Idiopathic Intracranial Hypertension-A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World

Central retinal artery occlusion with subsequent central retinal vein occlusion in the same eye is a rare entity. We present a 72-year-old man with biopsy-proven giant cell arteritis who developed bilateral arteritic anterior ischemic optic neuropathy and a left central retinal artery occlusion. Subsequently, he developed a left central retinal vein occlusion within 2 weeks of his initial vision loss. His vision did not improve with corticosteroids.

Original Contribution Idiopathic Intracranial Hypertension-A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World Amir Rosenblatt, MD, MPH, Ainat Klein, MD, Ségolène Roemer, MD, François-Xavier Borruat, MD, Dália Meira, MD, Marta Silva, MD, Figen Gökçay, MD, Neşe Çelebisoy, MD, Anat Kesler, MD Background: Idiopathic intracranial hypertension (IIH) is a well-characterized syndrome, most commonly affecting obese women of childbearing age. Differences in its prevalence have been reported in various populations. The aim of this article was to determine whether differences in clinical presentation and management exist for patients with IIH between different regions the world. Methods: Retrospective database analysis of adult patients with IIH from 4 different neuro-ophthalmology clinics. The data collected included gender, age of onset, body mass index (BMI), lumbar puncture opening pressure, initial visual acuity (VA), initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, final VA, and final VF MD. Results: The study population consisted of 244 patients, with significant regional variations of female to male ratio. Overall, there was no significant difference regarding the age of diagnosis or the BMI. Acetazolamide was the first line of treatment in all groups but there was a difference between countries regarding second-line treatment, including the use of surgical interventions. Mean initial VA differed between groups but the final change in VA was the same among all the study groups. Conclusions: There are differences in IIH presentation, treatment, and response to therapy among different countries. International prospective studies involving multiple centers are needed to determine the potential influence of environmental and genetic factors on the development of IIH and to improve the management of this potentially blinding disorder. Department of Ophthalmology (AR, A. Klein, A. Kesler), Tel AvivSourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Hôpital Ophtalmique JulesGonin (SR, F-XB), University of Lausanne, Lausanne, Switzerland; Centro Hospitalar de Vila Nova de Gaia/Espinho (DM), Vila Nova de Gaia, Portugal; Centro Hospitalar de S. João (MS), Faculdade de Medicina da Universidade do Porto, Porto, Portugal; and Department of Neurology, Ege University Medical School (FG, NÇ), Bornova, I_zmir, Turkey. METHODS The authors report no conflicts of interest. A. Rosenblatt and A. Klein contributed equally to this study. Address correspondence to Ainat Klein, Tel Aviv-Sourasky Medical Center, Department of Ophthalmology, Weizmann 6 st, Tel-Aviv, Israel 64239; E-mail: [e-mail] 280 Journal of Neuro-Ophthalmology 2016;36:280-284 doi: 10.1097/WNO.0000000000000402 © 2016 by North American Neuro-Ophthalmology Society I diopathic intracranial hypertension (IIH) is a disorder of unknown etiology for which the pathogenesis remains unclear (1). The syndrome affects predominantly obese women of childbearing age (2). About 10% of the diagnosed patients are male (3). The annual incidence of IIH is approximately 1-2 per 100,000 in the general population, 3.5 per 100,000 in females aged 20-44 years, and 19 per 100,000 in women who are 20% over ideal body weight (4-6). The incidence of IIH also varies depending on location (7). For example, the incidence of IIH was found to be only 0.03 per 100,000 (8) in Japan, whereas it was reported to be 2.2 per 100,000 (5) in Libya. Although the etiology of the disease is unknown, the differences in these data may be related to genetic and environmental factors. The aim of our study was to determine whether differences in clinical presentation and management existed for patients with IIH between different geographic regions. We conducted a retrospective database analysis of IIH patients from 4 different neuro-ophthalmology clinics: 1) Hôpital Ophtalmique Jules-Gonin, University of Lausanne, Lausanne, Switzerland, 2) Centrl Hospitalar de s. João/Faculdade de Medicina da Universidade do Porto and Centro Hospitalar de Vila Nova de Gaia/Espinho, Portugal, 3) Department of Neurology, Ege University Medical School, Bornova, Izmir, Turkey, 4) Tel AvivSourasky Medical Center, Sackler Faculty of Medicine, Rosenblatt et al: J Neuro-Ophthalmol 2016; 36: 280-284 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Tel Aviv University, Tel Aviv, Israel. The study was approved by the institutional review board/ethics committee of all 4 medical centers. Inclusion criteria were adult patients older than 18 years who fulfilled the modified Dandy criteria for IIH (9). Exclusion criteria were patients with secondary causes of increased intracranial pressure, such as hypervitaminosis A or hypovitaminosis A, hyperparathyroidism, use of tetracycline analog, roacutane, steroids, and lithium, and patients who were found to have cerebral venous sinus thrombosis. Patients with other ocular causes affecting their visual acuity (VA) also were excluded from the study. Data collected included gender, age of onset, body mass index (BMI), lumbar puncture (LP) opening pressure (OP), initial VA in logMAR, initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, recurrence rate, chronicity, final VA, and final VF MD. Statistical Analysis Data were recorded in Microsoft Excel (2010) and analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Continuous variables, such as VA, were compared within subjects using paired sample t test and between subjects using the independent sample t test or 1-way analysis of variance. For small group comparison and ordinal variables, Mann-Whitney nonparametric test was used. Binary variables were compared between subjects using the Fisher exact test or Pearson x2. To analyze the correlation between continuous variables, univariate Pearson correlation test was used. Multivariate linear regression was used to examine the independent effect of patient and clinical characteristics on final visual outcome. All tests were 2-tailed, and the threshold for statistical significance was defined as a P , 0.05. RESULTS We collected data from 244 IIH patients: 33 from Lausanne, Switzerland; 36 from Porto district, Portugal; 55 from Bornova, Turkey; and 120 from Tel Aviv, Israel. Baseline Characteristics Patient's characteristics in each group are presented in Table 1. The study population consisted of 217 female patients (88.9%) and 27 male patients (11.1%). The male prevalence ranged from 3.6% to 30.6% with regional variations; Israeli and Turkish patients had significantly lower prevalence of men compared with Swiss and Portuguese populations (P = 0.001). The mean age at diagnosis was 32.53 ± 10.69 years. Overall, Israeli patients were younger (mean age 30.4 years) and the Portuguese patients were older (mean age 37.6 years). Within each study group, female patients were younger. These differences were statistically significant (Table 1). The mean BMI was elevated in all 4 groups with a mean of 32.43 ± 6.95 kg/m2. There were no differences between groups and no difference in the average BMI between male and female patients. As the disease is a systemic one and to minimize the effect of outliers, we used the mean value of the 2 eyes. The mean initial VA was 0.073 ± 0.28 logMAR, and the mean initial MD was 25.74 ± 5.7 dB. Portuguese patients had statistically significantly worse VA compared with the Israeli and the Swiss patients. Turkish patients had relatively worse MD (28.41 ± 6.0 dB) vs the Portuguese patients (26.18 ± 5.1 dB). The mean LP OP for the IIH cohort was 349.72 ± 88.2 mm$H2O and was significantly higher among the Turkish population (396 ± 106.7 mm$H2O) vs the other groups. There was no correlation between the OP and VA (R = 0.147, Pv = 0.103). Treatment Acetazolamide was the first line of treatment in all groups and was initiated in 93.7% of patients. The daily dose ranged 750-2,000 mg (according to body weight and response to treatment). When a second medication was needed, furosemide was more commonly used in the Portuguese (33.3%) and Turkish (12.7%) patients, whereas in the Israeli cohort, topiramate was preferred (22.4%) (Table 2). Among 244 patients, 20 (8.2%) had undergone surgical intervention. In the Swiss cohort, more patients underwent TABLE 1. Demographic and clinical characteristics of patients with idiopathic intracranial hypertension Age, mean ± SD, yrs BMI, mean ± SD, kg/m2 Male gender, n (%) LP OP, mean ± SD, mm H2O Initial VA, mean ± SD, logMAR Initial VF MD, mean ± SD Portugal n = 36 Switzerland n = 33 Turkey n = 55 Israel n = 120 P value 37.6 ± 10.8 34.8 ± 6.0 11 (30.6) 353.2 ± 78.6 0.16 ± 21 26.18 ± 5.1 34.2 ± 10.4 36.4 ± 8.3 6 (18.2) 336.3 ± 65.6 0.04 ± 0.18 25.71 ± 7.1 32.82 ± 9.8 31.2 ± 7.1 2 (3.6) 396.0 ± 106.7 0.08 ± 0.14 28.41 ± 6.0 30.4 ± 10.6 32.2 ± 6.8 8 (6.7) 329.3 ± 77.2 0.05 ± 0.12 24.05 ± 3.7 0.003 0.063 0.001 ,0.001 0.002 ,0.001 Age, age of onset; BMI, body mass index; LP OP, opening pressure on initial lumbar puncture; MD, mean deviation; VA, visual acuity; VF, visual field. Rosenblatt et al: J Neuro-Ophthalmol 2016; 36: 280-284 281 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 2. Treatment options for patients with idiopathic intracranial hypertension Any pharmacological treatment, n (%) Acetazolamide, n (%) Topiramate, n (%) Furosemide, n (%) Any surgical treatment, n (%) Shunt, n (%) ONSF, n (%) Portugal Switzerland Turkey Israel P value 35 (97.2%) 26 (78.8%) 3 (8.3%) 12 (33.3%) 3 (8.3%) 3 (8.3%) 0 (0%) 26 (78.8%) 54 (98.2%) 0 (9%) 0 (0%) 9 (27.3%) 9 (27.3%) 0 (%) 55 (100%) 110 (95.7%) 1 (1.8%) 7 (12.7%) 3 (5.5%) 0 (9%) 3 (5.5%) 114 (98.3%) ,0.001 26 (22.4%) 4 (3.4%) 5 (4.2%) 5 (4.2%) 2 (1.7%) ,0.001 - 0.006 ,0.001 ,0.001 ,0.001 N/S ONSF, optic nerve sheath fenestration; SD, standard deviation; shunt, lumboperitoneal shunt. surgical treatment as compared with the other 3 groups (27.3% in Switzerland vs 4.2%-8.3% in the other groups). Regarding the specific surgical procedure, all the Swiss and Portuguese patients benefited from cerebral spinal fluid shunting procedures, the Turkish patients were treated with optic nerve sheath fenestration, and Israel patients benefited from either shunting procedures or both procedures. Follow-up and Outcomes The mean follow-up period of all patients was 54 months (range, 1-300 months). There was a statistically significant difference in the follow-up period between the centers, with the Israeli cohort having the longest mean follow-up of almost 71 months and the Swiss with the shortest period of nearly 30 months. The average follow-up period in the Turkish and Portuguese population was 43.1 and 46.7 months, respectively, and did not differ significantly (Table 3). The mean final VA for the IIH cohort was 0.043 ± 0.12 logMAR. There was a statistically significant difference in final VA between the groups (P = 0.006), ranging from 0.11 logMAR (in Portugal) to 0.02 logMAR (in Israel). The change in VA did not differ significantly between the different population groups, the predictor of final VA being the initial VA that averaged 0.0369 ± 0.11 logMAR. The mean final VF MD was 4.07 ± 4.5 dB, the average improvement being 1.68 ± 3.5 dB. This change in MD differed significantly between the Swiss (+0.38 dB) and Turkish (+3.6 dB) populations. In a multiple linear regression analysis, initial VA and MD were the only independent prognostic factors for the final visual outcome. The better initial visual function (VA and VF MD) was, the better was the final visual outcome, additionally the worse the initial visual function was, the larger was the visual functions improvement. Age at onset, gender, BMI, and LP OP had no effect on the final visual function. DISCUSSION In our patients with IIH, the mean age at diagnosis (32.5 ± 10.7 years) was similar to previous population studies (4,5,7,10). We found statistically significant age differences between our groups with younger patients among the Israelis (mean 30.4 years) and older patients among the Portuguese 282 (mean 37.6 years). However, the difference in age was not associated with a better or worse visual prognosis. The mean BMI in our cohort was elevated (32.4 ± 6.95 kg/m2) and did not differ between the 4 groups. This result was similar to previously published studies, which also demonstrated that the majority of patients with IIH were obese women of childbearing age, with a mean age of diagnosis of about 30 years (10,11). The overall prevalence of male patients in our study was 11.1%, similar to other published series (3). However, the prevalence of men in each group varied significantly. The Swiss and Portuguese groups showed a significantly higher prevalence of male (18.2% and 30.6%, respectively) compared with the Israeli and Turkish groups (3.6% and 6.7%, respectively). We could not find an explanation for that regional variation or previous reports of similar findings in the literature. In most patients, the primary drug of choice was acetazolamide, used in 93.7%. Overall, 8.2% of the cohort underwent surgical treatment but the prevalence of surgical procedures varied significantly between groups. Interestingly, the higher rate of surgical procedure was found in 2 groups with a higher proportion of male patients, Switzerland and Portugal. In Switzerland, surgical treatment was the first treatment of choice in 27.3% and in Portugal 8.3%. The explanation could be either the presence of an aggressive form of IIH or the late presentation of IIH patients with already significantly compromised visual function. Indeed, previous studies have suggested that male patients may have worse visual outcomes than female patients with IIH (2,3). The higher prevalence of male patients and the fact that they tend to have more severe disease might have influenced the treatment strategies in these countries. However, we found no significant difference between the gender of surgically treated patients, and the percentage of surgeries was equal among male and female patients (P = 1.00). Furthermore, analyzing the entire cohort and subdividing by the 4 different centers from different countries, we found no statistically significant difference between the initial VA, LP OP, or MD between men and women. Analyzing the entire cohort (not divided by country) it was found that, over all, the surgically treated patients had worse initial VA and MD than the nonsurgical patients. Subdividing the cohort by center did not allow comparing the clinical Rosenblatt et al: J Neuro-Ophthalmol 2016; 36: 280-284 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 0.006 0.085 0.012 0.001 ,0.001 0.02 ± 0.07 22.54 ± 2.6 22.54 ± 2.6 1.92 ± 3.5 71.2 ± 62.7 (6-300) MD, mean deviation; mo, months; SD, standard deviation; VA, visual acuity. 0.03 ± 0.05 24.86 ± 4.7 24.86 ± 4.7 3.6 ± 3.3 43.1 ± 28.0 (8-160) 0.03 ± 0.13 24.17 ± 6.6 24.17 ± 6.6 0.38 ± 3.4 29.9 ± 46.2 (1-228) 0.11 ± 21 25.52 ± 4.2 25.52 ± 4.2 1.24 ± 3.3 46.7 ± 45.8 (1-175) Final VA, mean ± SD, logMAR Change in VA, mean ± SD, logMAR Final MD, mean ± SD Change in MD, mean ± SD Follow-up, mean ± SD (range), mo Switzerland Portugal TABLE 3. Follow-up and outcomes of patients with idiopathic intracranial hypertension Turkey Israel P Original Contribution Rosenblatt et al: J Neuro-Ophthalmol 2016; 36: 280-284 characteristics between the surgically and the nonsurgically treated patients because the samples were too small. Despite significant differences in treatment protocols between medical centers, treatment outcomes were mostly similar. The mean initial VA differed between groups, and despite the different treatment protocols, the final change in VA was the same among all the study groups; all groups improved by the same degree. Furthermore, although the final VA was found to be statistically significantly different between the groups (P = 0.001), it had no clinical significance: the worst VA was 0.11 logMAR (20/25.7), and the best VA was 0.02 logMAR (20/20.9). There are a number of limitations of our study. First, it was retrospective and based on medical records. Some data were either missing or not suitable for comparison. The VF programs used were not identical in all patients, and the statistical analysis refers only to the MD. However, individual patients were followed using the same VF program throughout the treatment period. Second, the study groups were relatively small and unequal, with the Israeli group consisting of 120 patients while the other 3 groups were each smaller, consisting of 33, 36, and 55 patients, respectively. Third, the collection of data was limited to the initial examination and final observation, without any interim data sampling. This precluded trend analysis, and examination of recurrence predictors could not be performed. Finally, although there is good evidence that weight loss is beneficial in the treatment of IIH, and although all patients were counseled regarding weight loss, we did not collect the BMI at the last visit, so we cannot evaluate the importance and implication of the variation of this parameter in the treatment options and final visual outcomes. Our study is unique in comparing diagnosis and treatment of IIH patients in 4 different countries. The importance of this preliminary work is to encourage more cooperation among countries to better understand IIH. We believe that international multicenter prospective studies are needed to determine the potential influence of environmental factors on the development of IIH and to improve the management of this potentially blinding disorder. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. Rosenblatt, A. Klein, and A. Kesler; b. Acquisition of data: A. Rosenblatt, A. Kesler, S. Roemer, F-X. Borruat, D. Meira, M. Silva, F. 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