A Classic Neuro-Ophthalmic ODDity From a Modern Perspective

doi:10.62055/79402121Zy

INTRODUCTION

Welcome to the “Neuro Nuggets” column within the Journal of Medical Optometry (JoMO)! This column aims to make neuro-ophthalmic disease more approachable by blending real-world clinical cases with evidence-based medicine.  The patient in this edition’s column offers an opportunity to re-visit a well-known potential cause of “pseudopapilledema.” You might even consider it the classic “neuro nugget” of the optic disc. Enjoy!

 

CASE PRESENTATION

A 65-year-old white male presented for routine evaluation and reported stable vision. The patient’s past medical history included hypertension, hyperlipidemia, and hypothyroidism.

On examination, the patient’s best-corrected visual acuity was 20/20 in each eye.  Color vision by Ishihara was intact in each eye. Ocular motility evaluation and confrontation visual field testing were both normal in each eye. The patient’s refractive testing revealed a spherical equivalent of approximately four diopters of hyperopia in each eye. Slit lamp exam, intraocular pressure, and dilated retinal evaluation were normal and age-appropriate in each eye. However, the optic nerve head appeared to be relatively small in each eye, the neuro-retinal rim appeared heaped nasally with distinct margins, and several hyperreflective foci were noted at the superonasal rim in each eye.

Spectral-domain optical coherence tomography (SD-OCT) demonstrated relative thinning in the superior and nasal sectors of the peripapillary retinal nerve fiber layer (pRNFL) and mild relative thinning superotemporal to the foveal center on macular ganglion cell layer (GCL) segmentation (Figure 1). Fundus autofluorescence (FAF) demonstrated multiple areas of hyper-autofluorescence mostly superior and nasal within the optic nerve head in each eye (Figure 2).  Enhanced depth imaging OCT (EDI-OCT) centered around the optic nerve head revealed several variably sized lesions at different depths (both above and below the level of Bruch’s membrane opening); these lesions had a hyperreflective border and hyporeflective core (Figure 3). OCT angiography (OCTA) imaging around the optic nerve head revealed relatively less peripapillary vascular density in the superficial capillary layers mostly superonasally in each eye (Figure 4). Automated perimetry showed mild, non-specific, relative point defects in each eye.

The patient was diagnosed with optic disc drusen (ODD) in each eye and is currently being monitored serially for any impact on visual function.

 

 

 

DISCUSSION

Optic disc drusen (ODD) are benign, acellular, calcified deposits that may be observed at varying depths at the optic nerve head before the lamina cribrosa.¹  Recognition of ODD is useful in the differential diagnosis of so-called “pseudopapilledema” particularly in patients who appear to have an irregular, often lumpy-bumpy, optic nerve head morphology.² Patients with ODD are susceptible to visual loss from several mechanisms: impaired axonal function and damage resulting in visual field loss,³ development of peripapillary choroidal neovascularization,⁴ retinal vein occlusion,⁵ and development of non-arteritic ischemic optic neuropathy⁶ (especially in patients with “disc-at-risk” optic nerve anatomy). The exact pathogenesis of ODD formation remains uncertain, but they are thought to be a byproduct of impaired axonal metabolism.⁷

Several ancillary tests are available to supplement clinical evaluation in patients with ODD. A recent comparative diagnostic analysis found that enhanced depth imaging optical coherence tomography (EDI-OCT) was the most sensitive and accurate test in detecting ODD, outperforming B-scan ultrasonography, fundus autofluorescence (FAF), and fundus photography.⁸ The characteristic hyperreflective margin with signal-poor hyporeflective core on EDI-OCT helps to identify even smaller and buried ODD that might go overlooked using other imaging modalities.⁹ ODD lesions can be described based on size (over 200 microns in diameter considered “large”) and location (“deep” or “buried” if below Bruch’s membrane opening).^2,8  Research by Johannesen et al. found that patients with ODD-associated ischemic optic neuropathy (ION) tended to have a relatively smaller Bruch’s membrane opening and deeper ODD, which may contribute to axonal crowding near the lamina cribrosa creating a kind of compartment syndrome and provoke an ischemic cascade.⁶ Other studies have demonstrated that large ODD volume is associated with more gradual onset visual field deficits stemming from optic nerve dysfunction.³

OCT angiography (OCTA) is a recently developed non-invasive imaging modality that enables visualization of retinal and choroidal perfusion patterns and ocular blood flow. A study by Yan et al. found that the peripapillary superficial capillary vessel density (VD) on OCTA imaging was significantly lower in patients with ODD compared to control patients; this difference in VD was especially noted in the superior and nasal aspects of the optic nerve, regions where ODD are most commonly located.¹⁰ Another study from Lykkebirk et al. found that larger ODD volume was associated with a decrease in peripapillary VD (i.e. an inversely proportional relationship).¹¹ It remains unclear which occurs first: if ODD causes nerve fiber injury via axonal compression leading to a decrease in vascular support, or if vascular compromise leads to disturbances in axonal function and appearance of ODD. More severe visual field loss stemming from ODD may be correlated to decreases in peripapillary vessel density as well as peripapillary RNFL thinning.¹² However, there is tremendous variability of OCTA vascular parameters both in normal patients and those with pathology (even at the same clinical severity level), which complicates interpretation of angiographic findings.¹⁰

 

CLINICAL PEARLS:

• Patients with ODD are at risk for visual loss through several mechanisms, particularly if there is “disc-at-risk” anatomy.
• EDI-OCT has supplanted B-scan ultrasonography and other modalities as the “gold standard” in detecting ODD, though a multimodal approach is often helpful.
• OCT angiography can serve a helpful adjunct role in recognizing disruptions in peripapillary vascular perfusion in patients with ODD.

 

REFERENCES

1.  Douglas VP, Douglas KAA, Torun N. Optical coherence tomography angiography in neuro-ophthalmology. Curr Opin Ophthalmol. 2023 Jul 1;34(4):354-360. doi: 10.1097/ICU.0000000000000955. https://pubmed.ncbi.nlm.nih.gov/37070535/
2. Costello F, Rothenbuehler SP, Sibony PA, Hamann S; Optic Disc Drusen Studies Consortium. Diagnosing Optic Disc Drusen in the Modern Imaging Era: A Practical Approach. Neuroophthalmology. 2020 Oct 26;45(1):1-16. doi: 10.1080/01658107.2020.1810286. https://pubmed.ncbi.nlm.nih.gov/33762782/
3. Malmqvist L, Lindberg A-SW, Dahl VA, Jørgensen TM, Hamann S. Quantitatively measured anatomic location and volume of optic disc drusen: an enhanced depth imaging optical coherence tomography study. Invest Ophthalmol Vis Sci. 2017;58:2491–2497. DOI:10.1167/iovs.17-21608. https://pubmed.ncbi.nlm.nih.gov/28460051/
4. Saffra, Norman, Reinherz B.  Peripapillary Choroidal Neovascularization Associated with Optic Nerve Head Drusen Treated with Anti-VEGF Agents.  Case Rep Ophthalmol. 2015; 6: 51-55. DOI: 10.1159/000375480. https://pubmed.ncbi.nlm.nih.gov/25802505/
5. Rothenbuehler SP, Maloca PM, Belmouhand M, Hamann S, Larsen M. Branch retinal vein occlusion precipitated by compression between a major retinal artery and underlying optic disc drusen. Acta Ophthalmol. 2021 Dec;99(8):931-933. doi: 10.1111/aos.14840. https://pubmed.ncbi.nlm.nih.gov/33880859/
6. Johannesen RG, Lykkebirk L, Jørgensen M, Malmqvist L, Hamann S. Optic Nerve Head Anatomy and Vascular Risk Factors in Patients With Optic Disc Drusen Associated Anterior Ischemic Optic Neuropathy. Am J Ophthalmol. 2022 Oct;242:156-164. doi: 10.1016/j.ajo.2022.06.016. https://pubmed.ncbi.nlm.nih.gov/35764105/
7. 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. doi: 10.1111/aos.13748. https://pubmed.ncbi.nlm.nih.gov/29659172/
8. Youn S, Loshusan B, Armstrong JJ, Fraser JA, Hamann S, Bursztyn LLCD. A Comparison of Diagnostic Accuracy of Imaging Modalities to Detect Optic Disc Drusen: The Age of Enhanced Depth Imaging Optical Coherence Tomography. Am J Ophthalmol. 2023 Apr;248:137-144. doi: 10.1016/j.ajo.2022.12.004. https://pubmed.ncbi.nlm.nih.gov/36516916/
9. Malmqvist L, Bursztyn L, Costello F, Digre K, Fraser JA, Fraser C, Katz B, Lawlor M, Petzold A, Sibony P, Warner J, Wegener M, Wong S, Hamann S. 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. doi: 10.1097/WNO.0000000000000585. https://pubmed.ncbi.nlm.nih.gov/29095768/
10. Yan Y, Zhou X, Chu Z, Stell L, Shariati MA, Wang RK, Liao YJ. Topographic Quadrant Analysis of Peripapillary Superficial Microvasculature in Optic Disc Drusen. Front Neurol. 2021 May 19;12:666359. doi: 10.3389/fneur.2021.666359. https://pubmed.ncbi.nlm.nih.gov/34093412/
11. Lykkebirk L, Wessel Lindberg AS, Karlesand I, Heiberg M, Malmqvist L, Hamann S. Peripapillary Vessel Density in Relation to Optic Disc Drusen: A Multimodal Optical Coherence Tomography Study. J Neuroophthalmol. 2023 Jun 1;43(2):185-190. doi: 10.1097/WNO.0000000000001667. https://pubmed.ncbi.nlm.nih.gov/36166786/
12. Yan Y, Zhou X, Chu Z, Stell L, Shariati MA, Wang RK, Liao YJ. Vision Loss in Optic Disc Drusen Correlates With Increased Macular Vessel Diameter and Flux and Reduced Peripapillary Vascular Density. Am J Ophthalmol. 2020 Oct;218:214-224. doi: 10.1016/j.ajo.2020.04.019. https://pubmed.ncbi.nlm.nih.gov/32360344/