Evaluation and management of nonarteritic anterior ischemic optic neuropathy: a national survey

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most prevalent acute optic neuropathy affecting middle-aged and older individuals [1, 2]. Typical NAION manifests as a sudden, mostly painless monocular visual loss, often noticed upon awakening, with progression occurring over a span of days or weeks [1, 3]. Despite being a common cause of visual impairment [4], no current treatment exists [5, 6]. Management is aimed at decreasing the risk for fellow-eye NAION and improving overall cardiovascular health through control of associated risk factors common for both disorders.

The pathophysiology of NAION remains elusive. The leading theory implicates hypoperfusion of branches of the short posterior ciliary arteries that supply the optic nerve head. This sets in motion a vicious cycle involving axoplasmic flow stasis and axonal swelling, subsequently compressing small vessels within the confined space of a small optic disc (often referred to as the "disc at risk"), leading to aggravated ischemia [1, 7].

Debate persists concerning the risk factors associated with idiopathic NAION [8‐12]. Commonly accepted risk factors include age and a crowded optic disc, along with conditions like diabetes mellitus (DM), hypertension (HTN), dyslipidemia, obstructive sleep apnea (OSA), obesity, nocturnal hypotension, smoking, optic disc drusen (ODD), and specific medications including erectile dysfunction medications, amiodarone, and interferon [13]. No consensus exists to guide neuro-ophthalmologists on the best means to diagnose these commonly accepted risk factors for NAION.

Surveys examining routine management are a common alternative when evidence-based guidelines cannot be formed [14‐18]. Although these surveys lack objective quantitative outcomes, they offer valuable insights based on the collective experience of physicians within the field.

This study addresses a fundamental question: What constitutes the customary (routine) neuro-ophthalmological work-up and management of NAION? This query holds particular relevance given the absence of established guidelines and international consensus among neuro-ophthalmologists regarding the standard evaluation and management of NAION [13, 19]. As such, a pragmatic approach may involve adhering to the prevailing practices.

Between the years 2019 and 2021, there were 37 active fellowship-trained neuro-ophthalmologists in Israel. Thirty-six (97.3%) of these specialists consented to participate in our study. Figure 1 presents the accumulated responses of participants. The evaluation of risk factors is graphically summarized in Fig. 1A.

Secondary prevention and management guidelines in NAION remain a challenge to implement. Known systemic and ophthalmological risk factors are associated with NAION, yet established guidelines on the choice of tests with which to establish the presence of these risk factors are lacking. Adding to this challenge is the fact that while neuro-ophthalmologists are well-versed as to the risk factors, many of the tests with which the presence of these risk factors are established, fall within the routine practice of general practitioners. This nationwide survey provides several insights into the practical approaches adopted by neuro-ophthalmologists and highlights the importance of developing a set of consensus guidelines on which specific tests should be ordered to evaluate diabetes, hypertension dyslipidemia, or OSA.

There is robust evidence supporting the association between NAION and cardiometabolic risk factors [22, 23]. Our findings reveal that there is a high level of agreement among neuro-ophthalmologists regarding which risk factors should be screened for after NAION. Approximately 80% of respondents recommended work-up for DM, HTN, dyslipidemia, and OSA. However, the specifics of how these conditions ought to be assessed varied between physicians. For example, an acute NAION patient who is not aware of harboring diabetes may be referred for; fasting glucose levels; a glucose tolerance test; serum HbA1c levels, or both. Similarly, screening for HTN may rely on periodic testing or referral for 24-h BP monitoring.

Nocturnal hypotension, defined as excessive dipping of systolic BP at nighttime, has been associated with NAION [24, 25]. Sixty-five% of neuro-ophthalmologists recommended a 24-h Holter BP monitoring. The topic of timing of anti-hypertensive medication to prevent nocturnal hypotension is challenging because while neuro-ophthalmologists often discourage taking antihypertensive medication at bedtime, the cardiovascular literature promotes bedtime antihypertensive dosing, emphasizing its potential to reduce cardiovascular risks [26, 27]. Labowsky et al. argued that prioritizing overall health (over vision) may justify bedtime antihypertensive medications even when nocturnal BP dipping may result [28]. Thus, routinely obtaining 24-h BP monitoring may not be universally productive.

Another issue of contention relates to the embolic workup of patients with NAION. While a substantial number of physicians in our study sent patients for embolic work-up, such as carotid Doppler sonography, it is crucial to consider that the presumed pathogenesis of NAION primarily involves hypoperfusion of the optic nerve head rather than thrombus or emboli. Embolic NAION case reports are extremely rare[29‐31] and may lack evidence of causality. We contend that routine testing for internal carotid atheromatous plaque, cardiac valve thrombus, or arrhythmia is not recommended [1, 13] and may even deter primary care physicians from focusing on the most relevant risk factors and lifestyle modifications.

A specific challenge arises with screening for OSA. Several screening questionnaires for OSA with moderate sensitivity and specificity are available [32]. Fraser et al. recommended standardized and validated tools for OSA screening [33], highlighting that unstructured questions may decrease sensitivity and risk misdiagnosing this significant risk factor. Only a minority (11.1%) of respondents used the Berlin questionnaire following NAION, while 41.6% of neuro-ophthalmologists relied on unstructured OSA questions in their medical history. Given the high prevalence of OSA in NAION patients (55–89% [22]) and the limited sensitivity of existing screening questionnaires, it may be logical to consider unselectively referring all patients without a previous OSA diagnosis for polysomnography, as done by 41.6% of respondents in our study.

Screening for Ophthalmological risk factors also varied. While the association of optic disc drusen and NAION is well-documented [34], less than 40% routinely looked for optic disc drusen in NAION patients, nor was the type of imaging chosen to look for optic disc drusen uniform.

Over 91% of interviewees in our study recommended observation as the primary approach. Lifestyle and secondary prevention practices revealed a high level of inter-responder agreement. Unexpectedly, eighty percent of neuro-ophthalmologists recommended aspirin treatment, despite the paucity of evidence for its efficacy in reducing the risk for second-eye NAION [35]. Indeed, the largest study on this topic by Dr. Beck et al. retrospectively evaluated 431 patients experiencing their first NAION event. Among them, 153 who were prescribed aspirin and 278 who were not showed only a transient risk reduction for fellow-eye involvement within two years, with no long-term benefits observed [36]. Over 80% instructed their patients on the importance of lifestyle modifications (e.g. smoking cessation). Despite compelling evidence against the efficacy of high-dose steroids for NAION [6, 37, 38], 16% of respondents offered steroids in situations of second-eye involvement or progression. Our survey reveals that other therapeutic approaches, such as the administration of erythropoietin, have not gained widespread adoption in clinical practice.

In 2020, Lee et al. [16] conducted a similar survey on the management of NAION in South Korea. In their study, they evaluated the practice patterns of neuro-ophthalmologists in the diagnosis and management of NAION, traumatic optic neuropathy, and Leber's hereditary optic neuropathy. The authors sent a 15-question survey using Google Forms to all practicing neuro-ophthalmologists registered with the Korean Society of Neuro-ophthalmology. They had a higher number of responders (63) compared to our study (the population of South Korea is 5.5 times larger) but a lower response rate (78.8%). In their study, all neuro-ophthalmologists (100%) recommended routine neuro-imaging (an MRI) to patients suspected of having optic neuropathy compared to 22.2% in our study. Forty (63.5%) respondents recommended observation only, compared with more than 91% in our study. A much higher proportion of Korean neuro-ophthalmologists recommended corticosteroids in certain indications (38.1% gave IV steroids and an additional 20.6% gave P.O. steroids). Indications were variable and mainly included severe visual loss, fellow eye involvement, progressive visual loss, young age, old age, absence of vascular risk factors, and recurrent attack. Only 17.5% recommended aspirin (80.5% in our study). Eleven (17.5%) prescribed topical anti-glaucoma medications (5.5% in our study) and four (6.4%) treated patients with erythropoietin (none in our study). Comparing the two studies reveals significant disparities between countries. These findings underscore the ongoing debate surrounding the treatment of NAION.

This study has certain limitations. Like Lee et al. [16], the survey is confined to a single country and may not necessarily represent practices, which vary according to each country’s unique health-care system. Furthermore, unlike the Delphi method, a survey inherently lacks the structured iterative process necessary for achieving consensus among experts. However, it is crucial to clarify that our study was not designed to establish consensus guidelines for broader physician communities. Rather, we aimed to explore the prevailing approaches and the degree of controversy among neuro-ophthalmologists in managing patients with acute NAION. While a closed multiple-choice question format facilitated data compilation and uniformity, it may limit the depth of data acquisition. Results may also be influenced by the respondents' personal experiences and beliefs, which may diverge from evidence-based recommendations. Despite these limitations, this study had an excellent response rate of 97.3%, which was significantly higher than other surveys [15, 16] and the absence of missing responses was ensured through personal contact.

The conclusions drawn from this study are twofold. Firstly, the majority (~ 80%) of neuro-ophthalmologists find it significant to actively rule out DM, HTN, OSA, and dyslipidemia in NAION cases and avoid any treatment other than secondary prevention with aspirin. In forthcoming practice, neuro ophthalmologists may increasingly adhere to the continued use of aspirin following "the majority rule".

Secondly, contrary to the aforementioned agreement, there exists a considerable divergence in the preferred diagnostic approaches employed by clinicians. It appears that a prevailing sentiment persists that general practitioners may lack the requisite familiarity with NAION to conduct the appropriate workup. However, uniformity regarding the optimal diagnostic test for several risk factors remains lacking. Furthermore, our study highlights substantial disparities in clinical practices across different nations. These findings collectively emphasize the compelling need for the establishment of international guidelines for the evaluation and management of NAION. Adopting a uniform approach to diagnostic testing may help reduce the risk of second-eye involvement and overall patient disability, all while maintaining cost-effectiveness. From a legal perspective, adherence to standardized guidelines can mitigate the risk of malpractice claims by ensuring a consistent standard of care.