Literature Commentary

In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L. Moster, MD will discuss the following 6 articles:; 1. Novitskaya ES, Cates CA, Bowes OM, Vivian AJ. Triptans and third nerve paresis: a case series of three patients. Eye (Lond). 2017; 31:503-505.; 2. Moradi A, Kanagalingam S, Diener-West M, Miller NR. Post-Cataract Surgery Optic Neuropathy: Prevalence, Incidence, Temporal Relationship, and Fellow Eye Involvement. Am J Ophthalmol. 2017;175:183-193.; 3. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748-1761.; 4. Steinberg JA, Carter BS, Lee MB, Steinberg GK. Ipsilateral pupillary dilation following carotid endarterectomy: A temporary and benign phenomenon. Neurosurgery. 2017;80:E239-E244.; 5. Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE second, Parrott MB, Rosenfeld PJ, Flynn HW Jr, Goldberg JL. Vision loss after intravitreal injection of autologous 'Stem Cells' for AMD. N Engl J Med. 2017;376:1047-1053.; 6. Swanson JW; Aleman TS; XuW; Ying GS; PanW; Liu GT; Lang SS; Heuer GG; Storm PB; Bartlett SP; KatowitzWR; Taylor JA. Evaluation of optical coherence tomography to detect elevated intracranial pressure in children. JAMA Ophthalmology 2017;135:320-328.

Literature Commentary Section Editors: Mark L. Moster, MD M. Tariq Bhatti, MD Literature Commentary In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L. Moster, MD will discuss the following 6 articles: 1. Novitskaya ES, Cates CA, Bowes OM, Vivian AJ. Triptans and third nerve paresis: a case series of three patients. Eye (Lond). 2017; 31:503-505. 2. Moradi A, Kanagalingam S, Diener-West M, Miller NR. Post-Cataract Surgery Optic Neuropathy: Prevalence, Incidence, Temporal Relationship, and Fellow Eye Involvement. Am J Ophthalmol. 2017;175:183-193. 3. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748-1761. 4. Steinberg JA, Carter BS, Lee MB, Steinberg GK. Ipsilateral pupillary dilation following carotid endarterectomy: A temporary and benign phenomenon. Neurosurgery. 2017;80:E239-E244. 5. Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE second, Parrott MB, Rosenfeld PJ, Flynn HW Jr, Goldberg JL. Vision loss after intravitreal injection of autologous "Stem Cells" for AMD. N Engl J Med. 2017;376:1047-1053. 6. Swanson JW; Aleman TS; Xu W; Ying GS; Pan W; Liu GT; Lang SS; Heuer GG; Storm PB; Bartlett SP; Katowitz WR; Taylor JA. Evaluation of optical coherence tomography to detect elevated intracranial pressure in children. JAMA Ophthalmology 2017;135:320-328. Novitskaya ES, Cates CA, Bowes OM, Vivian AJ. Triptans and third nerve paresis: a case series of three patients. Eye (Lond). 2017;31:503-505 Purpose: The aim of this report is to increase awareness of a possible association between cranial nerve paresis and the use of sumatriptan in migraine sufferers, particularly in patients who have additional vascular risk factors. Patients and Methods: We describe a series of 3 cases where third nerve paresis developed in patients who were treated with the oral form of sumatriptan. All the patients had a clear history of repetitive migraine headache and none of them had previous third nerve paresis. Conclusion: Among a variety of medications for the treatment of migraine, there are some drugs with vasoconstrictive effects, particularly triptans. These drugs may be a contributing factor for microvascular damage of the cranial nerves and other organs. COMMENTS No doubt that a patient with a third nerve palsy is a "scary" clinical dilemma. The question that always comes to my mind is whether the patient is harboring a life-threatening (i.e., intracranial aneurysm) or a benign (i.e., microvascular ischemia) condition. In fact, it is not just these 2 disease entities that need to be considered but rather a relatively long list that includes neoplasm, infection, and inflammation. Well, now we can add one more possibility to this list-triptan therapy. Moster and Bhatti: J Neuro-Ophthalmol 2017; 37: 341-346 Unfortunately, we are not provided sufficient detail about the 3 cases presented in this article, but what we are told is that all the patients developed a pupil sparing third nerve palsy sometime after taking a triptan for migraine headache. Two of the patients had a partial third nerve palsy (the status of the third nerve palsy in the other patient was not noted). One patient developed the third nerve palsy 3 days after taking the medication and the other 5 days later. I would like to know your thoughts, Mark, but for me despite this case series, I still plan on obtaining a neuroimaging study in a patient who presents with a third nerve palsy who has taken a triptan. This article also reminds me to share with our JNO readership a very nice population-based study carried out at the Mayo clinic in Rochester, Minnesota (1). They found that the overall incidence of a third nerve palsy over a 37-year period was very low at 4.0 per 100,000. Microvascular ischemia was the cause in 43% of the patients and an intracranial aneurysm in only 6%. Sixteen percent of the microvascular ischemic third nerve palsies had pupil involvement and all 3 patients with a posterior communicating artery aneurysm had pupil involvement but 5 of the patients with an intracavernous sinus aneurysm initially presented with a pupil sparing third nerve palsy. The article was accompanied by an editorial written by Drs. Nancy J. Newman and Valerie Biousse (2). They stated: 1. "As demonstrated in this study, demographic information, the presence or absence of pain, the complete or partial nature of the oculomotor nerve paresis, and "rules" of the pupil regarding pupillary involvement 341 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary and to what degree, cannot distinguish microvascular third nerve palsies from those caused by more concerning underlying causes reliably enough to forego further diagnostic investigations." 2. "Given the physical, social, and economic costs of missing even 1 aneurysm that then ruptures, it is now fairly wellaccepted that every patient with a new-onset third nerve palsy, regardless of demographics, pain, or degree of cranial nerve involvement, should undergo noninvasive neuroimaging, and that this is cost-effective medicine." -M. Tariq Bhatti, MD I agree with you, Tariq. This article does not change the approach to workup in any way. The second and third patients were older than 60 years of age, and vasculopathic third nerve paresis is at least as likely as a triptan-related paresis. Many of our patients with a history of migraine present with a neuroophthalmologic deficit that in their mind started with a typical migraine. In my experience, this is particularly the case for optic neuritis and ischemic cranial neuropathy. In this article, I think the only case that is really suggestive of a triptan-related third nerve paresis is the 19-year-old man with only a history of migraine and occasional smoking. -Mark L. Moster, MD REFERENCES 1. Fang C, Leavitt JA, Hodge DO, Holmes JM, Mohney BG, Chen JJ. Incidence and etiologies of acquired third nerve palsy using a population-based method. JAMA Ophthalmol. 2017;135:23-28. 2. Newman NJ, Biousse V. Third nerve palsies-less frequent but just as concerning. JAMA Ophthalmol. 2017;135:29-30. Moradi A, Kanagalingam S, Diener-West M, Miller NR. Post-cataract surgery optic neuropathy: prevalence, incidence, temporal relationship, and fellow eye involvement. Am J Ophthalmol. 2017;175:183-193 Purpose: To reassess the prevalence and incidence of postcataract surgery optic neuropathy (PCSON) in the modern era. Design: Retrospective cohort study. Methods: Setting: Single-center tertiary care practice. Study Population: All patients with a diagnosis of nonarteritic anterior ischemic optic neuropathy (NAION) seen in the Wilmer Eye Network system between January 1, 2010, and December 31, 2014 were included. Inclusion was based on the following: 1) a history of an acute unilateral decrease in vision, 2) a visual field defect consistent with NAION, 3) a relative afferent pupillary defect, 4) observed optic disc swelling, and 5) no other etiology being found. Main Outcome Measures: The prevalence and incidence of PCSON and the temporal association between surgery and onset of PCSON. The secondary outcome was the risk of PCSON in the fellow eye of patients with previous unilateral spontaneous NAION. 342 Results: One hundred eighty-eight patients had developed NAION during the study period. Of these, 18 (9.6%) had undergone cataract surgery (CS) during the year before developing NAION. There was no significant temporal pattern associated with the distribution of NAION cases (P = 0.28). The incidence of PCSON in patients who had noncomplex CS was 10.9 cases per 100,000 (95% confidence interval [CI], 1.3-39.4). Conclusions: Our data indicate that both the prevalence and incidence of NAION after modern CS are comparable with those of the general population, and that there is no significant temporal relationship between modern CS and the subsequent development of NAION in the operated eye. Thus, although this study has inherent biases owing to its retrospective nature, concern regarding an increased risk of PCSON in the fellow eye in patients who have experienced it or spontaneous NAION in 1 eye may be unwarranted. COMMENTS One of the very difficult consults we get in neuroophthalmology is a patient with previous NAION who has contralateral visual symptoms related to cataract and a decision has to be made whether to operate. The literature suggests that approximately half of these patients will have NAION in the year after CS and I usually recommend waiting until visual symptoms are advanced. This suggestion robs a patient not destined for sequential NAION of years of good vision. The study by Moradi et al concludes a lack of increase in risk of NAION after modern CS. They attribute the differences from previous reports to the modernization of CS, for example, no longer using intracapsular and extracapsular techniques or retrobulbar injections and the decrease in operative time. That being said, the authors and the accompanying editorial by Mcculley et al (1) point out numerous limitations of the study. These include the retrospective nature and the real possibility of selection bias having missed some cases. In addition, one finding of concern is that there were significantly fewer vascular risk factors in the PCSON group suggesting that CS was truly a risk factor. So I still will tell patients that they may be at higher risk for PCSON but 50% is probably too high. -Mark L. Moster, MD Like you, Mark, I have quoted to my patients a risk of 50% of developing NAION after CS based on the report by Lam et al (2). I believe this issue remains unsettled given the limitations of the article of Modi et al, and further studies are needed. -M. Tariq Bhatti, MD REFERENCES 1. McCulley TJ, Lam BL, Feuer WJ. Nonarteritic anterior ischemic optic neuropathy and intraocular surgery. Am J Ophthalmol. 2017;175:xiv-xvi. Moster and Bhatti: J Neuro-Ophthalmol 2017; 37: 341-346 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary 2. Lam BL, Jabaly-Habib H, Al-Sheikh N, Pezda M, Guirgis MF, Feuer WJ, McCulley TJ. Risk of non-arteritic anterior ischaemic optic neuropathy (NAION) after cataract extraction in the fellow eye of patients with prior unilateral NAION. Br J Ophthalmol. 2007; 91:585-587. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748-1761 Background: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited the efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. Methods: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary endpoint was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of $3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary endpoints, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. Results: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared to 9 of 45 patients who received placebo (20%), had a response at week 24 (P , 0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P , 0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. Conclusions: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997.). COMMENTS Let me begin by congratulating the authors of this study; and just by the mere fact the results of this phase II Moster and Bhatti: J Neuro-Ophthalmol 2017; 37: 341-346 randomized, placebo-controlled, double-blinded study was published in the New England Journal of Medicine speaks to the significance of the findings and the need to find better treatments for active thyroid eye disease. Teprotumumab is a human monoclonal antibody that targets the IGF-IR and inhibits its function. Forty-five patients received placebo and 42 patients received teprotumumab (intravenous infusion every 3 weeks for a total of 8 infusions). Thirty-nine (89%) patients in the placebo group and 37 (88%) patients in the treatment group completed the 24-week trial with a 48-week follow-up period. All patients required a Clinical Activity Score (CAS) of $4 and symptom onset within 9 months of enrollment. The primary endpoint was a reduction in the CAS of $2 and a decrease in proptosis of $2 mm (without a corresponding worsening in the fellow nonstudy eye). Based on the intention-to-treat analysis, the primary endpoint (i.e., response rate) was met in 29/42 (69%) patients in the teprotumumab group compared with 9/45 (20%) patients in the placebo group. The response to treatment was rapid and seen within 6 weeks in 43% of the patients receiving treatment. I want to list a few important points from this study: 1. Very impressive results with an absolute treatment difference between the 2 groups of 49%! 2. Baseline characteristics of the 2 groups was unequal in terms of more smokers (41% vs 26%) and less noneuthyroid patients (30% vs 46%) in the placebo group, which could have skewed the results favorably to the teprotumumab group. 3. The drug was well tolerated. Serious adverse events occurred in 12% of the teprotumumab group vs. 2% of the placebo group. As expected, given the mechanism of action of the drug, hyperglycemia occurred more commonly in the teprotumumab group (12% vs 2%). 4. The study was financed by the maker of the drug-River Vision Development. -M. Tariq Bhatti, MD The findings in this trial are very impressive, with a 3mm decrease in proptosis, a 4-point decrease on the CAS and over 60% of patients in the treatment group achieving a CAS of 0-1. Unfortunately, the CAS at baseline and the change in the score does not allow us to sort out the effect on the most important complications, including optic neuropathy and corneal exposure. For example, the CAS allocates a score of 1 point equally to eyelid swelling and 2 lines of decreased visual acuity. Nonetheless, one would expect protection from these complications to parallel overall improvement in CAS. I look forward to the phase III clinical trials. -Mark L. Moster, MD 343 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Steinberg JA, Carter BS, Lee MB, Steinberg GK. Ipsilateral Pupillary Dilation Following Carotid Endarterectomy: A Temporary and Benign Phenomenon. Neurosurgery. 2017;80: E239-E244 Background and Importance: Cases of postcarotid endarterectomy (CEA) Horner syndrome have been reported, with symptoms attributed to manipulation of the sympathetic plexus situated along the carotid artery; however, these patients presented with the typical constricted pupil. We report the first 3 cases to our knowledge of mydriasis after CEA. Clinical Presentation: We present 3 cases of CEA followed by immediate postoperative development of ipsilateral mydriasis. The patients were otherwise at their neurologic baseline and the mydriasis resolved over the ensuing few days. Conclusion: We suggest that these cases are secondary to an ischemic phenomenon, specifically to parasympathetic structures, such as the ciliary ganglion and/or oculomotor nerve, resulting in autonomic dysfunction manifested by pupillary dilation. A similar finding of mydriasis occurring subsequent to other carotid pathology has been reported, with ischemic to parasympathetic structures also proposed as the underlying etiology. Although pupillary dilation often represents a worrisome neurosurgical sign indicating herniation, it should be recognized that after CEA this finding may be a transient, benign occurrence. COMMENTS The authors report 3 patients with ipsilateral transient pupillary mydriasis after CEA. One patient had a 7-mm pupil, the other 2 are described only as "dilated" and none of the pupils were reactive to light. None had ptosis or ophthalmoparesis and they returned to normal in 8 hours, 3 days, and 4 days, respectively. The postulated mechanism is ischemia to the ciliary ganglion or oculomotor nerve. All were worked up to exclude a large infarct or hemorrhage with herniation. With 3 cases, this qualifies as occurring "case after case after case." However, all the authors are listed in departments of neurosurgery, so we do not have examinations by a neuro-ophthalmologist and I wonder if these could have been pharmacologic. It would have to be anticholinergic to eliminate the reaction to light, which would not occur with sympathetic stimulation or overactivity. What I take home from this article is when I see my first case of this, I will try to figure it out. -Mark L. Moster, MD When I first read this article, I thought the same as you, Mark, that the mydriasis could have been the result of pharmacological dilatation. I also thought of the possibility 344 of the Pourfour Du Petit syndrome, but as you mentioned given the pupil was nonreactive to light, it could not be due to oculosympathetic overactivity. As you also mentioned, the authors are all neurosurgeons. I wonder what pharmacological testing would have shown and what other subtle ocular signs were not appreciated that could have given us clues as to the underlying pathophysiology of this observation. -M. Tariq Bhatti, MD Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE II, Parrott MB, Rosenfeld PJ, Flynn HW Jr, Goldberg JL. Vision loss after intravitreal injection of autologous "Stem Cells" for AMD. N Engl J Med. 2017;376:1047-1053 Abstract: Adipose tissue-derived "stem cells" have been increasingly used by "stem-cell clinics" in the United States and elsewhere to treat a variety of disorders. We evaluated 3 patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue-derived "stem cells" at one such clinic in the United States. In these 3 patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients' severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients' visual acuity ranged from 20/200 to no light perception. COMMENTS Just when you think you have seen or heard it all, an article like this is published! In fact the article was picked up by the New York Times (1) and the same authors wrote a brief editorial in the American Journal of Ophthalmology (2). I was quite disturbed by this report not just because of the tragedy these 3 patients suffered but also by the fact that something like this can happen here in the United States, despite all the regulatory controls. I am sure like you, Mark, I am often asked by patients about stem cell therapy for their optic neuropathy. I am amazed by the number of stem cell clinics that are not only in the United States but around the world that flaunt some unbelievable claims including high efficacy and no risk (3). It seems to me that the internet has fueled this phenomenon of stem cell therapy and stem cell tourism. Neil Miller, MD, wrote a wonderful letter to the editor in 2011-that in some ways was prophetic-emphasizing that there is currently no credible scientific evidence that stem cell treatment is efficacious (and potentially can be harmful) in both congenital and Moster and Bhatti: J Neuro-Ophthalmol 2017; 37: 341-346 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary acquired optic neuropathies (4). I was able to find a couple of articles regarding the use of autologous bone marrow-derived stem cell treatment for Leber hereditary optic neuropathy and autoimmune optic neuropathy (5,6). These articles discuss the results of the Stem Cell Ophthalmology Treatment Study (SCOTS), an open-label, nonrandomized study, that introduces stem cells through a variety of injection techniques (retrobulbar, subtenons, intravitreal, and intravenous). The authors state that SCOTS is "patient funded", reviewed, and approved by a local institutional review board and registered with www.clinicaltrials.gov. I want to be clear that I do not endorse SCOTS and frankly have some serious reservations regarding its methods and underlying science. -M. Tariq Bhatti, MD The terrible outcome in these 3 patients is very disturbing. Also disturbing is that some patients believe they are in a legitimate clinical trial, despite having to pay out of pocket for the treatment. Finally, even if an injectable therapy has scientific validity it should likely be first studied clinically one eye at a time and not with bilateral simultaneous injections. -Mark L. Moster, MD REFERENCES 1. Grady D. Patients lose sight after stem cells are injected into their eyes. New York Times, Health Section, 2017. Available at: https://www.nytimes.com/2017/03/15/health/eyes-stemcells-injections.html?_r=0. 2. Kuriyan AE, Albini TA, Flynn HW Jr. The growing "stem cell clinic" problem. Am J Ophthalmol. 2017;177:xix-xx. 3. Connolly R, O'Brien T, Faherty G. Stem cell tourism-a webbased analysis of clinical services available to international travellers. Travel Med Infect Dis. 2014;12:695-701. 4. Miller NR. Stem cell "tourism." Ophthalmology. 2011;118:2530-2531. 5. Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy. Neural Regen Res. 2015;10:1507-1515. 6. Weiss JN, Levy S, Benes SC. Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy. Neural Regen Res. 2016;11:1685-1694. Swanson JW, Aleman TS, Xu W, Ying GS, Pan W, Liu GT, Lang SS, Heuer GG, Storm PB, Bartlett SP, Katowitz WR, Taylor JA. Evaluation of optical coherence tomography to detect elevated intracranial pressure in children. JAMA Ophthalmology. 2017;135:320-328 Importance: Detecting elevated intracranial pressure (ICP) in children with subacute conditions, such as craniosynostosis or tumor, may enable timely intervention and prevent neurocognitive impairment, but conventional Moster and Bhatti: J Neuro-Ophthalmol 2017; 37: 341-346 techniques are invasive and often equivocal. Elevated ICP leads to structural changes in the peripapillary retina. Spectral domain optical coherence tomography (SD-OCT) can noninvasively quantify retinal layers to a micron-level resolution. Objective: To evaluate whether retinal measurements from OCT can serve as an effective surrogate for invasive ICP measurement. Design, Setting, and Participants: This cross-sectional study included patients undergoing procedures at the Children's Hospital of Philadelphia from September 2014 to June 2015. Three groups of patients (n = 79) were prospectively enrolled from the Craniofacial Surgery clinic, including patients with craniosynostosis (n = 40). The positive control cohort consisted of patients with hydrocephalus and suspected intracranial hypertension (n = 5), and the negative control cohort consisted of otherwise healthy patients undergoing a minor procedure (n = 34). Main Outcomes and Measures: SD-OCT was performed preoperatively in all cohorts. Children with cranial pathology, but not negative control patients, underwent direct intraoperative ICP measurement. The primary outcome was the association between peripapillary retinal OCT parameters and directly measured elevated ICP. Results: The mean (SD) age was 34.6 (45.2) months in the craniosynostosis cohort (33% women), 48.9 (83.8) months in the hydrocephalus and suspected intracranial hypertension cohort (60% women), and 59.7 (64.4) months in the healthy cohort (47% women). ICP correlated with maximal retinal nerve fiber layer thickness (r = 0.60, P # 0.001), maximal retinal thickness (r = 0.53, P # 0.001), and maximal anterior retinal projection (r = 0.53, P = 0.003). Using cut points derived from the negative control patients, OCT parameters yielded 89% sensitivity (95% CI, 69%-97%) and 62% specificity (95% CI, 41%-79%) for detecting elevated ICP. The SD-OCT measures had high intereye agreement (intraclass correlation, 0.83-0.93) and high intragrader and intergrader agreement (intraclass correlation $0.94). Conventional clinical signs had low sensitivity (11%-42%) for detecting intracranial hypertension. Conclusions and Relevance: Noninvasive quantitative measures of the peripapillary retinal structure by SD-OCT were correlated with invasively measured ICP. Optical coherence tomographic parameters showed promise as surrogate, noninvasive measures of ICP, outperforming other conventional clinical measures. SD-OCT of the peripapillary region has the potential to advance the current treatment paradigms for elevated ICP in children. COMMENTS The authors studied OCT at the time of surgery and correlated the findings with direct measurements of ICP. By simultaneous measurements of ICP and OCT performance, they verified what we already know-that OCT abnormalities go along with elevated ICP. They suggest this as a noninvasive measure of ICP. However, we do not know how OCT will change over time with ICP changes 345 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary and we still have a long way to go for a noninvasive correlate of ICP in real time. near-infrared spectroscopy, transcranial Doppler, and tympanic membrane displacement (1,2). -Mark L. Moster, MD -M. Tariq Bhatti, MD It would be wonderful to have a noninvasive way to measure ICP. However, I do not think OCT can supplant measuring ICP with a lumbar puncture just yet. As you know, there have been multiple attempts of measuring ICP indirectly via the eye, such as with the retinal venous pulse by way of ophthalmodynamometry, pupillary light reaction with the pupillometer, and optic nerve sheath diameter by ultrasonograpy; and noneye methods such as MRI, 346 REFERENCES 1. Stewart PS, Jensen OE, Foss AJ. A theoretical model to allow prediction of the CSF pressure from observations of the retinal venous pulse. Invest Ophthalmol Vis Sci. 2014;55:6319- 6323. 2. Nair S. Clinical review of noninvasive intracranial pressure measurement in medical cases. J Neuroanaesthesiol Crit Care. 2016;3:9-14. Moster and Bhatti: J Neuro-Ophthalmol 2017; 37: 341-346 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.