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

Malmqvist, Lasse MD; Bursztyn, Lulu Msc, MD; Costello, Fiona MD, PhD; Digre, Kathleen MD; Fraser, J. Alexander MD; Fraser, Clare MMed; Katz, Bradley MD, PhD; Lawlor, Mitchell FRANZCO, PhD; Petzold, Axel MD, PhD; Sibony, Patrick MD; Warner, Judith MD; Wegener, Marianne MD; Wong, Sui MD; Hamann, Steffen MD, PhD

doi: 10.1097/WNO.0000000000000585
Original Contribution
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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 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.

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 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.

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.

Address correspondence to Lasse Malmqvist, MD, Department of Ophthalmology, Rigshospitalet, Nordre Ringvej 57, 2600 Glostrup, Denmark; E-mail: lasse.malmqvist.larsen.01@regionh.dk

The authors report no conflicts of interest.

Optic 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 a collaborative consortium of neuro-ophthalmic experts was gathered to develop recommendations for the OCT diagnosis of ODD.

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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 meeting and by further email correspondence.

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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.

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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.

TABLE 1

TABLE 1

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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.

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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.

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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.

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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).

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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.

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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.

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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.

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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.

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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 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.

FIG. 1

FIG. 1

Blood vessels imaged cross-sectionally sometimes mimic ODD but may be recognized by their “figure of eight configuration,” vessel wall reflections and shadowing of underlying 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. 2

FIG. 2

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. 3

FIG. 3

FIG. 4

FIG. 4

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.

FIG. 5

FIG. 5

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.

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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), 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 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. 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.

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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.

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