A field guide to optic disc drusen

This article aims to discuss optic disc drusen (ODD, or pseudopapilloedema) in the context of differentiating it from true papilloedema. It is not an easy diagnosis to make, even for the most experienced clinicians, but hopefully 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 (ONHD) or drusenoid discs, the nomenclature may be different but they all relate to the same appearance. The incidence is 0.34% to 2.4% in the general population, with Caucasian patients affected more than any other races.¹

ODD may be round or oval, yellow, and classified into buried or visible. A lumpy-bumpy appearance can be misleading, especially in a child, where it mimics or masquerades as a suspected papilloedema (Figure). Additionally, 60% of ODD lie buried below the surface of the disc, where they are deeply located; these are non-calcified² and 70% are bilateral.³

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

Key: GCL, ganglion cell layer; IPL, inner plexiform layer; LC, lamina cribrosa; ODD, optic disc drusen; ONH, optic nerve head; RNFL, retinal nerve fibre layer; RPE, retinal pigment epithelium.

Not to be confused with retinal drusen associated with age-related macular degeneration, the ODD have a hard surface. This can then lead to anomalous branching of blood vessels, usually seen 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 the 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 up towards the surface of the optic nerve head. The calcification and migration typically occur in patients who are around 12 years of age, 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 & symptoms

Most patients will be asymptomatic. There may or may not be visual symptoms of two main classifications: transient visual obscurations (TVO) and/or visual field defects. These symptoms may or may not be coexisting.

Figures do differ between adult and paediatric presentations.TVO occurs in around 9% of patients. It is estimated that 25% to 70% of patients have visual field defects other than an enlarged blind spot, which can have very gradual onset and be totally asymptomatic.⁴

Visual field defects are much 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.⁵

Investigation and imaging

Utilising 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 sometimes be quite alarming to the clinician. It is recommended to take a comprehensive history, with special consideration for family history, as there does tend to 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/humour. An ODD will appear hyperechogenic due to the calcium, whereas a normal optic nerve head will be a hypoechogenic appearance because there will be no calcium present. Fundus autofluorescence can sometimes be helpful in visualising surface drusen, but 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 fibre layer (RNFL) thickening, followed by RNFL thinning as the drusen stabilise. In comparison, papilloedema will result in a constant increase in the thickening of the RNFL.

OCT can also be predictive of visual field loss.^4-6 While ultrasound and OCT provide excellent mechanism of identification, EDI-OCT provides superior visualisation. One study revealed a 100% detection rate of buried ODD through EDI-OCT, compared with 82% by non-EDI-OCT and 41% by ultrasound.⁷ Hyper-reflective lines, also known as horizontal hyper-reflective lines, may be detected with EDI-OCT and are considered an ODD precursor in children. Hyper-reflective lines were found in 3.4% to 12.3% of in the normal population.⁸

While it is suitable for imaging papilloedema, fluorescein angiography has limitations for ODD detection. Fluorescein angiography will reveal early diffuse hyperfluorescence with late leakage on and near the disc in cases of papilloedema, due to breakage in the blood-retina barrier. This is not visible in pseudopapilloedema.

Clinical associations and management

ODD can be associated with several ocular conditions. Among the most common are retinitis pigmentosa, non-arteritic anterior ischemic optic neuropathy (NAION), resolved papilloedema, 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.⁹ 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 the usual vasculopathic risk factors such as hypertension, diabetes or hyperlipidemia. This supports the hypothesis that ODD may be an independent risk factor for NAION.^10,11

The prevalence of ODD from resolved papilloedema is 19%, almost 10 times higher than that in the general population. The high prevalence of ODD after papilloedema has resolved suggests a non-coincidental relationship; therefore, new ODD formation can be a sequela of papilloedema.¹²

Rarely, the following vascular complications may occur due to ODD: 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 (pseudopapilloedema) and papilloedema is crucial. In 39.5% of patients referred for presumed idiopathic intracranial hypertension (IIH) to neuroophthalmologists, the most common errors were inaccurate detection of papilloedema following examinations from optometrists, ophthalmologists, neurologists and general practitioners. This unfortunately leads to unnecessary adjunct testing, neuro imaging and, at times, invasive lumbar puncture.¹²

There are two direct, succinct questions you could ask patients, which would increase the risk of suspicion of papilloedema 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 papilloedema cases. The patient may be asymptomatic at time of presentation, but there is bilateral disc oedema present.

• Do you have a ringing noise in your ear? Checking for pulsatile tinnitus
• Does your vision ever disappear momentarily? Checking for TVOs

Adjunct or ancillary tests may include the following: relative afferent pupillary defect, visual field defect, colour vision anomaly and ocular motility horizontal diplopia at distance.

Imaging techniques to differentiate papilloedema from optic disc drusen

Several different OCT measurements have been postulated to help differentiate ODD/pseudopapilloedema from papilloedema, such as RNFL thickness, macular ganglion cell inner plexiform layer thickness, forward displacement of 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 conditions.

There are only two measurements which are considered consistently reliable: retinal and choroidal folds and peri-papillary wrinkles, as detected by EDI-OCT. Folds in papilloedema are biomechanical signs of stress or strain on the optic nerve head, induced by IIH, which are not present in ODD. The presence of folds is key to the differential diagnosis between papilloedema and ODD. In data from the renowned Idiopathic Intracranial Hypertension Treatment Trial (NCT01003639), folds were found in 73% of patients with papilloedema.¹³

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. Data from some past studies have suggested IOP-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 to you that they were taking glaucoma medication drops in the past.

With paediatric patients, a shorter recall period for routine examinations and visual field testing is recommended.

No papilloedema is easy to diagnose on fundoscopy alone. The differential diagnosis between papilloedema and psuedopapilloedema can give rise to an increased level of false-positive referrals into neuroophthalmology. Luckily, EDI-OCT is well suited to distinguish between subtle papilloedema and ODD: just look for the hyporeflective core with hyper-reflective margin on the superior apex. EDI-OCT is the most conclusive imaging tactic. Remember to be aware of the potential for coexisting ODD and papilloedema, as they can be found together.

References

1. Baehring JM, Biestek JS. Optic nerve head Drusen mimicking papilloedema. 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. Lee KM, Woo SJ, Hwang JM. Factors associated with visual field defects of optic disc drusen. PLoS One. 2018;13(4):e0196001. Published 2018 Apr 30. doi:10.1371/journal.pone.0196001

5. Palmer E, Gale J, Crowston JG, Wells AP. Optic nerve head drusen: an update. Neuroophthalmology. 2018;42(6):367-384. Published 2018 Apr 25. doi:10.1080/01658107.2018.1444060

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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. Published 2016 Jul 1. doi:10.1080/01658107.2016.1198917

13. 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

14. Girard MJA, Panda S, Tun TA, et al. Discriminating between papilledema and optic disc drusen using 3D structural analysis of the optic nerve head. Neurology. 2023;100(2). doi:10.1212/wnl.0000000000201350

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

E: lorcan.butler@thebraintumourcharity.org

Dr 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.