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Show Undiagnosed Papilledema in a Morbidly Obese Patient Population: A Prospective Study Claudia M. Krispel, MD, PhD, John L. Keltner, MD, William Smith, BS, David G. Chu, MD, Mohamed R. Ali, MD Background: Idiopathic intracranial hypertension (IIH) is a rare condition that can lead to significant morbidity from visual loss. The cause of IIH is unknown, but IIH is known to be associated with obesity. Obese patients may be at particularly high risk for suffering vision loss from IIH. The purpose of the present study is to determine the preva-lence of undiagnosed or asymptomatic papilledema in a population of morbidly obese individuals and to de-termine if these patients should undergo routine screen-ing for papilledema. Methods: Patients presenting to the UC Davis Bariatric Surgery Clinic between February 2008 and January 2011 who met the National Institutes of Health criteria for bariatric surgery were invited to participate in the study. Those patients who met the inclusion criteria and con-sented to the study were included. Participants were screened for IIH by nonmydriatic fundus photographs and by concerning symptoms prompting direct referral for neuro-ophthalmologic evaluation. Images were reviewed by a neuro-ophthalmologist, and patients with suspicious optic discs underwent neuro-ophthalmologic evaluation. Patients with findings consistent with IIH were sent for neurological evaluation. Results: A total of 606 patients with an average body mass index of 47 kg/m2 were included in the study. Seventeen of these patients had photographic optic disc findings or symptoms suspicious for IIH. Seven of these patients did not have disc edema on clinical examination. Six patients were not evaluated in the clinic. Four of the 17 patients had subtle optic disc edema confirmed by clinical evaluation and were referred for full neurological workup. These 4 patients had normal neuroimaging, 3 of whom underwent lumbar punctures with borderline high opening pressures. All 4 patients had unremarkable visual field examinations. Fundus abnormalities other than optic disc edema were discovered in 33 patients. Conclusion: Our study suggests that in a morbidly obese patient population, papilledema with significant visual loss is rare. Routine screening with fundus photography of morbidly obese patients likely is not warranted. Journal of Neuro-Ophthalmology 2011;31:310-315 doi: 10.1097/WNO.0b013e3182269910 2011 by North American Neuro-Ophthalmology Society Idiopathic intracranial hypertension (IIH or pseudotu-mor cerebri) is a rare neurological disorder in which cerebrospinal fluid (CSF) pressure is elevated, leading to papilledema and visual disturbances. Patients present with a variety of symptoms, including transient visual obscura-tions (TVOs), blurred vision, tinnitus, diplopia, or head-aches (1-4). The etiology of IIH is unknown, and the diagnosis of IIH is determined by a set of criteria that has served as the standard for IIH diagnosis (modified Dandy criteria) (5). These criteria include 1) signs and symptoms of increased intracranial pressure, 2) normal neuroimaging, 3) absence of focal neurological signs aside from cranial nerve VI paresis, and 4) elevated CSF pressure with normal CSF composition. IIH is of concern to ophthalmologists and neurologists, as untreated disease can lead to significant morbidity from visual loss, including visual field defects and visual acuity loss, which in some cases is severe and permanent (6-9). Up to 25% of patients with IIH may be asymptomatic (10) that may delay diagnosis, leading to higher risk of permanent visual loss. Thus, it may be prudent to screen patients at the highest risk for IIH to prevent the development of this blinding disorder. Screening of the general population is unlikely to be cost-effective, as IIH is rare in the general population, University of California, Davis, Eye Center (CMK, JLK, DGC), Sacramento, California; and Departments of Neurology and Neu-rological Surgery (JLK) and Division of Bariatric Surgery, De-partment of Surgery (WS, MRA), University of California, Davis, Sacramento, California. Supported by the Departmental Funds (J.L.K. and M.R.A.) and by an unrestricted grant from the Research to Prevent Blindness, UC Davis. The authors report no conflicts of interest. Address correspondence to Claudia M. Krispel, MD, PhD, Uni-versity of California, Davis, Eye Center, 4860 Y Street, Suite 2400, Sacramento, CA 95817; E-mail: claudia.krispel@gmail.com 310 Krispel et al: J Neuro-Ophthalmol 2011; 31: 310-315 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. occurring with an annual incidence in the order of 1 to 2 per 100,000 (11-14). While obesity has not been shown to be a cause of IIH, obesity is clearly associated with IIH (3,15), and the incidence of IIH rises to 20 per 100,000 in obese females (11,12). As the prevalence of obesity has increased in the United States, defining the association between obesity and IIH has become increasingly more urgent. Recent updates from the Centers for Disease Control and Prevention place the percentage of obese individuals in the United States more than 30% (16). The percentage of morbidly obese individuals (body mass index [BMI] .40 kg/m2) is estimated to be roughly 6% (16). Interestingly, the risk of IIH increases with increasing BMI (17), and morbidly obese patients with IIH may have even worse visual outcomes (18). Thus, morbidly obese individuals may be at particularly high risk for severe and permanent visual loss from IIH. In this study, morbidly obese patients presenting for bariatric surgery evaluation at UC Davis were screened for the presence of undiagnosed or asymptomatic papilledema. The goal of our study was to determine if screening mor-bidly obese patients for IIH is a worthwhile endeavor and to gain insight into the association of IIH with obesity. METHODS The study design was approved by the University of California, Davis, Institutional Review Board. Patients between the age of 18 and 65 years who presented to the UC Davis Bariatric Surgery Program between February 2008 and January 2011 and met the National Institutes of Health requirements for bariatric surgery (19) were asked to participate in the study (Table 1). All patients presenting for evaluation were ques-tioned about headaches and visual symptoms, but patients who consented to the study were asked to fill out a screening questionnaire (Table 2) and had nonmydriatic fundus pho-tographs taken (Nidek nonmydriatic auto fundus camera, AFC 210 camera [Nidek Inc., Fremont, CA]). Patients were excluded if they had a preexisting diagnosis of IIH or if 1 or both of the fundus photographs were inadequate for in-terpretation. There were no monocular patients in this population. Patients who had at least 1 optic disc suspicious for edema were referred for neuro-ophthalmic evaluation. One patient had suspicious symptoms based on screening questions but did not have fundus photographs taken due to unavailability of the camera. This patient was also referred for neuro-ophthalmic testing (Patient P1) (Table 6). This included visual fields with automated perimetry (automated visual fields, SITA-standard 24-2), optic nerve and macula optical coherence tomography (OCT; Stratus [Carl Zeiss Meditec, Inc., Dublin, CA]), and fundus photography. Optic nerve images were graded for papilledema according to the mod-ified Frise´n scale (20,21). All of this information was used to diagnose optic disc edema by a single neuro-ophthalmologist (J.L.K.) and ophthalmology residents (C.M.K, D.G.C). Patients with confirmed disc edema underwent neuro-imaging and were referred to neurology for evaluation and lumbar puncture. Final diagnosis and treatment of IIH was determined by the Neurology Department at UC Davis. The diagnosis of IIH did not preclude patients from undergoing bariatric surgery. RESULTS From February 2008 to January 2011, 1,148 patients presented for evaluation for bariatric surgery. Of the 1,148 patients, 647 met the initial inclusion criteria and consented to the study. Of the excluded patients, 7 reported having a previous diagnosis of IIH. Those patients who declined enrollment did so for various reasons, including history of migraine headache, photophobia, mobility limitations preventing appropriate positioning for the TABLE 1. National Institutes of Health requirements for bariatric surgery 100 pounds or more above ideal body weight or a BMI of 40 kg/m2 or greater BMI of 35 kg/m2 or greater with 1 or more obesity-related health conditions High risk for obesity-associated morbidity or mortality Previous failed weight loss attempts involving an integrated nonsurgical weight loss program, including dietary modification, behavioral support, and appropriate exercise Possession of appropriate motivation and psychological stability to understand risks and benefits of the procedure as well as the commitment to lifelong postoperative lifestyle changes and medical surveillance Adapted from the Evidence Report of the National Institutes of Health (19). TABLE 2. Screening questionnaire for study enrollment 1A: Have you ever been diagnosed or treated for a condition called ‘‘Idiopathic Intracranial Hypertension'' (IIH) or ‘‘Pseudotumor Cerebri? (PTC)'' 1B: If NO, have you ever heard of a condition called IIH or PTC, which is caused by high pressures in the brain? 2: Do you ever have episodes of blurry vision or loss of vision? (that fade in and out and may last less than a minute) 3: Have you had a new onset of frequent headaches in the past year? 4: Have you had a new onset of frequent episodes of nausea this past year? 5: Have you had a new onset of episodes of double vision? Krispel et al: J Neuro-Ophthalmol 2011; 31: 310-315 311 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. fundus photography, and time constraints. Patients with mi-graine headache generally declined participation due to fear that the flash of the camera would trigger a migraine and were not further evaluated. Because fundus photographs were inadequate for eval-uation in 41 patients, a total of 606 patients were included in the study. Seventy-seven percent of these patients were women, and the average age was 45.3 years. The average BMI was 47.5 kg/m2, which is considered morbidly obese. Demographics of these patients are shown in Table 3. Of the 606 patients, 17 were identified on initial screening (either with photographs or with screening questions) as suspicious for having IIH and 11 underwent neuro-ophthalmic evaluation (Table 4). The patients who were not evaluated either failed to return at least 3 phone calls or declined evaluation for other reasons. Patients who declined evaluation were educated on the risks of their decisions. Of the 11 patients who were evaluated, 7 were deemed not to have true optic disc edema (Table 5). The results of these 7 patients were as follows. Two patients had mildly blurred disc margins on the screening photographs but were not evaluated clinically until 2 and 6 months following bariatric surgery. In both the cases, optic disc appearance was unchanged compared to the screening photographs, and the nerves were deemed to be a congenitally full and a variant of normal. One patient had prior photographs from 2005 that were identical to those taken in 2009. One patient was diagnosed with a hyaloid remnant and 1 with nonarteritic anterior ischemic optic neuropathy. The remaining 2 patients were deemed to have normal optic discs on clinical examination. Four of the 11 patients had optic disc edema (Table 5). None of these patients had ever been diagnosed with IIH nor were they familiar with the disease. Two of these patients (P2 and P3) had no symptoms of IIH (Table 6). One patient (P3) reported frequent severe headache associated with nausea but no visual symptoms. One patient (P1) reported previous episodes of diplopia, TVOs, and frequent severe headache. All 4 patients were women, and all had mild (Frise´n stage 1) optic disc edema. All had fundus photographs and corresponding OCT images (Fig. 1). All 4 patients had visual acuity of 20/20 bilaterally without detectible visual field changes. One of these patients (P1) was evaluated on a day where the nonmydriatic screening camera was unavailable, but the bariatric surgeons were suspicious of IIH, given the patient's severe headache symptoms. Patient P4 declined lumbar puncture. The other 3 patients had opening pressures of 24, 25, and 32 cm H2O, respectively (Table 6). Due to the body habitus, each of these patients had lumbar punctures performed by interventional radiology in the prone position rather than in the lateral de-cubitus position. Neuroimaging of these 4 patients did not identify an underlying cause for optic nerve edema and was consistent with a diagnosis of IIH. However, only 2 patients (Cases 1 and 2) had a magnetic resonance venography. DISCUSSION The diagnosis of IIH is traditionally made if the clinical findings meet the modified Dandy criteria (5). Of the TABLE 3. Demographics of morbidly obese patients Number of patients asked to participate 1148 Number of patients meeting initial criteria and consented to the study 647 Number of patients excluded due to poor quality photographs 41 Number of study participants 606 Male, n (%) 142 (23) Female, n (%) 464 (77) Average BMI, kg/m2 47.5 Age of participants (range), yr 45.3 (18-65) Ethnicity of participants Caucasian 445 Hispanic 77 African American 62 Asian 4 Pacific Islander 4 Native American 4 East Indian 3 Middle Eastern 1 Other/decline to state 6 TABLE 4. Test results of morbidly obese study patients Total patients enrolled 606 Normal screening photographs, n (%) 556 (91.7) Patients with one or both optic discs suspicious for edema, n (%) 16 (2.6) Abnormalities other than possible optic disc edema, n (%) 33 (5.4) Patients with suspicious symptoms only (no photographs available), n (%) 1 (0.2) TABLE 5. Results of patients with suspicious optic nerves Number of patients with suspicious nerves 17 Number of patients evaluated 11 Patients evaluated in clinic without optic disc edema 7 Normal nerves 5* Hyaloid remnant 1 Nonarteritic anterior ischemic optic neuropathy 1 Patients evaluated in clinic with mild optic disc edema 4 *This includes 2 patients with mild blurring that was unchanged several months after surgery and 1 patient for whom photographs from 2005 were available and demonstrated no change in ap-pearance. 312 Krispel et al: J Neuro-Ophthalmol 2011; 31: 310-315 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. TABLE 6. Results of evaluation of morbidly obese study patients with papilledema Patient Best-Corrected >Visual Acuity Symptoms Intraocular Pressure (mm Hg) Color Vision (H-R-R) Automated Visual Fields* Optic Disc Edema Stage (Frise´n) Neuroimaging Lumbar Puncture Opening Pressure (cm H2O)† P1 OD 20/20; OS 20/20 Severe headaches and nausea OD 18; OS 15 OD 5/6; OS 5/6 Normal 1 MRI/MRA: normal 32 MRV‡ P2 OD 20/20; OS 20/20 None OD 12; OS 12 OD 5/6; OS 5/6 Inconsistent 1 MRI/MRV: normal 24 P3 OD 20/20; OS 20/20 None OD 20; OS 16 Not tested Normal 1 MRI: normal aside from increased fluid in optic nerve sheath§ 25 P4 OD 20/20; OS 20/20 Diplopia, headaches, and TVOs OD 15; OS 15 6/6; 6/6 Normal 1 MRI: normal§ Not done *Automated visual fields with SITA-standard 24-2 progress. †In all cases, lumbar punctures were performed by interventional radiology under fluoroscopy, with the patient in the prone position. ‡MRA was normal; MRV showed ‘‘possible narrowing or turbulence in the transverse sinus sigmoid junctions and in the lower superior sagittal sinus.'' §MRV was not done. MRI showed no intensity changes to suggest venous thrombosis. H-R-R, Hardy-Rand-Rittler color plates; MRA, magnetic resonance angiography; MRV, magnetic resonance venography; OD, right eye; OS, left eye; TVO, transient visual obscuration. Krispel et al: J Neuro-Ophthalmol 2011; 31: 310-315 313 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 606 patients, 3 (0.50%) (Patient P1, P2 and P3) met these criteria for IIH. This number does not include Patient P4 who declined lumbar puncture. All cases identified in the current study had very mild papilledema, which was not visually sig-nificant at the time of diagnosis. Whether these patients would have progressed to more severe papilledema is unknown. While obesity is clearly associated with IIH (2,15), the relationship between obesity and IIH remains complex and is not fully understood.One study even suggested that IIH may have a role in causing obesity (22). Several reports support the notion that recent weight gain contributes to the de-velopment of IIH (17,23). Daniels et al (17) found that weight gain in previously nonobese patients was as much of a risk factor for development of IIH as obesity itself. The fact that weight loss (2), including due to bariatric surgery (24,25), improves or resolves signs and symptoms of IIH supports the strong association of obesity and IIH. Yet, it is difficult to be certain of a direct causal link between changes in weight and IIH or possibly the relationship is due to the myriad of metabolic and inflammatory changes that occur with obesity, weight gain, and weight loss (3). Our study examined a large population of morbidly obese patients and found that none had papilledema with significant visual loss. Whether the 6 patients with suspicious optic nerves who were not evaluated in clinic could have undiagnosed IIH is unknown. However, all 6 of these patients had mild optic disc edema (stage 1) on screening photographs (Fig. 2); therefore, it seems unlikely that any cases of papilledema with significant visual loss were excluded. One interpretation of these data is that obesity alone is not a direct causal factor in the development of IIH. Because our study population comprised chronically obese patients, we are unable to assess if recent weight gain is a major risk factor for developing IIH. Previous studies suggest that if this is the case, then treatment with aggressive weight loss, including bariatric surgery, may be beneficial (2,25). This study has several limitations. First, the large body habitus of our patients precluded in-office lumbar punc-tures in the lateral decubitus position. Normative data for opening pressures are known for the lateral decubitus position, but similar normative data do not exist for lumbar punctures performed in the prone position (26). Therefore, it is unclear how to interpret these opening pressure values. We did not analyze the comorbidities of our patients. Obesity is associated with numerous chronic medical conditions that may affect the development of IIH, including obstructive sleep apnea, hypertension, diabetes mellitus, and hypercoagulability. Further research into this FIG. 1. Fundus photographs of Patient 1 demonstrating bilateral stage 1 optic disc edema. Corresponding OCT images (Stratus) are shown below the photographs, confirming mildly increased retinal nerve fiber layer thickness. FIG. 2. Screening fundus photographs from 1 of the 6 patients who was not evaluated in the clinic. (This is a representative example. Based on these screening photographs, we recommended the patient be seen for a full neuro-ophthalmologic evaluation, but this patient declined evaluation.) 314 Krispel et al: J Neuro-Ophthalmol 2011; 31: 310-315 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. area is ongoing. Finally, only 2 of the 4 patients with mild optic disc edema had magnetic resonance venograms. The magnetic resonance venogram for patient P1 was incon-clusive. The other 2 patients had MRI only. It is possible that these imaging studies could have missed cerebral venous thromboses causing papilledema. To our knowledge, this is the first prospective study evaluating the prevalence of previously undiagnosed IIH in morbidly obese patients. We found that, in this patient population, asymptomatic or previously undiagnosed papilledema with significant visual loss is extremely low. 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