The Optic Disc Drusen Studies Consortium Recommendations for Diagnosis of Optic Disc Drusen Using Optical Coherence Tomography

Making an accurate diagnosis of optic disc drusen (ODD) is important as part of the work-up for possible life-threatening optic disc edema. It also is important to follow the slowly progressive visual field defects many patients with ODD experience. The introduction of enhanced depth imaging optical coherence tomography (EDI-OCT) has improved the visualization of more deeply buried ODD. There is, however, no consensus regarding the diagnosis of ODD using OCT. The purpose of this study was to develop a consensus recommendation for diagnosing ODD using OCT. The members of the Optic Disc Drusen Studies (ODDS) Consortium are either fellowship trained neuro-ophthalmologists with an interest in ODD, or researchers with an interest in ODD. Four standardization steps were performed by the consortium members with a focus on both image acquisition and diagnosis of ODD. Based on prior knowledge and experiences from the standardization steps, the ODDS Consortium reached a consensus regarding OCT acquisition and diagnosis of ODD. The recommendations from the ODDS Consortium include scanning protocol, data selection, data analysis, and nomenclature. The ODDS Consortium recommendations are important in the process of establishing a reliable and consistent diagnosis of ODD using OCT for both clinicians and researchers.

Original Contribution The Optic Disc Drusen Studies Consortium Recommendations for Diagnosis of Optic Disc Drusen Using Optical Coherence Tomography Lasse Malmqvist, MD, Lulu Bursztyn, Msc, MD, Fiona Costello, MD, PhD, Kathleen Digre, MD, J. Alexander Fraser, MD, Clare Fraser, MMed, Bradley Katz, MD, PhD, Mitchell Lawlor, FRANZCO, PhD, Axel Petzold, MD, PhD, Patrick Sibony, MD, Judith Warner, MD, Marianne Wegener, MD, Sui Wong, MD, Steffen Hamann, MD, PhD Background: Making an accurate diagnosis of optic disc drusen (ODD) is important as part of the work-up for possible life-threatening optic disc edema. It also is important to follow the slowly progressive visual field defects many patients with ODD experience. The introduction of enhanced depth imaging optical coherence tomography (EDI-OCT) has improved the visualization of more deeply buried ODD. There is, however, no consensus regarding the diagnosis of ODD using OCT. The purpose of this study was to develop a consensus recommendation for diagnosing ODD using OCT. Methods: The members of the Optic Disc Drusen Studies (ODDS) Consortium are either fellowship trained neuroophthalmologists with an interest in ODD, or researchers with an interest in ODD. Four standardization steps were performed by the consortium members with a focus on both image acquisition and diagnosis of ODD. Results: Based on prior knowledge and experiences from the standardization steps, the ODDS Consortium reached a consensus regarding OCT acquisition and diagnosis of ODD. The recommendations from the ODDS Consortium Department of Ophthalmology (LM, MW, SH), Rigshospitalet, University of Copenhagen, Denmark; Department of Ophthalmology (LB, AF), Western University, London, Ontario, Canada; Departments of Clinical Neurosciences and Surgery (FC), University of Calgary, Calgary, Canada; John A. Moran Eye Centre (KD, BK, JW), University of Utah, Salt Lake City, Utah; Department of Clinical Neurological Sciences (AF), Western University, London, Ontario, Canada; Save Sight Institute (CF), University of Sydney, New South Wales, Australia; Sydney Eye Hospital (ML), Sydney, New South Wales, Australia; Department of Neurology (AP, SW), Moorfields Eye Hospital, London, United Kingdom; Neuro-ophthalmology Expertise Centre (AP, SW), VUmc, Amsterdam, the Netherlands; and Department of Ophthalmology (PS), State University of New York at Stony Brook, Stony Brook, New York. The authors report no conflicts of interest. Address correspondence to Lasse Malmqvist, MD, Department of Ophthalmology, Rigshospitalet, Nordre Ringvej 57, 2600 Glostrup, Denmark; E-mail: [e-mail] Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 include scanning protocol, data selection, data analysis, and nomenclature. Conclusions: The ODDS Consortium recommendations are important in the process of establishing a reliable and consistent diagnosis of ODD using OCT for both clinicians and researchers. Journal of Neuro-Ophthalmology 2018;38:299-307 doi: 10.1097/WNO.0000000000000585 © 2017 by North American Neuro-Ophthalmology Society O ptic disc drusen (ODD) are predominantly calcified deposits in the optic nerve head with an estimated prevalence of 2.4% (1). The condition is generally benign, with rare complications such as anterior ischemic optic neuropathy (2,3) and retinal vascular occlusions (4,5). Confusion can arise because the frequently observed protrusion of the optic disc and blurring of the optic disc margin can be mistaken for optic disc swelling (6-8). Separating ODD from other causes of optic disc elevation such as papilledema is clinically important, as the latter is a manifestation of increased intracranial pressure. Accurate diagnosis poses a challenge, as buried ODD can be difficult to detect. Enhanced depth imaging optical coherence tomography (EDI-OCT) has proven to be more reliable in ODD diagnosis than B-scan ultrasound (9), which previously had been considered the gold standard (10). The technique behind EDI-OCT was first described in 2008 by Spaide et al (11). The resulting visualization and high resolution of the deeper layers of the optic nerve head has made it possible to better detect and diagnose ODD. To date, however, there are conflicting descriptions of ODD morphology, and no agreement of a scanning protocol to best visualize ODD using OCT. Therefore 299 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution a collaborative consortium of neuro-ophthalmic experts was gathered to develop recommendations for the OCT diagnosis of ODD. METHODS The Optic Disc Drusen Studies Consortium The Optic Disc Drusen Studies (ODDS) Consortium was established in 2015 as an international research alliance and in 2016 it was added to the European Reference Network of eye diseases. The aim of the ODDS Consortium is to provide an international forum for ODD research to elucidate the mechanisms of ODD-related visual loss, and thereby develop potential treatment options. At the North American Neuro-Ophthalmology Society meeting in 2016, agreement was made among members of the consortium to develop consensus recommendations for the diagnosis of ODD. ODD morphology and a scanning protocol were discussed at this correspondence. meeting and by further email Patient Selection A total of 38 patients diagnosed with ODD were included. The patients had been diagnosed at the Department of Ophthalmology, Rigshospitalet, Denmark, between November 2015 and January 2016. All patients had been diagnosed using slit-lamp ophthalmoscopy, B-scan sonography or OCT. Only patients 18 years of age or older and without other ocular pathology visible on OCT were included. Patient selection and data acquisition have been described previously (12). In our study, we exclusively assessed EDI-OCT data. Further, EDI-OCT scans from healthy volunteers were obtained for use as control subjects. Examination of the patients had been approved by the local Scientific Ethics Committee (H-4, 2013-040) and conducted under the principles of the Helsinki Declaration. Written informed consent was obtained from all patients before inclusion. TABLE 1. OCT protocol for diagnosis of optic disc drusen Before scanning Acquisition Dense optic nerve head scan Radial optic nerve head scan Peripapillary scan Macula scan Autofluorescence Ensure optimal conditions a. Dilate pupils before examination b. Measure corneal curvature and refraction for later transverse magnification adjustment (to ensure accurate measurements)* Visualize deeper structures a. Use SD-OCT in EDI mode b. If no SD-OCT is available, adjust the distance from the OCT apparatus to the eye to get an inverted view of the optic nerve head for better visualization of deeper structures c. Type in corneal curvature value and refraction in the operator system* Identification, quantification and classification of ODD a. Use EDI mode or invert scan b. Select high-resolution acquisition if possible c. Center a scan area of only 15 · 10° over the optic disc d. Scan with 97 sections in that area (30 mm between each scan) e. Average at least 30 frames f. Perform the volume scan in both horizontal and vertical directions Assessment of scleral canal size a. Use EDI mode or invert scan b. Select 20° 6-line radial scan (star pattern scan) c. Center scan at optic disc Evaluation of RNFL thickness a. Deselect EDI mode (if on) b. Select 12° peripapillary scan (circle scan) c. Center scan at optic disc Exclude macular pathology a. Deselect EDI mode (if on) b. Center a scan area of 20 · 20° over macula. c. Scan with at least 25 sections (240 mm between each scan) d. Average at least 9 frames Identification of autofluorescence positive ODD a. Center the scan at the optic disc b. Average 100 frames *Only applicable when using Heidelberg OCT. EDI, enhanced depth imaging; OCT, optical coherence tomography; ODD, optic disc drusen; RNFL, retinal nerve fiber layer; SD-OCT, spectral domain optical coherence tomography. 300 Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Enhanced Depth Imaging Optical Coherence Tomography EDI-OCT (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany) was obtained in all patients using a preliminary ODDS Consortium ODD scanning protocol (Table 1). All scans were obtained by the same experienced operator. The scanning procedure included a dense horizontal and vertical high resolution EDI-OCT scan of the optic nerve head. The scans were assessed and selected by the writing committee for the individual exercises using specialized software (Heidelberg Eye Explorer, version 1.9.10.0 and version 1.9.13.0; Heidelberg Engineering). Single B-scans were exported as individual image files, while volume scans were exported as E2E files. Enhanced Depth Imaging Optical Coherence Tomography: Developing a Process to Identify Optic Disc Drusen A preliminary recommendation for ODD diagnosis and grading based on various discussions was developed by the writing committee and circulated together with the standardization steps. The scans from 1 patient with ODD were excluded due to disagreement in the diagnosis, resulting in inclusion of 74 scans with ODD. As grading of the scans was very time consuming, the first 3 steps included only a sampling of different representative scans from the master group of 74 scans. Step 1: Consensus Approach to Identify Known ODD on EDI-OCT Images Eight researchers participated in this step. A total of 22 EDI-OCT images, all with ODD, were included. The level of difficulty in diagnosing ODD varied among the images. The researchers were instructed to comment on localization, size and number of ODD and comment how they interpreted the image. Based on the replies, an updated preliminary recommendation to diagnose ODD was circulated among the researchers. Step 2: Detection of the Absence or Presence of ODD on EDI-OCT Scans Eight researchers participated in this step. A total of 20 EDI-OCT scans were included. The scans were a mix of eyes with and without ODD. The researchers were instructed to report presence or absence of ODD and to comment on the findings. FIG. 1. A. An isolated ODD is present nasally (arrow). B. With fundus autofluroscence, the visible ODD is detected nasally (white arrow). Larger and more diffuse signals correspond to larger and deeper ODD (red arrows). Another isolated ODD was detected on OCT B-scan and is seen on autofluroscence (yellow arrow) but is not visible on fundus photography. C. With en face infrared image, the green square represents scan area and green horizontal line shows scan direction and level. A visible ODD (white arrow) is seen corresponding to the visible ODD seen in (A) and (B). D. OCT B-scan with green line corresponding to the horizontal green line in (C) showing the visible ODD (white arrow) corresponding to the one detected (white arrow) in (A, B, C). Another ODD (yellow arrow) is seen corresponding to one detected (yellow arrow) in (B), as are other deeper ODD (red arrows). Blue arrows indicate blood vessels. OCT, optical coherence tomography; ODD, optic disc drusen. Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 301 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Step 3: Grading the Size and Anatomic Location of ODD on EDI-OCT Scans Eight researchers participated in this step. A total of 10 scans were included. All scans were from eyes with known ODD. The researchers were instructed to grade ODD according to size and anatomic location above or below the level of Bruch's membrane (superficial or deep). Step 4: Combining the Knowledge A total of 74 EDI-OCT scans were included. The scans were from eyes with ODD. The researchers were instructed to grade the scans according to size, structure, and anatomic location of ODD. The researchers graded the same scans a second time, with a minimum of 2 weeks between the assessments, to determine intraindividual and interindividual variability. The anonymization and order of the scans was different between the 2 assessments. Ten researchers completed the first grading and 8 researchers completed the second grading. Two researchers did not have the time to complete second grading. Development of the Optic Disc Drusen Studies Recommendations The preliminary version of the ODDS recommendations for diagnosing ODD was a synthesis process, based on the results, comments and discussions from the 4 ODD standardization steps. EDI-OCT findings were further compared with histopathological specimens from the literature (13,14). The writing committee generated a version of the protocol that was sent to all ODDS Consortium members. This protocol was later discussed, edited, and approved by consensus. RESULTS A total of 16 out of 74 eyes included in the grading had exclusively buried ODD (no visible ODD on ophthalmoscopy). However, 51 out of 58 eyes diagnosed with superficial ODD also had 1 or more buried ODD, and a broad variability in anatomic ODD location in patients diagnosed with visible ODD was found. In the 16 scans with exclusively buried ODD, the OCT morphology of ODD was indistinguishable from the morphology of visible ODD, reassuring us that these deeper structures were also ODD. Recommended Optical Coherence Tomography Protocol for Diagnosing Optic Disc Drusen The recommended ODDS Consortium OCT protocol for diagnosis of ODD is seen in Table 1. The protocol is comprehensive but is designed to diagnose ODD with the best possible sensitivity and specificity. Furthermore, the protocol allows analysis of retinal and optic nerve head morphology for research purposes. Optic Disc Drusen Studies Recommendation for Diagnosing Optic Disc Drusen Based on the steps and discussions, a consensus regarding ODD morphology was reached. The morphology was confirmed in several cases where isolated autofluorescence FIG. 2. En face infrared view (A) and OCT scan (B) with green square delineating scan area and green horizontal line showing scan directions and level. Asterisks indicate vessels in cross-section. White arrowheads show vessels recorded in an oblique angle while arrows indicate vessels imaged longitudinally recognized by the trilayer profile. A layer hypercellular ODD is present at the level of Bruch's membrane opening. C. Magnified view of "figure of eight" blood vessel configuration. OCT, optical coherence tomography; ODD, optic disc drusen. 302 Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution or visible ODD on OCT en face view corresponded to underlying ODD visualized on OCT (Fig. 1). The OCT appearance of confirmed superficial ODD was extrapolated to identify buried ODD that could not be identified clinically. The ODDS Consortium defined ODD as hyporeflective structures with a full or partial hyperreflective margin. The hyperreflective margin is often most prominent superiorly, and can be difficult to detect. Blood vessels imaged cross-sectionally sometimes mimic ODD but may be recognized by their "figure of eight configuration," vessel wall reflections and shadowing of underly- ing optic nerve head tissue. Vessels imaged along the vessels in longitudinal direction demonstrate a trilayer profile with decreased intravascular reflectivity. Vessels imaged in more oblique planes often have a hyperdense "head" without visible "figure of eight configuration" but with underlying shadowing (Fig. 2). Furthermore, because our recommended OCT protocol allows one to "scroll" through parallel OCT slices to determine the 3D nature of optic nerve head structures, a review of several adjacent OCT slices can reveal the long tubular nature of a blood vessel, as opposed to the discrete "lump-like" nature of an ODD. FIG. 3. En face infrared and EDI-OCT images in a patient with ODD with pseudopapilledema (A, B) and in a patient with ODD without pseudopapilledema (C). Green square represents scan area and green lines are the location of the B-scan. A. PHOMS is seen temporally (white arrow). The patient has optic disc protrusion caused by optic disc drusen. B. The PHOMS (red overlay) surrounds a large portion of the optic disc causing blurred margins. C. Optic nerve head scan in a patient without blurred disc margins. No PHOMS is visible and there is no disc protrusion. Asterisks indicate ODD. Red arrows indicate blood vessels. Yellow arrows indicate optic disc drusen conglomerates. EDI-OCT, enhanced depth imaging optical coherence tomography; ODD, optic disc drusen; PHOMS, peripapillary hyperreflective ovoid mass-like structures. Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 303 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution A peripapillary hyperreflective ovoid mass-like structure (PHOMS) has been described in patients with ODD (15-20). Some arguably have asserted that these represent a precursor or variant of ODD (21). We observed these structures in 28 out of 38 patients with ODD (Fig. 3). The histopathological origin of PHOMS in ODD is unknown but there are several features that appear to be inconsistent with our understanding of ODD: 1) unlike ODD, they are hyperreflective without a sharp outer margin or hyporeflective core; 2) they often lie external to and surrounding large parts of the disc corresponding to funduscopically recognized pseudopapilledema; 3) they do not autofluoresce; 4) they are not visible on B-scan ultrasound despite their superficial location; 5) this OCT finding can be seen in patients with papilledema without ODD (14); 6) the histopathology of papilledema suggests that PHOMS might correspond to the lateral bulging or herniation of distended axons into the peripapillary retina (Fig. 4). Until or unless there is histopathological evidence to the contrary PHOMS should be excluded as a criterion for the OCT diagnosis of ODD. FIG. 4. Comparison of OCT and histopathologic morphology of PHOMS. (A) Enhanced depth imaging OCT of a 28-year-old patient with ODD showing a PHOMS (white arrow). (B) A similar PHOMS (white arrow) in a 35-year-old patient with idiopathic intracranial hypertension with the same morphological characteristics as the structure seen in the patient with ODD. A shadow from an overlaying vessel is traversing the structure. (C) Histopathologic section of another patient with papilledema showing lateral bulging (white arrows) of nerve fibers corresponding to PHOMS seen by OCT. (D) When section is stained by Cajal method the course of the peripheral bundle is compressed until at the level above Bruch membrane where it forms the mass of the lateral bulge. (E) Histopathologic section of a patient with ODD showing lateral bulging (black arrow) of nerve fibers corresponding to PHOMS seen in eyes with ODD using OCT. OCT, optical coherence tomography; ODD, optic disc drusen; PHOMS, peripapillary hyperreflective ovoid mass-like structures. Portions reprinted with permission from (13) and (14). 304 Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 5. ODD morphology on enhanced depth imaging optical coherence tomography. ODD are seen as signal-poor structures with a partial hyperreflective margin. Internal reflectivity represents the fusion of 2 ODD. Hyperreflective horizontal lines might be early ODD or, in this case because of the deep location, signal from the lamina cribrosa. PHOMS circumscribe the disc and are not ODD. White asterisks indicate blood vessels. Red asterisks indicate ODD. ODD, optic disc drusen; PHOMS, peripapillary hyperreflective ovoid mass-like structures. The ODDS Consortium recommendation for diagnosing ODD using OCT is seen in Figure 5. As described previously, ODD always have a signal-poor, hyporeflective core. Without a signal-poor core other pathologies should be considered. ODD are often but not always seen with hyperreflective margins, most prominent superiorly. Sometimes collections of several smaller ODD coalesce to form ODD conglomerates that present with patchy internal reflectivity within a larger hyporeflective area (Fig. 3). Most likely, fragments of calcified margin cause the internal reflectivity from the many ODD that coalesce. Hyperreflective horizontal lines are sometimes found in eyes with ODD or in otherwise healthy eyes in patients with unilateral ODD, and might possibly reflect early ODD changes. DISCUSSION The goal of the ODDS Consortium is to establish a reliable and consistent diagnosis of ODD using OCT for both clinicians and researchers. Better detection of ODD using OCT might, in time, improve differentiation between buried ODD and mild papilledema, but currently OCT requires further study to make it as the sole means of differentiation. The distinguishing OCT features between buried ODD and papilledema have been widely investigated (15,16,20,22-25), Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 with some studies focusing on retinal nerve fiber layer (RNFL) thickness differences (15,16,20,23,24) and others on a subretinal hyporeflective space (22-24). The use of RNFL thickness to differentiate between the 2 was found to be clinically unreliable (16). This is supported by studies finding normal or increased RNFL thickness in patients with buried ODD (26). The use of the subretinal hyporeflective space to differentiate between the 2 is based on older OCT technology, which had limited penetrance. With newer OCT modalities such as EDI-OCT, there is no longer a subretinal hyporeflective space, but instead the entire optic nerve head is visible down to lamina cribrosa. This suggests that the previously described subretinal hyporeflective space is likely an imaging artifact, and should not be relied on to differentiate cases of ODD from papilledema. The ODDS Consortium reached a consensus to define ODD as hyporeflective structures with a full or partial hyperreflective margin. This is in agreement with most studies assessing ODD morphology using OCT (9,27-30). Some studies, however, have described ODD as hyperreflective structures with no hyporeflective core (17,20,31) similar to what we, in the ODDS Consortium label PHOMS. These contradictory descriptions of ODD morphology using OCT have resulted in diagnostic confusion (32). After thoroughly reviewing and discussing the issues, the ODDS Consortium, finds that there is no substantial evidence to diagnose PHOMS as ODD. In fact 305 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution there is histopathological evidence that PHOMS are lateral bulges of retinal nerve fibers (Fig. 4). However, there is a need to study PHOMS longitudinally to better understand how to classify these structures. Unless other evidence becomes available, we recommend not to diagnose these structures as ODD. Another point of confusion is the hyperreflective horizontal lines often found in patients with ODD. Merchant et al (9) have suggested that the hyperreflective bands may be a sign of nascent ODD. This is supported in a study by Ghassibi et al (28). Including these isolated bands in the definition of ODD resulted in an ODD prevalence of 14.6% among 130 clinically normal subjects (28). This prevalence is several times higher than ever reported and should be interpreted with caution. As it is still unclear whether isolated hyperreflective bands are ODD, we recommend not diagnosing the hyperreflective horizontal lines as ODD until further evidence from longitudinal OCT studies emerges. The ODDS Consortium recommendations hopefully will help researchers and clinicians to diagnose ODD. The recommendations are based on the individual experiences of the involved researchers, detailed study of the literature, 4 sets of ODD standardization steps, and discussions by the ODDS Consortium. There are several limitations to this report. Our recommendations are based on a selection of relevant studies but not on systematic reviews of the literature. These recommendations might change as new evidence becomes available. The recommendations are based on the currently available OCT technology. Although we are able to visualize the optic nerve head down to lamina cribrosa there are still artifacts, "noise", and shadowing from overlying ODD and protruding optic discs, which provide challenges in interpretation. Even with an agreement on ODD morphology using OCT, buried ODD are still difficult to detect reliably. Differentiating buried ODD from papilledema in some cases can be challenging. The absence of ODD on OCT does not entirely rule out the diagnosis nor does it support the diagnosis of papilledema. In such cases, other modalities are needed. These include fundus autofluorescence, B-scan ultrasonography, and other clinical and OCT signs of pathological disc edema such as peripapillary wrinkles and folds and alteration is the orientation of the peripapillary retinal pigment epithelium/Bruch's membrane layers (33,34). Future improvements in OCT technology will likely provide visualization of deeper ocular structures in higher resolution without shadowing and other imaging artifacts. We regard our recommendations as a preliminary, but an important step towards improving the diagnosis of ODD. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: L. Malmqvist, L. Bursztyn, F. Costello, K. Digre, J. A. Fraser, C. Fraser, B. Katz, M. Lawlor, A. Petzold, P. Sibony, J. Warner, M. Wegener, S. Wong, S. Hamann; b. Acquisition of data: L. Malmqvist, S. Hamann; c. Analysis and interpretation of data: L. Malmqvist, L. Bursztyn, F. Costello, K. 306 Digre, J. A. Fraser, C. Fraser, B. Katz, M. Lawlor, A. Petzold, P. Sibony, J. Warner, M. Wegener, S. Wong, S. Hamann. Category 2: a. Drafting the manuscript: L. Malmqvist, S. Hamann; b. Revising it for intellectual content: L. Malmqvist, L. Bursztyn, F. Costello, K. Digre, J. A. Fraser, C. Fraser, B. Katz, M. Lawlor, A. Petzold, P. Sibony, J. Warner, M. Wegener, S. Wong, S. Hamann. Category 3: a. Final approval of the completed manuscript: L. Malmqvist, L. Bursztyn, F. Costello, K. Digre, J. A. Fraser, C. Fraser, B. Katz, M. Lawlor, A. Petzold, P. Sibony, J. Warner, M. Wegener, S. Wong, S. Hamann. ACKNOWLEDGMENTS This study was supported by Fight for Sight, Denmark, Synoptik-Fonden, and in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY, to the Department of Ophthalmology & Visual Sciences, University of Utah. Collaborators: Nitza Goldenberg-Cohen, MD, Alison Crum, MD, Ruth Huna-Baron, MD, Hanna Leiba, MD, Hadas Stiebel-Kalish, MD, on behalf of the ODDS Consortium. REFERENCES 1. Friedman AH, Gartner S, Modi SS. Drusen of the optic disc. A retrospective study in cadaver eyes. Br J Ophthalmol. 1975;59:413-421. 2. Purvin V, King R, Kawasaki A, Yee R. Anterior ischemic optic neuropathy in eyes with optic disc drusen. Arch Ophthalmol. 2004;122:48-53. 3. Nanji AA, Klein KS, Pelak VS, Repka MX. Nonarteritic anterior ischemic optic neuropathy in a child with optic disk drusen. J AAPOS. 2012;16:207-209. 4. Green WR, Chan CC, Hutchins GM, Terry JM. Central retinal vein occlusion: a prospective histopathologic study of 29 eyes in 28 cases. Retina. 1981;1:27-55. 5. Newsom RS, Trew DR, Leonard TJ. Bilateral buried optic nerve drusen presenting with central retinal artery occlusion at high altitude. Eye (Lond). 1995;9:806-808. 6. Braun A, Doniger SJ. Point-of-care ultrasonography for the identification of 2 children with optic disc drusen mimicking papilledema. Pediatr Emerg Care. 2014;30:505-507. 7. Sahin A, Cingu AK, Ari S, Cinar Y, Caca I. Bilateral optic disc drusen mimicking papilledema. J Clin Neurol. 2012;8:151-154. 8. Rott D, Leibowitz D. Optic nerve head drusen mimicking papilledema and malignant hypertension. Eur J Intern Med. 2009;20:e112-e113. 9. Merchant KY, Su D, Park SC, Qayum S, Banik R, Liebmann JM, Ritch R. Enhanced depth imaging optical coherence tomography of optic nerve head drusen. Ophthalmology. 2013;120:1409-1414. 10. Kurz-Levin MM, Landau K. A comparison of imaging techniques for diagnosing drusen of the optic nerve head. Arch Ophthalmol. 1999;117:1045-1049. 11. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146:496-500. 12. Malmqvist L, Lindberg ASW, Dahl VA, Jørgensen TM, Hamann S. Quantitatively measured anatomic location and volume of optic disc drusen: an enhanced depth imaging optical coherence tomography study. Invest Ophthalmol Vis Sci. 2017;58:2491-2497. 13. Tso MO. Pathology and pathogenesis of drusen of the optic nervehead. Ophthalmology. 1981;88:1066-1080. 14. Paton L, Holmes G. The pathology of pailloedema: a historical study of sixty yes. Brain. 1911;33:389-432. 15. Lee KM, Woo SJ, Hwang JM. Differentiation of optic nerve head drusen and optic disc edema with spectral-domain Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution 16. 17. 18. 19. 20. 21. 22. 23. 24. optical coherence tomography. Ophthalmology. 2011;118:971-977. Kulkarni KM, Pasol J, Rosa PR, Lam BL. Differentiating mild papilledema and buried optic nerve head drusen using spectral domain optical coherence tomography. Ophthalmology. 2014;121:959-963. Lee KM, Hwang JM, Woo SJ. Optic disc drusen associated with optic nerve tumors. Optom Vis Sci. 2015;92:S67-S75. Lee KM, Woo SJ. Fundus autofluorescence in the buried optic disc drusen: optical coherence tomography findings. Can J Ophthalmol. 2017;52:e52-e53. Gili P, Flores-Rodriguez P, Yanguela J, Orduna-Azcona J, MartinRios MD. Sensitivity and specificity of monochromatic photography of the ocular fundus in differentiating optic nerve head drusen and optic disc oedema: optic disc drusen and oedema. Graefes Arch Clin Exp Ophthalmol. 2013;251:923- 928. Bassi ST, Mohana KP. Optical coherence tomography in papilledema and pseudopapilledema with and without optic nerve head drusen. Indian J Ophthalmol. 2014;62:1146- 1151. Traber GL, Weber KP, Sabah M, Keane PA, Plant GT. Enhanced depth imaging optical coherence tomography of optic nerve head drusen: a comparison of cases with and without visual field loss. Ophthalmology. 2017;124:66-73. Johnson LN, Diehl ML, Hamm CW, Sommerville DN, Petroski GF. Differentiating optic disc edema from optic nerve head drusen on optical coherence tomography. Arch Ophthalmol. 2009;127:45-49. Flores-Rodriguez P, Gili P, Martin-Rios MD. Sensitivity and specificity of time-domain and spectral-domain optical coherence tomography in differentiating optic nerve head drusen and optic disc oedema. Ophthalmic Physiol Opt. 2012;32:213-221. Sarac O, Tasci YY, Gurdal C, Can I. Differentiation of optic disc edema from optic nerve head drusen with spectral-domain Malmqvist et al: J Neuro-Ophthalmol 2018; 38: 299-307 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. optical coherence tomography. J Neuroophthalmol. 2012;32:207-211. Katz BJ, Crum AV, Digre KB, Warner JEA. Optic disc edema and optic nerve head drusen. J Neuroophthalmol. 2013;33:204- 205. Katz BJ, Pomerantz HD. Visual field defects and retinal nerve fiber layer defects are uncommon in patients with buried optic nerve drusen. J Invest Med. 2005;53:S398. Sato T, Mrejen S, Spaide RF. Multimodal imaging of optic disc drusen. Am J Ophthalmol. 2013;156:275-282.e271. Ghassibi MP, Chien JL, Abumasmah RK, Liebmann JM, Ritch R, Park SC. Optic nerve head drusen prevalence and associated factors in clinically normal subjects measured using optical coherence tomography. Ophthalmology. 2017;124:320-325. Slotnick S, Sherman J. Buried disc drusen have hypo-reflective appearance on SD-OCT. Optom Vis Sci. 2012;89:E704-E708. Yi K, Mujat M, Sun W, Burnes D, Latina MA, Lin DT, Deschler DG, Rubin PA, Park BH, de Boer JF, Chen TC. Imaging of optic nerve head drusen: improvements with spectral domain optical coherence tomography. J Glaucoma. 2009;18:373-378. Lee KM, Woo SJ, Hwang JM. Morphologic characteristics of optic nerve head drusen on spectral-domain optical coherence tomography. Am J Ophthalmol. 2013;155:1139-1147.e1131. Slotnick S, Sherman J. Disc drusen. Ophthalmology. 2012; 119:652; author reply 652-653 e651. Sibony P, Kupersmith MJ, Honkanen R, Rohlf FJ, Torab-Parhiz A. Effects of lowering cerebrospinal fluid pressure on the shape of the peripapillary retina in intracranial hypertension. Invest Ophthalmol Vis Sci. 2014;55:8223-8231. Kupersmith MJ, Sibony P, Mandel G, Durbin M, Kardon RH. Optical coherence tomography of the swollen optic nerve head: deformation of the peripapillary retinal pigment epithelium layer in papilledema. Invest Ophthalmol Vis Sci. 2011;52:6558-6564. 307 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.