks. The observation period was 8 weeks. The first group received an intravitreal injection of ET-1 followed by a subconjunctival injection of unoprostone (0.12%, 50 microL). The second group received the same amount of ET-1 followed by a subconjunctival injection of the vehicle of unoprostone. The third group received the intravitreal vehicle of ET-1. The blood flow and topography of the optic nerve head (ONH) were measured by laser speckle flowgraphy and confocal scanning ophthalmoscopy, respectively. The number of cells in the retinal ganglion cell layer and inner nuclear layer was determined histologically. RESULTS: We found that ET-1 decreased the ONH blood flow, decreased the cells in the ganglion cell layer and inner nuclear layer, enlarged the cup area of the ONH, and reduced the rim area of the ONH. When unoprostone was given with ET-1, no such changes occurred. CONCLUSION: Unoprostone can suppress the effects of ET-1 on the circulation and topography of the ONH. CLINICAL RELEVANCE: Unoprostone could be a candidate for treating eyes with ischemic ONH.