Szewka, Aimee J. MD; Bruce, Beau B. MD; Newman, Nancy J. MD; Biousse, Valérie MD
Departments of Ophthalmology (AJS, BBB, NJN, VB), Neurology (BBB, NJN, VB), and Neurological Surgery (NJN), Emory University School of Medicine, Atlanta, Georgia.
Address correspondence to Nancy J. Newman, MD, Neuro-ophthalmology Unit, Emory University, 1365-B Clifton Road, NE, Atlanta, GA 30322; E-mail: firstname.lastname@example.org
Supported in part by a departmental grant (Department of Ophthalmology) from the Research to Prevent Blindness, Inc, New York, and by core grant P30-EY06360 (Department of Ophthalmology). Dr Bruce receives research support from the National Institutes of Health/National Eye Institute (K23-EY019341) and received the American Academy of Neurology Practice Research Fellowship. Dr Newman is a recipient of the Research to Prevent Blindness Lew R. Wasserman Merit Award. None of the authors have any relevant financial disclosures.
Background: Increased body mass index (BMI) has been associated with increased risk of idiopathic intracranial hypertension (IIH), but the relationship of BMI to visual outcomes in IIH is unclear.
Methods: A retrospective chart review of all adult cases of IIH satisfying the modified Dandy criteria seen at our institution between 1989 and 2010 was performed. Demographics, diagnostic evaluations, baseline visit and last follow-up examination data, treatment, and visual outcome data were collected in a standardized fashion. Groups were compared, and logistic regression was used to evaluate the relationship of BMI to severe visual loss, evaluating for interaction and controlling for potential confounders.
Results: Among 414 consecutive IIH patients, 158 had BMI ≥40 (World Health Organization Obese Class III) and 172 had BMI 30–39.9. Patients with BMI ≥40 were more likely to have severe papilledema at first neuro-ophthalmology encounter than those with a lower BMI (P = 0.02). There was a trend toward more severe visual loss in 1 or both eyes at last follow-up among those patients with BMI ≥40 (18% vs 11%, P = 0.067). Logistic regression modeling found that 10-unit (kilogram per square meter) increases in BMI increased the odds of severe visual loss by 1.4 times (95% confidence interval, 1.03–1.91, P = 0.03) after controlling for sex, race, diagnosed hypertension, and diagnosed sleep apnea.
Conclusion: Our finding of a trend for severe papilledema and visual loss associated with increasing BMI suggests that very obese IIH patients should be closely monitored for progression of visual field loss.
Idiopathic intracranial hypertension (IIH) is a syndrome characterized by increased intracranial pressure of unknown cause, occurring most commonly in obese women of childbearing age (1). Multiple studies have found an association between IIH and obesity (2–4), but it is unclear whether obesity is also a risk factor for poor visual outcomes in IIH. We hypothesized that higher body mass index (BMI) at diagnosis was a risk factor for worse visual outcomes in IIH.
The study was approved by our Institutional Review Board. All consecutive postpubertal patients with definite IIH, according to the modified Dandy criteria (5), seen at our neuro-ophthalmology service from 1989 to 2010 were included.
Although the study was a retrospective chart review, all patients had been evaluated in a standardized fashion by experienced neuro-ophthalmologists (N.J.N., V.B., and B.B.B.), including documentation of height, weight, blood pressure, and complete neuro-ophthalmic examination with formal visual fields, fundus photography, and review of neuroimaging tests. Demographic information regarding age, gender, and race was collected. Symptoms, medication use (particularly antibiotics, immunosuppressant agents, oral contraceptives, and vitamin A preparations), associated factors (recent weight gain, known sleep apnea, anemia [hemoglobin <12 g/dL], systemic hypertension, pregnancy, and endocrine disorders [polycystic ovarian syndrome, diabetes mellitus, and thyroid dysfunction]) were recorded (6). Prediagnosis duration of symptoms, cerebrospinal fluid (CSF) opening pressure, medical and surgical treatments, follow-up duration, and visual outcomes were also recorded. MRIs were all reviewed at the time of diagnosis, and magnetic resonance venography or CT venography was obtained when there was a doubt regarding possible cerebral venous thrombosis. Those patients who could not have an MRI had a head CT with contrast, often accompanied by CT venography. BMI was routinely documented on all IIH patients, and where it was not available, it was calculated from documented height and weight. BMI was divided into categories corresponding to World Health Organization BMI cutoff points (7,8): normal (18.5–24.9), overweight (25–29.9), Class I/II obesity (30–39.9), and Class III obesity (≥40).
Snellen visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) for analysis. Visual fields (kinetic or automated) were systematically reviewed and graded on a 1–4 scale as 1) normal, 2) enlargement of the blind spot, 3) nasal or temporal defect, or 4) diffusely constricted. Papilledema was graded with the Frisén (9) staging scheme by systematic review of fundus photography: Stage 0 defines a normal optic nerve head, and Stage 5 defines severe papilledema. Severe visual loss in an eye was defined by the US criteria for legal blindness (best-corrected visual acuity ≤20/200 or total central visual field <20°) and assessed at the last available visit.
Statistical analysis was performed with R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing; http://www.R-project.org). Continuous and ordinal variables were compared using the Mann–Whitney U test. Pearson χ2 test with Yates continuity correction or Fisher exact test, as appropriate, was used to compare categorical variables. A test for linear trend of proportions was performed using the median of each BMI category. Tests were 2 tailed, and significance was set at 5%. With severe visual loss in at least 1 eye as the outcome, the effect of BMI as primary exposure of interest was assessed with logistic regression. Race, gender, sleep apnea, hypertension, the patient's grade of papilledema at first visit (calculated as the mean of the 2 eyes), and diagnosed endocrine disease were the variables studied as potential confounders/effect modifiers based on their significance in univariate analyses of BMI and severe visual loss. The final model was determined by the method described by Kleinbaum and Klein (10).
We included 414 patients with IIH. There were 383 women (93%). The median age at diagnosis was 28 years (range, 13–62 years). Overall, 44% of our study population were black, with the nonblack population including whites (Hispanic and non-Hispanic) and Asians.
The characteristics of our patients with BMI <40 and BMI ≥40 are summarized in Table 1. There was a higher percentage of black patients in the BMI ≥40 group (48.7%) compared with the BMI <40 group (40.6%). Patients with BMI ≥40 had higher rates of several medical conditions: diagnosed sleep apnea (16.5% vs 5.1%, P < 0.001), endocrine disorders (18.4% vs 8.6%, P = 0.003), and hypertension (25.3% vs 13.7%, P = 0.003). Except for possibly fewer patients with transient visual obscurations as the first sign of disease in the BMI ≥40 group (7.6% vs 13.3%, P = 0.07), there were no other differences in presenting symptoms. Patients with BMI ≥40 seemed less likely to be symptomatic at presentation (0.8% vs 3.8%, P = 0.06). There was no difference in prediagnosis duration of symptoms, frequency of recent weight gain, medication use, CSF shunting procedures, or optic nerve sheath fenestration between groups (Table 1). Mean recent weight gain was higher among patients with BMI ≥40 (6.0 vs 3.6 kg, P = 0.04, independent sample t test), but there was no difference in the mean recent weight gain between patients with severe visual loss and those without (3.9 vs 4.6 kg, P = 0.61).
There was a trend toward worse visual acuity and visual field grade among patients with BMI ≥40 compared with those with a lower BMI (Table 2), but there was no difference in the mean deviation of automated visual field testing. Median stage of papilledema was equal between the 2 groups, but there was an overrepresentation of stages 4 and 5 papilledema seen in patients with BMI ≥40 at both first and last examinations. Severe visual loss occurred more frequently at last follow-up (in 1 or both eyes) among those with BMI ≥40 compared with those with a lower BMI (18% vs 11%, P = 0.067).
There was an unadjusted linear trend of an increasing proportion of patients with visual loss with increasing obesity class (Table 3, P < 0.05). In multivariable logistic regression analysis, black race (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.22–4.07) and male gender (OR, 2.91; 95% CI, 1.09–7.20) were independent risk factors for visual loss. Hypertension and sleep apnea were not found to have a significant effect on severe visual loss, nor did their exclusion from the model change the magnitude of effect attributed to BMI by more than 10%, but they were retained in the final model based on their potential confounding effects suspected from previous studies (6,11). Diagnosed endocrine disorder and papilledema grade were excluded from the model because they did not change the magnitude of effect attributed to BMI by more than 10% and led to reduced precision of the estimates. In addition, papilledema grade was excluded from the model because controlling for intermediates (i.e., papilledema grade) in the causal pathway between the exposure of interest (i.e., BMI) and the outcome (i.e., severe visual loss) could lead to bias in the exposure's estimate of effect (10). The logistic model shows that there is a 1.4 times greater odds (95% CI, 1.03–1.91, P = 0.03) of severe vision loss for every 10-unit increase in BMI and a 2.0 times greater odds of severe visual loss for every 20-unit increase in BMI after controlling for sex, race, diagnosed hypertension, and diagnosed sleep apnea (Table 4).
Our study shows that higher BMI at diagnosis is associated with increased risk of severe visual loss in IIH, independent of other known risk factors, providing another variable to consider when evaluating IIH patients. This is especially important information in light of the growing epidemic of obesity throughout the world (12,13). Few studies have addressed the role of the degree of obesity in vision loss in IIH. One multicenter retrospective review of 107 patients found that weight alone was not significantly different between groups with no visual dysfunction, definite visual function deterioration, and severe visual loss (14). A case–control study of 34 IIH patients reported an increased risk of IIH with increasing BMI but found no association between visual outcomes and increasing BMI when using vision-specific quality-of-life surveys (3). Another study showed no association between visual field deficits at time of diagnosis and BMI, weight gain, or percent change in ideal body weight but did not specifically consider severe visual loss (15). In a case–control study of 50 patients (2), the amount of recent weight gain, but not the degree of obesity, was significantly higher among the 5 patients who experienced visual deterioration. We did not find a similar association in our study, although the severely obese patients reported a higher amount of recent weight gain, as might be expected. In a recent report of 18 IIH patients with normal BMI, none of the patients had severe visual loss (7). To our knowledge, no prior study has demonstrated a relationship between obesity and vision loss. The size of these older studies likely limited their power to detect such a difference, and most failed to control for confounding effects, such as gender and race. In addition, because visual outcomes in IIH are usually good, particularly central visual acuity, summary measures (e.g., means and medians) are unsurprisingly similar and may mask the substantial differences in the risk of severe visual loss as BMI increases. Our failure to demonstrate a difference in mean deviation on automated visual field testing, while finding a trend toward a worse visual field grade at the last visit in more obese patients, likely reflects our practice to obtain kinetic visual fields when patients cannot reliably perform automated testing (e.g., those with severe visual loss).
Previous reports have found an association between papilledema grade and visual loss, especially in cases of severe papilledema (1). In our study, although there was no obvious difference in median papilledema grades between the groups, there was an overrepresentation of Grades 4–5 papilledema among more obese patients. Since severely obese patients were also more likely to be asymptomatic, they may have been exposed to the deleterious effects of papilledema for a longer period before presentation, and this could explain their higher risk for visual loss.
Limitations of our study include its retrospective nature. However, all patients were systematically evaluated in a standardized fashion in a single neuro-ophthalmic center. Because most of our patients are referred by ophthalmologists or neurologists, they may manifest a more severe clinical presentation, resulting in referral bias. Additionally, this referral pattern makes it likely that in some cases, treatment may have begun prior to our first documented neuro-ophthalmic examination. Finally, we measured visual acuity using Snellen charts as a part of routine clinical practice rather than in a standardized research setting using Early Treatment Diabetic Retinopathy Study charts, but we appropriately converted our measurements to the logMAR scale for analysis.
Our finding of a trend for severe papilledema and visual loss associated with increasing BMI suggests that very obese IIH patients should be closely monitored for progression of visual field loss. If progression is seen, early consideration for definitive surgical intervention may be especially important in IIH patients with multiple risk factors for severe vision loss, including black race, male sex, anemia, hypertension, and very high BMI. While it has been definitively shown that aggressive efforts at weight loss often lead to remission of the disease, whether these efforts also reduce the risk of severe visual loss in very obese IIH patients remains to be determined.
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