A field guide to optic disc drusen

(Image credit: AdobeStock/furyon)

This article aims to discuss optic disc drusen (ODD, or pseudopapilledema) in the context of differentiating it from true papilledema. It is not an easy diagnosis to make, even for the most experienced clinicians, but some of the following salient points may be of assistance.

Drusen are a normal clinical finding made up of refractive hyaline-like fatty deposits and protein that are located within the optic nerve head. Known as ODD, optic nerve head drusen, or drusenoid discs, the nomenclature may be different, but they all relate to the same appearance. Incidence is 0.34% to 2.4% in the general population, with Caucasian patients affected more than patients of any other race.¹

ODD may be round or oval, yellow, and classified as buried or visible. A “lumpy-bumpy” appearance can be misleading, especially in a child, where it can mimic a suspect papilledema. Additionally, 60% lie below the surface of the disc, where they are deeply located or buried; these are noncalcified,² and 70% are bilateral.³

Not to be confused with retinal drusen associated with age-related macular degeneration, ODD have a hard surface. This can then lead to anomalous branching of blood vessels, usually noted when a blood vessel is seen deflecting from its original course by deflecting by 90° or bifurcating. The presence of these branched vessels may aid in the detection of ODD. Bifurcation of the blood vessels on the optic nerve head can be a normal physiological finding, but its presence may require more than a cursory glance.

ODD are usually congenital and form early in life, just anterior to the lamina cribrosa. They may change in the early years and are often stable in adulthood. The condition rarely affects anyone under the age of 4, and usually changes from buried to visible as the ODD rise toward the surface of the optic nerve head. The calcification and migration typically occur in patients who are aged approximately 12 years, but it can be seen before the age of 10 in some children. With age, the overlying axons become atrophied and the drusen become exposed and more visible.

Visual signs and symptoms

Most patients are asymptomatic. There may or may not be visual symptoms, of which there are 2 main classifications: transient visual obscurations (TVO) and/or visual field defects. These may or may not be coexisting.

Figures differ between adult and pediatric presentations. TVO occurs in approximately 9% of patients.⁴ An estimated 25% to 70% of patients have visual field defects other than an enlarged blind spot, which can have a gradual onset and be asymptomatic.⁵

Visual field defects are more common than visual symptoms. Field defects are more severe with visible ODD rather than buried ODD. Arcuate visual field defects, enlarged blind spots, nasal steps, and constricted visual field are the most common.⁶

Investigation and imaging

Utilizing multimodal imaging is now classified as being the best practice method for identifying ODD. Fundus examination will have the typical lumpy-bumpy, suspicious disc, which can sometime be quite alarming to the clinician. It is recommended to take a comprehensive history, with special consideration for family history, as there can be a 10-fold risk of ODD if a sibling has been diagnosed.

In an ocular ultrasound, the drusen may be seen pushing into the vitreous cavity or humor. ODD will appear hyperechogenic due to the calcium, whereas a normal optic nerve head will have a hypoechogenic appearance because there will be no calcium present. Fundus autofluorescence can sometimes be helpful in visualizing surface drusen, but it is not very good at showing buried drusen. Instead, it has been superseded by enhanced depth imaging (EDI), considered the optimal method of drusen imaging by the Optic Disc Drusen Society.

Optical coherence tomography (OCT) is helpful in detecting early retinal nerve fiber layer (RNFL) thickening, followed by RNFL thinning as the drusen stabilize. In comparison, papilledema will result in a constant increase in the thickening of the RNFL. OCT can also be predictive of visual field loss.^5-7

While ultrasound and OCT provide excellent mechanism of identification, EDI-OCT provides superior visualization. One study revealed a 100% detection rate of buried ODD through EDI-OCT, compared with 82% by non–EDI-OCT and 41% by ultrasound.⁸ Hyperreflective lines, also known as horizontal hyperreflective lines, may be detected with EDI-OCT and are considered an ODD precursor in children. Hyperreflective lines were found in 3.4% to 12.3% of the normal population.⁹

While it is suitable for imaging papilledema, fluorescein angiography has limitations for ODD detection. Fluorescein angiography reveals early diffuse hyperfluorescence with late leakage on and near the disc in cases of papilledema due to breakage in the blood-retina barrier. With pseudopapilledema this is not visible.

Clinical associations and management

Optic disc drusen can be associated with quite a few ocular conditions. Among the most common are retinitis pigmentosa, nonarteritic anterior ischemic optic neuropathy (NAION), resolved papilledema, Usher syndrome, Noonan syndrome, and angioid streaks.

Among patients with retinitis pigmentosa, ODD occurrence can be up to 15 times higher than in the general population.¹⁰ In a study of younger people who have NAION, ODD were detected in 51% of the study cohort. Patients with NAION and ODD tend to be younger and typically do not have usual vasculopathic risk factors such as hypertension, diabetes, or hyperlipidemia. This supports the hypothesis that ODD may be an independent risk factor for NAION.^11,12

The prevalence of ODD from resolved papilledema is 19%, almost 10 times higher than the general population. The high prevalence of ODD after papilledema has resolved suggests a noncoincidental relationship; therefore, new ODD formation can be a sequela of papilledema.¹³

Rarely, the vascular complications may occur due to ODD, such as flame hemorrhages at the disc (usually upon the superior margin), NAION, and central retinal artery occlusion.

Differential diagnosis from papilloedema

Understanding the difference between ODD (pseudopapilledema) and papilledema is crucial. In 39.5% of patients referred for presumed idiopathic intracranial hypertension (IIH) to neuro-ophthalmologists, the most common errors were inaccurate detection of papilledema following examinations from optometrists, ophthalmologists, neurologists, and general practitioners. This leads to unnecessary adjunct testing, neuroimaging, and, at times, invasive lumbar puncture.¹³

There are 2 direct, succinct questions you could ask patients that would increase your risk of suspicion of papilledema if answered yes. This information may not be volunteered by the patient so you may have to probe. Atypical phenotype presentation represents approximately 10% of papilledema cases. The presentation is not as straightforward. The patient may be asymptomatic at time of presentation, but there is bilateral disc edema present.

1. Do you have a ringing noise in your ear? (Checking for pulsatile tinnitus)
2. Does your vision ever disappear momentarily? (Checking for transient visual obscurations)

Adjunct or ancillary tests may include reverse relative afferent pupillary defect, visual field defect, color vision anomaly, and ocular motility horizontal diplopia at distance.

Figure.Manual segmentation of enhanced images shows healthy patients, those with papilloedema and those with ODD.¹⁴ (Image used with permission of Michaël J.A. Girard, MSc, PhD)

Imaging techniques to differentiate papilledema from ODD

Several different OCT measurements have been postulated to help differentiate ODD/pseudopapilledema from papilledema, such as RNFL thickness, macular ganglion cell–inner plexiform layer thickness, forward displacement of the Bruch membrane, and subretinal hyporeflective spacer. However, none of these has extremely high levels of predictability and therefore cannot be relied upon to distinguish between the 2 conditions.

Only 2 measurements are considered consistently reliable: retinal and choroidal folds and peripapillary wrinkles (FIGURE)¹⁴, as detected by EDI-OCT. Folds in papilledema are biomechanical signs of stress or strain on the optic nerve hypoplasia, induced by IIH, which are not present in ODD. The presence of folds is key to the differential diagnosis between papilledema and ODD. In the Idiopathic Intracranial Hypertension Treatment trial [NCT01003639], folds were found in 73% of patients with papilledema.¹⁵

Take-home messages

There is no treatment required for ODD, as there is currently no effective treatment for patients who have gradual visual field loss associated with ODD. Some past studies have suggested intraocular pressure–lowering medication for the condition, but there is no conclusive evidence to support its efficacy. As such, in your practice, you may come across some patients with ODD who explain that they were taking glaucoma medication eye drops in the past. With pediatric patients, a shorter recall period for routine examinations and visual field testing is recommended.

No papilledema is easy to diagnose using fundoscopy alone. The differential diagnosis between papilledema and psuedopapilledema can give rise to an increased level of false-positive referrals into neuro-ophthalmology. Luckily, EDI-OCT is well suited to distinguish between subtle papilledema and ODD: just look for the hyporeflective core with hyperreflective margin on the superior apex. EDI-OCT is the most conclusive imaging tactic, and remember to be aware of the potential for coexisting ODD and papilledema.

References

1. Baehring JM, Biestek JS. Optic nerve head drusen mimicking papilledema. J Neurooncol. 2005;72(1):47. doi:10.1007/s11060-005-7432-6

2. Auw-Haedrich C, Staubach F, Witschel H. Optic disk drusen. Surv Ophthalmol. 2002;47(6):515-532. doi:10.1016/s0039-6257(02)00357-0

3. Golnik KC. Congenital optic nerve anomalies. Curr Opin Ophthalmol. 1998;9(6):18-26. doi:10.1097/00055735-199812000-00004

4. The patient with decreased vision; classification and management: optic disc drusen. In: American Academy of Ophthalmology. Basic and Clinical Science Course: Neuro-Ophthalmology. 2007-2008:129.

5. Lee KM, Woo SJ, Hwang JM. Factors associated with visual field defects of optic disc drusen. PLoS One. 2018;13(4):e0196001. doi:10.1371/journal.pone.0196001

6. Palmer E, Gale J, Crowston JG, Wells AP. Optic nerve head drusen: an update. Neuroophthalmology. 2018;42(6):367-384.
doi:10.1080/01658107.2018.1444060

7. Ortiz-Toquero S, Muñoz-Negrete FJ, Rebolleda G. Enhanced depth imaging optical coherence tomography technology reveals a significant association between optic nerve drusen anterior displacement and retinal nerve fiber layer thinning over time. J Neuroophthalmol. 2021;41(4):e483-e489. doi:10.1097/WNO.0000000000001103

8. Merchant KY, Su D, Park SC, et al. Enhanced depth imaging optical coherence tomography of optic nerve head drusen. Ophthalmology. 2013;120(7):1409-1414. doi:10.1016/j.ophtha.2012.12.035

9. Malmqvist L, Li XQ, Eckmann CL, et al. Optic disc drusen in children: the Copenhagen Child Cohort 2000 Eye Study. J Neuroophthalmol. 2018;38(2):140-146. doi:10.1097/WNO.0000000000000567

10. Steensberg AH, Schmidt DC, Malmqvist L, et al. Optic disc drusen prevalence in patients with retinitis pigmentosa: a cross-sectional study. J Neuroophthalmol. Published online November 17, 2023. doi:10.1097/WNO.0000000000002038

11. Rueløkke LL, Malmqvist L, Wegener M, Hamann S. Optic disc drusen associated anterior ischemic optic neuropathy: prevalence of comorbidities and vascular risk factors. J Neuroophthalmol. 2020;40(3):356-361. doi:10.1097/WNO.0000000000000885

12. Hamann S, Malmqvist L, Wegener M, et al. Young adults with anterior ischemic optic neuropathy: a multicenter optic disc drusen study. Am J Ophthalmol. 2020;217:174-181. doi:10.1016/j.ajo.2020.03.052

13. 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;40(4):171-180. doi:10.1080/01658107.2016.1198917

14. All about IIH. Idiopathic Intracranial Hypertension UK. https://www.iih.org.uk/section/9/1/all_about_iih_also_known_as_benign_intracranial_hypertension

15. Sibony PA, Kupersmith MJ, Feldon SE, Wang JK, Garvin M; OCT Substudy Group for the NORDIC Idiopathic Intracranial Hypertension Treatment Trial. Retinal and choroidal folds in papilledema. Invest Ophthalmol Vis Sci. 2015;56(10):5670-5680. doi:10.1167/iovs.15-17459

Lorcan Butler, BSc (Hons), MCOptom, Prof Cert Paed Eye Care

e: lorcan.butler@thebraintumourcharity.org

Butler is a dual-trained optometrist and optician in Newtownards, Northern Ireland, and serves as the optical engagement manager at The Brain Tumour Charity in Fleet, England. Butler has no financial disclosures to declare.