Imaging to differentiate disc drusen from papilledema

When a 24-year-old female with moderate headaches and a body mass index (BMI) of 40 is sitting in your chair, the optic nerve head evaluation is the moment of truth. The presence of latent hyperopia may not be enough to quiet your concern if you note bilateral optic nerve head elevation and an absent spontaneous retinal venous pulsation (SVP). If you can provide yourself with physical evidence of optic disc drusen as the cause, unnecessary tests and referrals may be avoided, and the sense of urgency eliminated.

Optic nerve head drusen are commonly seen during the dilated fundus exam, occurring in 2 percent to 4 percent of the population,^1,2 but given their perceived benign nature and lack of management options, drusen are most notable for the diagnostic dilemma they can create. According to a histological study of 1713 eyes with disc drusen, 54 percent caused elevated optic discs.³ This not only highlights that many cases will lead doctors down a rabbit hole of expensive and invasive testing to rule out a brain mass but also how many cases are out there that ODs are not noticing at all.

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Review natural history

While there is some debate regarding their natural history, it is agreed that disc drusen, buried and physically invisible in early stages, are made up of acellular, calcified deposits of nucleic acids and mucopolysacharides. It is also well-established that disc drusen occur in genetically predisposed individuals—who might otherwise be at risk for damage to optic nerve head tissues—from conditions such as small scleral canals. These deposits are known to occur anterior to the lamina cribosa and can make their way to a more anterior position over the years, displacing and damaging adjacent tissues, subsequently disrupting axonal transport.^2,4

During childhood, disc drusen are uncalcified and often missed or difficult to diagnose. When pronounced, these optic nerves can paint the picture of papilledema. With a child in the chair and a concerned parent as well, the optometrist’s confidence in the latest technology can be a game changer in this tedious situation. In later adulthood, the condition tends to stabilize with the most progression and possible loss of visual field occurring during adolescence. Experts agree that the progressive clinical visibility of disc drusen into adolescence is likely due to a combination of growing size and/or number of the deposits, anterior migration of the deposits, and normal age-related retinal nerve fiber layer (RNFL) thinning superficial to the deposits.^2,4

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FIGURE 1. Natural history of drusen

Review of tools for differentiation

Because disc drusen are bilateral most of the time, and because many cases of drusen cause elevated discs,³ bilateral cases of suspiciously elevated optic discs should always be differentiated from disc drusen.

While buried, or when the condition is mild, a firm diagnosis of disc drusen often requires the assistance of advanced imaging. However, once the condition becomes more clinically obvious with age, the diagnosis is more clear and technology may not be needed at all.

Given the potential urgency of an elevated optic disc, the optometrist who suspects disc drusen should always ask and answer two questions:

– Can it be ruled out that papilledema (bilateral disc edema with an etiology of increased intracranial pressure) is present?

– Can disc drusen be confirmed?

Utilization of each of the imaging modalities discussed below will be addressed with this approach.

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B-scan ultrasonography

Can it be ruled out that papilledema is present?

The diameter of the scleral canal just posterior to the optic disc can be measured and approximated using an ultrasound, providing insight to the anatomy and potential vulnerability to the optic nerve.

Clinical literature suggests taking this measurement at 3 mm posterior to the optic disc. Scleral canals greater than 5 mm in diameter at this location should prompt further investigation for increased intracranial pressure (ICP).^5,6

A scleral canal narrower than 3 mm, on the other hand, may be suggestive of an anatomically crowded optic disc.

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Can disc drusen be confirmed?

B-scan ultrasonography has long been considered the standard approach for confirming a diagnosis of disc drusen with its ability to detect subtle hyperreflections at the disc,when the visual “noise” (gain measured in decibels) is reduced.

Figure 2 demonstrate an eye with optic disc drusen.

Figure 2. A: The ultrasound is set to a gain of 55 dB. A bright white hyperreflection is noted consistent with the optic disc, along with an accompanying spike in the A-scan below. B: With the gain reduced to 15 dB, the visibility of the hyperreflectivity is increased. If with the gain reduced, both the hyperreflectivty and A-scan spike remain, the results are consistent with optic disc drusen.

Figure 3. A: Disc topography is non-uniform, like a jagged mountain range, consistent with optic disc drusen, whereas (B) the disc has smooth, uniform elevation, like a hill, consistent with disc edema.

Figure 4. A: Disc topography is non-uniform, consistent with optic disc drusen. The globe itself is seen to be slightly concave, as is expected. B: The disc has smooth, uniform elevation, consistent with edema. The globe has a convex shape due to scleral flattening secondary to increased ICP. In addition, end of Bruch’s membrane at the temporal edge of the disc appears subtly upturned, as its position remains intact relative to the anterior bowing of the adjacent RPE.

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Optical coherence tomography

Spectral domain OCT (SD-OCT) can also be useful in determining presence of drusen and also in monitoring related structural damage to the inner retinal layers.

Can it be ruled out that papilledema is present?

Advanced visualization of optic disc topography can be somewhat subjective; however, is nevertheless often useful in correlation of data. Carefully consider other etiologies to a non-uniform elevation, such as superficial disc vasculature, which can mimic drusen.

High-definition raster scans using enhanced depth imaging (EDI) can produce images of both disc topography and also the deeper retinal layers, including Bruch’s membrane. Using a longer scan (9 mm), the peripapillary retinal pigment epithelium (RPE) and therefore contour of the globe can be evaluated.⁷

SD-OCT with EDI allows for the highest sensitivity near the inner sclera and can be utilized clinically for improved visibility in many other clinical conditions occurring in the deeper retinal layers and choroid, including choroidal nevi, central serous retinopathy, and age-related macular degeneration (AMD).

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TABLE 1: Suggested OCT protocol

Can disc drusen be confirmed?

SD-OCT with EDI can detect disc drusen structure and location, allowing it to be a strong differentiator for drusen versus papilledema. Some have reported a higher detection rate than with B-scan.^2,8,9

High-definition raster scans using EDI can produce images of the deeper optic nerve head where the drusen occur. Drusen are visualized as signal-poor areas anterior to the lamina cribosa, whose borders (most easily appreciated anteriorly) are hyperreflective. Smaller, individual drusen, or larger clusters may be present.

Of note, disc drusen can appear similarly as blood vessels on the OCT; however, blood vessels are often perfectly oval shaped and tend to create more shadowing beneath. Furthermore, the adjacent enface image of any B-scan on OCT can be referenced for anatomical consistency of suspected findings.^2,8,9

In addition, the RNFL thickness report can be useful in management of disease progression and structural loss. Based on histopathological studies, RNFL thickening is often present with large, deeply positioned drusen, while thinning is present with drusen of the same size but a less deep position.³ Progressive RNFL thinning which stabilizes later in adulthood, along with the disc drusen position and size, is expected.

Not as often clinically noted, on the other hand, acute change in the condition and disease activity may actually cause RNFL thickening. This of course can create further confusion in a cloudy diagnostic picture.^3,9

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Figure 5. A high-definition radial scan centered over the disc is taken using the EDI setting, allowing for higher resolution of deeper structures. The highlighted B-scan image shows evidence of buried optic disc drusen hyporeflective cores, and hyperreflective anterior margins.

Fundus autofluorescence

Lastly, FAF can be utilized to detect the presence of drusen. In contrast to B-scan and OCT, FAF does not offer information specific to the presence or absence of papilledema. It does, however, have the potential to provide physical evidence of disc drusen. FAF uses an extremely bright light flash to capture evidence of fluorescence tissues. While lipofuscion is its common target, indicating RPE disruption, disc drusen themselves will hyperfluoresce when superficial enough. Unfortunately, the deeply buried, and/or most subtle of cases are when the need for confirmation is greatest and also when FAF is least likely to deliver a positive result.¹¹

Table 2 summarizes the clinical tools that can be utilized in both the exam room and with specialty imaging equipment if differentiating disc drusen from other causes of a bilaterally elevated discs.

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TABLE 2: Clinical tools to differentiate disc drusen

Figure 6. Both images below are of optic nerves with disc drusen confirmed with both B-scan and OCT. A: Hyperfluorescence noted on FAF in large, advanced drusen. B: Negative FAF in a case of very subtle, small, and deep disc drusen.

Not always so benign

While ODs are relieved to determine that elevated discs are in fact disc drusen (versus the scary and often urgent alternative), it is important to bear in mind when discussing the condition with the patient and planning management that drusen are not entirely benign.

As disc drusen expand and move anteriorly, unfortunately there comes a higher risk of subsequent overlying RNFL damage along with visual field loss. Frequency of visual field defects varies based on study; however, most recently defects were reported to occur in approximately half of patients with confirmed disc drusen. Defects range from enlarged blind spots to nasal, arcuate or partial arcuate, consistent with RNFL defects, and can impeded visual function in advanced cases, as seen in Figure 7.¹²

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Figure 7. Advanced visual field loss due to disc drusen. A: Superior arcuate defect. B: Concentric narrowing of field.

Disc drusen may be associated with other clinical findings, highlighting their impact of anatomical structures. Vascular changes associated with the disc include disc and adjacent retinal hemorrhages, typically flame-shaped. Nonarteritic anterior ischemic optic neuropathy (NAION), retinal artery occlusions, and deeper choroidal neovascular membranes have also been reported. Disc drusen are thought to crowd the axonal fibers, leading to vascular compression.^1,12,13 In patients who have optic nerve head tumors, disc drusen are more prevalent. In this case, tumor compression of optic nerve fibers may promote disc drusen formation.¹⁵

It is suggested, given their predilection to occur together, that disc drusen and papilledema may in fact be associated, reminding the clinician that multiple diagnoses can be present. Even in the most clear pictures of drusen, papilledema may still need to be ruled out.

While the relationship is unclear, it is suggested that in these patients who have suffered from an increase in intracranial pressure (ICP), and therefore mechanical obstruction and ischemia leading to eventual axoplasmic stasis, there is impaired axoplasmic metabolism and therefore a risk for drusen development. Or, could it be the other way around in which case the disc drusen cause crowding at the optic nerve, creating a vulnerability to disc edema?¹⁶

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Treatment options

Multiple treatment options for disc drusen have been explored; however, unfortunately we are left with little to none when it comes to preventing vision loss.

The possible benefit of decreasing intraocular pressure (IOP) has long been debated, but is perhaps the most commonly recommended attempt at preventing RNFL damage. Various studies demonstrate conflicting evidence regarding the benefit of hypotensive measures, ranging from increasing retinal ganglion cell function and stabilization of RNFL thickness with a possible delay in optic neuropathy to no association.^2,17,18 Reports of treatment with vasoactive therapy such as pentoxifylline as well as neuroprotective measures are anecdotal but show some promise.^2,19 Further investigation is clearly needed.

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References

1. Auw-Haedrich C, Flemming S, Heinrich W. Optic disk drusen. Surv Ophthalmol. 2002 Nov-Dec;47(6):515-532.

2. Hamann S, Malmqvist L, Costello F. Optic disc drusen: understanding an old problem from a new perspective. Acta Ophthalmol. 2018 Nov;96(7):673-684.

3. Skougaard M, Heegaard S, Malmqvist L, Hamann S. Prevalence and histopathological signatures of optic disc drusen based on microscopy of 1713 enucleated eyes. Acta Ophthalmol. 2020 Mar;98(2):195-200.

4. Malmqvist L, Lund-Andersen H, Hamann S. Long-term evolution of superficial optic disc drusen. Acta Ophthalmol. 2017 Jun;95(4):352-356.

5. Kimberly HH, Shah S, Marill K, Noble V. Correlation of optic nerve sheath diameter with direct measurement of intracranial pressure. Acad Emerg Med. 2008 Feb;15(2):201-204.

6. Stone MB. Ultrasound diagnosis of papilledema and increased intracranial pressure in pseudotumor cerebri. Am J Emerg Med. 2009 Mar;27(3):376.e1–376.e2.

7. 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 Aug 22;52(9):6558-64.

8. Malmqvist L, Bursztyn L, Costello F, Digre K, et al. The optic disc drusen studies consortium recommendations for diagnosis of optic disc drusen using optical coherence tomography. J Neuroophthalmol. 2018 Sep;38(3):299-307.

9. 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 Jun;34(2):198-205.

10. Gaier ED, Rizzo 3rd JF, Miller JB, Cestari DM. Focal capillary dropout associated with optic disc drusen using optical coherence tomographic angiography. J Neuroophthalmol. 2017 Dec;37(4):405-410.

11. Loft FC, Malmqvist L, Wessel Lindberg AS, Hamann S.The influence of volume and anatomic location of optic disc drusen on the sensitivity of autofluorescence. J Neuroophthalmol. 2019 Mar;39(1):23-27.

12. Lee KM, Woo SJ, Hwang JM. Factors associated with visual field defects of optic disc drusen. PLoS One. 2018 Apr 30;13(4):e0196001.

13. Purvin V, King R, Kawasaki A, Yee R. Anterior ischemic optic neuropathy in eyes with optic disc drusen. Arch Ophthalmol. 2004 Jan;122(1):48–53.

14. Lee KM, Hwang JM, Woo SJ. Hemorrhagic complications of optic nerve head drusen on spectral domain optical coherence tomography. Retina. 2014 Jun;34(6):1142-1148.

15. Lee KM, Hwang JM, Woo SJ. Optic disc drusen associated with optic nerve tumors. Optom Vis Sci. 2015 Apr;92(4 Suppl 1):S67-75.

16. Birnbaum FA, Johnson GM, Johnson LN, Jun B, Machan JT. Increased prevalence of optic disc drusen after papilloedema from idiopathic intracranial hypertension: on the possible formation of optic disc drusen. Neuroophthalmology. 2016 Jul 1;40(4):171-180.

17. Pojda-Wilczek D, Wycisło-Gawron P. The effect of a decrease in intraocular pressure on optic nerve function in patients with optic nerve drusen. Ophthalmic Res. 2019;61(3):153-158.

18. Nolan KW, Lee MS, Jalalizadeh RA, Firl KC, Van Stavern GP, McClelland CM. Optic Nerve Head Drusen: The relationship between intraocular pressure and optic nerve structure and function. J Neuroophthalmol. 2018 Jun;38(2):147-150.

19. Cybulska-Heinrich AK, Mozaffarieh M, Flammer J. Ginkgo biloba: an adjuvant therapy for progressive normal and high tension glaucoma. Mol Vis. 2012;18:390-402.