OCT and Optic Nerve Head Drusen (abstract)

Optic nerve head drusen (ONHD) are deposits of calcium, amino and nucleic acids, and mucopolysaccharides, which may be buried within the optic nerve or lie at the surface of the optic disc.1 These deposits often become calcified over time. Clinically apparent ONHD are estimated to occur in 0.3% of the population; in approximately 75% of cases, ONHD are bilateral.

OPTICAL COHERENCE TOMOGRAPHY AND OPTIC NERVE HEAD DRUSEN Fiona Costello, MD, FRCP Associate Professor, Departments of Clinical Neurosciences and Surgery, University of Calgary Calgary, Alberta, Canada LEARNING OBJECTIVES 1. Identify spectral domain optical coherence tomography (SD-OCT) features of optic nerve head drusen (ONHD) 2. Determine what potential advantages SD-OCT may offer relative to other ancillary tests to facilitate the detection of ONHD 3. Compare SD-OCT findings that differentiate papilledema from pseudo-papilledema secondary to ONHD 4. Highlight advancements in OCT that might improve upon our current understanding of how this technology can be used in the diagnosis and management of ONHD 3. EDI-OCT provides what advantage over conventional OCT methods in the detection of ONHD: a. EDI-OCT has made it possible to visualize structures, including ONHD, 500-800μm deeper than with SD-OCT b. Reduced optic disc drusen diameter correlates with increased sectors of thinned RNFL with EDI-OCT c. EDI-OCT has shown that reduced drusen within the optic canal has been associated with thinner RNFL values d. EDI-OCT provides more patient comfort than SD-OCT KEYWORDS 1. Spectral-Domain OCT 2. Superficial ONHD CME QUESTIONS 1. Name one potential advantage of SD-OCT over standard ancillary tests in the diagnosis of ONHD: a. SD-OCT can help localize non-calcified drusen b. SD-OCT has been reported to demonstrate correlations between ONHD, RNFL thickness, and visual field defects c. SD-OCT is a non-invasive, high resolution ocular imaging technique d. All of the above 2. OCT features that may help distinguish ONDH from papilledema include: a. Thicker nasal RNFL values in cases of ONHD b. Thinner temporal RNFL values in cases of ONHD c. Thicker subretinal hyporeflective space values in cases of ONHD compared to eyes with optic disc edema d. The angling of Bruch's membrane towards the vitreous in cases of papilledema 3. Buried ONHD 4. Enhanced Depth Imaging OCT 5. Swept Source OCT 6. Papilledema 7. Pseudopapilledema INTRODUCTION Optic nerve head drusen (ONHD) are deposits of calcium, amino and nucleic acids, and mucopolysaccharides, which may be buried within the optic nerve or lie at the surface of the optic disc.1 These deposits often become calcified over time. Clinically apparent ONHD are estimated to occur in 0.3% of the population; in approximately 75% of cases, ONHD are bilateral.1 While ONHD may occur in association with several clinical conditions including: retinitis pigmentosa, pseudoxanthoma elasticum, and Alagille syndrome, the majority of affected individuals have no underlying ocular or systemic abnormalities.1 Associated visual field abnormalities are observed in 24%-87% of ONHD cases, and these deficits may progress at variable rates over time.1 Previously, Lee and Zimmerman3 reported a 1.6% per year increase in severity of ONHD-related visual field loss during a 36-month follow up period. While the mechanism(s) of vision loss in ONHD has not been fully elucidated, it has been postulated that mechanical stress 2017 Annual Meeting Syllabus | 229 on structures within the prelaminar scleral canal may lead to retrograde axonal degradation and ganglion cell death.1 Currently there are no treatments available to prevent or ameliorate vision loss caused by ONHD. IDENTIFYING OPTIC NERVE HEAD DRUSEN: THE ROLE OF ANCILLARY TESTING When ONHD are superficial, the diagnosis can readily be made with careful ophthalmoscopic observation. In this setting, the examination will typically reveal optic disc elevation, blurred optic disc margins without obscuration of peripapillary retinal vessels, and a nodular appearance of the optic disc border.4 In clinical practice, these fundus findings have conventionally been relied upon to help distinguish ONHD from papilledema, which, in contrast, is characterized by: opacification with obscuration of retinal vessels, capillary dilation over the optic disc surface, and retinal hemorrhages.4 It has been posited that superficial ONHD become visible in an age-dependent fashion because of drusen-related growth, or alternatively, loss of overlying neural tissue which may have initially obscured visualization.1 In contrast, when ONHD are "buried" and lie relatively to the lamina cribrosa, they can be difficult to detect and differentiate from papilledema by ophthalmoscopy alone.1 In this setting, ancillary testing may be needed to confirm the diagnosis. To this end, B-scan ultrasonography, has been used to identify calcified ONHD, which appear as highly reflective round structures that can also be identified by their acoustic shadowing.1 Ultrasonography also provides some detail regarding the posterior limits and dimensions of ONHD,1 however this testing modality offers relatively poor resolution and provides no information regarding the neuroaxonal integrity of the optic nerve and retinal structures. Fundus auto-fluorescence exploits the auto-fluorescent properties of ONHD, and can be useful for differentiating ONHD from optic disc edema. Yet this technique is relatively insensitive in the detecting deeper, buried drusen.1 Fluorescein angiography uses a fluorescent dye and camera to provide information regarding retinal and choroidal circulation. Pineles and Arnold 4 reported that fluorescein angiography can be effective in differentiating between ONHD and optic disc edema, even in cases of buried optic disc drusen. According to their findings, optic disc edema tends to be associated with diffuse, early fluorescein leakage whereas buried ONHD are characterized by late peripapillary staining, which could be either circumferential (80%) or nodular (20%) in appearance.4 One disadvantage of fluorescein angiography, however, is that it is a relatively invasive procedure that poses some discomfort and potential risk to patients. 230 | North American Neuro-Ophthalmology Society OPTIC NERVE HEAD DRUSEN: WHAT ADVANTAGES DOES OPTICAL COHERENCE TOMOGRAPHY OFFER? Optical coherence tomography (OCT) is a noninvasive ocular imaging technique that can be used to quantify neuroaxonal integrity within the afferent visual pathway. As the "optical analog of ultrasound B-mode imaging" 5 OCT enables visualization and quantification of retinal nerve fiber layer (RNFL) and ganglion layer (GCL) structures. In a recent review, Rebolleda and colleagues 6 reported that OCT measured peripapillary RNFL and GCL values are reduced in ONHD eyes. As ONHD become more superficial, RNFL thickness tends to decrease. Moreover, there is an association between lower OCT-measured RNFL and GCL values, increased numbers of clinically visible ONHD, and worsening VF defects.6 In eyes with buried ONHD, GCL measures are more likely to be abnormal than RNFL values. Thus, GCL analysis may be more useful for detecting early neuroaxonal damage in this context.6 Lee and colleagues7 used SD-OCT to identify features of ONHD that help differentiate these cases of from optic disc edema. They evaluated 45 patients with ONHD, 15 patients with optic disc edema, and 32 normal controls.
 Cases of ONHD revealed the drusen to be focal, hyper-reflective, subretinal masses with discrete margins.7 The RNFL was deformed in cases of ONHD, demonstrating features of pseudo-edema and high reflectance.7 The outer nuclear layer was shown to smoothly cover the drusen, which created a distinctive adjacent hypo-reflective, boot-shaped area.7 These investigators also reported that in cases of ONHD, the RNFL thickness was thinner in the nasal area and thicker in the temporal areas than that in control eyes.7 Moreover there was a negative correlation between the height of drusen and the RNFL thickness in the nasal region.7 These investigators postulated that this finding may occur because sub-retinal drusen are usually located in the nasal area, and displace the RNFL into the superior, inferior, and temporal areas.7 These displaced nerve fibers may, in turn alter the normal distribution of RNFL thickness patterns resulting in relatively thin nasal layers and correspondingly thick superior, inferior, and temporal layers.7 They also hypothesized that the compressive effects of drusen might result in the atrophy of the nasal retinal nerve fibers, whereas increased thickness of other areas might result from the crowding effect caused by the reduced optic disc size they observed in ONHD eyes.7 Recently, Malmqvist and colleagues8 performed a retrospective study involving 149 eyes of 84 ONHD patients (65% female; 76% bilateral ONHD cases) with the objective of comparing the peripapillary RNFL thickness and visual field defects with anatomic location of the drusen (superficial or buried). Visual field defects were seen in 81% of all eyes with a significant difference between superficial (88%) and buried (55%) ONHD cases (p = 0.0004). 8 In this study, OCT- measured RNFL thinning was more pronounced in eyes with superficial ONHD compared with eyes with buried ONHD (p = 0.001).8 Correlation analysis between mean peripapillary RNFL thinning and visual field defects showed worse visual field function was associated with decreased peripapillary RNFL thickness.8 When the investigators stratified ONHD by anatomic location in the optic disc (superficial or buried), a significant correlation between RNFL loss and pattern mean deviation was only seen in the group of eyes with superficial drusen.8 The investigators postulated that the difference in RNFL thinning between superficial and buried ONHD could be that "early" (buried) drusen do not affect the optic nerve head to the same degree as superficial drusen.8 Specifically, they suggested that buried ONHD are less likely to be calcified, and by extension may be less damaging to optic nerve axons.8 From their findings the authors recommended that future studies aimed at quantifying ONHD volume with measures of optic nerve function are needed.8 While SD-OCT has advanced our ability to detect ONHD, the disadvantage of this technology is that as depth increases, resolution decreases. This means that deeper ONHD are often poorly demarcated.1 Recent advances including enhanced depth imaging (EDI-OCT) and swept source OCT (SS-OCT) have made it possible to quantify optic disc drusen dimensions and examine the integrity of neighboring structures in the retina and optic disc. These devices may therefore enhance our understanding of relationships between ONHD, RNFL and GCL loss, and visual field defects among ONHD patients. Specifically, EDI-OCT has made it possible to visualize structures 500-800μm deeper than with SD-OCT. Sato and colleagues 9 demonstrated that EDIOCT is effective in detecting ONHD, obtaining images of the posterior limits of disc drusen, and measuring drusen area. In a prospective comparative cross-sectional study, Merchant and colleagues10 noted that EDI-OCT was able to detect ONHD more frequently than B-scan ultrasonography. In this study superficial ONHD visible on the optic disc surface were identified by both EDI-OCT and B-scan ultrasonography.10 However, in 25 eyes with suspected ONHD, EDI-OCT detected drusen in 17 eyes compared to B-scan which detected drusen in only 7 eyes.10 In the study by Merchant and colleagues,10 ONHD were evident either as signal-poor regions surrounded by short hyper-reflective bands, or as isolated hyper-reflective bands without a signal poor core. EDI-OCT also has the advantage of being able to assess the shape and structure of the drusen; and, has utility in establishing correlations between ONHD and RNFL.1 EDI-OCT has shown a negative correlation between the diameter of disc drusen and the mean RNFL thickness in ONHD eyes.1 A significant positive correlation has been shown between disc drusen diameter and the number of sectors of thinned RNFL. Moreover, increased presence of drusen within the optic canal has been associated with thinner RNFL values in ONHD eyes.1 Finally, EDI-OCT might aid in the detection of early drusen formation, by showing the presence of deep hyper-reflective bands within the optic nerve head.1 Swept Source OCT uses a laser that sweeps across a range of wavelengths to produce an image with a scanning speed of 100,000 Hz at the 1μm wavelength region.1 The SS-OCT light source has a center wavelength of 1,050 nm, yielding approximately 8μm axial resolution. This OCT technique has been shown to significantly improve visualization of the posterior ocular structures compared to conventional OCT techniques.1 Similar to EDI-OCT, SS-OCT has the advantage of providing a complete cross-sectional area of the druse.1 SS-OCT also allows evaluation of drusen-associated RNFL thinning.1 In the aforementioned study by Sato and colleagues, 9 SS-OCT demonstrated ONHD to be visible as ovoid regions of low reflectivity with hyperreflective curvilinear borders. DISTINGUISHING OPTIC NERVE HEAD DRUSEN FROM PAPILLEDEMA The ability to differentiate papilledema from pseudopapilledema caused by ONHD can be challenging, particularly when the degree of optic disc edema is mild.11 Kulkarni and colleagues 12 attempted to define OCT differences in cases of buried ONHD and mild papilledema, but reported no statistically significant differences between the groups. In this study, the ability of 5 clinicians to differentiate buried ONHD from mild papilledema using the OCT images alone was poor, as was the inter-reader agreement.12 Unfortunately, as previously stated, the challenge to using conventional SD-OCT techniques to detect ONHD is that as depth increases, the resolution of the OCT images decreases, leading to poor demarcation of deeper drusen.12 The posterior limits of drusen are also difficult to visualize due to the hyper-reflective anterior surface, which causes shadowing.12 As an alternative Savini and colleagues13 have proposed using the sub-retinal hyporeflective space, which is located between the retinal pigment epithelium and the choriocapillaris, to differentiate cases of papilledema from ONHD.. The subretinal hyporeflective space thickness tends to be greater in eyes with optic disc edema compared to those with ONHD.13 In a previous elegant review, Kardon has highlighted the merits of OCT in the evaluation of patients with papilledema. 11 One OCT-based feature, which provides information about the direction of force vectors at the optic disc in papilledema, is the deformation of Bruch's membrane surrounding the neural canal. This deformation is due to a pressure differential between the retrobulbar optic nerve and vitreous cavity.11 The angling of Bruch's membrane towards the vitreous, can help monitor the force differential over time as the intracranial pressure changes, and may also help to differentiate papilledema from pseudopapilledema.11 EDI-OCT and SS-OCT could potentially provide even greater resolution of deeper structures, such as Bruch's membrane, even in the presence of optic disc edema.11 Going forward, the next step is to map other OCT and fundus-based features in cases of papilledema to a continuous scale of disc volume. 2017 Annual Meeting Syllabus | 231 This will further enhance the ability to differentiate papilledema from other forms of optic disc edema and pseudopapilledema. According to Kardon, 11 this approach will also allow features of digital fundus photographs (including obscuration of optic disc margins, discontinuity of optic disc vessels, and texture of the peripapillary RNFL) to be mapped to OCT disc volume. 11 In this manner, it may be possible to provide a continuous scale software measure of papilledema that can be derived and embedded in teleretinal imaging devices at the site of image capture for immediate diagnosis.11 CONCLUSIONS As OCT technology continues to advance, there may be a means to quantify optic ONHD dimensions, and evaluate the integrity of functionally eloquent structures in the retina and optic nerve. If OCT can enhance our understanding regarding the relationships between optic disc drusen, RNFL loss, and visual field defects, this technology may facilitate longitudinal assessment, and enhance the care of ONHD patients. CME ANSWERS 1. d 2. d 3. a REFERENCES 1. Silverman AL, Tatham AJ, Medeiros FA, Weinreb RN. Assessment of Optic Nerve Head Drusen Using Enhanced Depth Imaging and Swept Source Optical Coherence Tomography. J Neuroophthalmol 2014; 34(2): 198-205 2. Pineles SL, Arnold A. Fluorescein Angiographic Identification of Optic Disc Drusen With and Without Optic Disc Edema. J Neuroophthalmol 2012; 32(1): 17-22 3. Lee AG, Zimmerman MB. The rate of visual field loss in optic nerve head drusen. Am J Ophthalmol. 2005; 139:1062-1066 4. Pineles SL, Arnold A. Fluorescein Angiographic Identification of Optic Disc Drusen With and Without Optic Disc Edema. J Neuroophthalmol 2012; 32(1): 17-22 5. Sakai RE, Feller DJ, Galetta KM, MS, Galetta SL, Balcer LJ. Vision in Multiple Sclerosis: The Story, Structure- Function Correlations, and Models for Neuroprotection. J Neuroophthalmol 2011; 31: 362-373
 6. Rebolleda G, Diez-Alvarez L, Casado A, Sánchez-Sánchez C, de Dompablo E, González-López JJ, Muñoz-Negrete FJ. OCT: New perspectives in neuroophthalmology
. Saudi J Ophthalmol 2015; 29: 9-25 7. Lee KM, Woo SJ, Hwang JM. Differentiation of Optic Nerve Head Drusen and Optic Disc Edema with Spectral-Domain Optical Coherence Tomography. Ophthalmology 2011; 118: 971-977 232 | North American Neuro-Ophthalmology Society 8. Malmqvist L, Wegener M, Sander BA, Hamann S. Peripapillary Retinal Nerve Fiber Layer Thickness Corresponds to Drusen Location and Extent of Visual Field Defects in Superficial and Buried Optic Disc Drusen. J Neuroophthalmol 2016; Journal of Neuro-Ophthalmology 2016; 36: 41-45
 9. Sato T, Mrejen S, Spaide RF. Multimodal imaging of optic disc drusen. Am J Ophthalmol. 2013; 156: 275-282 10. 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 11. Kardon RH. Optical Coherence Tomography in Papilledema: what am I missing? J Neuroophthalmol 2014 Sep; 34 Suppl: S10-7 12. Kulkarni KM, Pasol J, Rosa PR, and Lam BL. Differentiating Mild Papilledema and Buried Optic Nerve Head Drusen Using Spectral Domain Optical Coherence Tomography. Ophthalmology 2014; 121(4): 959-963 13. Savini G, Bellusci C, Carbonelli M, Zanini M, Carelli V, Sadun AA, Barboni P. Detection and quantification of retinal nerve fiber layer thickness in optic disc edema using stratus OCT. Arch Ophthalmol 2006; 124:1111-1117