Journal of Neuro-Ophthalmology:
Undiagnosed Papilledema in a Morbidly Obese Patient Population: A Prospective Study
Krispel, Claudia M. MD, PhD; Keltner, John L. MD; Smith, William BS; Chu, David G. MD; Ali, Mohamed R. MD
University of California, Davis, Eye Center (CMK, JLK, DGC), Sacramento, California; and Departments of Neurology and Neurological Surgery (JLK) and Division of Bariatric Surgery, Department 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, University of California, Davis, Eye Center, 4860 Y Street, Suite 2400, Sacramento, CA 95817; E-mail: firstname.lastname@example.org
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 prevalence of undiagnosed or asymptomatic papilledema in a population of morbidly obese individuals and to determine if these patients should undergo routine screening 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 consented 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.
Idiopathic intracranial hypertension (IIH or pseudotumor 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 obscurations (TVOs), blurred vision, tinnitus, diplopia, or headaches (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, 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 morbidly obese patients for IIH is a worthwhile endeavor and to gain insight into the association of IIH with obesity.
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 questioned 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 photographs 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 interpretation. 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 modified Frisén 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 neuroimaging 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.
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 fundus photography, and time constraints. Patients with migraine 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 evaluation 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 (Frisén 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 decubitus 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.
The diagnosis of IIH is traditionally made if the clinical findings meet the modified Dandy criteria (5). Of the 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 significant 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 development 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 punctures 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 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 inconclusive. 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. Based on our results, routine screening for papilledema with nonmydriatic fundus photographs for asymptomatic obese patients is likely not warranted. However, bariatric surgeons should be vigilant in screening for any symptoms consistent with IIH and refer these patients promptly for neuro-ophthalmic evaluation.
The authors thank Raymond Kong for his assistance with creating the figures.
1. Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri). Curr Neurol Neurosci Rep. 2008;8:87–93
2. Wall M. Idiopathic intracranial hypertension. Neurol Clin. 2010;28:593–617
3. Fraser C, Plant GT. The syndrome of pseudotumour cerebri and idiopathic intracranial hypertension. Curr Opin Neurol. 2011;24:12–17
4. Friedman DI. Idiopathic intracranial hypertension with Dan and beyond: the 2010 Jacobson Lecture. J Neuroophthalmol. 2010;30:380–385
5. Smith JL. Whence pseudotumor cerebri? J Clin Neuroophthalmol. 1985;5:55–56
6. Ahlskog JE, O'Neill BP. Pseudotumor cerebri. Ann Intern Med. 1982;97:249–256
7. Wall M, George D. Idiopathic intracranial hypertension. A prospective study of 50 patients. Brain. 1991;114:155–180
8. Corbett JJ, Savino PJ, Thompson HS, Kansu T, Schatz NJ, Orr LS, Hopson D. Visual loss in pseudotumor cerebri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol. 1982;39:461–474
9. Radhakrishnan K, Ahlskog JE, Garrity JA, Kurland LT. Idiopathic intracranial hypertension. Mayo Clin Proc. 1994;69:169–180
10. Galvin JA, Van Stavern GP. Clinical characterization of idiopathic intracranial hypertension at the Detroit Medical Center. J Neurol Sci. 2004;223:157–160
11. Radhakrishnan K, Thacker AK, Bohlaga NH, Maloo JC, Gerrya SE. Epidemiology of idiopathic intracranial hypertension: a prospective and case-control study. J Neurol Sci. 1993;116:18–28
12. Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol. 1988;45:875–877
13. Craig JJ, Mulholland DA, Gibson JM. Idiopathic intracranial hypertension; incidence, presenting features and outcome in Northern Ireland (1991-1995). Ulster Med J. 2001;70:31–35
14. Carta A, Bertuzzi F, Cologno D, Giorgi C, Montanari E, Tedesco S. Idiopathic intracranial hypertension (pseudotumor cerebri): descriptive epidemiology, clinical features, and visual outcome in Parma, Italy, 1990 to 1999. Eur J Ophthalmol. 2004;14:48–54
15. Shin RK, Balcer LJ. New developments in idiopathic intracranial hypertension. Curr Neurol Neurosci Rep. 2001;1:463–470
16. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010;303:235–241
17. Daniels AB, Liu GT, Volpe NJ, Galetta SC, Moster MC, Newman NJ, Biousse V, Lee AG, Wall M, Kardon R, Acierno MD, Corbett JJ, Magoic MG, Balcer LJ. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007;143:635–641
18. Rowe FJ, Sarkies NJ. The relationship between obesity and idiopathic intracranial hypertension. Int J Obes Relat Metab Disord. 1999;23:54–59
19. . Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the Evidence Report. National Institutes of Health. Obes Res. 1998;6(Suppl 2):51S–209S
20. Frisén L. Swelling of the optic nerve head: a staging scheme. J Neurol Neurosurg Psychiatry. 1982;45:13–18
21. Scott CJ, Kardon RH, Lee AG, Frisén L, Wall M. Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch Ophthalmol. 2010;128:705–711
22. Hannerz J, Ericson K. The relationship between idiopathic intracranial hypertension and obesity. Headache. 2009;49:178–184
23. Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study. Neurology. 1991;41:239–244
24. Sugerman HJ, Felton WL III, Sismanis A, Kellum JM, DeMaria EJ, Sugerman EL. Gastric surgery for pseudotumor cerebri associated with severe obesity. Ann Surg. 1999;229:634–640 discussion 40–42
25. Fridley J, Foroozan R, Sherman V, Brandt ML, Yoshor D. Bariatric surgery for the treatment of idiopathic intracranial hypertension. J Neurosurg. 2011;114:34–39
26. Whiteley W, Al-Shahi R, Warlow CP, Zeidler M, Lueck CJ. CSF opening pressure: reference interval and the effect of body mass index. Neurology. 2006;67:1690–1691
© 2011 Lippincott Williams & Wilkins, Inc.