This is due to ischemia of the optic nerve head. Etiologically and pathogenetically, AION is of two types [10, 14–16].

This is due to the involvement of the rest of the optic nerve. Etiologically, PION can be classified into three types:

Thus, ischemic optic neuropathy actually comprises six distinct clinical entities. AION is by far the most common and one of the most prevalent and visually crippling diseases in the middle aged and elderly. A-AION, though less common, is an ocular emergency and requires early diagnosis and immediate treatment with systemic high-dose corticosteroids to prevent further visual loss, which is entirely preventable.

Since ischemic optic neuropathy is an ischemic disorder of the optic nerve, the first basic requirement is a good understanding of the blood supply of the optic nerve and the role of various factors in the production of acute optic nerve ischemia.

The total number of patients seen in my clinic with this condition was about 1,350. Of those, about 90 % had non-arteritic anterior ischemic optic neuropathy (NA-AION) and 10 % arteritic anterior ischemic optic neuropathy.

There were about 50 patients. Of those, about 66 % had non-arteritic PION, 26 % arteritic PION, and 7 % surgical PION. This depends upon the referral pattern.

Of course, the relative proportion of the various types of ischemic optic neuropathy will vary among different clinics, depending upon the total number of patients seen and the type of practice, but the above data provides a useful general guide.

I have always performed fluorescein angiography (normally stereoscopic) regularly in all eyes with AION. It provides important and useful information when performed during the initial stages of the disease. The telltale impaired circulation and its location in AION are seen on angiography only during early stages of the disease and during the very early retinal arterial phase of dye filling in the fundus. In my clinical studies on AION, angiography has provided crucial information about its pathogenesis as well as the differential diagnosis of arteritic from NA-AION. In eyes with arteritic AION, there is PCA occlusion caused by GCA; angiography shows absent filling of the choroid and the optic disc in the distribution of the occluded PCA (Fig. 19.2). No such filling defect is seen in NA-AION, where there is usually delayed filling of the peripapillary choroid, unless NA-AION is due to embolic occlusion of the PCA. It is most unfortunate that this extremely useful and readily available test is not used by neuro-ophthalmologists as often as it should be for the evaluation of AION. Many NA-AION patients who consult me, having previously seen neurologists/neuro-ophthalmologists, come with records of extensive investigations, including computerized tomography, magnetic resonance imaging, and/or magnetic resonance angiography ordered by the neurologists/neuro-ophthalmologists, showing no abnormality at all. I have also seen patients who lost vision in one eye due to occult GCA and had multiple neuroradiological evaluations done by neurologists/neuro-ophthalmologists, when fluorescein angiography would have immediately provided a definite diagnosis; delay in some of these cases resulted in bilateral complete blindness which could have been entirely prevented. I have found over the past four decades of dealing with AION that fluorescein angiography provides much more useful information in evaluation of AION than neuroradiological evaluations which rarely reveal any abnormality. Fluorescein angiography is also much cheaper than those neuroradiological evaluations, yet it is rarely performed.

I routinely do the following hematologic evaluations in all patients first seen with visual loss.

This is done when a diagnosis of arteritic AION is suspected from clinical findings or GCA is suspected from the elevated ESR and CRP and other clinical findings. The use of temporal artery biopsy in GCA is discussed at length elsewhere [18, 19]. In patients suspected to have GCA, there is no urgency to do a temporal artery biopsy immediately; rather an immediate start of the treatment with high-dose corticosteroid therapy is most critical in these cases to prevent any visual loss. Corticosteroid therapy does not alter the outcome of a temporal artery biopsy [19, 20]. To wait for a temporal artery biopsy result before starting corticosteroid therapy may lose precious time and result in permanent visual loss which is quite preventable; therefore, my advice always has been not to wait for the temporal artery biopsy result to start the corticosteroid therapy. I do not recommend doing temporal artery biopsy on both sides at the same time – after all, temporal artery biopsy is not a benign procedure and I have seen scalp necrosis following this practice. To get reliable information from a temporal artery biopsy, it is essential to keep the following two important considerations in mind: (1) there should be at least a one inch piece of temporal artery, and (2) the artery must be serially sectioned. For example, in one of my cases, only 1 of about 300 sections showed definite evidence of GCA.

If the diagnosis of AION or PION is definite, then the patient requires complete systemic evaluation because both NA-AION and PION are multifactorial in nature, with systemic risk factors playing a role in their development. This includes evaluation for various risk factors, including diabetes mellitus, hyperlipidemia, arterial hypertension, arterial hypotension, collagen vascular diseases, sleep apnea, and other possible risk factors, depending upon a patient’s health status. Information about these risk factors is essential to the management of NA-AION and non-arteritic PION. I advise all patients to have a complete physical checkup.

Briefly, NA-AION is due to acute ischemia of the optic nerve head, and it is a multifactorial disease. This means many risk factors play roles in its development, and there is no one culprit which causes it. Various risk factors can be divided into two main categories: (1) predisposing and (2) precipitating risk factor(s) [17].

These may be systemic or local, in the optic nerve head itself.

I did 24-h ambulatory blood pressure monitoring studies, recording blood pressure every 10 min during waking hours and every 20 min during sleeping hours in about 700 patients [45, 46]. Those revealed that, while blood pressure may be perfectly normal during the day, it drops during sleep – much more in some persons than in others. Figure 19.3 shows the 24-h ambulatory blood pressure monitoring graph of a patient who developed NA-AION, first in one eye and later in the second. It shows that during her waking hours, her blood pressure was within normal limits, but soon after going to sleep, her systolic blood pressure fell from 140 to 90 mmHg and diastolic from about 80 mmHg to about 50 mmHg. Her blood pressure was low throughout her sleeping hours. This is nocturnal arterial hypotension. My 24-h ambulatory blood pressure monitoring studies showed that daytime blood pressure is not at all a guide to the blood pressure during sleep, as can be seen in Fig. 19.3. Unfortunately, most of the information on blood pressure is based on daytime recording.

A certain amount of fall of blood pressure during sleep is physiological, but it can be aggravated by medication, most commonly by aggressive antihypertensive therapy with beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, and other hypotensive drugs, especially when those are taken at bedtime or in the evening [24, 44–46]. Figure 19.4 demonstrates that very well. This patient was taking verapamil (a calcium channel blocker) three times a day (160 mg morning and bedtime and 80 mg noon) for migraine; with that the systolic blood pressure dropped from about 130 mmHg during waking hours to as low as about 80 mmHg during sleep, and diastolic blood pressure dropped from about 70 mmHg during the day to as low as about 40 mmHg during sleep. On stopping the bedtime dose, there was a marked decrease in the fall of blood pressure during sleep. Nocturnal arterial hypotension can occasionally develop without any such medication, as was the case shown in Fig. 19.3; this is most probably due to defective cardiovascular autoregulation.

It is notable that before 1960, that is, before the advent of beta-blockers and other potent modern blood-pressure-lowering drugs, NA-AION was an uncommon disease. Now, as potent antihypertensive drugs are frequently prescribed by physicians, NA-AION has become common, indicating the likelihood that they may be playing a role in its increased incidence.

In persons with predisposing risk factors, precipitating factors then act as the final insult and produce NA-AION. As discussed above, in the vast majority, visual loss develops during sleep [44]. This indicates that nocturnal arterial hypotension is the most common precipitating risk factor. In view of all this information, we can say confidently that NA-AION is a hypotensive disorder. It is due to transient nonperfusion or hypoperfusion of the blood vessels in the optic nerve head during sleep, and not due to occlusion of the PCAs as often stated. Fluorescein fundus angiography provides the best proof of that, as shown by Fig. 19.5.

The argument put forward by those who doubt the role of nocturnal arterial hypotension in the pathogenesis of NA-AION and the hypotensive nature of NA-AION is that in the prospective NA-AION Multicenter Decompression Trial Study [47], only 42 % of the 418 patients reported the onset of visual loss within 2 h of awakening. This is in sharp contrast to the findings of my prospective study [44] where, as mentioned above, 73 % of patients gave a definite history, when specifically asked, of discovering their visual loss on awakening in the morning or from a nap or at the first opportunity in the day to use their vision critically (the rest were not sure of the time). The findings of these two prospective studies do conflict, and that has resulted in controversy on the important concept of the hypotensive nature of NA-AION. However, study design determines the quality of the data. The accuracy of this historical information can be largely influenced by: (1) the expertise of the person asking the questions and (2) the manner in which the patient is asked about when his/her visual loss was first noticed and the circumstances of how he/she became aware of it. In my study [44], I personally collected the historical information from each patient with NA-AION and learned that the accuracy of a patient’s recall depends upon non-suggestive, unbiased, yet thorough questioning. Often the patient needs to be made aware of the importance of their recollection of their discovery of visual loss. In the NA-AION Multicenter Decompression study [47], historical information was collected by many individuals (of different levels of expertise) at different study sites, by necessity, and may not be as rigorous as in my study. It is more challenging in such a heterogeneous study to collect such historical information methodically, uniformly, and reliably, so as to reach an accurate estimate of the true proportion of patients whose visual loss occurred soon after awakening. Estimates of visual loss on awakening may be largely underestimated if based on primarily what the patients volunteer rather than the answers to specific, directed questioning. Moreover, the criterion used in that study of onset of visual loss occurring “within 2 h of awakening” was not valid, because the answer depends upon when the patients first tried to use their vision critically during the day. I think that explains the discrepancy between my study [44] and that of the NA-AION Multicenter Decompression Trial Study [47].

In conclusion, the pathogenesis of NA-AION is known, but it is highly complex. It is multifactorial in nature. Whole hosts of systemic and local risk factors, acting in different combinations, predispose an optic nerve head to develop NA-AION. There are serious confounding factors in determining risk factors for NA-AION; those are discussed in detail elsewhere [48]. One of the arguments often put forward by those who believe the pathogenesis of NA-AION is not yet known is that some patients with NA-AION seem perfectly healthy, with no apparent risk factors. The inability to pinpoint a risk factor may be due to several reasons (discussed elsewhere [48]). Thus, the axiom should be that just because one does not find any evident risk factor, that does not necessarily mean that it does not exist.

A population-based study in the state of Missouri and Los Angeles County, California, USA, found that among persons 50 or older the estimated mean annual incidence rate of NA-AION was 2.30 per 100,000 population, and it was significantly higher among white individuals than blacks or Hispanics [52]. Another epidemiological study in the population of Olmsted County, Minnesota, USA, in persons 50 and older, reported the incidence of NA-AION as 10.2 per 100,000 individuals [53]. Such a large discrepancy between the two studies indicates the problems of obtaining reliable information and the differing ethnic nature of populations since the latter study was based mostly on Caucasians.

NA-AION is mostly a disease of the middle-aged and elderly, although no age is immune to it. In a study of 624 patients with NA-AION, mean + SD age was 61.0 + 12.3 SD, range 18–100 years, with 11 % in young (<45 years), 49 % in middle aged (45–64 years), and 40 % in the elderly (≥65 years) persons [54]. In another study of 727 consecutive patients with NA-AION, 23 % were younger than 50 years (median 43 years; range, 13–49 years) [55]. Thus, the prevalent impression that NA-AION is a disease only of the elderly is not correct – no age is immune. It is seen somewhat more often in men than in women – in one study the ratio was 59 % versus 41 % [54] and in another study 58 % versus 42 % [55]. This would be in keeping with the greater prevalence of cardiovascular diseases among men than women. It is apparently far more common among the white population than in other racial groups [52, 54, 55] but that may be misleading for a variety of reasons.

In the vast majority, these are typical. There is a sudden and painless deterioration of vision, usually discovered on waking in the morning [44]. Progressive visual deterioration in some eyes with NA-AION is well known; in them, again, patients usually notice it on waking in the morning. Some patients may complain of intermittent blurring of vision when the visual field defect passes through the fixation point, because of unconscious shifting of fixation between the seeing and the blind areas near the fixation (Fig. 19.6). NA-AION patients often complain of loss of vision toward the nose and less commonly altitudinal loss. Later on, photophobia is a common complaint, particularly in bilateral cases. Some patients may complain of simultaneous onset of visual loss in both eyes; however, I found in studying more than a thousand patients with NA-AION, the perceived “simultaneous” visual loss in both eyes usually occurred because the patient was unaware of the prior visual loss in the first eye and discovered it only when the second eye became involved. Simultaneous bilateral onset of NA-AION is extremely rare; it may be seen in patients who develop NA-AION during shock with marked fall of blood pressure, hemodialysis, or spinal surgery.

I [44] investigated seasonal variation of the onset of NA-AION for 839 episodes. The data showed that NA-AION onset was significantly more frequent in the summer Iowa City (USA) (the hot months, with temperatures from the 60s to low 90s) than in the winter (the cold months, when the maximum temperature is usually much below freezing) (p = .0030), with spring/fall or the mild months intermediate.

In a study of 500 consecutive NA-AION eyes, when patients were seen within 2 weeks after the onset of visual loss, initial visual acuity was 20/20 in 33 %, better than 20/40 in 51 %, and 20/200 or worse in 21 % [57, 58]. This shows that the presence of normal visual acuity does not rule out NA-AION. Comparison of refraction in NA-AION patients 50 years and older with that of an age-matched general population showed no significant difference between the two groups [37].

In contrast to visual acuity, which can be within normal limits in almost one third of the eyes with NA-AION, visual field defects are a universal occurrence. Therefore, perimetry is the most important and essential visual function test to evaluate the visual loss. These eyes can present with a variety of optic nerve-related visual field defects. In a study of 312 consecutive NA-AION eyes, manual kinetic perimetry (i.e., visual fields plotted with a Goldmann perimeter) showed an overall prevalence of general visual field defects in 83 % with I-2e, 79 % with I-4e, and 69 % with V-4e and of scotoma(s) within the central 30° in 55, 49, and 36 %, respectively [56]. Central scotoma was seen in 49 % with I-2e, 44 % with I-4e, and 29 % with V-4e. Relative inferior altitudinal defect was common (35 % with I-2e and 22 % with I-4e), but absolute inferior altitudinal defect was seen in only 8 %. By contrast, absolute inferior nasal sector visual loss was the most common defect detected in NA-AION (22 %). Thus, a combination of a relative inferior altitudinal defect with absolute inferior nasal defect is the most common pattern in NA-AION (Fig. 19.6a). This contradicts the commonly held belief that inferior altitudinal visual field defect is typical of NA-AION.

Currently, visual fields are usually plotted using automated perimetry; unfortunately, automated perimetry provides information on only up to about 24–30° in the periphery. Kinetic perimetry, by contrast, provides peripheral visual field information all the way to about 80–90° temporally, 70° inferiorly, 60–70° nasally, and 50–60° superiorly. This has two important implications.

Therefore, in NA-AION the visual field plotted with manual kinetic perimetry provides far superior information about the type of visual field defect and the peripheral field and for evaluating visual functional disability [56].

Information on the natural history of visual outcome in NA-AION is vital to determine if any treatment modality advocated for these diseases is really beneficial or not. The gold standard is to compare the outcome of treatment with the natural history of the disease. The importance of information about the natural history of visual outcome is very well illustrated by the following example: A study of optic nerve sheath decompression for the treatment of NA-AION claimed to improve visual loss in this disease – “a disorder without any previously effective therapy” [57]. This “finding” was considered so important that it was published on an expedited basis by the Archives of Ophthalmology, and the procedure became widely popular, till a multicenter clinical trial [47] showed that it was actually harmful; eyes that had the procedure suffered significantly greater (24 %) loss of vision than those left alone (12 %). This clinical trial also showed that 32.6 % of those who had optic nerve sheath decompression had visual improvement compared with 42.7 % of the untreated group. This study concluded that this procedure is “not an appropriate treatment for non-arteritic anterior ischemic optic neuropathy.”

Two prospective studies have evaluated the natural history of visual outcome in NA-AION, one based on 125 eyes [47] and the other on 386 eyes [58]; both arrived at the same conclusion. They showed that patients seen within 2 weeks of onset of visual loss, with initial visual acuity of 20/70 or worse, experienced spontaneous improvement in 41–43 % of the cases and worsening in 15–19 %, at 6 months. One of these studies that evaluated visual fields with kinetic perimetry showed that 26 % of those who were first seen ≤2 weeks of onset with moderate to severe visual field defect showed improvement at 6 months [58]. Visual acuity and visual fields showed improvement or further deterioration mainly up to 6 months, with no significant change after that [58]. My study also showed that there is no correlation between the visual outcomes in the two eyes when a patient develops NA-AION in the second eye [59].

This invariably shows no abnormality except for the presence of relative afferent pupillary defect in unilateral NA-AION eyes, and in some there may be raised intraocular pressure.

Since 1974, several studies have shown that eyes with NA-AION have a significantly higher prevalence of absent or small cup than the general population [37, 60]. This has resulted in a misconception in the ophthalmic community that a small or absent cup is actually the primary factor in the development of the disease; this has resulted in catchy terms like “disc at risk.” The role of an absent or small cup in the pathogenesis of development of NA-AION is discussed in detail elsewhere [36, 37]. That showed that in the multifactorial scenario of the pathogenesis of NA-AION, contrary to the prevalent impression, an absent or small cup is simply a secondary contributing factor, once the process of NA-AION has started, and not a primary factor [36, 61, 62].

In NA-AION, at the onset of visual loss, there is always optic disc edema [64]. There are several misconceptions about optic disc edema in NA-AION. The most common one is that in NA-AION the optic disc edema is always pale – that is not true at all initially, because the color of optic disc edema in NA-AION initially does not differ from optic disc edema due to other causes – in some cases there may even be hyperemia of the optic disc (Figs. 19.7, 19.8, and 19.9b). A splinter hemorrhage at the disc margin is common (Fig. 19.8). Optic disc pallor starts to develop about 2–3 weeks after the onset of NA-AION [62]. A study based on the evaluation of various aspects of optic disc edema in 749 eyes showed that the overall median time (25th–75th percentile) to spontaneous resolution of optic disc edema from the onset of visual loss was 7.9 (5.8–11.4) weeks [62]. The time it took to resolve depended on several factors, e.g., longer in diabetics than in nondiabetics, and worse initial visual field defect and visual acuity were associated with a faster resolution of optic disc edema. When patients were treated with corticosteroid therapy within 2 weeks after onset of NA-AION, there was a significantly faster optic disc edema resolution than in untreated cases. There is a characteristic evolutionary pattern of optic disc edema in NA-AION [62]. The involved part of the disc (i.e., corresponding to the location of visual field loss) initially has edema, with the rest of the disc normal or showing much less edema → after several days the entire disc may show generalized edema → still later, the optic disc in the originally involved part begins to develop pallor and the edema gradually starts to regress in that part, so that the uninvolved part (corresponding to the normal visual field) may have more edema than the ischemic part (that has caused confusion) → then the involved part has pallor but is not edematous any more, while the rest of the disc may show mild edema and even some pallor → the optic disc edema gradually resolves → pallor of the involved region only or the entire disc (Fig. 19.9c). In the latter case, the pallor may or may not be more marked in the involved part. Therefore, the sector of the optic disc showing edema usually corresponds to the location of the visual field defect only during the very early stage, and not later on. Similarly, Arnold and Hepler [63] recorded “no consistent correlation” of the sector of the disc edema with the visual field defect. On resolution of optic disc edema, the distribution of optic disc pallor does not always correspond with the extent and location of visual and nerve fiber loss [62].

In the fellow normal eye, the optic disc usually shows either a small cup or none. This can be a helpful clue to the diagnosis of NA-AION in doubtful cases. If both eyes originally have small disc cups, I have seen that in unilateral NA-AION, once the disc edema resolves, the cup in the involved eye may become slightly larger than the fellow eye because of the loss of nerve fibers. This has also been reported by others [64].

In an occasional case, where NA-AION is due to embolism into the PCA, the optic disc edema usually has a chalky white appearance, unlike in the classical NA-AION.

In diabetics, optic disc changes in NA-AION may have some characteristic diagnostic features. During the initial stages, the optic disc edema is usually (but not always) associated with characteristic prominent, dilated, and frequently telangiectatic vessels over the disc and much more numerous peripapillary retinal hemorrhages than in nondiabetics (Fig. 19.10a, c) [26, 65]. These findings may easily be mistaken for proliferative diabetic retinopathy associated with optic disc neovascularization. When the optic disc edema resolves spontaneously, these prominent telangiectatic disc vessels and retinal hemorrhages also resolve spontaneously (Fig. 19.10b, d). The presence of these characteristic fundus changes in some diabetics with NA-AION has resulted in a good deal of controversy because it has been thought to be a separate clinical entity – described under different eponyms, the most common being “diabetic papillopathy,” when in fact it is NA-AION [26].

It is only angiography during the very early arterial phase of dye filling in the fundus that demonstrates the telltale impaired circulation and its location in NA-AION. In my studies, there is almost invariably a filling defect/delay in the prelaminar region and in the peripapillary choroid (Fig.19.12) and/or choroidal watershed zones (Figs. 19.12b and 19.13) at the onset of NA-AION [35]. Others have also noted this [68, 69]. In the occasional case, where NA-AION is due to embolism into the PCA, the part of the choroid supplied by the occluded PCA or short PCA does not fill (Fig. 19.14). Late optic disc staining is a nonspecific finding of optic disc edema and has no diagnostic importance for NA-AION.

The cumulative probability of the fellow eye developing NA-AION has varied among different studies: 25 % within 3 years in 438 patients [70], 17 % in 5 years in 431 patients [49], and 15 % over 5 years in 326 patients [50]; however, different criteria were used to determine the probability, which may explain the differences. According to one study [70], the risk is greater in men, particularly young diabetic men, while according to another study [50] increased incidence was associated with poor baseline visual acuity and diabetes mellitus. The risk of the second eye getting involved by NA-AION was evaluated in 655 patients (206 diabetics and 449 nondiabetics) and that showed a significantly (p = 0.003) greater risk in diabetics than in nondiabetics [26]; that study also showed that the median (25th–75th percentile) time to involvement of the fellow eye by NA-AION was 6.9 (0.4–16.9) years in diabetics and 9.1 (1.8–19.0) years in nondiabetics. My study has shown that there is no correlation between the visual outcomes in the two eyes when a patient develops NA-AION in the second eye [59].

There are reports in the literature of simultaneous onset of bilateral NA-AION. As discussed above, in my study of more than a thousand patients with NA-AION, the reported “simultaneous” visual loss in both eyes due to NA-AION usually occurred because the patient was unaware of the NA-AION in the first eye until the second eye lost vision. The pattern of optic disc edema during the initial stages of NA-AION is different from that later on (see above), and that is helpful to assess the time of onset in bilateral NA-AION. Simultaneous bilateral onset of NA-AION is extremely rare, except in patients who develop sudden, severe arterial hypotension, e.g., during hemodialysis or surgical shock.

Such recurrences mentioned in the literature are often more a progression of NA-AION during the acute stage rather than actual new episodes after the first episode has resolved completely. In a study of 829 NA-AION eyes, the overall cumulative percentage of recurrence of NA-AION in the same eye was at 3 months 1.0 ± 0.4 % (SE), at 6 months 2.7 ± 0.7 %, at 1 year 4.1 ± 0.9 %, and 2 years 5.8 ± 1.1 % [71]. The only significant association of recurrence of NA-AION was with nocturnal arterial hypotension. Thus, this study indicated that nocturnal diastolic arterial hypotension might be a risk factor for recurrence of NA-AION; however, since NA-AION is a multifactorial disease, other risk factors so far unknown may also play a role.

In a study of 655 consecutive NA-AION patients (931 eyes) – 206 patients with diabetes and 449 without – comparison of various clinical features of NA-AION in diabetics and nondiabetics showed no significant difference in age, but diabetics had slightly more women than men (45 % vs. 38 %; p = 0.078) and a higher prevalence of arterial hypertension (p < 0.0001), ischemic heart disease (p = 0.0001), transient ischemic attacks (p = 0.0003), and second eye involvement by NA-AION (p = 0.003) [26]. Initial visual acuity did not differ significantly between diabetics and nondiabetics; however, of those seen within 2 weeks of onset of NA-AION, diabetics had less severe visual field defect (p = 0.010). At 6 months after onset, there was no significant difference in visual acuity and visual field improvement between diabetics and nondiabetics. Time to optic disc edema resolution was (p = 0.003) longer in diabetics than nondiabetics. As discussed above, the optic disc edema in diabetics usually has characteristic, diagnostic dilated telangiectatic vessels during early stages of NA-AION (Fig. 19.10).

Sergott et al. [57] in 1989 claimed that optic nerve sheath decompression improved visual function in “progressive” NA-AION. But based on my studies on different basic aspects of the subject, I [82] concluded that there was no scientific rationale for doing optic nerve sheath decompression in NA-AION and that the procedure can be harmful. After the report by Sergott et al. [57] and a few other anecdotal reports [83, 84], the procedure gained worldwide favor not only in “progressive” but also in all types of NA-AION. A multicenter Ischemic Optic Neuropathy Decompression clinical trial [47] subsequently established that this procedure is “not effective” and “not an appropriate treatment for non-arteritic AION” and “may be harmful,” because 24 % of the eyes with the optic nerve sheath decompression suffered further visual loss as compared to only 12 % simply left alone. This study also showed that 42 % of cases showed improvement in visual acuity spontaneously, without any procedure.

It is common practice to prescribe aspirin in NA-AION. One study [85], based on 131 patients, claimed that aspirin prevented the development of NA-AION in the fellow eye. A much larger study, based on 431 patients with unilateral NA-AION, revealed no long-term benefit from aspirin in reducing the risk of NA-AION in the fellow eye [49]. Similarly, Newman et al. [50] found no association between regular aspirin use and the incidence of new NA-AION in the fellow eye. Botelho et al. [86] also found that use of aspirin does not improve the visual outcome in NA-AION patients. These findings are not surprising, since NA-AION is not a thromboembolic disorder but a hypotensive disorder and aspirin has no effect on the blood pressure or nocturnal arterial hypotension.

The role of systemic corticosteroid therapy in NA-AION has become highly controversial; therefore, it requires detailed discussion.

A small study by Foulds [87] at the University of Glasgow, Scotland, in 1969, and my own preliminary study [11] at the University of Edinburgh, Scotland, in 1972, indicated that systemic corticosteroids may improve visual acuity in NA-AION. Based on that information, in 1973 I planned a large, multicenter randomized clinical trial to investigate systematically in a large cohort of NA-AION patients whether systemic corticosteroids improved visual outcome or not. Unfortunately, that clinical trial was not funded by the National Institute of Health (the main research funding agency in the United States), because of a firm belief among neuro-ophthalmologists (equating ischemic stroke and NA-AION as pathogenetically similar in nature) that corticosteroid therapy has no role in NA-AION. Since no alternative treatment existed, I felt that it was crucial to find out whether corticosteroid therapy was actually beneficial, ineffective, or conceivably harmful in NA-AION. Because no funds were available, instead of the “conventional randomized study,” I decided on a “patient choice” study – the next best option. Every NA-AION patient seen in my clinic was given a free and informed “patient choice.” The decision was left entirely up to the patient, to opt for corticosteroid therapy or no treatment, in consultation with their physicians or other sources. Most importantly, we had no influence at all on their choice. I specifically told all patients that I really did not know whether the treatment was beneficial, ineffective, or even harmful.

I collected the data for 28 years, completely masked about visual outcomes, numbers, and other aspects of patients in the study. The study finally included 613 consecutive NA-AION patients (696 eyes) seen in my clinic. The results are discussed at length elsewhere [88].