Literature Commentary

Literature Commentary Section Editors: Mark L. Moster, MD M. Tariq Bhatti, MD Literature Commentary Mealy MA, Whetstone A, Orman G, Izbudak I, Calabresi PA, Levy M. Longitudinally extensive optic neuritis as an MRI biomarker distinguishes neuromyelitis optica from multiple sclerosis. J Neurol Sci. 2015;355:59-63. Objective: To differentiate magnetic resonance imaging (MRI) characteristics of optic neuritis associated with neuromyelitis optica (NMO) and relapsing-remitting multiple sclerosis (RRMS). Background: Optic neuritis is a common presenting feature of both NMO and MS. Distinguishing between NMO and RRMS is important in guiding treatment, but biomarkers of NMO and MS can be absent early in the disease process. We looked for differences in MRI characteristics of optic neuritis associated with NMO and MS that provide an early clue in the diagnostic workup. Design/Methods: We conducted a retrospective analysis of 26 NMO and 26 RRMS patients presenting to the Johns Hopkins Hospital with MRI-confirmed acute optic neuritis. Magnetic resonance images were assessed to identify the location and longitudinal extent of each contrast enhancing lesion. For the purposes of this study, the optic nerve was divided into intraorbital, canalicular, prechiasmal, chiasmal, and optic tract. Results: There are distinct differences in MRI characteristics between NMO-associated and RRMS-associated optic neuritis. The majority of NMO lesions were longitudinally extensive measuring at least 17.6 mm in length and involving at least 3 optic nerve segments. At a cut-off of 17.6 mm of lesion length, the specificity for NMO is 76.9% with a sensitivity of 80.8% and a positive likelihood ratio of 3.50. Conversely, MS lesions were more commonly focal in 1 optic nerve segment localized anteriorly. Conclusions: Optic neuritis in NMO has a distinct pattern on MRI as compared with RRMS and can help differentiate these 2 neuroinflammatory diseases at presentation. One of the challenges in the acute optic neuritis patient is deciding when to be concerned about neuromyelitis optica (NMO). This study found that similar to lesions of the spinal cord, extensive optic nerve lesions are highly suggestive but not exclusive to NMO. Additionally, lesions that are bilateral, involving the optic tract or chiasm are more likely NMO than multiple sclerosis (MS). One limitation of the study is that only approximately half of the patients had dedicated orbital magnetic resonance images. Another issue is that with bilateral lesions (25% of the time with NMO), the lengths of the 2 lesions were added together. This might be a confounding factor, 438 because bilateral disease by itself increases the likelihood of NMO even with a short lesion. Finally, the radiologist was not "masked" in this study, which makes little sense to me. Despite the limitations, it is clear that a lengthy lesion, particularly posteriorly in the optic nerve, increases the likelihood of a diagnosis of NMO rather than MS. -Mark L. Moster, MD I just want to point a few things out that are germane to the subject matter of NMO. First, compared with acute idiopathic demyelinating optic neuritis or MS-associated optic neuritis, NMO-associated optic neuritis is uncommon in terms of frequency (in other words, it is more likely a patient has MS than NMO in the setting of first-attack optic neuritis). In addition, aside from this neuroimaging observation, the clinical findings of recurrent vision loss, simultaneous bilateral vision loss, profound vision loss (worse than hand motions), and irreversible vision loss should alert clinicians to the possibility of NMO. -M. Tariq Bhatti, MD Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372:2285-2295. Background: Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (IV t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to IV t-PA, increases reperfusion rates and may improve long-term functional outcome. Methods: We randomly assigned eligible patients with stroke who were receiving or had received IV t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemiccore lesions. The primary outcome was the severity of Moster and Bhatti: J Neuro-Ophthalmol 2015; 35: 438-443 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). Results: The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with a stent retriever plus IV t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P , 0.001). The rate of functional independence (modified Rankin scale score, 0-2) was higher in the intervention group than in the control group (60% vs 35%, P , 0.001). There were no significant betweengroup differences in 90-day mortality (9% vs 12%, P = 0.50) or symptomatic intracranial hemorrhage (0% vs 3%, P = 0.12). Conclusions: In patients receiving IV t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days (funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461). I think we are all familiar with the expression "time is money"; well in the case of a cerebral ischemic stroke-"time is brain." In 1996, after the results of the acute stroke trial sponsored by the National Institute of Neurological Disorders and Stroke, patients needed to be seen within 3 hours for the thrombolytic to be administered. However, since then additional studies with pooled analysis of the data have extended that time period to 4.5 hours (1). From a practical point of view, it has always been difficult to not only get patients to recognize the symptoms of a cerebral stroke to seek immediate medical care, but also to activate the necessary hospital resources to administer thrombolytic therapy (2). To lessen the burden of these potential obstacles, it would be ideal to try to extend the critical time period in which a patient can be successfully treated. A total of 196 patients with ischemic stroke due to proximal occlusion of the middle cerebral artery or internal carotid artery were given intravenous tissue plasminogen activator (IV t-PA). Ninety-eight of these patients also underwent endovascular mechanical thrombectomy using a newer generation device known as the Solitaire 2 device (manufactured by Covidien, Dublin, Ireland, sponsors of the clinical trial). The primary functional outcome measure of the study was based on the Modified Rankin Scale at 90 days. Those patients who underwent IV t-PA and mechanical thrombectomy had a 25% point better chance of being functionally independent than those patients who received IV t-PA alone (60% vs 35%). The median time from stroke onset to randomization was 188 minutes in the IV t-PA alone group and 190.5 minutes in the stent retriever plus IV t-PA group with a median time of stent deployment of 252 minutes. There was no difference in the primary outcome between the 2 groups based on time (,or .189 min, maximum of 360 min). In terms of safety, the stent retriever plus IV t-PA group had a greater number of Moster and Bhatti: J Neuro-Ophthalmol 2015; 35: 438-443 serious adverse events compared with the IV t-PA alone group (36% vs 31%), but this was not statistically significant. In a second clinical trial of endovascular thrombectomy and thrombolysis, published in the same issue of the New England Journal of Medicine, efficacy was shown to extend to 8 hours! (3). In fact, these 2 trials and several others have heralded a new era in the treatment of stroke that has started the discussion on developing a new organizational framework for the current existing stroke system to not only have hospitals ready to deliver this type of care, but also to transport patients to the appropriate stroke care facility (4). -M. Tariq Bhatti, MD This is one more advance that will eliminate disability in some patients and decrease degree of disability in others after ischemic stroke. The percent of patients with functional independence at 90 days increased from 35% to 60%, which is quite impressive after a large vessel occlusion. All these patients had t-PA, but further studies should address the possible benefits of thrombectomy in patients who present beyond the time frame to receive t-PA or those who otherwise have a contraindication to t-PA. -Mark L. Moster, MD REFERENCES 1. Lansberg MG, Bluhmki E, Thijs VN. Efficacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a metaanalysis. Stroke. 2009;40:2438-2441. 2. Meretoja A, Strbian D, Mustanoja S, Tatlisumak T, Lindsberg PJ, Kaste M. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology. 2012;79:306-313. 3. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Román L, Serena J, Abilleira S, Ribó M, Millán M, Urra X, Cardona P, López-Cancio E, Tomasello A, Castaño C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Pérez M, Goyal M, Demchuk AM, von Kummer R, Gallofré M, Dávalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372:2296-2306. 4. Smith EE, Schwamm LH. Endovascular clot retrieval therapy: implications for the organization of stroke systems of care in North America. Stroke. 2015;46:1462-1467. Thompson BG, Brown RD Jr, Amin-Hanjani S, Broderick JP, Cockroft KM, Connolly ES Jr, Duckwiler GR, Harris CC, Howard VJ, Johnston SC, Meyers PM, Molyneux A, Ogilvy CS, Ringer AJ, Torner J; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, and Council on Epidemiology and Prevention. Guidelines for the management of patients with unruptured intracranial aneurysms: a guideline for healthcare professionals from the american heart Association/American stroke association. Stroke. 2015;46:2368-2400. Purpose: The aim of this updated statement is to provide comprehensive and evidence-based recommendations for management of patients with unruptured intracranial aneurysms. 439 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Methods: Writing group members used systematic literature reviews from January 1977 to June 2014. They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulated recommendations using the standard American Heart Association criteria. The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Stroke Scientific Statement Oversight Committees, before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Results: Evidence-based guidelines are presented for the care of patients presenting with unruptured intracranial aneurysms. The guidelines address presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging, and outcomes from surgical and endovascular treatment. Admittedly, this article is a bit of a departure from the typical original research/clinical trial article that we often review in Literature Commentary, but I thought it was important to discuss because, at least for me, guidelines on the management of a particular disease based on a comprehensive review of the literature using an evidence-based approach is a very useful and practical resource. I think we can all agree with the notion that diagnosing an intracranial aneurysm before it ruptures is critical, but the next step in the evaluation of such patients is what to do with that aneurysm? In the past, surgical clipping was nearly exclusively the treatment of choice but now with advancements of endovascular coiling and stenting, the issue arises which patient should be treated with what treatment modality. This tour-de-force article (19-member writing committee, 21 pages in length, and 329 references) is an update from 2000 that covers from "A to Z" the care of a patient with an unruptured intracranial aneurysm (UIA). Recommendations are based on the size of treatment effect (Class I, IIa/IIb, III) and certainty of treatment effect (Level of Evidence: A, B, C). Nine categories are discussed and rated: 1. Risk factors for aneurysm development, growth, and rupture 2. Clinical presentation 3. Diagnosing/imaging 4. Screening 5. Natural history 6. Surgical clipping 7. Endovascular treatment 8. Comparative efficacy of clipping vs coiling 9. Aneurysm follow-up (patients treated without surgery or endovascular coiling). I want to highlight a few points from the guidelines that I think are particularly important to neuro-ophthalmologists: 1. Digital subtraction angiography is the "gold standard" to diagnosis an UIA 2. Computed tomography angiography and MRA are "useful" for the detection of an UIA (Class I; Level of Evidence B) 440 3. Patient age and aneurysm location and size are important factors in considering treatment with surgical clipping (Class I; Level of Evidence B) 4. Surgical clipping is an effective treatment (Class I; Level of Evidence B). Endovascular coiling is also an effective treatment (Class IIa, Level of Evidence B) 5. Endoluminal flow diversion is to be considered in select patients (Class IIb; Level of Evidence B) 6. Surgical clipping and endovascular treatment should be performed at high-volume centers (Class I; Level of Evidence B). -M. Tariq Bhatti, MD Other recommendations from these guidelines in caring for patients being followed with an UIA are smoking cessation and treatment of hypertension. Patients with an UIA should be followed with some type of neuroimaging study because aneurysmal growth may increase the risk of rupture. With documented enlargement, treatment should be offered in the absence of prohibitive comorbidities (Class I; Level of Evidence B). Some features specifically related to posterior communicating artery aneurysms were reviewed. Early treatment is generally indicated for patients presenting with cranial nerve palsy caused by an UIA (Class I; Level of Evidence C). Small observational studies have reported improvement in cranial nerve function but no randomized trials have evaluated this practice. For patients presenting with third nerve palsy secondary to posterior communicating aneurysms, several retrospective studies have indicated better resolution with surgery than endovascular therapy. -Mark L. Moster, MD Peeler CE, De Lott LB, Nagia L, Lemos J, Eggenberger ER, Cornblath WT. Clinical utility of acetylcholine receptor antibody testing in ocular myasthenia gravis. JAMA Neurol. 2015. Epub ahead of print. Importance: The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. Objectives: To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. Design, Setting, and Participants: A retrospective observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] y; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. Moster and Bhatti: J Neuro-Ophthalmol 2015; 35: 438-443 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Main Outcomes and Measures: Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. Results: Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.04; P = 0.007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = 0.02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = 0.002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = 0.002). Conclusions and Relevance: We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease. This study found a higher percentage of positive acetylcholine receptor antibody (AchRAb) in ocular myasthenia gravis (OMG) patients of 70.9% than previous reports. There is difficulty in estimating this percentage because of the lack of a "gold standard" in identifying those antibody negative patients who truly have MG. This study's standard was "the clinical impression of 1 of 4 experienced neuroophthalmologists who followed up each patient longitudinally for a mean of 60 months." It is difficult to tell how many antibody-negative patients who truly had OMG were excluded because they did not fit this standard. Nonetheless, I am not suggesting that I have a better way of making the diagnosis than the 5-year follow-up of an experienced neuro-ophthalmologist. Therefore, the bottom line is that we are probably diagnosing more of our patients with a positive AchRAb titer and sending fewer for single fiber electromyography, which is good. Finding that both AchRAb positivity and a higher level of antibody were associated with an increased risk of progression to generalized MG also is very helpful, if borne out in further studies. One of the explanations from the authors for the increased positivity is that over time the assay has improved. This study includes patients seen between 1986 and 2013, and I wonder if the percentage of positivity is even greater with today's assays. Assuming I do not take a long weekend off, what do I change next Monday based on this article? I am more Moster and Bhatti: J Neuro-Ophthalmol 2015; 35: 438-443 comfortable that I am missing fewer diagnoses of OMG than before when the AchRAb is negative and I will pay more attention to the antibody level as a possible predictor for developing generalized MG. -Mark L. Moster, MD Not that I am questioning your work ethic Mark, but I would not be surprised if you take a lot of long weekends off. Here at Duke, we send the patient's blood to the Mayo Clinic Laboratories (Rochester Main Campus, 200 First Street SW, Rochester, MN 55905) for acetylcholine receptor binding antibody testing, which is part of a panel that also includes acetylcholine receptor modulating antibodies and striational antibodies. It would have been interesting for the authors to have reported the results of other myasthenia gravis antibody tests, especially in those patients who were acetylcholine receptor binding antibody negative. -M. Tariq Bhatti, MD Saidha S, Al-Louzi O, Ratchford JN, Bhargava P, Oh J, Newsome SD, Prince JL, Pham D, Roy S, van Zijl P, Balcer LJ, Frohman EM, Reich DS, Crainiceanu C, Calabresi PA. Optical coherence tomography reflects brain atrophy in MS: a four year study. Ann Neurol. 2015. Epub ahead of print. Objective: To determine whether atrophy of specific retinal layers and brain substructures are associated over time, to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS). Methods: Cirrus high-definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46-mo). Three-Tesla magnetic resonance imaging brain scans (including brainsubstructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history. Results: Rates of ganglion cell + inner plexiform layer (GCIP) and whole brain (r = 0.45, P , 0.001), gray matter (GM; r = 0.37, P , 0.001), white matter (WM; r = 0.28, P = 0.007), and thalamic (r = 0.38, P , 0.001) atrophy were associated. GCIP and whole brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r = 0.67, P , 0.001) than relapsing-remitting MS (RRMS; r = 0.33, P = 0.007). However, correlation between the rates of GCIP and whole brain (and additionally GM and WM) atrophy in RRMS increased incrementally with stepwise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect), the correlation increased to 0.45 and 0.60, respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r = 20.30, P = 0.02) and inner nuclear layer (r = 20.25, P = 0.04) atrophy rates. Interpretation: Over time GCIP atrophy seems to mirror whole brain, and particularly GM atrophy, especially in 441 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials. In neurology, I think the greatest value of optical coherence tomography (OCT) has not been so much in clinical practice but in clinical research. Although I use OCT in my practice to detect subtle optic nerve or retinal (macular) pathology, in the majority of cases I believe I could provide optimal care to the patient without performing an OCT. In striking contrast, the application of OCT in the research setting of neurodegenerative diseases such as multiple sclerosis (MS) has been invaluable as a biomarker to understand the underlying pathophysiology and progression of disease. In addition, OCT may serve as a very useful end point metric for interventional clinical trials assessing for neuroprotection. This study provides what I think is very valuable information on retinal segmentation as a measure of brain atrophy, which has been shown to correlate with disability progression better than magnetic resonance imaging (MRI) metric. Advancements in OCT technology, in particular the development of segmentation algorithm, has allowed a more detailed evaluation of the changes (thinning and thickening) in the various layers of the retina. One example of this is the findings by Saidha et al that the rate of ganglion cell + inner plexiform layer (GCIP) thinning is associated with whole brain, gray matter, white matter, and thalamic atrophy in the patient with progressive MS more so than the patient with relapsing MS over an approximately 4-year period. After adjusting for multiple comparisons, peripapillary retinal nerve fiber layer thinning was only associated with brainstem and caudate atrophy. GCIP thinning may be a marker of disease activity and disability progression, representing a global neurodegenerative process. A history of optic neuritis (ON) had a less pronounced effect on GCIP atrophy over time, which needs to be taken into consideration when performing OCT segmentation analysis. The authors go on to explain that this effect of ON on the OCT findings may be the result of disproportionate retinal tissue injury and does not reflect the overall cerebral neurodegenerative process. Saidha et al point out several limitations of their study but the one that I am particularly interested in is the effect of treatment with disease-modifying drugs (DMDs) on the OCT. I am not sure if OCT is ready to be used as a single primary end point in Phase III clinical trials trying to determine the efficacy of a particular DMD but certainly has been used as a secondary/tertiary outcome metric. -M. Tariq Bhatti, MD This study is part of a growing literature supporting the notion that neurodegeneration may be studied with retinal OCT as a biomarker. The correlation of GCIP with brain atrophy is important, and I wonder whether future studies may find that when the GC layer is segmented separately 442 that it may correlate even more closely with brain atrophy than the GCIP segment. -Mark L. Moster, MD Aptel F, Khayi H, Pépin JL, Tamisier R, Levy P, Romanet JP, Chiquet C. Association of nonarteritic ischemic optic neuropathy with obstructive sleep apnea syndrome: consequences for obstructive sleep apnea screening and treatment. JAMA Ophthalmol. 2015;133:797-804. Importance: The prevalence of obstructive sleep apnea syndrome (OSAS) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and its influence on second eye involvement is not well known. Objective: To evaluate the prevalence of OSAS in patients with NAION and risk factors of second eye involvement. Design, Setting, and Participants: In this cohort study, we examined 118 patients with anterior ischemic optic neuropathy referred to a tertiary care center from January 1, 2003, through December 31, 2010. Exposures: Patients underwent polysomnography to detect OSAS and were prospectively followed up to assess the risk of second eye involvement. Main Outcomes and Measures: The prevalence of OSAS in patients with NAION and the risk of second eye involvement using survival analysis based on the presence of OSAS, indication for ventilation treatment with continuous positive airway pressure, and other potential ocular and systemic confounders. Results: In 89 patients with NAION who underwent polysomnography, 67 (75%) had OSAS. Second eye involvement was found in 10 (13.7%) of 73 patients at 3 years: 8 (15.4%) of 52 patients with OSAS at 3 years and 2 (9.5%) of 21 patients without OSAS at 3 years; P = 0.04. In multivariate analysis, nonadherence to ventilation treatment with continuous positive airway pressure in patients with severe OSAS increased the risk of second eye involvement (hazard ratio, 5.54; 95% confidence interval, 1.13-27.11; P = 0.04). Conclusions and Relevance: These results suggest that OSAS is common in patients with NAION and that polysomnography should be considered in these patients. These findings also suggest that patients with severe OSAS who are to ventilation treatment with continuous positive airway pressure have an increased risk of second eye involvement. There are 4 findings of this study that I think are important. First, the prevalence of obstructive sleep apnea syndrome (OSAS) in nonarteritic anterior ischemic optic neuropathy (NAION) is higher than we thought, approximately 75%. However, there was no non-NAION control population in this study, and the authors quote studies of an 18% prevalence in the over 50-year-old population. Second, although numbers are small, the risk of second eye involvement is greater in those with OSAS. Third, patients with severe OSAS who are not compliant in using CPAP have a much greater risk of second eye involvement. Finally, this study suggests that various questionnaires are not sensitive enough to pick up all patients who have OSAS. Moster and Bhatti: J Neuro-Ophthalmol 2015; 35: 438-443 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary So how does this change my practice? Instead of my current discussion with the patient (and preferably the patient's roommate) about whether the patient snores, I will order polysomnography on all NAION patients. I realize it is only 1 study and the number with second eye involvement is small, but with the devastating consequences of second eye involvement I want to err on the side of being overly protective. -Mark L. Moster, MD I agree with you Mark, given the implications of second eye involvement with NAION, I think it is imperative that as neuro-ophthalmologists we do our best to minimize the risk factors associated with NAION. Therefore, in addition to Moster and Bhatti: J Neuro-Ophthalmol 2015; 35: 438-443 asking about arterial hypertension, diabetes mellitus, and hypercholesterolemia, it is imperative we try to assess the possibility of OSAS (snoring, obesity, male, large neck size). The only question in my mind is should I, as a neuroophthalmologist, order the polysomnography, or request the primary care physician to perform the test, or refer the patient to a sleep specialist? Admittedly, I am not a sleep specialist and therefore I would feel more comfortable if the patient was thoroughly evaluated by someone who can not only establish the diagnosis, but also initiate treatment with continuous positive airway pressure and manage the risk factors associated with OSAS. -M. Tariq Bhatti, MD 443 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.