Optic Nerve Head and Macular Optical Coherence Tomography Measurements in Papilledema Compared With Pseudopapilledema

Background:To compare macular and optic nerve headoptical coherence tomography (OCT) measurements in mildto moderate papilledema and pseudopapilledema.Methods:One hundred nineteen eyes of 61 patients withmild to moderate papilledema, 84 eyes of 48 patients withpseudopapilledema, and 60 eyes of 60 healthy normalindividuals were enrolled in this cross-sectional study. UsingSpectralis SD-OCT, macular scans with macular ganglioncell-inner plexiform layer (GCIPL) and macular retinal nervefiber layer (RNFL) segmentation were performed and dividedinto 2 regions (inner and outer, with a diameter of 3 and6 mm, respectively); in addition, Bruch membrane opening(BMO) area and peripapillary RNFL thickness were obtained.Results:BMO area was similar in papilledema (1.83 ±0.34 mm2), pseudopapilledema (1.85 ± 0.37 mm2), andcontrols (1.85 ± 0.32 mm2). Average inner region macularGCIPL thickness in the papilledema, pseudopapilledema,and control groups was 87.2 ± 14.4mm, 90.8 ± 6.1mm,and 91.2 ± 9.8mm, respectively (P.0.05). Outer temporalregion macular GCIPL was significantly thinner in the papil-ledema group compared with control group (P= 0.01). Bycontrast, outer inferior and outer nasal macular RNFL sec-tors were significantly thicker in the papilledema group com-pared with control groups (P= 0.01 andP,0.01,respectively). Those measures were not different betweenpseudopapilledema and control eyes.Conclusions:In papilledema eyes, outer temporal regionmacular GCIPL thickness decreased and outer inferior andouter nasal macular RNFL sectors thickness increased compared with the control group. These changes were notobserved in the pseudopapilledema group.

Original Contribution Optic Nerve Head and Macular Optical Coherence Tomography Measurements in Papilledema Compared With Pseudopapilledema Masoud Aghsaei Fard, MD, FICO, Sara Okhravi, MD, Sasan Moghimi, MD, Prem S. Subramanian, MD, PhD Background: To compare macular and optic nerve head optical coherence tomography (OCT) measurements in mild to moderate papilledema and pseudopapilledema. Methods: One hundred nineteen eyes of 61 patients with mild to moderate papilledema, 84 eyes of 48 patients with pseudopapilledema, and 60 eyes of 60 healthy normal individuals were enrolled in this cross-sectional study. Using Spectralis SD-OCT, macular scans with macular ganglion cell-inner plexiform layer (GCIPL) and macular retinal nerve fiber layer (RNFL) segmentation were performed and divided into 2 regions (inner and outer, with a diameter of 3 and 6 mm, respectively); in addition, Bruch membrane opening (BMO) area and peripapillary RNFL thickness were obtained. Results: BMO area was similar in papilledema (1.83 ± 0.34 mm2), pseudopapilledema (1.85 ± 0.37 mm2), and controls (1.85 ± 0.32 mm2). Average inner region macular GCIPL thickness in the papilledema, pseudopapilledema, and control groups was 87.2 ± 14.4 mm, 90.8 ± 6.1 mm, and 91.2 ± 9.8 mm, respectively (P . 0.05). Outer temporal region macular GCIPL was significantly thinner in the papilledema group compared with control group (P = 0.01). By contrast, outer inferior and outer nasal macular RNFL sectors were significantly thicker in the papilledema group compared with control groups (P = 0.01 and P , 0.01, respectively). Those measures were not different between pseudopapilledema and control eyes. Conclusions: In papilledema eyes, outer temporal region macular GCIPL thickness decreased and outer inferior and outer nasal macular RNFL sectors thickness increased Eye Research Center (MAF, SO, SM), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Ophthalmology (SM), University of California, San Francisco, San Francisco, California; and Department of Ophthalmology (PSS), University of Colorado School of Medicine, Aurora, Colorado. Supported in part by a Challenge Grant from Research to Prevent Blindness to the Department of Ophthalmology, University of Colorado School of Medicine. The authors report no conflicts of interest. Address correspondence to Prem S. Subramanian, MD, PhD, Department of Ophthalmology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045; E-mail: prem.subramanian@ ucdenver.edu 28 compared with the control group. These changes were not observed in the pseudopapilledema group. Journal of Neuro-Ophthalmology 2019;39:28-34 doi: 10.1097/WNO.0000000000000641 © 2018 by North American Neuro-Ophthalmology Society T he differentiation of pseudopapilledema caused by congenital optic disc elevation or optic disc drusen from papilledema is of critical importance because papilledema may indicate a life-threatening condition (1). Previously, we have shown that peripapillary total retinal volume is a useful measure to differentiate congenitally elevated optic discs from mild papilledema (2). It has been reported that anomalous optic discs in pseudopapilledema contain axons that are crowded into small scleral canals (1,3) and an abnormally small optic disc has been reported in pseudopapilledema using optic disc photographs (4). Using optical coherence tomography (OCT), imaging of deep optic nerve head (ONH) structures such as Bruch membrane opening (BMO) area might identify the purported differences in ONH morphology between discs with papilledema and pseudopapilledema. In addition, loss of the macular ganglion cell-inner plexiform layer (GCIPL) complex with different patterns has been reported in several optic neuropathies (5). Elevated intracranial pressure (ICP) in papilledema also leads to axoplasmic stasis and subsequent death of the retinal ganglion cell fibers and ganglion cell layer thinning (1) as well as macular region GCIPL thinning (6). This is in contrast to the expected stability in pseudopapilledema, in which thickness of retinal layers remains stable, or a gradual, chronic axonal loss with optic disc drusen. Our study was designed to compare macular GCIPL, macular retinal nerve fiber layer (mRNFL) thickness, and ONH structures including BMO area and peripapillary RNFL Aghsaei Fard et al: J Neuro-Ophthalmol 2019; 39: 28-34 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution thickness in papilledema and pseudopapilledema, with the goal of identifying distinguishing features between the 2 conditions. METHODS This was a cross-sectional study conducted in Farabi Eye Hospital. The study was approved by the local ethics committee of the Tehran University of Medical Science and all investigations adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from each participant after receiving a detailed explanation of the nature and objective of the study. Patients referred to the neuro-ophthalmology clinic between September 2010 and February 2016 suspected of having papilledema or pseudopapilledema were eligible. All patients underwent a comprehensive ophthalmic evaluation with ancillary testing, including visual acuity, intraocular pressure (IOP) measurement, fundus examination, ocular B-scan ultrasound, perimetry using the 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard protocol on the Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA), and spectral domain optical coherence tomography (SD-OCT) (Spectralis, HEYEX software 6.0; Heidelberg Engineering, Heidelberg, Jena, Germany). Additional neuroradiologic studies (brain magnetic resonance imaging and magnetic resonance venography) and lumbar puncture (cerebrospinal fluid pressure measurements) were obtained in most patients. The papilledema group consisted of 56 patients with idiopathic intracranial hypertension (all had lumbar punctures showing ICP of more than 250 mm H2O), 9 patients with intracranial hypertension secondary to cerebral venous sinus thrombosis, and 7 patients with a space occupying lesion. Inclusion criteria for pseudopapilledema (n = 48) were congenital optic disc elevation with stable optic nerve appearance during follow-up, and/or having ICP of less than 250 cm H2O, as described previously (2). Patients with severe (Frisén grade 4-5) papilledema, optic disc drusen visible by ophthalmoscopy or B-scan, chronic papilledema as defined by swelling with pallor and/or macular exudate, and patients with .6 months duration of diagnosed papilledema were excluded from the study. The control group comprised the same age and sex distribution as the papilledema group using frequency matching, with visual acuity better than or equal to 20/ 30, IOP #21 mm Hg, normal optic disc appearance on fundus examination, and no visual field or RNFL defects. In all groups, patients with refractive errors $+6.00 or #26.00 D or more than ±3.00 D astigmatism, a history of ocular surgery (except for uncomplicated cataract surgery), or glaucoma also were excluded. Optical Coherence Tomography Measurements After pupillary dilation, patients underwent imaging with SD-OCT. Three sets of scans were obtained for each eye: Aghsaei Fard et al: J Neuro-Ophthalmol 2019; 39: 28-34 a): macular scan to measure GCIPL and mRNFL thicknesses; b): peripapillary RNFL; and c): ONH enhanced depth imaging (EDI). Peripapillary RNFL thickness was measured using a 3.4-mm circular scan around the optic nerve head, and the thickness values were recorded in 7 sectors: global, superonasal, nasal, inferonasal, inferotemporal, temporal, and superotemporal. For macular scans, 25 horizontal optical coherent tomographic sections were obtained in a 15 · 30° rectangle centered around the fovea. In each B-scan, the boundaries between the individual retinal layers were automatically segmented. Individual layer segmentation correction was made if necessary as published previously (5,7). Excellent repeatability and reproducibility of each of 8 individual retinal layer thickness measurements using Spectralis software was demonstrated in a healthy cohort (8). After retinal layer segmentation, values from ganglion cell and inner plexiform layers were added manually to calculate GCIPL thickness. Macular RNFL thickness also was measured. For both mRNFL and GCIPL thicknesses, 3 circular lines representing 1-, 3-, and 6-mm scan diameters were obtained. Data of 2 regions (inner and outer, with a diameter of 3 and 6 mm, respectively) and 8 sectors (4 each sectors in the inner and outer regions; i.e., inner and outer nasal, temporal, superior, and inferior sectors) were used (Fig. 1) (5,7). We also averaged the inner and outer sectors thicknesses to report the mean outer and inner region thicknesses. For the ONH scan, the EDI-OCT device was set to image a 15 · 15° rectangle centered on the optic disc. This rectangle was divided into approximately 73 sections and each one had 42 OCT frames on average. The BMO was defined as the termination of the Bruch membrane, and BMO area was measured manually. For BMO area measurement, the location of the inner tip of the BMO on B-scans was projected onto SD-OCT en face infrared images and these locations were connected together (Fig. 1) (9). Scans above 20 dB were considered of acceptable quality. Statistical Analysis The distribution of numerical data was tested for normality using the Shapiro-Wilk test. Descriptive statistics were calculated as the mean and SD for normally distributed variables. Categorical variables were compared using the x2 test. Then, we used a linear mixed model to evaluate the BMO area, RNFL thickness, and macular parameters between groups using the Bonferroni correction for multiple comparisons and intereye correlation. Pearson correlation statistic in all groups was used to assess the relationship between the visual field mean deviation and mean inner and outer GCIPL after selecting the right eye of each patient. All other statistical analyses were performed using the SPSS software (IBM Corp, Released 2013, IBM SPSS Statistics for Windows, Version 22.0; IBM Corp, Armonk, NY). Pvalues ,0.05 were considered significant. 29 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Representative spectral domain optical coherence tomography images and measurement techniques used to assess the optic disc, Bruch membrane opening (BMO), and macular area. A. An infrared image of the optic nerve with papilledema used to measure BMO area. Several BMO lines were marked on all optic nerve head raster scans. B. These lines on B-scan were projected onto en face infrared images. Ends of lines were connected and BMO area was measured. In this case, BMO area is 1.75 mm2. Macular ganglion cell (C) and inner plexiform thickness measurements (D). There is a decrease in ganglion cell thickness in the outer temporal ring in this papilledema case (black outline). E and F. Images of the optic nerve with pseudopapilledema used to measure BMO area. Macular ganglion cell (G) and inner plexiform thickness (H) measurements in pseudopapilledema. RESULTS Bruch Membrane Opening Area Measurement One hundred twenty patients met inclusion criteria and were enrolled in our study. Eleven patients in the papilledema group with poor retinal layer segmentation were excluded from data analysis. Therefore, 119 eyes of 61 patients (58 bilateral and 3 unilateral) with mild to moderate papilledema, and 84 eyes of 48 patients (36 bilateral and 12 unilateral cases) with pseudopapilledema were included. Sixty eyes of 60 healthy normal individuals also were analyzed. There were 49 female patients with papilledema, 35 with pseudopapilledema, and 45 in the control group (x2, P = 0.63). Peripapillary RNFL thickness data of 112 eyes, macular GCIPL and RNFL data of 62 eyes, and BMO data of 87 eyes with papilledema were analyzed. Peripapillary RNFL thickness data of 82 eyes, macular GCIPL and RNFL data of 19 eyes, and BMO data of 72 eyes with pseudopapilledema were analyzed. Both optic nerve and macular OCT measurements were reported on all 60 control eyes. Mean age of papilledema and pseudopapilledema patients was 36.7 ± 12 and 40.46 ± 16.3 years, respectively, which were not different from control subjects (41.5 ± 12.5) (P = 0.07 and P = 0.099, respectively). Mean visual acuity was 0.09 ± 0.11 logarithm of the minimum angle of resolution (logMAR), 0.05 ± 0.07 logMAR, and 0.05 ± 0.1 logMAR, in papilledema, pseudopapilledema and control groups, respectively. BMO area was 1.83 ± 0.34 mm2 in patients with papilledema, 1.85 ± 0.37 mm2 in patients with pseudopapilledema, and 1.85 ± 0.32 mm2 in control eyes. A significant difference was not found between pseudopapilledema and papilledema, papilledema vs control, and pseudopapilledema vs controls (all P . 0.99). 30 Peripapillary Retinal Nerve Fiber Layer Thickness Average peripapillary RNFL thickness in the papilledema, pseudopapilledema, and control groups was 171.9 ± 74.6 mm, 114.9 ± 20.3 mm, and 99.2 ± 10 mm, respectively. Average and sectoral peripapillary RNFL thickness was significantly greater in the papilledema group compared with pseudopapilledema and control groups (all P , 0.001). Comparing the pseudopapilledema and control groups, there were apparent differences in peripapillary RNFL thicknesses in the inferonasal and inferotemporal sectors (inferior quadrants) (Table 1). Macular Ganglion Cell-Inner Plexiform Layer Thickness There were no significant differences in sectoral inner macular GCIPL thickness between the papilledema group vs pseudopapilledema group, papilledema group vs control group, and pseudopapilledema group vs Aghsaei Fard et al: J Neuro-Ophthalmol 2019; 39: 28-34 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Mean and SD values for peripapillary retinal nerve fiber layer thickness (mm) in control participants, papilledema, and pseudopapilledema patients Groups Control Pseudopapilledema vs Papilledema 114.9 ± 20.3 151 ± 38.5 99.2 ± 10 131.8 ± 23.1 0.000* 0.000* 0.000* 0.000* 0.24 0.56 129.3 ± 40.5 113.7 ± 25.6 0.000* 0.000* 0.60 88.1 ± 26.7 149.5 ± 39.5 76.5 ± 11.3 117.3 ± 22.5 0.000* 0.000* 0.000* 0.000* 0.95 0.03* 171.4 ± 37.3 137.3 ± 16.8 0.000* 0.000* 0.03* 74.1 ± 20.7 67.4 ± 11.7 0.000* 0.000* Papilledema Pseudopapilledema Average 171.9 ± 74.6 Temporal 215.3 ± 121.7 superior Nasal 188.1 ± 99.1 superior Nasal 146.1 ± 93.8 Nasal 204.6 ± 113.8 inferior Temporal 226.4 ± 113.8 inferior Temporal 122.4 ± 70 Papilledema Pseudopapilledema vs vs Control Control .0.99 *Significant values based on linear mixed model. control group (P = 0.84, 0.22, and .0.99, respectively). However, of the 4 outer macular GCIPL sectors, the outer temporal sector was thinner in the papilledema group compared with control group (P = 0.01) (Table 2). We also evaluated the relationship between macular GCIPL thickness and perimetric results. Automated perimetry revealed mild defects in the papilledema group with average mean deviation of 23.75 ± 2.06 dB. Average mean deviations of the pseudopapilledema and control groups were 21.11 ± 2.52 and 20.52 ± 1.67 dB, respectively. In all studied groups, there was a positive correlation between visual field mean deviation and mean inner (r = 0.29, P , 0.001) and outer GCIPL thicknesses (r = 0.31, P = 0.001). Macular Retinal Nerve Fiber Layer Thickness There were no significant differences in sectoral inner mRNFL thickness between the papilledema group vs pseudopapilledema group, papilledema group vs control group, and pseudopapilledema group vs control group. Of the 4 outer macular RNFL sectors, the outer inferior and outer nasal sectors were significantly thicker in the papilledema group compared with control group (P = 0.01 and P , 0.001) (Table 3). DISCUSSION We have shown that the BMO does not differ among eyes with papilledema, eyes with pseudopapilledema, and TABLE 2. Mean and SD values for macular ganglion cell-inner plexiform layer thickness (mm) in control participants, papilledema, and pseudopapilledema patients Groups Papilledema Pseudopapilledema Mean inner Inner superior Inner inferior Inner nasal Inner temporal Mean outer Outer superior Outer inferior Outer nasal Outer temporal Control Pseudopapilledema vs Papilledema Papilledema vs Control Pseudopapilledema vs Control 87.2 ± 14.4 89.7 ± 15.3 90.8 ± 6.1 94.9 ± 6.4 91.2 ± 9.8 93.3 ± 0.8 0.84 0.59 0.22 0.37 .0.99 .0.99 87.9 ± 15.2 88 ± 13.9 83.3 ± 15.6 90.6 ± 6.7 92.1 ± 9.1 85.7 ± 8.6 92 ± 10.1 92.3 ± 0.4 87.3 ± 10 .0.99 0.81 .0.99 0.20 0.20 0.32 .0.99 .0.99 .0.99 63.1 ± 7.6 61.2 ± 7.8 67.8 ± 11.8 66.6 ± 11.3 65.1 ± 6.1 63.1 ± 6.1 0.51 0.20 0.82 0.79 .0.99 0.71 60.1 ± 7.2 63 ± 13.7 60.9 ± 7.7 .0.99 .0.99 .0.99 67.7 ± 9.6 63 ± 9.8 72.6 ± 11.2 68.9 ± 13.6 67.5 ± 6.9 68.5 ± 7.7 0.57 0.30 .0.99 0.01* 0.40 .0.99 *A significant value based on linear mixed model. Aghsaei Fard et al: J Neuro-Ophthalmol 2019; 39: 28-34 31 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Mean and SD values for macular retinal nerve fiber layer thickness (mm) in control participants, papilledema, and pseudopapilledema patients Groups Papilledema Pseudopapilledema Mean inner 23.8 ± 6.2 Inner 25.6 ± 8.4 superior Inner 27.6 ± 7.9 inferior Inner 23.5 ± 8.1 nasal Inner 18.4 ± 1.8 temporal Mean outer 40 ± 10.3 37.6 ± 10 Outer superior Outer 41.4 ± 10.4 inferior Outer 61.8 ± 22.8 nasal 19 ± 2.9 Outer temporal Control Pseudopapilledema vs Papilledema vs Pseudopapilledema Papilledema Control vs Control 23 ± 3.7 24.7 ± 4.5 21.4 ± 2.1 23 ± 3.8 .0.99 .0.99 0.09 0.09 0.98 .0.99 26.7 ± 5.2 24.3 ± 4 .0.99 0.09 0.73 22.4 ± 5 20.4 ± 1.7 .0.99 0.08 .0.99 18.2 ± 2.2 18.1 ± 2.1 .0.99 .0.99 .0.99 37.3 ± 7.2 38.5 ± 6.8 33.2 ± 4.3 34.5 ± 4.9 .0.99 .0.99 0.002 0.17 0.19 0.21 39.4 ± 9.5 35.7 ± 5.6 .0.99 0.01* 0.31 52.8 ± 14 43.5 ± 6.9 0.38 0.000* 0.25 19.5 ± 3 19.4 ± 1.9 .0.99 .0.99 .0.99 *Significant values based on linear mixed model. controls. In addition, we have demonstrated that mean inner GCIPL sectoral thicknesses were not different between 3 groups, outer temporal region macular GCIPL thickness was decreased in papilledema eyes vs controls, mean inner mRNFL thickness and all its sectoral thicknesses were not different among 3 groups, and outer mRNFL (nasal and inferior) increased in the papilledema, but not pseudopapilledema eyes. In both this report and in a previous study (2), we found that patients with mild to moderate papilledema had a statistically significant increase in mean peripapillary RNFL thickness compared with normal controls and patients with pseudopapilledema, although there remains some overlap in RNFL values between papilledema and pseudopapilledema. Previous studies based on optic disc photographs have suggested that pseudopapilledema may arise from a smaller disc and scleral canal causing mild stasis of axoplasmic flow with secondary enlargement of the peripapillary nerve fibers (1,3,4). However, we found that the BMO area was similar in pseudopapilledema eyes (1.85 ± 0.37 mm2) and control eyes (1.85 ± 0.32 mm2). One study using time-domain OCT reported that eyes with optic disc drusen and those of first-degree relatives of these patients did not have small scleral canals, and in fact both had scleral canal areas significantly larger than controls (10). It seems that the discrepancy between the optic disc size in previous studies and the BMO area in our study could be explained by the fact that the BMO does not always coincide with the optic disc margins seen ophthalmoscopically. Chauhan and Burgoyne 32 (11) found the termination of Bruch membrane (BM), the true landmark for the scleral opening, infrequently colocalized with the visible optic disc margin. Sibony et al (12,13) used a statistical-shape analysis to demonstrate the presence of an inverted-U shape of the BM/retinal pigment epithelium (RPE) in papilledema patients. Another study used a semi-automated approach for the placement of 20 BM/ RPE landmarks to compute a statistical-shape model (14). By contrast, our manual measurement of the BMO area using multiple points from the OCT scan data are simple and although time-consuming, may give more representative data. In addition, we recorded macular GCIPL thickness in 4 inner and 4 outer sectors at 3 and 6 mm diameter, respectively, to explore the pattern of GCIPL loss; the Spectralis software also permitted mRNFL thickness calculation and manual correction of any GCIPL segmentation errors (15). We found that mean inner GCIPL sectoral thicknesses were not different among papilledema, pseudopapilledema, and control eyes. In contrast to our findings, baseline OCT measurements of papilledema in the IIH Treatment Trial using Cirrus OCT showed macular region GCIPL thinning in 7.3% of eyes compared with age-matched controls, and there were correlations between final visual outcomes and GCIPL thickness (6). Eyes that had an initial GCIPL thickness of ,70 mm, or progressive thinning of $10 mm within 2-3 weeks compared with baseline have been found to have poor visual outcomes (16). However, the Cirrus Aghsaei Fard et al: J Neuro-Ophthalmol 2019; 39: 28-34 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution OCT algorithm has segmentation errors with optic disc edema, and individual retinal layer segmentation correction is not possible (6,15). Another of our findings was that outer temporal region macular GCIPL thickness was decreased in papilledema eyes vs controls. Different patterns of GCIPL thinning have been reported in different types of optic neuropathies such as ischemic optic neuropathy and glaucoma (6). Earlier studies have shown that the temporal area in the macula is the most susceptible to glaucomatous changes (17-19). Mwanza et al (20) demonstrated that minimum and inferotemporal GCIPL thicknesses had the best predictive value by ROC analysis for early glaucoma detection. Thus, outer temporal macular GCIPL is affected in both mild to moderate papilledema and early glaucoma. We hypothesize 2 reasons for this shared propensity to affect the outer temporal GCIPL sector. First, both glaucoma and papilledema share a high-pressure gradient across the lamina cribrosa (albeit in opposite directions) that contribute to arrested axoplasmic flow in this region, with damage at the 6 o'clock peripapillary RNFL and its corresponding outer temporal GCIPL (4). Second, visual field loss with principal involvement of the arcuate bundles in the nasal field with preservation presentation of visual acuity is observed in the early stages of both glaucoma and papilledema. Therefore, there are similarities between the optic neuropathy of papilledema and the optic neuropathy of glaucoma (1). Finally, we found that the thicknesses of inferior and nasal quadrants of mRNFL were greater in papilledema compared with control eyes, reflecting adjacent peripapillary nerve fiber layer edema. However, the mean inner mRNFL thicknesses did not differ among papilledema, pseudopapilledema, and control eyes. We believe that peripapillary nerve fiber edema in papilledema extends to the nasal and inferior macular area and causes the increase in outer region mRNFL thickness. Our study has several limitations. We collected macular and ONH OCT measures on most, but not all patients. Intereye correlation is another potential confounder, but we have used linear mixed models to account for this possibility. When correlated measurements from both eyes are available, a simple statistical method is to use information from only one eye, but this approach may not reflect the true extent of the disease, and the number of data points decreases. Therefore, we elected to perform modeling of paired eye data using a mixed-effect regression modeling that provides a framework for analyzing cluster data with multilevel structures (21, 22). In conclusion, we have shown that the BMO area was similar in pseudopapilledema eyes, papilledema eyes, and control eyes. Outer macular region RNFL thicknesses increased in papilledema, but not in pseudopapilledema eyes as compared to control eyes. In contrast to pseudopaAghsaei Fard et al: J Neuro-Ophthalmol 2019; 39: 28-34 pilledema eyes, outer temporal region macular GCIPL thickness seems to decrease in eyes with papilledema eyes. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Fard, Moghimi, Subramanian; b. Acquisition of data: Okhravi, Fard; c. Analysis and interpretation of data: Fard, Okhravi, Moghimi, Subramanian. Category 2: a. Drafting the manuscript: Fard, Okhravi; b. Revising it for intellectual content: Fard, Okhravi, Moghimi, Subramanian. Category 3: a. 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Aghsaei Fard et al: J Neuro-Ophthalmol 2019; 39: 28-34 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.