Asymptomatic Fellow Eye Involvement in Nonarteritic Anterior Ischemic Optic Neuropathy

Sequential nonarteritic anterior ischemic optic neuropathy (NAION) has been reported to occur in approximately 15% of patients within 5 years of the first episode. However, the incidence of presumed previous asymptomatic episode of NAION in fellow eye of patients presenting with acute NAION has not been previously reported. We reviewed charts of patients with acute NAION seen over a 5-year period to determine the frequency of visual field (VF) defect in the fellow eye secondary to presumed previous asymptomatic episode of NAION.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Asymptomatic Fellow Eye Involvement in Nonarteritic Anterior Ischemic Optic Neuropathy Natalie Brossard Barbosa, MD, MSc, Laura Donaldson, MD, PhD, Edward Margolin, MD Background: Sequential nonarteritic anterior ischemic optic neuropathy (NAION) has been reported to occur in approximately 15% of patients within 5 years of the first episode. However, the incidence of presumed previous asymptomatic episode of NAION in fellow eye of patients presenting with acute NAION has not been previously reported. We reviewed charts of patients with acute NAION seen over a 5year period to determine the frequency of visual field (VF) defect in the fellow eye secondary to presumed previous asymptomatic episode of NAION. Methods: Retrospective chart review of all patients presenting to single, tertiary university-affiliated neuro-ophthalmology practice from January 2016 to September 2021 with diagnosis of acute NAION. Patients were determined to have had a presumed previous episode of asymptomatic NAION in the fellow eye if VF defect and corresponding optic nerve head pallor as well as thinning on peripapillary ocular coherence tomography (OCT) and ganglion cell analysis of macular complex were present and alternate causes of VF were excluded. Results: One hundred ninety-two patients with the diagnosis of acute NAION were identified. One hundred thirty-nine had reliable VFs and were included in this study. VF defects in the fellow eye were present in 63 patients (45.4%). Of these, 54 (39%) were determined to represent previous NAION. In 14 of 139 patients (10%), a presumed episode of previous NAION in the fellow eye was asymptomatic. The most prevalent defect in asymptomatic eye was inferior altitudinal defect sparing fixation (7 of 14, 50%). The presence of obstructive sleep apnea, hypertension, diabetes, age, or sex was not predictive of previous episode of asymptomatic NAION. Conclusion: Unrecognized presumed previous episode of NAION occurred in a significant proportion of patients with acute NAION (14 of 139, 10.1%). In 100% of cases, the VF Department of Ophthalmology and Vision Sciences (NBB, LD, EM), Faculty of Medicine, University of Toronto, Toronto, Canada; and Department of Medicine (EM), Division of Neurology, Faculty of Medicine, University of Toronto, Toronto, Canada. The authors report no conflicts of interest. Address correspondence to Edward Margolin, MD, Department of Ophthalmology and Medicine (Neurology), Faculty of Medicine, University of Toronto, 801 Eglinton Avenue, West Suite 301, Toronto, ON M5N 1E3; E-mail: [e-mail] 82 defect in the asymptomatic fellow eye was in a hemifield where there was a new loss in the symptomatic eye. Journal of Neuro-Ophthalmology 2023;43:82–85 doi: 10.1097/WNO.0000000000001644 © 2022 by North American Neuro-Ophthalmology Society N onarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in older adults (1). It is presumed to occur due to hypoperfusion of ONH which is supplied by short posterior ciliary arteries (2). A resultant compartment syndrome then develops with swollen axons causing edema of the surrounding healthy ones thus propagating the edema. Once NAION occurs in one eye, the risk of fellow eye involvement in the next 5 years has been reported to be approximately 15%; however, recurrent episodes in the previously affected eye are very uncommon (3,4). When previous studies analyzed VFs in the “unaffected” fellow eye in patients presenting with acute NAION, they were often found to have a VF defect (5,6). These asymptomatic defects were mostly mild and occurred in a variety of patterns but always involved the inferior or superior visual field (VF) sparing central fixation (5,6). It is unclear whether these VF defects were related to other ocular comorbidities or previous subclinical episodes of NAION; however, w25% seem to be related to test performance and learning effect because the defects were not present on follow-up assessments (5). In our study, we reviewed all cases of acute NAION seen over 5 years in a single neuro-ophthalmology practice to determine the frequency of VF defects in the fellow asymptomatic eye. We then determined which VF defects were consistent with the presumed previous episode of asymptomatic NAION in the fellow eye with corresponding ONH pallor with thinning on peripapillary optical coherence tomography (OCT) and ganglion cell analysis of the macular complex and no other explanation for the VF defect (normal Brossard Barbosa et al: J Neuro-Ophthalmol 2023; 43: 82-85 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution MRI orbits with contrast, normal intraocular pressures (IOPs), and normal fundus autofluorescence and enhanced depth imaging OCT of the optic nerve head). We also determined whether certain patterns of VF defect were more likely to be asymptomatic. METHODS Retrospective chart review of all patients in a single, tertiary university-affiliated neuro-ophthalmology practice from January 2016 to September 2021 with the diagnosis of acute NAION was performed. The study protocol was approved by the Health Sciences Research Ethics Board at the University of Toronto and adhered to the tenets of the Declaration of Helsinki. The following data were collected for each patient: presence of NAION risk factors (diabetes, hypertension, dyslipidemia, obstructive sleep apnea, and smoking history), Snellen visual acuity in each eye, ocular examination findings, mean deviation and shape of VF defect on automated 24–2 perimetry in the symptomatic and fellow eye, OCT of the peripapillary retinal nerve fiber layer (RNFL), and ganglion cell complex–inner plexiform layer (GCC-IP) thickness. VF defects were classified into 3 main categories: diffuse, altitudinal (superior or inferior), and nerve fiber bundle defects (superior or inferior). VFs with more than 33% of fixation losses or more than 15% false positives were considered unreliable and excluded from analysis. Patients with no VF or OCT data, lack of follow-up visits after the initial assessment, or with ocular comorbidities that would impede analysis (i.e., history of retinal detachment, stroke, branch retinal vein occlusion, or epiretinal membranes) were also excluded. All included patients had at least 2 VFs with consistent defect and acceptable reliability indices. An asymptomatic VF defect was classified as being due to a presumed previous episode of NAION if there was corresponding ONH pallor with thinning on peripapillary OCT and GCC-IP thickness and no other explanation for these findings (normal IOPs, normal MRI of the orbits with contrast, and absence of superficial and/or buried optic nerve head drusen). ONH edema in the fellow eye. The remaining 10 patients’ VF defects were determined to be secondary to optic disc drusen in 3 patients, lid artifact in 1 patient, and in 6 remaining cases, the cause of VF defect could not be determined because it did not correspond to optic disc pallor or edema, and OCT of the peripapillary RNFL and GCC were normal. Overall, 54 of 139 patients had sequential NAION (14 had a previous episode of NAION in the fellow eye unbeknown to them and 40 had a known symptomatic previous episode of NAION in the fellow eye). Forty of 54 (74.1%) were men, and in the subgroup of patients determined to have had a previous episode of asymptomatic NAION in the fellow eye, 9 of 14 were men (64.2%). The mean age of patients with sequential NAION was 71.0 ± 12.3 years and 69.4 ± 9.2 years in the group of patients with asymptomatic fellow eye involvement. Prevalence of preexisting risk factors for NAION (hypertension, diabetes, or sleep apnea) was similar between the 2 groups, with hypertension being the most prevalent risk factor in both (Table 1). Eyes with presumed asymptomatic NAION in the fellow eye had significantly better visual acuity: 0.22 ± 0.17 logMAR units compared with 0.81 ± 0.71 logMAR units in the group who were known to have NAION in the fellow eye (P = 0.0058). The mean deviation (MD) on VF in the fellow eye was also significantly better in asymptomatic eyes (212.5 ± 4.8 dB) compared with symptomatic sequential NAION eyes (–20.6 ± 4.8 dB, P = 0.0038). The most prevalent defect found in the asymptomatic NAION eye was inferior altitudinal defect sparing the fixation (7 of 14, 50%). Superior VF defects were almost 3 times more prevalent in asymptomatic NAION eyes vs. symptomatic eyes (28.6% [4 of 14] vs. 11.2% [20 of 179] VFs of symptomatic eyes). There was a 35.7% (5 of 14) correlation in the type of VF defect between the symptomatic and asymptomatic eyes, but more importantly, in 100% of cases, the VF defect in the asymptomatic eye occurred in a hemifield where there was a new field loss in the symptomatic eye (Table 2). DISCUSSION RESULTS One hundred ninety patients who presented with acute NAION were identified. Fifty-one had unreliable VFs and were excluded from further analysis. In 139 remaining patients, VF defects in the fellow eye were present in 45.3% (63 of 139). Twenty-four of 139 of these patients (17.3%) were not aware of VF defect in the fellow eye. Fourteen patients (10%) with VF defects in the fellow eye were determined to have had a previous presumed asymptomatic episode of NAION because they all had corresponding pallor of the ONH on clinical examination and thinning of peripapillary OCT and GCC-IP. No one had coexisting Brossard Barbosa et al: J Neuro-Ophthalmol 2023; 43: 82-85 The goal of our study was to determine the prevalence of presumed subclinical NAION in the fellow eye of patients presenting with acute NAION. Within our group, 10.1% (14 of 139) of patients presented with subclinical optic neuropathy in the fellow eye that was determined to be secondary to a presumed previous episode of NAION. The proportion of patients with any VF defect in the fellow eye was 45.4%, which is less than that reported previously in some studies (74.6% by Scherer et al 2008), but similar to others (50% reported by Falavarjani et al (5,6)). Notably, in 6 of our patients with VF defect in the fellow eye, no obvious cause for VF defect was identified. 83 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Demographic and clinical variables in patients with sequential nonarteritic anterior ischemic optic neuropathy. Male Age (mean ± SD) Risk factors Hypertension Dyslipidemia Diabetes Obstructive sleep apnea Smoking history Bilateral Symptomatic Bilateral-Fellow Eye Asymptomatic P 27/40 (67.5%) 71.0 ± 12.3 9/14 (64.3%) 69.4± 9.2 1 1 21/40 (52.5%) 15/40 (37.5%) 9/40 (22.5%) 7/40 (17.5%) 3/40 (7.5%) 9/14 (64.3%) 5/14 (35.7%) 1/14 (7.1%) 2/14 (14.3%) 0 (0%) 0.65 1 0.26 1 0.56 P values are from the chi-square testing or Fisher exact test for expected values ,5. Fifty percent of patients with asymptomatic fellow eye involvement presented with an inferior altitudinal defect sparing the center of fixation. Although less common, superior VF defects were relatively more prevalent in asymptomatic eyes vs. symptomatic eyes, in 28.6% vs. 11.1%. Theoretically, a superior VF defect is more easily disregarded. In a previous study of patients with carotid transient ischemic attacks or minor strokes, asymptomatic VF defects were found in 29% and 57% of cases, respectively. More than 80% of the defects in these patients involved superior hemifield (7). In patients with asymptomatic VF defects related to demyelinating optic neuritis, superior hemifield loss is also common (8). Notably, in all 14 cases with presumed asymptomatic fellow eye NAION in our study, the asymptomatic VF defect occurred in a hemifield which was now affected in the symptomatic eye. This could be explained by the fact that the VF of each eye overlaps in the central 120° with that of the fellow eye, and only when a field defect in the same area occurred in the fellow eye (previously normal), they became aware of the new deficit. Determining factors that could predict the increased likelihood of fellow eye involvement in NAION is important for informing patient prognosis and guiding preventative measures after the first episode. We could not find a correlation between the presence of obstructive sleep apnea, hypertension, diabetes, age, or sex and probability of having had a previous episode of asymptomatic NAION in the fellow eye. A strong correlation between severity of visual acuity loss and pattern and magnitude of VF defect between fellow eyes was previously reported in patients with sequential NAION (8–11). Our study similary demonstrated a very strong (100%) correlation between the location of the VF defect in the symptomatic and asymptomatic fellow eyes with a presumed previous NAION event. Our study highlights the importance of careful examination of the fellow eye on funduscopy as well as the results of formal VF testing and peripapillary OCT and GCC-IP thickness at onset and in follow-up of patients presenting with acute NAION. Previous involvement of the fellow eye by presumed NAION is not uncommon which is important to recognize as recurrent NAION in the same eye is very rare (5); thus, the patients who are determined to have had a presumed NAION in the fellow eye are at low risk of further vision loss from NAION and likely do not need to strictly follow risk modification strategies (such as not taking phosphodiesterase inhibitors or aggressive treatment of sleep apnea). Patients with bilateral VF defects must also be assessed for driving eligibility and may benefit from education on strategies to adapt to bilateral peripheral vision loss. CONCLUSIONS Previous presumed asymptomatic episode of NAION in the fellow eye of patients presenting with acute NAION is not uncommon, present in 10.1% of cases in our series. The TABLE 2. Visual field patterns Visual Field Pattern Superior NFBD Inferior NFBD Superior and inferior NFBD Superior altitudinal Inferior altitudinal Superior and inferior altitudinal-fovea sparing Diffuse Other (paracentral, nonspecific) 84 Symptomatic Eyes Asymptomatic Eyes 12/180 (6.7%) 41/180 (22.8%) 9/180 (0.5%) 8/180 (4.4%) 40/180 (22.2%) 5/180 (2.8%) 55/180 (30.6%) 10/180 (5.6%) 2/14 (14.3%) 1/14 (7.1%) 2/14 (14.3%) 2/14 (14.3%) 7/14 (50%) 0/14 (0%) 0/14 (0%) 0/14 (0%) Brossard Barbosa et al: J Neuro-Ophthalmol 2023; 43: 82-85 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution clinician might consider reassuring these patients about low likelihood of having another episode of NAION in the future. STATEMENT OF AUTHORSHIP Conception and design: N. Brossard Barbosa, E. Margolin, L. Donaldson; Acquisition of data: N. Brossard Barbosa, E. Margolin, L. Donaldson; Analysis and interpretation of data: N. Brossard Barbosa, E. Margolin, L. Donaldson; Drafting the manuscript: N. Brossard Barbosa, E. Margolin, L. Donaldson; Revising the manuscript for intellectual content: N. Brossard Barbosa, E. Margolin, L. Donaldson; Final approval of the completed manuscript: N. Brossard Barbosa, E. Margolin, L. Donaldson. REFERENCES 1. Kaup M, Plange N, Arend KO, Remky A. Retrobulbar haemodynamics in non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol. 2006;90:1350–1353. 2. Kerr NM, Chew SS, Danesh-Meyer HV. Non-arteritic anterior ischaemic optic neuropathy: a review and update. J Clin Neurosci. 2009;16:994–1000. 3. Newman NJ, Scherer R, Langenberg P, Kelman S, Feldon S, Kaufman D, Dickersin K. Ischemic Optic Neuropathy Decompression Trial Research Group. 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