Optical Coherence Tomography Should Be Used Routinely to Monitor Patients With Idiopathic Intracranial Hypertension

Point Counter-Point Section Editors: Andrew G. Lee, MD Gregory Van Stavern, MD Optical Coherence Tomography Should Be Used Routinely to Monitor Patients With Idiopathic Intracranial Hypertension John J. Chen, MD, PhD, Jonathan D. Trobe, MD Optical coherence tomography (OCT) is increasingly being used to evaluate and monitor many neuro-ophthalmic disorders, including optic neuritis, ischemic optic neurop- athy, and other conditions. Two experts discuss whether OCT has a role in the routine monitoring of patients with idiopathic intracranial hypertension. Pro: John J. Chen, MD, PhD Opening Statement Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure of unknown cause producing papilledema and visual loss (1-3); the major morbidity of IIH is visual impairment, which can be progressive and insidious (4,5). The visual loss is often reversible if treatment is initiated in a timely fashion but can be permanent in up to 40% of patients (5,6). If the disease remains untreated or unmonitored, patients can develop severe irreversible visual field constriction (5). Optical coherence tomography (OCT) has revolutionized ophthalmology and should be embraced by ophthalmologists taking care of patients with IIH. There are 3 main advantages of OCT in the care of patients of IIH. First, it is helpful in the diagnosis of patients with IIH. Second, it provides an objective measurement of treatment success. Finally, OCT can help determine the cause of vision loss in the setting of active papilledema. Diagnosis of Idiopathic Intracranial Hypertension Patients with IIH are typically obese females with headaches. The onset of migraines is frequently in young adulthood (7), which is also the typical age of onset for IIH. Obesity is an epidemic worldwide with 34.9% of the population now considered obese in the United States (8). Patients are often referred to ophthalmology clinics to Department of Ophthalmology and Visual Sciences (JJC), Mayo Clinic, Rochester, Minnesota; and Kellogg Eye Center (JT), University of Michigan, Ann Arbor, Michigan. Supported in part by an unrestricted grant to the Department of Ophthalmology by Research to Prevent Blindness, Inc, New York, NY. The authors report no conflicts of interest. Address correspondence to Jonathan Trobe, MD, Kellogg Eye Institute, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105; E-mail: [e-mail] Chen and Trobe: J Neuro-Ophthalmol 2016; 36: 453-459 evaluate for papilledema because of this constellation of common features: female, headaches, and obesity. At times, papilledema can be difficult to diagnose based on ophthalmoscopy alone. Patients can have small tilted anomalous optic nerves that can appear elevated and mimic papilledema (pseudopapilledema). Getting an objective measurement of the peripapillary retinal nerve fiber layer (RNFL) thickness with OCT is very helpful in differentiating papilledema from pseudopapilledema. The OCTderived peripapillary RNFL measurement is compared with age-matched controls and therefore can be objectively evaluated for thickening or thinning. In patients with a crowded optic nerve head mimicking the appearance of optic disc edema, OCT is able to demonstrate a normal RNFL thickness and provide an objective measurement of the optic disc, which can help confirm that these cases are a normal variant. Optic nerve drusen, especially those that are buried, can also contribute to the appearance of pseudopapilledema. Enhanced depth imaging on OCT can detect optic nerve head drusen (9,10), and the OCT RNFL thickness measurements are helpful in differentiating optic disc drusen from papilledema (11-13). The configuration of Bruch membrane on OCT also has been shown to correlate with intracranial pressure (14). In papilledema, Bruch membrane is often angled toward the vitreous because of the raised intracranial pressure, and, therefore, a large deflection of Bruch membrane toward the vitreous cavity can help confirm the suspicion of papilledema (Fig. 1). However, the Bruch membrane angle can vary in normal eyes without papilledema and, therefore, appearance can be very helpful in monitoring the disease process as discussed below. Objective Measurement of Treatment Success After obtaining baseline measurements of the peripapillary RNFL thickness on OCT, it becomes easier to monitor for 453 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point FIG. 1. Raised intracranial pressure can alter the position and angular displacement of Bruch membrane on OCT. A. This patient presented with Grade IV optic disc edema in both eyes from idiopathic intracranial hypertension. Initial OCT shows a significantly upturned Bruch membrane (arrow). The patient underwent a lumbar puncture for diagnostic and therapeutic purposes. B. OCT analysis immediately after the lumbar puncture shows that Bruch membrane has returned to a more neutral position (arrow), indicating that the position of Bruch membrane correlates with intracranial pressure. OCT, optical coherence tomography. improving or worsening disease. Although the Frisén grading scale for papilledema ranges from Grade I to V, the peripapillary RNFL thickness can range from 50 mm to over 500 mm, giving it a much larger dynamic range to objectively evaluate for change. In addition, there is significant variability even among experts in grading papilledema based on the Frisén grading scale, which can make it difficult to evaluate for change especially among different providers (15-17). Charting the OCT-derived RNFL thickness over time can objectively determine the rate of improvement and detect worsening disease or relapse. The RNFL thickness measurements can be used to discuss the disease course with patients, reinforce treatment regimens, and provide encouragement in patients who are having difficulties with either weight loss or medication tolerance. After the papilledema resolves in patients with IIH, there is often mild gliosis that gives the appearance of an elevated optic nerve. A normalization of the peripapillary RNFL thickness can provide objective evidence that the papilledema has completely resolved. In addition, after a reduction in intracranial pressure, the Bruch membrane angle on OCT will change to a more posterior configuration, which is another objective measurement of treatment success (14,18). Patients with IIH often have concordant headaches from raised intracranial pressure and other forms of headaches, such as migraine (19). During the course of treatment, 454 patients may present with worsening headaches with a concern that this could be due to refractory or relapse of the disease. Evaluation of the RNFL thickness and the Bruch membrane complex with OCT can detect worsening papilledema and objectively differentiate between an increase in intracranial pressure and other causes of headache. After successful treatment of the papilledema and raised intracranial pressure, patients are sometimes left with persistent headaches that should be treated separately from the raised intracranial pressure (19). OCT can provide objective evidence that the papilledema has completely resolved, so the treatment can be focused on other forms of headaches, such as migraine and analgesic overuse. Determine the Cause of Vision Loss From Idiopathic Intracranial Hypertension Decreased visual acuity from IIH can be caused by optic neuropathy or macular changes, such as subfoveal fluid. This is an important distinction because patients with optic neuropathy from severe papilledema require more aggressive treatment, whereas decreased vision due to subretinal fluid under the fovea is largely reversible with medication alone (20,21). Subretinal fluid can be visualized with OCT and help differentiate patients with decreased vision due to subretinal fluid from patients with vision loss from optic neuropathy (21). OCT also can help detect and follow choroidal folds (22), which are Chen and Trobe: J Neuro-Ophthalmol 2016; 36: 453-459 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point another potential source of decreased vision in patients with IIH (21,23,24). It is sometimes difficult to detect optic neuropathy in active IIH because papilledema obscures evaluation of the nerve making pallor difficult to assess. A reduction of the optic disc edema and thinning of the peripapillary RNFL thickness on OCT during the disease course may be due to improvement of papilledema or due to axon loss from worsening of the disease (25-27). Discerning between these 2 scenarios is critical for the management of patients with IIH because more aggressive treatment is necessary for the latter. Although OCT-derived RNFL thickness alone is sometimes not helpful in differentiating treatment response from worsening optic atrophy (25), we are now able to evaluate the integrity of the optic nerve in the setting of disc edema by analyzing the inner layers of the macula with OCT, specifically the ganglion cell layer-inner plexiform layer (GCL-IPL) (28). Optic nerve injury results in atrophy and thinning of the retinal ganglion cells, which is reflected as thinning of the macular GCL-IPL on OCT and found to have a strong relationship with visual loss in optic nerve diseases, such as glaucoma, optic neuritis, ischemic optic neuropathy, hereditary optic neuropathy, toxic optic neuropathy, optic nerve glioma, and recently IIH (21,29-36). The ability to monitor the integrity of the optic nerve in the setting of papilledema is arguably the most compelling reason to use OCT for monitoring IIH. Successful treatment will cause a reduction in the peripapillary RNFL thickness with a preserved macular GCL-IPL thickness. However, a simultaneous reduction in the RNFL thickness and macular GCL-IPL thickness indicates worsening optic neuropathy and could be an indication of treatment failure or fulminant IIH (21). By combining the peripapillary RNFL analysis with the macular GCL-IPL analysis, we can now differentiate between treatment response and worsening disease. In addition to the routine monitoring of patients with IIH, OCT is especially important in patients who have cognitive impairments or a component of nonorganic vision loss. Patients with IIH also may have nonorganic overlay (37), which can make it difficult to monitor the disease and differentiate overlay from true worsening disease. Because both visual acuity and visual fields have a subjective component, OCT may be critical in these patients because the test is quantitative and objective. Among patients who are unable to perform a visual field test or have nonorganic overlay, a stable macular GCL-IPL thickness provides reassuring evidence that there is not worsening optic neuropathy from papilledema. Despite its clear strengths, it is important to note that commercial OCT algorithms can sometimes fail in correctly identifying the GCL-IPL boundaries in the setting of papilledema (21). These artifacts are easy to identify because they present as significant reductions in the GCL-IPL thickness in a nonphysiologic pattern. Research-derived algorithms that take advantage of three-dimensional information are more robust and can accurately segment GCL-IPL thickness in almost all cases of papilledema (21,38). It is only a matter of time before the commercially available algorithms become more reliable because of increased resolution of OCT and improved segmentation algorithms. For the time being, it is important to be able to identify artifacts in the GCL-IPL measurements. Despite this limitation for some patients, the GCL-IPL thickness is very valuable in many patients with IIH in providing an objective evaluation of the integrity of the optic nerve. Con: Jonathan D. Trobe, MD If someone offered you a harmless, quick, objective test that would complement perimetry and ophthalmoscopy in managing patients with a chronic active optic neuropathy, would you take it? Of course you would. Papilledema in IIH is such a chronic active optic neuropathy, so why not use OCT routinely? Here are 5 reasons to just say no. Optical Coherence Tomography Gives You Information That Is Not Clinically Useful in Most Cases OCT peripapillary RNFL thickness reasonably correlates with the ophthalmoscopic assessment of optic disc elevation in IIH, no matter what grading scale of papilledema you use (37,39,40). Fine, so that OCT measure tells us what we can already see with the ophthalChen and Trobe: J Neuro-Ophthalmol 2016; 36: 453-459 moscope. In 2 studies (27,41), OCT peripapillary thickness decreased in tandem with improvement in visual field, indicating that OCT is an objective backup in the minority of patients whose visual acuity and visual field results we do not trust. Is macular OCT thickness the answer? After all, as measured by the Iowa Reference Algorithm, it escapes confounding from retinal surface edema. Using that measure, a recent study (21) found that a thin GCL-IPL, which presumably indicated loss of retinal ganglion cell axons, predicted a poor visual outcome. This suggested that initial visual dysfunction in nearly 50% of 48 eyes with papilledema from IIH resulted from outer retinal fluid, folds, or neovascularization. In those cases, visual function was almost entirely reversible with intracranial-pressure-lowering treatment, that is helpful prognostic information. But the authors acknowledge 455 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point that GCL-IPL thickness was usually normal at outset, so that this measure "was not useful in predicting outcome for most patients." Would you hold back on aggressive measures based on the GCL-IPL thickness? I would not. Conventional Diagnostic Tools Give Useful Information The combination of perimetry and ophthalmoscopy has worked well for eons. Yes, perimetry is sometimes unreliable in patients with IIH, but then you have the optic disc to look at. The degree of optic disc edema at initial diagnosis and in follow-up is a reasonable guide to management. True, the congenitally elevated optic disc can sometimes fool you, but there are better ways to recognize that than OCT. In the rare cases in which the optic disc cannot be used as a guide (previous optic nerve sheath fenestration, anomalous optic disc) and in which visual fields are unreliable, an objective assessment tool might help. But I do not trust a small amount of thinning in a tiny nerve fiber layer to guide me. I prefer to be guided by intracranial pressure-from spinal tap or intracranial pressure monitoring-to justify further aggressive intervention (42,43). A normal ICP derived from continuous short-term intraparenchymal monitor has saved me from recommending aggressive interventions (43). Managing Idiopathic Intracranial Hypertension Is Usually Not a Big Problem Once you have made the diagnosis of IIH, management is relatively straightforward. In my experience, most patients recover normal or near-normal vision on acetazolamide treatment or spontaneously. Those rare patients who need aggressive intervention-cerebrospinal fluid shunt or optic nerve sheath fenestration-declare themselves very early, often at the first encounter. And in those few patients with "malignant IIH," OCT is of no help in deciding whether to chance a short trial of acetazolamide or move directly to surgery. Paying Attention to Optical Coherence Tomography Takes Your Eyes Off the Prize The more complicated the OCT algorithm, the more difficult it will be to interpret. Moreover, OCT thickness can be normal, yet axons are failing. Obsessing over minuscule changes in retinal thickness distracts from the real clues-perimetry, ophthalmoscopy, compliance, and other sociodemographic factors. Optical Coherence Tomography Is Expensive With refinements that improve diagnostic accuracy, OCT is becoming a high ticket item. Perform this test on every patient visit, and that is real money. Of course, someone else is paying. Rebuttal-Dr. Chen Dr. Trobe makes some excellent points arguing against the use of OCT for IIH. However, I believe the positives of OCT overcome its shortcomings. The main limitation of OCT is that we are analyzing structure rather than function and, therefore, there is approximately a 2-week lag between optic nerve damage and visible thinning of the GCL-IPL (16,44), which can potentially limit its utility at a patient's initial presentation. However, it is still helpful in some patients presenting with "malignant IIH" because it can readily diagnose the more benign causes of decreased vision that are reversible, such as subretinal fluid tracking under the fovea. As with any tool, OCT has to be interpreted in the context of other tests and examination findings. Although OCT can be expensive, its objective measurements of the optic nerve are invaluable. As discussed in the opening statement, one of the main advantages of OCT is the ability to monitor patients with IIH. In some patients, it can be hard to determine whether they are improving or worsening based on their subjective symptoms. OCT measurements of the peri456 papillary RNFL serve as the ideal noninvasive barometer of intracranial pressure (when taken into context of a stable macular GCL-IPL thickness). Alternative mechanisms of measuring ICP include serial lumbar punctures and even continuous ICP monitoring. Although a spinal tap can be used to measure opening pressure, there are fluctuations in ICP and, therefore, a single measurement is not very reliable (42,45,46). Continuous ICP monitoring can provide definitive measurements of the IC P (42,43), but intraparenchymal monitoring is an invasive and potentially dangerous procedure. OCT can save money by preventing the need for these unnecessary diagnostic procedures for monitoring patients with IIH in most instances. Even more importantly, allowing us to monitor the integrity of the nerve in the setting of disc edema has the potential to prevent unwarranted invasive procedures, such as optic nerve sheath fenestration or ventriculoperitoneal shunt, which inherently carry the risk of morbidity and even mortality. Going back to the original question posed by Dr. Trobe, "If someone offered you a harmless, quick, objective test that would complement perimetry and Chen and Trobe: J Neuro-Ophthalmol 2016; 36: 453-459 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Point Counter-Point ophthalmoscopy in managing patients with a chronic active optic neuropathy, would you take it?" Of course you would, and we should embrace OCT in diagnosing and monitoring patients with IIH. Rebuttal-Dr. Trobe My respected opponent in this debate has placed before you 3 reasons to use OCT in managing IIH. I have listed them with my responses. Helpful in Diagnosis Dr. Chen states that OCT can differentiate congenitally anomalous optic discs from papilledema by showing a normal peripapillary nerve fiber layer, lack of a deflection in Bruch membrane, and buried optic disc drusen. These are notable refinements in diagnosis. But I do not think I have had trouble making this differentiation by relying on conventional ophthalmoscopic indicators and the patient's symptoms. For example, I think I can spot thickness and obscuration of the peripapillary nerve fiber layer in papilledema with the ophthalmoscope. I do not know much about this "deflection of Bruch membrane" as a sign of papilledema. It is for real? With regard to buried drusen, I admit that even I cannot see them, but usually there are other signs of congenitally anomalous optic discs-such as the dome shape, the excessive vascular tortuosity, and a clean peripapillary nerve fiber layer to inspection. Provides Objective Measurement of Treatment Success Dr. Chen defends OCT for this purpose by citing 2 of the indicators used in differential diagnosis: the peripapillary RNFL thickness and the Bruch membrane angle. I think he is saying that thickening of the RNFL means worsening and thinning means getting better. But is it really so hard to tell better or worse on ophthalmoscopy? And do we not have visual fields and the patient's symptoms as additional guides? By the way, Dr. Chen acknowledges that axon death from chronic papilledema will make the peripapillary nerve fiber layer thinner and that to sort out this problem, we must rely on thinning of the macular GCL-IPL as a sign of worsening. Thus, we must now reach for a special algorithm to tell us whether an already thin structure has become even thinner. If this GCL-IPL thing proves to be more reliable than the old way, I would support it, but still insisting that it, like these other new tools, would not come into play very often. Helps Determine Cause of Vision Loss in Active Papilledema To defend OCT for this purpose, Dr. Chen is drawing on an elegant article in which he and coauthors demonstrated that OCT can show subretinal fluid and choroidal folds, which might contribute to vision loss in patients with IIH. Dr. Chen argues that OCT differentiation of optic neuropathy vision loss from retinal vision loss influences management- you would be more aggressive in optic nerve vision loss. Sure, but this differentiation can sometimes be established by ophthalmoscopy and often by visual field examination, which will show arcuate nerve fiber bundle defects when the optic nerve is damaged and not when the outer retina is damaged. Yes, some patients are not reliable visual field takers, and an objective adjunct would be valuable here. So, in those rare instances when ophthalmoscopy and visual fields fail you, I will concede that OCT might be helpful in making this distinction. I hope that it proves to be reliable and that it will not continue to be overapplied. Conclusion: (Andrew G. Lee, MD and Greg Van Stavern, MD) OCT is an imaging technique that is rapidly being applied to many neuro-ophthalmic conditions. As with any other paraclinical test, OCT is best used as a complement to, rather a substitute for, a careful history and examination. It could be argued that OCT imaging might be most useful to REFERENCES 1. Wall M. Idiopathic intracranial hypertension. Neurol Clin. 2010;28:593-617. 2. Friedman DI. Idiopathic intracranial hypertension. Curr Pain Headache Rep. 2007;11:62-68. 3. Chen J, Wall M. Epidemiology and risk factors for idiopathic intracranial hypertension. Intl Ophthalmol Clin. 2014;54:1-11. Chen and Trobe: J Neuro-Ophthalmol 2016; 36: 453-459 someone who is not an "expert examiner" of the optic disc -but the evaluation of OCT images may require a similar level of expertise. 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