Weight Loss in Idiopathic Intracranial Hypertension: A Retrospective Review of Outcomes in the Clinical Setting

Weight loss is important in the management of idiopathic intracranial hypertension (IIH); however, extremely caloric restrictive diets have been used in published studies, which may not be practical for all patients. We aim to review the weight loss outcomes of IIH patients and weight loss methods used by patients who achieve clinical remission (CR) in a standard clinical setting

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Weight Loss in Idiopathic Intracranial Hypertension: A Retrospective Review of Outcomes in the Clinical Setting Juan Lyn Ang, MD, MSc, Kai Z. Teo, MD, Clare L. Fraser, MBBS (Hons), MMed, FRANZCO Background: Weight loss is important in the management of idiopathic intracranial hypertension (IIH); however, extremely caloric restrictive diets have been used in published studies, which may not be practical for all patients. We aim to review the weight loss outcomes of IIH patients and weight loss methods used by patients who achieve clinical remission (CR) in a standard clinical setting. Methods: The medical records of IIH patients were retrospectively reviewed. Measures evaluated included: reported symptoms, visual acuity, retinal nerve fiber layer analysis, automated visual fields, optic disc appearance, and cessation of medications. Patients were divided into different outcome groups and weight changes were compared. Patients who achieved CR were contacted to assess weight loss methods used. Results: Of the 39 patients included in the analysis, 28 patients (71.8%) achieved CR with concomitant weight loss, 6 patients (15.4%) improved clinically with concomitant weight loss but did not achieve CR. Among the patients with CR, 10 patients (35.7%) were successfully weaned off their medications completely, whereas another 10 patients (35.7%) are in the process of this. Median weight loss from baseline to lowest weight for this group was 10.5 kg (11.5%) achieved using self-directed methods. Conclusion: This study demonstrated that a large proportion of IIH patients were able to achieve CR or improvement with self-directed weight loss regimens, reinforcing the evidence and the practicality of weight loss in the management of IIH in the clinical setting. Journal of Neuro-Ophthalmology 2021;41:e458–e463 doi: 10.1097/WNO.0000000000001107 © 2020 by North American Neuro-Ophthalmology Society The Princess Alexandra Eye Pavilion (JLA), Edinburgh, United Kingdom; Sydney Hospital & Sydney Eye Hospital (CLF), Sydney, New South Wales, Australia; Nepean Hospital (KZT), Penrith, New South Wales, Australia; and Save Sight Institute (CLF), Faculty of Health and Medicine, The University of Sydney, New South Wales, Australia. The authors report no conflicts of interest. Address correspondence to Juan Lyn Ang, MD, MSc, The Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh EH3 9HA; E-mail: [e-mail] e458 I diopathic intracranial hypertension (IIH) is a condition most prevalent in young, obese women, causing disabling headaches and visual impairment (1–3). Recent weight gain (WG) is a significant factor for its development (4,5). A recent United Kingdom consensus guidelines highlighted weight loss as a disease-modifying therapy (6). A 1974 study reported 9 IIH patients placed on a 400–1,000 calorie rice diet lost 13%–38% of body weight within 3 months and had reduction of papilloedema (7). A prospective study placed 25 women with IIH on a 3-month 1,777 kJ/day diet, resulting in a mean weight reduction of 15.7 kg, significant intracranial pressure (ICP) reduction, improved symptoms and reduced papilloedema (8). Retrospective studies also support the importance of weight loss (9–11). The IIH Treatment Trial (IIHTT) was a randomized, double-blind, placebo-controlled study to evaluate whether acetazolamide was beneficial in improving vision in IIH patients when added to a low-sodium weight-reduction diet. Participants received weekly telephone communication, exercise goals, and cognitive behavioral therapy. A balanced diet was designed from estimated caloric needs. Those on acetazolamide had significantly larger improvement in perimetry mean deviation (MD) and weight loss (1.43 dB, mean loss 7.5 kg, 7.8%) compared with controls (mean loss 3.5 kg, 3.5%). Acetazolamide likely contributed to the weight loss, making it a possible confounder (12). In these studies, highly caloric restrictive diets and resource-intensive weight loss programs have been effective. However, this may not be practical for all patients and there are doubts as to whether patients outside the trial setting are able to realistically lose weight and achieve clinical remission (CR). To help guide clinicians on the practicalities of weight loss as part of the management plan, we aim to review the real-world weight loss outcomes of IIH patients and to assess the weight loss methods used by those who achieved CR. Ang et al: J Neuro-Ophthalmol 2021; 41: e458-e463 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution METHODS Sample Consecutive IIH patients between 2014 and 2018 were identified from multiple tertiary referral neuroophthalmology clinics in Sydney, Australia. IIH was diagnosed according to the modified Dandy criteria (13), with all patients having papilloedema and ICP .25cmH2O. The patients were managed by a single neuro-ophthalmologist. Patients were excluded if they did not have complete weight records or at least 3 follow-up visits. Ethical approval was granted by the Local Health District Research Support Office. Study Design A retrospective review of medical records was performed. As standard of care, patients were advised to aim for weight loss of 10% or more from their starting body weight. General weight loss advice was given. Patients could choose any weight loss method. Treatment was determined by symptoms, visual function and appearance of optic discs. First line therapy was acetazolamide unless disease activity was considered mild, or if there were contraindications. Topiramate was second line therapy. Surgical interventions were implemented if medical therapy was failing. Records were reviewed for weight changes (selfreported), patients’ reported symptoms, best-corrected visual acuity (BCVA), automated visual field (VF) MD (Humphrey 24-2 or 30-2 central threshold), optic disc appearances, and medication status. Peripapillary retinal nerve fiber layer (RNFL) thickness was measured by optical coherence tomography (Cirrus HD-OCT 5000; Carl Zeiss Meditec, Dublin, CA). A VF defect was defined as a Humphrey VF (HVF) MD of 22 dB or more, as used in the IIHTT (12). Standard questions were asked at visits: headache and its semiology, presence of pulsatile tinnitus, visual changes including transient visual obscurations, and follow-up of any symptoms previously reported. Patients were determined to have achieved CR, clinical improvement, no improvement, or clinical deterioration at the time of last clinic visit. Primary outcome was the proportion of patients who achieved CR with weight loss. CR was defined as the resolution of all symptoms and reversible clinical signs. In cases with stable optic atrophy and associated field loss, patients could still be considered to have achieved CR based on neuro-ophthalmic review. For patients with ongoing improvement of clinical signs without full resolution, they were classified as having “clinical improvement.” Patients’ outcomes were compared with their weight changes. Patients successful with CR were asked about adopted weight loss methods. Ang et al: J Neuro-Ophthalmol 2021; 41: e458-e463 Statistical Analysis Statistical analyses were performed with SPSS version 23. Weight loss was calculated from baseline body weight to the lowest weight achieved. Body mass index (BMI) was calculated only for patients with height recorded, baseline BMI between subgroups were compared using one-way analysis of variance. Significance was set at P , 0.05. As data was not normally distributed, Wilcoxon-sign rank test was used to analyze changes in weight, RNFL, and HVF MDs from baseline. HVF MDs, are presented as the median change in MD for all eyes, and the subgroup of patients with at least 1 eye with VF defect at baseline, where the median change in HVF MDs are presented only for the worse eyes. Patients were divided into 4 subgroups: (a) patients in CR with weight loss (CR + WL), (b) clinical improvement (not remission) with weight loss (CI + WL), (c) no clinical improvement despite weight loss (WL 2 CI), and (d) clinical deterioration with WG (WG + CD). As data were not normally distributed within each subgroup, medians and interquartile ranges were reported for changes in weight, RNFL and MD of HVF of the subgroups, and Mann– Whitney U test was used to compare the outcomes between the subgroups. Patients with various cut-offs of percentages of weight loss were compared against those that did not achieve corresponding weight loss cut-offs using Fisher exact test to determine whether there was a certain percentage of weight loss that was required before CR is achieved. RESULTS One hundred two patient charts were reviewed. Sixty-three were excluded for not meeting the inclusion criteria, lacking weight records or inadequate follow-up. Thirty-nine patients were included in the analysis. Table 1 shows the cohort’s baseline characteristics. At baseline, median weight was 101 kg (interquartile range [IQR] 23.7) and median LP opening pressure was 30 cm H2O (IQR 5.5). For the 24 patients with height records, the overall baseline BMI was 36 kg/m2 (SD 7.6) with a subgroup mean ranging from 32.4 kg/m2 (WG + CD) to 40 kg/m2 (WL 2 CI). There was no significant difference in BMI between subgroups (P = 0.750). All patients had BCVA 6/9 or better. One patient had missing baseline and 3 were missing follow-up HVFs. For the remaining 35 patients, baseline MD ranged from 227.5 dB to +1.29 dB and the median was 22.30 dB across all eyes. Median HVF MD at baseline was 23.08 dB (IQR 23.34) in the worse eye and 21.34 dB (IQR 22.04) in the better eye. Of the 38 patients with a baseline HVF, 12 (30%) did not have a VF defect in either eye (MD , 22dB). Baseline median RNFL thickness was 151mm (IQR 92). Mean follow-up period was 24.7 (SD 13.5) months. e459 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Baseline demographics of 39 patients before starting weight loss process Data Median age, years (IQR) Females, n (%) Median weight, kg (IQR) Mean BMI overall, kg/m2 (SD)‡ Mean BMI CR+WL, kg/m2 (SD) Mean BMI CI+WL, kg/m2 (SD) Mean BMI CL-CI, kg/m2 (SD) Mean BMI WG+CD, kg/m2 (SD) Opening pressure on lumbar puncture, cmH2O (IQR) Median of MD of HVF for all eyes, dB (IQR)* Median of MD of HVF for only patients with VF defect in the worse eye, dB (IQR)† Median RNFL thickness, mm (IQR) Follow-up time from baseline visit to last visit, months (SD) 35 37 101 36 35.6 36.5 40 32.4 30 (10.5) (94.9) (23.7) (7.6) (7.7) (4.8) (11.7) (6.6) (5.5) 22.30 (3.33) 23.86 (5.08) 151 (92) 24.7 (13.5) *For 35 eyes with both baseline and follow-up records of HVFs. †Only 26 patients with at least 1 eye with MD $ 22dB. ‡ Only for 24 patients with records of height. BMI, body mass index; CR, clinical remission; HVF, Humphrey VF; RNFL, retinal nerve fibre layer; MD, mean deviation; VF, visual field; WG, weight gain. Most (37/39, 94.9%) were started on medication; 30 (76.9%) acetazolamide, 2 (5.1%) topiramate. Five (12.8%) patients switched to topiramate during management. Two patients (5.1%) were on metformin for insulin resistance and another 7 (17.9%) subsequently commenced metformin. Of those who achieved CR, 3 (10.3%) required optic nerve sheath fenestration for vision threatening disease. Outcomes for Entire Cohort The median change of weight was a loss of 10 kg (IQR 8, P , 0.001). The median RNFL thickness significantly decreased by 45mm (IQR 107, P , 0.001) right eyes and 45mm (IQR 88, P , 0.001) left eyes. The HVF MD of patients with baseline and follow-up HVF improved significantly; right eye changed by a median of 1.06 dB (IQR 2.58, P = 0.02) and left eyes, 0.65 dB (IQR 2.23, P = 0.02). For the 26 patients with an initial VF defect in at least 1 eye, there was a median of 1.97 (IQR 2.34) dB improvement in the worse eye (P , 0.001). Twenty-eight patients (71.8%) achieved CR with concomitant weight loss (CR + WL), 6 patients (15.4%) improved clinically (CI + WL), 3 patients (7.7%) did not improve despite weight loss (WL 2 CI), and 2 patients (5.1%) had clinical deterioration with WG (WG + CD). No patients had clinical improvement or remission without weight loss. Figure 1 summarizes the patient selection process and the subgroups. Outcomes for the Subgroups Table 2 shows the changes in weight, RNFL thickness, and MD of HVF of the subgroups. The WL 2 CI and WG + CD cohorts were combined on subgroup comparison because of very small numbers in both cohorts. Weight Loss See Figure 2 for details of how much weight patients lost. Comparing the CR + WL cohort with the WL 2 CI and WG + CD cohorts combined, there was a significant difference in the percentage weight loss (P = 0.02). However, when CR + WL and CI + WL groups were compared, there was no significant difference (P = 0.88). Patients with $5%, $10%, and $15% weight loss from baseline were compared with corresponding groups that did not achieve stated weight loss cut-offs, and there were no significant differences in the number of patients that achieved remission in these comparisons. FIG. 1. Summary of patient selection process and subgroups according to outcome. e460 Ang et al: J Neuro-Ophthalmol 2021; 41: e458-e463 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 2. Outcomes in each subgroup Outcomes Weight change, kg Percentage weight change, % Right eye RNFL thickness, mm Left eye RNFL thickness, mm Right eye HVF MD, dB (n = 35)* Left eye HVF MD, dB (n = 35)* HVF MD in worse eye, dB (only for those with at least 1 eye ,2 dB at baseline) (IQR) (n = 25)* CR + WL (n = 28) 210.5 211.5 247 240.5 20.90 20.58 21.79 (7.4) (7.1) (94.5) (112.8) (2.40) (2.42) (2.32) CI + WL (n = 6) 211.5 212.4 220 247.5 20.86 20.15 21.15 WL 2 CI (n = 3) and WG + CD (n = 2) (6.3) (6.4) (271.8) (108) (3.97) (1.78) (3.45) 23.8 23.7 259 280 22.25 22.54 22.91 (18) (20.1) (84.5) (55) (12.18) (11.88) (11.94) Results are presented as median changes (IQR). *Only for eyes with records of both baseline and follow-up results. CR, clinical remission; HVF, Humphrey VF; RNFL, retinal nerve fibre layer; MD, mean deviation; WG, weight gain. Retinal nerve fiber layer thickness No significant differences were found in change of RNFL thickness from baseline when these cohorts were compared: (a) CR + WL vs CI + WL cohorts (right eye [RE]: P = 0.527, left eye [LE]: P = 0.769) and (b) CR + WL vs combined WL 2 CI and WG + CD (RE: P = 1, LE: P = 0.442). Visual fields There were no significant differences found in the change of MD between cohorts CR + WL vs CI + WL (RE: P = 0.889, LE: P = 0.420). There was a significant difference only for the left eye, but not the right eye when cohorts CR + WL vs combined WL 2 CI and WG + CD were compared (RE: P = 0.062, LE: P = 0.015). For patients with at least 1 eye with a VF defect at baseline, there were no significant differences found in the change of MD of HVF of worse eyes when these cohorts were compared: (a) CR + WL vs CI + WL cohorts (P = 0.571), (b) CR + WL vs WL 2 CI and WG + CD cohorts combined (P = 0.117). Follow-up of Cohort With Clinical Remission Ten patients (35.7%) with CR were successfully weaned off all medications, and another 10 (35.7%) were in the process of weaning. Two (7.1%) were never medicated, whereas 2 (7.1%) ceased medication during pregnancy. Four (14.3%) were maintained on medications because of potential for WG (e.g., upcoming knee surgery). 85.7% had follow-up from point of remission; mean follow-up time was 11 months (SD 9 months). After a mean of 8 months, 8/28 (28.6%) gained weight, and 5/8 of those had recurrence of symptoms. The remaining 66.7% maintained their weight and sustained CR. Weight Loss Strategies Used by Patients Who Achieved Clinical Remission and Concomitant Weight Loss Table 3 shows a summary of weight loss strategies adopted by patients who achieved CR. Of those who were contactable, 12/21 (57.1%) solely used dietary interventions and a further 7/21 (33.3%) combined dietary interventions with exercise. Within the group that used solely dietary intervention, 3/12 (25%) used formal dietary interventions such as the use of preprepared meals or engagement of a dietician, whereas 9/12 (75%) used informal interventions that is, reducing snacks, reducing carbonated drinks, portion control, and more conscientious eating. More patients (11/19, FIG. 2. Percentage weight loss from baseline in the CR + WL cohort, CI + WL cohort, and WL 2 CI and WG + CD cohorts combined. Ang et al: J Neuro-Ophthalmol 2021; 41: e458-e463 e461 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Weight loss strategies used by patients that achieved clinical remission and were contactable Weight loss strategy Type of dietary intervention Dietary intervention only 12 (57.1%) Dietary intervention and exercise 7 (33.3%) Ceased medication Gastric sleeve surgery Total 1 (4.8%) 1 (4.8%) 21 57.9%) utilized informal dietary interventions compared with formal dietary interventions (8/19, 42.1%). A small group, 2/21 (9.5%) lost weight via cessation of medications causing WG and gastric sleeve surgery. CONCLUSION In this study, over 70% of patients with IIH in a routine clinic setting achieved CR with weight loss by any method of their choice, in combination with standard medical management. More than half (70%) of these patients have had or are in the process of having their medications ceased. Previous studies have used very caloric restrictive and resource-intensive weight loss programs with success (8,14), but extremely low energy diets may not tolerable long-term and can be associated with side effects such as halitosis, light-headedness, and constipation (8,15) and therefore, there are uncertainties as to whether weight loss among IIH patients is a realistic goal outside the trial setting. Our findings suggest that self-directed weight loss is achievable and should be discussed in the clinical setting. We attribute this success to sensitive patient counselling about the importance of weight loss early after diagnosis. Second, a 10% weight loss goal is a less daunting task that patients can work toward. Our results are contrary to a 2year study where obese patients directed their own weight loss. The study reported that less than 20% lost .5% of baseline weight (16). This may be because of our patients’ greater motivation to resolve their IIH symptoms and stop acetazolamide. Acetazolamide itself may have weight loss benefits, through appetite suppression and a change in the taste of carbonated beverages (17). Our patients took 11.6 months (average) to achieve the weight loss and enter CR. This is a longer period than intensive diet studies, but a large proportion (66.7%) of our patients maintained or lost more weight after another 11 months of follow-up. In the study by Sinclair et al., although successful in losing weight and achieving CR initially (8), patients regained weight in the subsequent 12 months and experienced an IIH relapse (15), a phenomenon observed previously (18,19). Therefore, our study suggests that self-directed weight loss can be more sustainable approach compared with extremely lowcalorie diets. In addition, our patients were given the e462 Formal dietary intervention Informal dietary intervention Formal dietary intervention Informal dietary intervention — — — 3 (25%) 9 (75%) 5 (71.4%) 2 (28.6%) — — 19 freedom to choose their weight loss method, possibly contributing to the longer-term success. We could not compare the weight loss strategies adopted by the group that achieved CR and the group that gained weight and deteriorated as the number of patients in the latter group was too small. Although weight loss is recognized as a diseasemodifying therapy for IIH, the amount of weight loss required for remission is unclear (6). It has been reported that IIH is associated with 5%–15% WG in the preceding year (20) and in another study, patients with IIH recurrence demonstrated a mean WG 8.7% (18). In previous studies, patients’ weights were analyzed after a fixed period of time; in 1 cohort, participants achieved remission with a mean of 15.3% weight loss after 3-month diet intervention (8), whereas in another study, approximately 6% weight loss was associated with resolution of marked papilloedema after a 24-week period (10). In our study, although the CR group had 11.5% weight loss from baseline, we could not find a significant association between percentage of weight loss and CR at 5%, 10%, and 15%. Therefore, we were unable to determine a cut-off percentage of weight loss that was associated with CR from our data. However, a higher percentage of weight loss is likely to be associated with better chance of remission. RNFL thickness and MD of HVF changed significantly for the entire cohort. There were inconsistencies when cohorts with remission were combined and compared with cohorts with no improvement or deterioration combined. This may be because of small and unequal sample sizes, particularly for the groups with no improvement and deterioration. Alternatively, changes in RNFL thickness may not necessarily correlate with CR or progress (21). Finally, RNFL thickness cannot discriminate between the resolution of papilloedema and axonal loss in optic atrophy (22). Among the group who achieved CR, most patients used dietary interventions only. Informal dietary interventions were more popular in our cohort. This is in line with evidence for greater feasibility and long-term sustainability in introducing small changes in diet and physical activity compared with large changes (23). Simple dietary changes are cheap and effective, and should form part of the management discussion with IIH patients. Ang et al: J Neuro-Ophthalmol 2021; 41: e458-e463 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution The weaknesses in our study are the reliance on selfreported weight loss and the small sample size. Patients who did not have weights recorded were excluded from the study, which may have introduced selection bias, because these patients did not know their weights or refused to be weighed. Patients were also treated with medications such as acetazolamide, which may have contributed to weight loss through a reduction in caloric intake due to dysgeusia, nausea, and dyspepsia (14). This is a retrospective review, and treatment was not standardized across the cohort. However, the use of acetazolamide and variations in treatment use is likely reflective of the clinical setting outside a trial. Although this is a small study, our findings suggest that counselling and encouraging patients with IIH to lose weight can result in CR and is achievable through selfdirected methods. 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