Multimodal Ophthalmic Imaging of Nonarteritic Anterior Ischemic Optic Neuropathy With and Without Optic Disc Drusen

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Multimodal Ophthalmic Imaging of Nonarteritic Anterior Ischemic Optic Neuropathy With and Without Optic Disc Drusen Sangeethabalasri Pugazhendhi, MBBS, Yan Yan, MD, PhD, Yaping Joyce Liao, MD, PhD A 28-year-old Caucasian woman with a history of left greater than right optic disc drusen (ODD) and migraine presented with new left eye vision loss due to nonarteritic anterior ischemic optic neuropathy (ODD-AION). At baseline, 5 months prior, she had 20/20 visual acuities, left relative afferent pupillary defect (RAPD), and full optic nerves with a raised, lumpy-bumpy appearance typical of ODD compared with the flat appearance of the normal optic nerve on color fundus images (Fig. 1A–C). On near-infrared reflectance (NIR) imaging (Spectralis HRA + OCT, Heidelberg Engineering, Germany), her optic discs had volcano-like elevation with irregular, white borders (Fig. 1C). Blue-light autofluorescence (AF) imaging (Spectralis HRA + OCT) revealed the presence of hyperautofluorescent deposits on the optic discs that were typical of ODD (Fig. 1B–C). On OCT retinal nerve fiber layer (RNFL) analysis, there was left greater than the right eye, superior greater than inferior thinning (Cirrus HD-OCT, Carl Zeiss Meditech Inc, Germany) (See Supplemental Digital Content, Fig. E1B-E1C, http://links.lww.com/WNO/ A461) and no evidence of visual field defects on static perimetry (Fig. 1B, C). Seven days after developing vision loss from ODD-AION in the left eye, her visual acuity remained 20/20, and static perimetry revealed a new inferior field defect (Fig. 1D). RNFL thickness map showed pseudonormalization because of new disc edema on top of prior thinning during acute ODDAION (See Supplemental Digital Content, Fig. E1D, Department of Ophthalmology (SP, YY, YJL), Stanford University School of Medicine, Stanford, California; Department of Ophthalmology (YY), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; and Department of Neurology (YJL), Stanford University School of Medicine, Stanford, California. Supported by the National Eye Institute (R01EY028753), Carl Zeiss Meditec, Inc. (Dublin, CA) and an unrestricted grant from Research to Preventing Blindness, Inc. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Yaping Joyce Liao, MD, PhD, Department of Ophthalmology, Stanford University Medical Center, 2452 Watson Court, Palo Alto, CA 94303-5353; E-mail: [e-mail] Pugazhendhi et al: J Neuro-Ophthalmol 2022; 42: e349-e351 http://links.lww.com/WNO/A461). On color fundus photography, there was left optic disc edema with a superonasal, deep sectoral circumpapillary hemorrhage and more superficial papillary hemorrhage, which obscured the drusen clusters (Fig. 1D). Compared with the optic disc of an 88-year-old woman with acute AION, which showed diffuse severe optic disc edema (Fig. 1E) and RNFL of 165 mm, the optic disc of ODD-AION seemed more prominently elevated. Potential ODD were excluded in the patient with acute AION using enhanced depth imaging optical coherence tomography (EDIOCT) and AF imaging. On NIR imaging, the optic disc edema of acute ODD-AION seemed to drape over the volcano-like disc elevation like lava. In comparison, on NIR imaging, the optic disc of acute AION without ODD remained relatively dark like that of the control, with prominent edema and tortuous vessels that only slightly blurred the disc margin (Fig. 1E). On AF imaging, the bright superficial drusen seemed obscured in ODD-AION by edema and the diameter of the normally dark disc area seemed wider due to blockade of the peripapillary bright retinal pigment epithelium by optic disc edema. After ODD-AION, the patient underwent comprehensive evaluation including erythrocyte sedimentation rate, and C-reactive protein, which were within normal limits, and the patient did not have symptoms of giant cell arteritis. MRI of orbit with and without contrast was unremarkable. The patient underwent a sleep study and was diagnosed with mild obstructive sleep apnea but was unable to tolerate CPAP. She had no vascular risk factors or history of coagulopathy. The patient presented 8 years later for follow-up and had 20/20 visual acuities, left RAPD, persistent inferior visual field defect (Fig. 1F) exhibited after AION, and 11 mm thinning of RNFL compared with baseline (See Supplemental Digital Content, Fig. E1F, http://links.lww.com/ WNO/A461), likely a result of the combination of ODD and AION. On color fundus photography, the optic disc of chronic ODD-AION seemed paler, and on NIR imaging, the optic disc was much flatter with less distinct drusen foci compared with baseline (Fig. 1F). Curiously, on AF imaging, 2 of the very bright superficial drusen in chronic ODDAION seemed relatively less bright compared with baseline, e349 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Multimodal en face imaging of acute and chronic AION in patient with ODD (ODD-AION) compared with acute and chronic anterior ischemic optic neuropathy (AION), optic disc drusen (ODD), and control. A. Control (contralateral eye of E and G). B. ODD right eye. C. ODD left eye (same patient as B). D. Acute ODD-AION left eye imaged 7 days after onset (same eye as C, F). E. Acute AION left eye 14 days from onset (same eye as G). F. Chronic ODD-AION left eye (same eye as C, D). G. Chronic AION left eye 4 months from onset (same eye as E). Note (B, C, D, F) (yellow-filled label) are from a 28-year-old woman with bilateral ODD who developed ODD-AION in left eye. A, E, G. (blue-filled label) are from an 88-year-old woman with the control right eye and the AION left eye. Top row: color fundus images. Optos: (A), (E), (G) and Zeiss: (B), (C), (D), (F). Eyes with ODD have a lumpy-bumpy appearance. Second row: near-infrared reflectance (NIR) imaging (Spectralis). Eyes with ODD have a gray, raised appearance, whereas eyes without ODD have a black, flat appearance. Third row: blue-light autofluorescence (AF) imaging (Spectralis). Eyes with ODD have variably bright deposits. Bottom row: static perimetry using automated visual field analyzer (Zeiss). although more of the optic disc seemed hyperautofluorescent with variably dim clusters (Fig. 1F vs C). OCT angiography (OCTA) was performed for the first time 8 years after ODD-AION (AngioPlex, Carl Zeiss Meditec, Inc). In the ODD right eye, there was prominence of the papillary microvasculature, which looked like a white halo on the optic disc, which is not present in the control eye (Fig. 2B vs A). On OCTA of the chronic ODD-AION (left eye, same patient), this white halo was much less distinct, but there was still slight halo of optic disc vessels (Fig. 2D vs B). In acute AION without ODD, there was slight increase in papillary and peripapillary microvasculature due to optic disc edema, but this did not look like a localized halo concentrated on the optic disc (Fig. 2C). To better examine the peripapillary vessel density, we analyzed the superficial capillary plexus using a custom script, which performed a threshold analysis and removed large vessels (MATLAB R2016a; MathWorks, Natick, MA) (1). On threshold analysis, the decrease in peripapillary vasculature in chronic ODD-AION is more easily seen (Fig. 2D). Although we did not have e350 OCTA of the same eye at baseline, there was obvious vascular dropout in the chronic ODD-AION left eye compared with the contralateral ODD right eye. This is presumably because of a combination of greater vascular dropout before AION and further loss after AION. The decrease in vascular density in chronic AION was more than that of ODD-AION, but this was expected given more severe visual field loss in this AION eye. Nonarteritic AION is the most common cause of acute vision loss in patients with ODD, and ODDAION can occur at a young age (2). ODD-AION is hypothesized to be due to hypoperfusion of the anterior optic nerve due to severe crowding of the optic disc, that is, commonly seen in NAION (2,3). Risk factors of nonarteritic AION include age, vascular factors, sleep apnea, and others (3,4). This study demonstrates the key en face ophthalmic imaging features of acute ODD-AION compared with that of acute AION, ODD, and control eyes and provides an 8year follow-up of the multimodal imaging changes in ODD-AION. Our case confirms that color fundus and Pugazhendhi et al: J Neuro-Ophthalmol 2022; 42: e349-e351 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Optical coherence tomography angiography (OCTA) of optic disc superficial capillary plexus in chronic AION in patient with ODD (ODD-AION), acute and chronic anterior ischemic optic neuropathy (AION), optic disc drusen (ODD), and control. A. Control. B. ODD. C. Acute AION. D. Chronic ODD-AION. E. Chronic AION. Note these are same eyes as Fig. 1. Top row: OCTA 6 · 6 original image (Cirrus Angioplex). Second row: threshold images of same eyes with large vessel removal. Bottom row: OCT B-scan showing segmentation of the superficial capillary plexus. The segmentation lines are difficult to see, but they were enlarged and visually inspected to ensure good segmentation. AF imaging are helpful in the diagnosis of ODD (2). The addition of NIR imaging, which is easily obtained as part of the commercial multimodal ophthalmic imaging instrument, provides a striking alteration of the optic disc appearance as a result of ODD. Eyes with ODD often seem gray and raised, whereas eyes without ODD often seem black and flat, even when there is presence of severe optic disc edema. NIR imaging also provides a pseudo threedimensional visualization of the optic disc in ODD and improves our ability to detect peripapillary involvement from optic disc edema in acute ODD-AION. On OCTA imaging, there is prominent superficial papillary vasculature in ODD, which is likely from a combination of vascular loss at baseline and further dropout after ODD-AION. There is also a decrease in peripapillary vasculature in ODD-AION, as previously reported for AION (5). Unfortunately, we do not have OCTA imaging of acute ODD-AION because this technology was not commercially available at the time. Future studies of ODD-AION and the examination of the presence of ODD in patients with AION can improve our understanding of the fundamental characteristics of ODD-AION. Such studies can potentially help to diagnose ODD, to understand papillary and peripapillary changes in acute ODD-AION, and perhaps 1 day, to predict visual prognosis. Pugazhendhi et al: J Neuro-Ophthalmol 2022; 42: e349-e351 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. Pugazhendhi, Y. Yan, and Y. J. Liao; b. Acquisition of data: S. Pugazhendhi, Y. Yan, and Y. J. Liao; c. Analysis and interpretation of data; S. Pugazhendhi, Y. Yan, and Y. J. Liao. Category 2: a. Drafting the manuscript: S. Pugazhendhi, Y. Yan, and Y. J. Liao; b. Revising it for intellectual content: S. Pugazhendhi Y. Yan, and Y. J. Liao. Category 3: a. Final approval of the completed manuscript: S. Pugazhendhi, Y. Yan, and Y. J. Liao. REFERENCES 1. 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;218:214–224. 2. 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