Very Poor Visual Acuity in Non-Arteritic Anterior Ischaemic Optic Neuropathy

ABSTRACT

Very poor (hand motion or worse) visual acuity at presentation is highly unusual in non-arteritic anterior ischaemic optic neuropathy. We retrospectively reviewed the medical records of 151 consecutive non-arteritic anterior ischaemic optic neuropathy patients seen at our institution between July 2014 and April 2016 to evaluate the frequency and characteristics of patients with very poor visual acuity in non-arteritic anterior ischaemic optic neuropathy. Hand motion or worse visual acuity was documented in 17 patients (11%); all patients had at least one vascular risk factor and 14 (82%) had at least two vascular risk factors. Although severe vision loss at presentation does occur in non-arteritic anterior ischaemic optic neuropathy, an extensive workup should be obtained to rule out another cause, especially arteritic anterior ischaemic optic neuropathy.

Introduction

Anterior ischaemic optic neuropathy (AION) is a common cause of acute optic neuropathy in people over the age of 50.^1–4 Differentiating non-arteritic AION (NAION) from arteritic AION (usually related to giant cell arteritis [GCA]) is an essential part of the initial evaluation and may be challenging. Obvious red flags that strongly suggest a diagnosis of arteritic AION include profound visual loss, systemic symptoms of GCA and abnormal laboratory testing consistent with an inflammatory syndrome.^5–9 Very severe visual loss (hand motion or worse) is classic in arteritic AION and relatively rare in NAION.^10–12 Indeed, more than 50% of patients with NAION retain 20/60 or better visual acuity (VA).^10,11,13 In the “Ischemic Optic Neuropathy Decompression Trial” (IONDT), only 34 of 420 NAION patients 50 years of age or older (8%) had hand motion (HM) or worse VA (21 HM and 13 light perception [LP]). This may have been an underestimate, since no light perception (NLP) VA was an exclusion criterion for the IONDT.¹⁰ Hayreh et al.¹¹ reported 34 of 237 NAION patients (14%) with VA of counting fingers (CF) or worse. In young patients (<50 years old) with NAION, Preechawat et al.¹³ reported that only six out of 169 patients (3.6%) had VA of HM or worse. The aim of our study was to report the frequency of very poor VA in NAION patients seen in one tertiary-care academic neuro-ophthalmology service and to describe the characteristics of patients with NAION and very poor presenting VA.

Methods

This study was approved by our institutional review board. This research was performed in accordance with the Health Insurance Portability and Accountability Act regulations and adhered to the tenets of the Declaration of Helsinki.

The medical records of all consecutive patients with NAION evaluated in our neuro-ophthalmology service between July 14, 2014 and April 27, 2016 were reviewed. All patients had been evaluated in a standardised fashion by experienced neuro-ophthalmologists. Only NAION patients with HM, LP or NLP VA at their initial presentation were included in this study. The data we collected included: comorbidities; presence of vascular risk factors; age at onset of visual loss; use of antiplatelet agents before and after onset of visual loss; laboratory studies, including haemoglobin, haematocrit, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelets; treatment with oral or intravenous steroids; neuro-imaging obtained at the time of vision loss; and temporal artery biopsy results when performed. The VA and visual field results at presentation and at final follow-up were recorded. Fundus photographs of the posterior pole obtained within two weeks of visual loss were reviewed when available.

Results

Of the 151 consecutive NAION patients evaluated at our institution over 21 months, 17 patients (11%) had HM or worse VA at presentation and were included in this study (Table 1).

Table 1.

Characteristics of non-arteritic anterior ischaemic optic neuropathy patients with very poor visual acuity

NAION patients with HM or worse visual acuity	17/151 patients (11%)
Median age (Range)	63 years (29–86 years)
Gender	11/17 male (63%)
Race	14 Caucasian, 2 African American, 1 Indian
Disc-at-risk	17/17 (100%)*
Vascular risk factors	17/17 (100%) with ≥114/17 (82%) with ≥26/17 (35%) with ≥41 with 8
Visual acuity at presentation (18 eyes)	2 NLP, 6 LP, 10 HM1 patient had bilateral HM visual acuity
Bilateral NAION	10/17 (59%)
Recurrent NAION	2/17 (12%)
Brain and orbital imaging (MRI/CT)	13/17 (76%); all normal
Blood tests (ESR/CRP)	16/17 (94%); 5 abnormal
Temporal artery biopsy	7/17 (41%); all negative for GCA
Use of anti-platelet agents	1st NAION: 13/17 (76%); 11 prior to NAION2nd NAION: 6/10 (60%); 5 prior to 2nd NAION
Use of steroids	1st NAION: 7/17 (41%)2nd NAION: 7/10 (70%)

*A disc-at-risk was noted in the contralateral eye in patients who had acute optic disc oedema from NAION or in the NAION eye following resolution of optic disc oedema.

CRP = C-reactive protein; CT = computed tomography; ESR = erythrocyte sedimentation rate; GCA = giant cell arteritis; HM = hand motion; LP = no light perception; MRI = magnetic resonance imaging; NAION = non-arteritic anterior ischaemic optic neuropathy; NLP = no light perception.

The median age of the 17 NAION patients with poor VA was 63 years, with a range of 29 to 86 years. Eleven patients (65%) were men and there were 14 Caucasian patients, two African American patients, and one Indian patient. All patients had at least one vascular risk factor, 14 (82%) had two or more vascular risk factors, six (35%) had four or more vascular risk factors, and one patient had eight vascular risk factors. The most common vascular risk factors were hypertension (82%) and hypercholesterolaemia (41%). Additionally, six patients (35%) were obese; five patients (29%) reported cerebrovascular disease, diabetes, or current use of tobacco; two patients (12%) had coronary artery disease; obstructive sleep apnoea, peripheral arterial disease and congestive heart failure were each reported by one patient. Anaemia (haemoglobin of 12.4 g/dL or less) was found in four patients (24%). The haemoglobin levels in these four patients were 12.4, 9.5, 8.2, and 6.9 g/dL. End-stage renal disease was present in three patients (18%) who were all receiving haemodialysis.

In the 17 patients with NAION and very poor VA, 18 eyes were affected; one patient had HM VA in both eyes from bilateral, sequential NAION (NAION occurred in the second eye 123 days after the first NAION). VA at presentation was HM in 10 eyes, LP in six eyes, and NLP in two eyes. Severe, pallid oedema was seen in all six patients with NAION and poor VA who were seen within two weeks of symptom onset (Figure 1).

Figure 1.

Representative fundus photographs of four of the six NAION patients with very poor visual acuity who were seen acutely (within two weeks of symptom onset). All photographs show severe optic disc oedema, with associated peripapillary haemorrhages. The disc appearance in these patients suggested severe ischaemia with pallid colour

Given the severity of vision loss and the severity of the disc oedema, there was a high concern for GCA and other causes of optic neuropathies. Therefore, a majority of the patients underwent further investigations, including neuro-imaging, laboratory studies, and temporal artery biopsy (Table 1). Magnetic resonance imaging or computed tomography was obtained in 13 patients (76%); all imaging studies were normal. Laboratory testing, including ESR, CRP, and a complete blood count, were obtained in 16 patients (94%). In 31% of these patients (5/16 patients), ESR and/or CRP were abnormal (ESR 33–62 mm/hr and CRP 1.5–5.5 times the upper limit of normal), prompting a temporal artery biopsy in all of these patients. Elevated ESR or CRP was only seen in patients who had four or more vascular risk factors. Two of the five patients with an abnormal ESR or CRP had end-stage renal disease on chronic haemodialysis and three patients had chronic anaemia. Temporal artery biopsies were obtained in seven patients (41%), including two patients with a normal ESR and CRP due to a high concern for GCA in these patients (one patient had no light perception VA on presentation and the other patient had bilateral, sequential AION with HM VA in each eye). All temporal artery biopsies were negative for GCA.

Bilateral, sequential NAION occurred in 10 patients (59%) (mean time between eyes of 742 days [range, 61–2912 days]). Three of these 10 patients had an incidentally discovered prior NAION in the contralateral eye at the time of initial presentation. Recurrent NAION (NAION in an eye that had previously had NAION) occurred in two patients (12%).

Due to the severity of the vision loss and the concern for GCA, most patients were initially treated with steroids while further testing was obtained (Table 1). Eleven patients (65%) were on an anti-platelet agent (aspirin or clopidogrel) prior to the onset of the initial NAION and two patients (12%) were started on an anti-platelet agent after the initial NAION. In the 10 patients with bilateral, sequential NAION, five (50%) were on an anti-platelet agent prior to the second episode of NAION and one patient was started on an anti-platelet agent following the second episode. Steroids were used in seven patients (41%) following the initial NAION (five received oral steroids and two received intravenous steroids), and seven of the 10 patients (70%) with bilateral NAION were treated with steroids following the second NAION (four received oral steroids and three received intravenous steroids). The majority of the patients who received oral steroids were prescribed oral steroids by the referring providers, prior to our evaluation of the patients. The dosage of steroids prescribed by the referring providers varied between 40 mg per day and 120 mg per day of oral prednisone. Oral steroids were prescribed by our team in three patients. Two patients were prescribed 60 mg of oral prednisone per day after the second NAION in an attempt to hasten resolution of the optic disc oedema. The third patient had a diagnosis of systemic lupus erythematosus (SLE), therefore oral steroids were prescribed to treat any potential inflammatory component of the optic disc oedema related to SLE.

All patients were followed until resolution of disc oedema and stable visual function was documented. The average length of follow-up for all patients included in the study was 225 days (range 37–725 days). Patients with bilateral, sequential NAION had a longer average follow-up period than patients with unilateral involvement (283 days versus 133 days). Some improvement in VA was seen in 10 out of 18 eyes (56%) with HM or worse VA and two of these patients had a marked improvement in VA. One patient improved from NLP to 20/50 VA over approximately 2.5 months and another patient improved from HM to 20/125 VA over 4.5 months. Neither patient with NLP VA at presentation had NLP VA at the conclusion of the study; one patient had a final VA of 20/50 and the other patient had a final VA of LP. Although improvement in VA was seen in more than half of our patients with NAION and poor VA, most patients continued to have profound vision loss; 16 eyes (89%) had a final VA of 20/400 or worse at their last follow-up visit.

Discussion

In our study, 11% of patients with NAION had profound visual loss at presentation, defined as VA of HM or worse. Although 20/60 or better VA is seen in 31% to 73% of patients with NAION,^10–16 very poor VA does occur in NAION. Several large series have reported a prevalence of very poor visual acuity in NAION ranging from 4% to 14%,^10,11,13 depending on the defining criteria. Although these studies did not specifically analyse the characteristics of NAION patients with profound visual loss in detail, the overall age of presentation, the ethnicity, and the slight male predominance are similar in our cohort of NAION patients to the demographics previously reported for NAION.^10,17,18 All of our poor VA NAION patients had at least one vascular risk factor (Table 1), and a large proportion of our patients (82%) had multiple vascular risk factors. This contrasts with the reported 60% of patients with at least one known vascular risk factor in the IONDT¹⁰ and the 68% of patients reported by Hayreh et al.¹⁷

In addition, our cohort of patients with poor VA and NAION had a higher rate of bilateral involvement and recurrent NAION than what is commonly reported in the literature. We found that 10/17 patients (59%) had bilateral, sequential NAION and two patients (12%) had recurrent NAION. The incidence of bilateral NAION in our cohort of NAION patients with poor VA was 3–4 times higher than the incidence of bilateral NAION reported in the IONDT¹⁹ and the incidence of recurrent NAION in our cohort was about two times higher than the reported incidence of recurrent NAION.²⁰ The higher incidence of bilateral and recurrent NAION in our patients is likely related to the higher prevalence of vascular risk factors in our patients.

All of our patients with very poor VA had a disc-at-risk in the contralateral eye in patients who had acute optic disc oedema from NAION or in the NAION eye following resolution of optic disc oedema. Pallid optic disc oedema was seen in all six of our patients who were evaluated within two weeks of symptom onset (mean 6 days [range 1–14 days]) (Figure 1). In contrast, patients who did not have pallid optic disc oedema at the time of our evaluation were seen more than two weeks after symptom onset (mean 85 days [range 16–185 days]). These patients had resolving optic disc oedema or subsequent optic atrophy at the time of our evaluation. Pallid optic disc oedema is usually more suggestive of an arteritic mechanism (such as from GCA) than NAION and, in concert with the profound visual loss, prompted us to perform extensive ancillary testing and often prolonged follow-up (mean of 225 days), all of which failed to demonstrate an alternative cause of optic neuropathy and ruled-out an arteritic cause.

In addition to the time from symptom onset to presentation, pallid optic disc oedema was also associated with the presence of multiple vascular risk factors, including end-stage renal disease requiring haemodialysis. Indeed, all of our patients with end-stage renal disease on haemodialysis had pallid optic disc oedema, similar to the optic disc appearance previously reported in haemodialysis patients with NAION.²¹ Therefore, we believe the pallid disc oedema observed in our patients with NAION was due to severe ischaemia, likely related to the higher prevalence of vascular risk factors in these patients.

We found mildly elevated ESR and/or CRP in five patients, all of whom were therefore treated with steroids acutely while undergoing further diagnostic testing, including neuroimaging and temporal artery biopsy. Eight of the 10 patients treated acutely with steroids had a VA of 20/400 or worse at last follow-up. Of the 17 NAION patients included in this study, 11 (65%) were on an anti-platelet agent (aspirin or clopidogrel) prior to the onset of the initial NAION and five of the 10 patients with bilateral, sequential NAION were on an anti-platelet agent prior to the second NAION.

The main limitations of our study include the retrospective collection of subjects and the fact that our institution is a tertiary care centre, likely resulting in referral bias for more atypical cases. However, our patient population is not so dissimilar from that of Hayreh’s studies and the IONDT series.^10,17

In conclusion, we observed very poor VA in 11% of our consecutive NAION patients. Most patients had multiple vascular risk factors and all patients seen acutely had severe, pallid disc oedema. These patients also had bilateral involvement and recurrent episodes of NAION more frequently than previously reported.^{11–13,19,20,22,23} Treatment with steroids did not appear to improve visual outcome and pre-existing treatment with antiplatelet agents did not prevent NAION.

Declaration of interest statement

The authors report no conflict of interest.