Title | Peripapillary Retinal Nerve Fiber Layer Thickness Corresponds to Drusen Location and Extent of Visual Field Defects in Superficial and Buried Optic Disc Drusen |
Creator | Lasse Malmqvist, MD; Marianne Wegener, MD; Birgit A. Sander, MSc, PhD; Steffen Hamann, MD, PhD |
Affiliation | Department of Ophthalmology, Glostrup Hospital, Denmark |
Abstract | A 45-year-old woman with ptosis and diplopia was found to have myasthenia gravis (MG) associated with amyloidosis of the thymus gland. Systemic MG is frequently associated with thymomas or thymic hyperplasia but has only once previously been reported in association with amyloidosis of the thymus. This case demonstrates that isolated ocular MG rarely may also be associated with amyloidosis of the thymus. |
Subject | Adolescent; Adult; Older people; Older people, 80 and over; Cross-Sectional Studies; Eye Diseases, Hereditary; Female; Humans; Male; Middle Older people; Nerve Fibers; Optic Disk; Optic Disk Drusen; Optic Nerve Diseases; Retinal Ganglion Cells; Retrospective Studies; Scotoma; Tomography, Optical Coherence; Vision Disorders; Visual Field Tests; Visual Fields |
OCR Text | Show Original Contribution Peripapillary Retinal Nerve Fiber Layer Thickness Corresponds to Drusen Location and Extent of Visual Field Defects in Superficial and Buried Optic Disc Drusen Lasse Malmqvist, MD, Marianne Wegener, MD, Birgit A. Sander, MSc, PhD, Steffen Hamann, MD, PhD Background: Optic disc drusen (ODD) are hyaline deposits located within the optic nerve head. Peripapillary retinal nerve fiber layer (RNFL) thinning is associated with the high prevalence of visual field defects seen in ODD patients. The goal of this study was to investigate the characteristics of patients with ODD and to compare the peripapillary RNFL thickness to the extent of visual field defects and anatomic location (superficial or buried) of ODD. Methods: Retrospective, cross sectional study. Results: A total of 149 eyes of 84 ODD patients were evaluated. Sixty-five percent were female and 76% had bilateral ODD. Of 149 eyes, 109 had superficial ODD and 40 had buried ODD. Peripapillary RNFL thinning was seen in 83.6% of eyes, where optical coherence tomography was performed (n = 61). Eyes with superficial ODD had greater mean peripapillary RNFL thinning (P # 0.0001) and visual field defects (P = 0.002) than eyes with buried ODD. There was a correlation between mean peripapillary RNFL thinning and visual field defects as measured by perimetric mean deviation (R-0.66; P = 0.0001). The most frequent visual field abnormalities were arcuate and partial arcuate defects. Conclusions: Peripapillary RNFL thickness correlates with anatomic location (superficial or buried) of ODD. Frequency and extent of visual field defects corresponded with anatomic location of ODD and peripapillary RNFL thickness, suggesting increased axonal damage in patients with superficial ODD. Journal of Neuro-Ophthalmology 2016;36:41-45 doi: 10.1097/WNO.0000000000000325 © 2015 by North American Neuro-Ophthalmology Society Department of Ophthalmology, Glostrup Hospital, Denmark. Supported by grants from Værn om Synet, Kleinsmed Svend Helge Arvid Schröder og hustrus Fond, and Synoptikfonden, Denmark. The authors report no conflicts of interest. Address correspondence to Lasse Malmqvist, MD, Department of Ophthalmology, Rigshospitalet-Glostrup, Nordre Ringvej 57, 2600 Glostrup, Denmark; E-mail: lasse.malmqvist.larsen.01@regionh.dk Malmqvist et al: J Neuro-Ophthalmol 2016; 36: 41-45 O ptic disc drusen (ODD) are acellular hyaline deposits within the optic nerve head. The condition has been known since the introduction of the ophthalmoscope in the mid-19th century but today, 150 years later, pathogenesis and genetics are still unknown, and there is no available treatment. Superficial ODD are seen as elevated, lumpy irregularities on the anterior most portion of the disc. Buried ODD are located deep in the optic nerve head, sometimes mimicking papilledema (1-3). Buried ODD are not visible by ophthalmoscopy rendering B-scan ultrasonography and optical coherence tomography (OCT), the preferred methods for detection (4). In most cases, ODD are a random finding and a benign condition, but up to 87% have visual field defects (5) and in 20% associated vascular abnormalities such as retinochoroidal venous collaterals and abnormal vascular branching (6-8). OCT is a well-established tool for measuring retinal nerve fiber layer (RNFL) thickness. Peripapillary RNFL thickness changes are believed to be an indicator of anatomic (superficial or buried) ODD location and visual field defects (9). However, conflicting results on RNFL thickness in superficial and buried ODD patients have been reported in previous studies (9-12). Although visual symptomatology, type of visual field defects and quadrant distribution of the defects, and frequency and type of complications have been described in these reports, differences in patient demographics, inclusion criteria, and study methodology make any definitive conclusions uncertain. The aim of our retrospective study was to examine a large patient cohort to compare the peripapillary RNFL thickness and visual field defects with anatomic location (superficial or buried) of ODD. METHODS A Retrospective, cross-sectional study is approved by the Scientific Ethics Committee of the Capital Region, Denmark (H-4, 2013-040). 41 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Patient Selection We reviewed the files of 106 patients, classified by the ICD10 diagnosis code H47.3: "Drusen of the optic disc; pseudopapilledema," who were seen in the neuroophthalmology clinic, Department of Ophthalmology, Glostrup Hospital, Denmark, from January 2009 to October 2014. Inclusion criteria were 1) visible ODD by slitlamp biomicroscopy or B-scan ultrasonography, 2) 18 years or older, and 3) signed informed consent. Twenty-two patients did not meet the inclusion criteria, primarily because of misdiagnosis. ODD visible by slit-lamp biomicroscopy were classified as superficial ODD, whereas ODD not visible by slit-lamp biomicroscopy, but only by B-scan ultrasonography, were classified as buried ODD. In the visual field and RNFL subanalyses, the exclusion criteria were 1) ODD-associated complications that affect visual acuity or visual field, and 2) eye disease unrelated to ODD that affect visual acuity and visual fields. Data Acquisition All patients had a full ophthalmological examination including best-corrected visual acuity, slit-lamp biomicroscopy with fundus lens, and intraocular pressure measurements. Automated perimetry, B-scan ultrasonography, OCT, and fundus photography were assessed when available. Correlation Analysis Between Mean Peripapillary Retinal Nerve Fiber Layer Thinning and Visual Field Defects Visual fields were obtained by automated perimetry (Octopus; Haag-Streit, Switzerland). RNFL thickness was measured using OCT (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany) with analysis of peripapillary scans using specialized software (Heidelberg eye explorer, Version 1.7.0.0; Heidelberg Engineering). A correlation analysis between the peripapillary RNFL thickness and visual field defects was calculated using deviation in average peripapillary RNFL thickness compared with normative database values and perimetric mean deviation (PMD) measured by automated perimetry. neuropathy, 2 with unclassified optic neuropathy, 3 with glaucoma, 2 with amblyopia, 2 with visual fields affected by pituitary tumor, 1 with optic neuritis, and 1 with central retinal vein occlusion. For visual field classification, we used the method described by Keltner et al (14) in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). This classification system showed a high reader agreement of 90% and test- retest reliability of 95%. Visual field defects were categorized into 5 general groups (localized nerve fiber bundle, other, diffuse, enlarged blind spot, and neurologic-like) and 13 categories. The classification was performed independently by experienced neuro-ophthalmologists (S.H., M.W.) who were masked to the clinical data. In case of discordance, the categorization was agreed on jointly by the 2 neuro-ophthalmologists. A supplementary, quantitative subanalysis was performed to assess, which visual field quadrants were most frequently affected by ODD. We ascribed the pattern deviation plot value points in the 4 quadrants according to probability level values: ,0.5% = 10 points, ,1% = 5 points, ,2% = 2 points, and ,5% = 1 point. The total of the value points was calculated in each quadrant, and the distribution of the average points was compared among quadrants. Statistics Baseline characteristics were compared using student t test and x 2 test. When expected count was less than 5, Fisher exact test was used. Peripapillary RNFL thickness was compared between eyes with superficial and buried ODD using unpaired t test. The quadrant subanalysis was tested using analysis of variance with Bonferroni correction. Peripapillary RNFL thickness and visual field PMD were analyzed by parametric correlation analysis confirmed by Spearman nonparametric correlation analysis. Only eyes without ODD-associated complications were included in this subanalysis. The predetermined level of statistical significance for the comparisons was P = 0.05. The statistical analysis was performed using the SAS program for Windows (Version 9.1; SAS Institute, Cary, NC). RESULTS Analysis of Type and Perimetric Distribution of Visual Field Defects Demographics The Collaborative Normal-Tension Glaucoma Study Group reliability criteria were applied for perimetry data. Inclusion criteria were pupil diameter of 2.5 mm or greater, false-positive rate 15% or less, false-negative rate 30% or less, and fixation loss less than 15% (13). Exclusion criteria were MD equal to or worse than 22.0 dB, noncompliance to the reliability criteria, or any concomitant eye disorder that could affect the visual field. These disorders included 7 patients with drusen-associated anterior ischemic optic The files of 84 patients were included in our study. Stratified by anatomic ODD location, 40 eyes had buried ODD and 109 eyes had superficial ODD. More female (100 eyes) than male patients (49 eyes) were included (P = 0.001), with a mean age of 43.5 years ranging from 18 to 83 years (±18.85 years). Mean Snellen best-corrected visual acuity ranged from 20/16 to 20/63 with a mean of 20/20. Seventy-four patients had refractive errors including 48 myopic (65%) and 26 hyperopic (35%) eyes. A total of 42 Malmqvist et al: J Neuro-Ophthalmol 2016; 36: 41-45 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Presenting visual symptoms of patients with ODD Superficial ODD (n = 43) Buried ODD (n = 24) P Value 24 (55.8%) 12 (27.9%) 1 (2.3%) 4 (9.3%) 0 (0%) 7 (16.3%) 5 (11.6%) 10 (41.7%) 5 (20.8%) 0 (0%) 0 (0%) 1 (4.17%) 3 (12.5%) 2 (8.3%) 0.27 0.52 1.00 0.29 0.36 1.00 0.71 Visual symptoms Blurring of vision Change in color perception Flickering Obscurations Glasses "not good enough" Affected visual field ODD, optic disc drusen. 76.2% had bilateral ODD. Patients with buried ODD were significantly younger than patients with superficial ODD (35.4 and 45.8 years, respectively, P = 0.0028). Gender, bilaterality, visual acuity, and refractive errors did not differ between the 2 groups. Presenting Visual Symptoms A total of 67 patients were included in this analysis. Four patients were excluded because of lack of historical information, and 13 were excluded because of concomitant eye disease. Presenting symptoms was reported by 50.8%, mostly as blurring of vision (Table 1). Subjective visual field defects were only noted by a minority of patients, and mostly by those with superficial ODD. When stratified in superficial and buried ODD, the reported subjective visual symptoms did not differ significantly between the 2 groups. Visual Field Defects and Peripapillary Retinal Nerve Fiber Layer Thickness With Regard to Anatomic Optic Disc Drusen Location A normal visual field was defined as a MD equal or better than 22.0 dB. Of the 149 eyes, 18 were excluded because of concomitant eye disease. In total, 82 eyes were included in the visual field defect analysis. In RNFL analysis, 57 patients with eligible OCT data were included. In Table 2, visual field defects and peripapillary RNFL thickness were compared in eyes with superficial and buried ODD. Visual field defects were seen in 80.5% of all eyes with a significant difference between superficial (88.3%) and buried (54.6%) ODD (P = 0.0004). MD was significantly lower in eyes with superficial ODD compared with buried ODD (P , 0.0001). Peripapillary RNFL thinning was significantly more pronounced in eyes with superficial ODD compared with eyes with buried ODD (P = 0.001), and the peripapillary RNFL thickness was significantly thinner in the group of eyes with superficial ODD (P = 0.001). Type and Quadrant Distribution of Visual Field Defects in Optic Disc Drusen Patients A total of 66 eyes were included in this analysis. Each had a MD ,22.0 dB and met the collaborative NormalTension Glaucoma Study Group reliability criteria. In Table 3, the visual field defects were classified into types and perimetric quadrant location. The most common visual field defects were localized nerve fiber bundle defects, either arcuate (21.2%) or partial arcuate defects (18.2%). The superonasal and inferonasal quadrants were prone to harbor the most frequent and severe defects compared with the temporal quadrants (P . 0.0001). Visual Field Mean Deviation as a Function of Peripapillary Retinal Nerve Fiber Layer Thickness Fifty-five eyes without current or previous comorbidity known to cause visual field defects, and with available OCT and automated perimetry, were included in this analysis. Correlation analysis between mean peripapillary RNFL thinning and visual field defects as measured by MD showed a worse MD with decreasing peripapillary RNFL thickness TABLE 2. Visual field defects and peripapillary RNFL thickness according to anatomic ODD location Visual field defects PMD (db) Peripapillary RNFL thinning Peripapillary RNFL thickness (mm) Superficial ODD (n = 60) Buried ODD (n = 22) P Value 53 (88.3%) 28.45 (26.8 to 210.07) 12 (54.6%) 23.38 (21.83 to 24.93) 0.0004 0.0006 Superficial ODD (n = 39) Buried ODD (n = 18) P Value 10 (55.6%) 92.94 (89.24 to 96.65) 0.001 0.001 37 (94.9%) 66.03 (60.7 to 71.35) ODD, optic disc drusen; PMD, perimetric mean deviation; RNFL, retinal nerve fiber layer. Malmqvist et al: J Neuro-Ophthalmol 2016; 36: 41-45 43 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Type and quadrant distribution of visual field defects in ODD patients Visual field defect types (frequency) Arcuate Partial arcuate Partial arcuate/enlarged blind spot Widespread Nasal step Superior depression/enlarged blind spot Arcuate/widespread Distribution of visual field defects 14 12 7 5 4 4 4 (21.2%) (18.2%) (10.6%) (7.7%) (6.1%) (6.1%) (6.1%) ODD, optic disc drusen. ([R 20.66; P = 0.0001] [Fig. 1]). Adjusting for correlated eyes in mixed model analysis, we found similar results (P , 0.0001). Stratifying ODD by anatomic location in the optic disc (superficial or buried), a significant correlation between RNFL loss and PMD was only seen in the group of eyes with superficial ODD (R 20.67; P , 0.0001). DISCUSSION In this study, peripapillary RNFL thickness was significantly decreased in patients with superficial ODD compared with patients with buried ODD. This finding is in agreement with some previously published reports (9,11) but not others (10,12). One explanation for the difference in RNFL thinning between superficial and buried ODD could be that "early" buried ODD do not affect the optic nerve head to the same degree as superficial ODD. The exterior of the buried ODD is known to be less calcified and thereby less damaging to optic nerve axons (1). Also, progression in size from buried to superficial ODD might lead to greater axonal damage (15). We found that fewer patients with buried ODD experienced visual field defects compared with those with superficial ODD. Possibly, as buried ODD progress to a more superficial location, axonal damage results in RNFL thinning causing visual field loss. Another possibility is that ODD becomes more visible because of progressive RNFL thinning. Loss of RNFL leads to development of visual field defects. To fully understand the pathophysiology behind ODD, studies that quantitatively correlate ODD volume and location with optic nerve function are needed. With a superficial location of ODD, alterations in retinal blood flow might be expected. Abegao Pinto et al (16) reported significantly lower systolic and diastolic blood flow FIG. 1. Visual field MD as a function of retinal nerve fiber layer (RNFL) thickness. MD, mean deviation. 44 Malmqvist et al: J Neuro-Ophthalmol 2016; 36: 41-45 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution velocities in the central retinal artery of patients with ODD compared with healthy individuals, suggesting a direct druseninduced external compression of the retinal vessels. Impaired blood flow to the peripapillary retina in a patient with ODD has been proposed to be responsible for retinal ischemia and stimulating the growth of new blood vessels resulting in a subretinal neovascular membrane (17). More research investigating blood flow patterns in patients with buried and superficial ODD are required to establish the pathophysiological role of RNFL loss and visual field defects in these individuals. A major limitation of our study was that it was retrospective. Although the files of 106 patients were reviewed, smaller and varying cohort sizes, especially in the subanalyses, were unavoidable because of concomitant eye disease, and lack of OCT or perimetry data. The examinations were not performed by the same physicians and with the same examination techniques. Presenting symptoms were assessed from hospital records and not from specific questionnaires, thereby relying on the quality of medical history taking in individual cases. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: L. Malmqvist, S. Hamann, M. Wegener, and B. Sander; b. Acquisition of data: L. Malmqvist, S. Hamann, and M. Wegener; c. Analysis and interpretation of data: L. Malmqvist, S. Hamann, and M. Wegener. Category 2: a. Drafting the manuscript: L. Malmqvist; b. Revising it for intellectual content: L. Malmqvist, S. Hamann, M. Wegener, and B. Sander. Category 3: a. Final approval of the completed manuscript: L. Malmqvist, S. Hamann, M. Wegener, and B. Sander. REFERENCES 1. Sahin A, Cingu AK, Ari S, Cinar Y, Caca I. Bilateral optic disc drusen mimicking papilledema. J Clin Neurol. 2012;8:151-154. Malmqvist et al: J Neuro-Ophthalmol 2016; 36: 41-45 2. Arbabi EM, Fearnley TE, Carrim ZI. Drusen and the misleading optic disc. Pract Neurol. 2010;10:27-30. 3. Fong CY, Williams C, Pople IK, Jardine PE. Optic disc drusen masquerading as papilloedema. Arch Dis Child. 2010;95:629. 4. Slotnick S, Sherman J. 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Date | 2016-03 |
Language | eng |
Format | application/pdf |
Type | Text |
Publication Type | Journal Article |
Collection | Neuro-ophthalmology Virtual Education Library: NOVEL http://NOVEL.utah.edu |
Publisher | Lippincott, Williams & Wilkins |
Holding Institution | Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E SLC, UT 84112-5890 |
Rights Management | © North American Neuro-Ophthalmology Society |
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Setname | ehsl_novel_jno |
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Reference URL | https://collections.lib.utah.edu/ark:/87278/s6z936wk |