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Optical coherence tomography angiography in acute non-arteritic anterior ischaemic optic neuropathy
  1. Sourabh Sharma1,2,
  2. Marcus Ang1,2,3,
  3. Raymond P Najjar2,3,
  4. Chelvin Sng3,
  5. Carol Y Cheung4,
  6. Annadata V Rukmini2,
  7. Leopold Schmetterer2,5,6,7,
  8. Dan Milea1,2,8
  1. 1Singapore National Eye Center, Singapore, Singapore
  2. 2Singapore Eye Research Institute, Singapore, Singapore
  3. 3Department of Ophthalmology and Visual Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore
  4. 4Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, New Territories, Hong Kong
  5. 5Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  6. 6Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  7. 7Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  8. 8Neuroscience and Behavioral Disorders, Duke-NUS, Singapore, Singapore
  1. Correspondence to Dr Dan Milea, Visual Neuroscience Group, Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore; dan.milea{at}


Purpose To characterise vascular changes in eyes with acute non-arteritic anterior ischaemic optic neuropathy (NAION), using optical coherence tomography angiography (OCT-A) imaging.

Methods This hospital-based observational case-control study included included five patients with acute NAION (6 eyes), within 7 days after onset of symptoms and 19 age-matched healthy controls (19 eyes). OCT-A (RTVue XR 100; Optovue, Fremont, California, USA), covering a 4.5×4.5 mm scan area, was used to evaluate peripapillary blood flow in cases and controls. The flow densities at the retinal and choroidal level were measured using the split-spectrum amplitude-decorrelation angiography algorithm.

Results The mean age of the NAION and normal subjects was 69 (61–82) and 68 (58–82) years, respectively (p=0.3). At the acute stage, OCT-A disclosed global reduction of the mean peripapillary flow density in eyes with NAION (53.5±3.7%) compared with normal eyes (64.3±2.4%) (p<0.001). The mean vascular flow density was also reduced in the peripapillary choroid layer of eyes with NAION (53.2±7.8%) compared with controls (69.5±3.0%) (p<0.001). In patients (3 eyes) with resolution of optic disc oedema, a repeated OCT-A analysis (at 4–22 weeks) of the full segment (including retina and choroid) revealed spontaneous improvement of the average total peripapillary flow density by 8.1±2.7%.

Conclusions Using OCT-A, we revealed a global and sectorial reduction of retinal and choroidal peripapillary flow densities at the acute stage of NAION, followed by partial subsequent spontaneous recovery. Further studies are needed to establish the potential value of OCT-A for evaluating NAION and other optic neuropathies.

  • Optic Nerve

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Non-arteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in the elderly population, affecting predominantly patients with morphologically smaller optic nerve heads (ONHs).1 The prevalence of NAION depends on the disc size, explaining interethnic differences,2 that is, highest NAION incidence in Caucasians (who have smaller discs compared with Asians and even more than in Africans).3 The overall annual incidence of NAION in patients over 50 years of age varies widely, from 10.2/100 000 in the USA to 1.08/100 000 in Singapore.4 ,5 Clinically, NAION is characterised by acute, painless, typically unilateral visual loss and an altitudinal visual field (VF) defect, associated with optic disc swelling, occurring in patients with local and systemic predisposing factors.6 NAION is most likely caused by transient hypoperfusion within the capillary bed of the ONH, which is closely connected with the choroidal vasculature.3 Although choroidal perfusion explored with fluorescein angiography (FA) is classically preserved in NAION,7 recent structural studies have shown thinning of the subfoveal or of the peripapillary choroid layer, both at the acute8 and chronic phase,9 suggesting that a thinner choroid may be a risk factor for NAION.8

Optical coherence tomography angiography (OCT-A) is a novel, non-invasive imaging system able to delineate the microvasculature within the retina,10 the anterior segment11 ,12 and around the optic nerve.13 ,14 Novel OCT-A developments currently allow quantification of vascular flow areas within the retina and the choroid, generating flow density maps.15 An increasing number of studies have recently evaluated the peripapillary microvasculature in various non-glaucomatous optic neuropathies due to ischaemia, inflammation, compression, hereditary causes, as well as in intracranial hypertension and in optic disc atrophy.13 ,16–21

Given the vascular dysfunction in NAION, we hypothesised that OCT-A might be used to evaluate the microvascular abnormalities in this condition. Thus, the aim of this hospital-based observational comparative pilot clinical study was to assess the ability of OCT-A to quantify the peripapillary microvasculature in the retina and in the choroid, in patients with acute NAION.


This prospective pilot study included five consecutive patients (six affected eyes), diagnosed with typical NAION, based on standard clinical criteria,6 and who presented within 1 week after visual loss. Patients were included after ruling out other causes of optic neuropathies (ie, arteritic, inflammatory, infectious, compressive causes). All included patients had normal neuroimaging findings. Patients with other previous ophthalmic conditions (except uncomplicated cataract surgery) were excluded. Three patients had a follow-up, being evaluated clinically and with OCT-A examination, after resolution of the optic disc swelling. A group of 19 aged-matched normal controls with no ophthalmic history and a normal ocular examination was also included in the study. Written informed consent was obtained from all included subjects. The study was approved by the local institutional review board and was conducted in accordance with the tenets of the Declaration of Helsinki.

Clinical examination

All included subjects underwent a standardised ophthalmic examination including best corrected visual acuity (BCVA) testing, slit lamp examination (Model BQ 900; Haag-Streit, Bern, Switzerland), stereoscopic optic disc assessment, refraction using an autokeratometer (RK-5, Canon, Tokyo, Japan), colour vision assessment by Ishihara pseudo-isochromatic plates and VF assessment by Humphrey Field Analyzer II-750i (SITA-Standard 24-2 program; Carl Zeiss Meditec, Dublin, California, USA). If the visual acuity did not allow evaluation with Humphrey perimetry, patients underwent Goldmann perimetry (I-2e, I-4e and IV-4e targets). The optic disc photographs of both eyes of the patients in this study were digitised, and the horizontal and vertical optic disc diameters were measured.22 ,23

Image acquisition and processing

Each included subject underwent OCT-A using the RTVue system (XR 100, Avanti; Optovue). The instrument operates at 70 000 A-scans per second and provides an axial resolution of 5 μm in tissue. Each image set comprised two raster volumetric patterns (one vertical priority and one horizontal priority) covering 4.5×4.5 mm. Three consecutive scans were obtained from each eye, and OCT-A imaging was performed on both eyes. Quantified optic disc perfusion indexes were automatically calculated and generated by the software using the split-spectrum amplitude-decorrelation angiography algorithm. An en-face angiogram of the blood flow was obtained by the maximum flow (decorrelation value) projection. The flow density was evaluated in the superficial retinal and deeper choroidal layers. The segmentation was based on the detection of the highest gradient magnitude in OCT reflectance for specific tissue interfaces. The OCT-A software was used to delineate a region of interest with an inner border at the level of the outer aspect of the internal limiting membrane (ILM) (seen as a red line on the corresponding OCT scan) and an outer border 180 µm below the Bruch membrane (shown as a green line on the corresponding OCT scan) (figure 1A). Analysis of the choroidal layer was performed within a segmented region, defined as a layer located between the Bruch's membrane and a line situated 180 μm below, using a semi-automated chorioretinal algorithm.13 An artefact removal toggle function within the software was used to remove retinal vessel shadowing from the en-face flow image. Images with a signal strength index <40 or with residual motion artefacts (discontinuous vessel pattern or disc boundary) were excluded from the analysis. Angiography information is displayed as the average of the decorrelation values when viewed perpendicularly through the retinal and optic disc thickness. RTVue XR beta version software was used to provide the peripapillary flow density, defined as the percentage of vascular areas on en-face angiograms in the peripapillary region within the defined 750 µm wide elliptical annulus extending from the optic disc boundary.15 ,24 The OCT-A images were separately evaluated by two independent readers (SS and SML).

Figure 1

Optical coherence tomography angiography (OCT-A) in a healthy control eye. (A) Cross-sectional colour OCT-A. The arrows show the internal limiting membrane (ILM), the Bruch's membrane and a limit located 180 µm below Bruch's membrane (B) 4.5×4.5 mm en-face angiogram showing dense microvascular network around the optic disc. The inner elliptical contour is obtained by fitting an ellipse to the disc margin. The ring width between inner and outer elliptical contour is 0.75 mm. The green horizontal line shows the level of the cross-sectional scan as depicted in panel (A). (C) Diagram representing the mean flow densities of the peripapillary sectors in the 10 included healthy control eyes. The sectors are defined based on the disc margin and Garway-Heath map (six sectors).

Statistical analysis

OCT-A results were compared between the six eyes (five patients) with NAION and the 19 eyes of normal controls (one eye per subject). Statistical analyses were performed using SPSS statistics for Windows (SPSS 2010, IBM, Armonk, New York, USA). BCVA was converted to a log of the minimum angle of resolution (logMAR). Because the study sample was small, a non-parametric Mann-Whitney test was used to compare global and sectorial flow densities in normal and NAION eyes. Intra-individual repeatability of the flow density, reported as the per cent coefficient of variation, was calculated from a subset of normal subjects (n=5) with two sets of scans performed, at the same location, within a single visit. The image analysis was also done by another reader (SML) in the same subset of normal subjects. Interobserver repeatability was determined from measurements made by the two operators. Statistical significance was set at p<0.05. All OCT-A data are presented as mean±SD.


All five included patients were diagnosed with typical NAION in at least one eye, presenting with acute, painless visual loss, VF deficits and optic disc swelling, associated with cup-at-risk discs in the fellow, non-affected eye (in four patients). The mean age (range) of the NAION patients and control subjects was 69 (61–82) and 68 (58–82) years, respectively (p=0.3). Four patients (1, 2, 4 and 5) presented with typical unilateral NAION; one patient (patient 3) presented initially with a typical unilateral NAION and an asymptomatic incipient NAION in the other eye, which subsequently progressed to classical NAION, 4 weeks later. Three patients (patients 3, 4 and 5), who were not treated, had follow-up evaluations with OCT-A (at 4, 7 and 22 weeks, respectively). All OCT-A scans had a good quality (mean signal strength: 57.1±10.5). The demographic characteristics and the associated systemic diseases of all NAION subjects are summarised in table 1. Intra-individual and interobserver variability of the global peripapillary flow density were 3.1% and 1.2%, respectively. The interindividual variability among the normal subjects was 3.8%.

Table 1

Demographic profile, visual acuity and systemic disease associations in patients with NAION

OCT-A in healthy controls showed a dense microvascular network around the optic disc (figure 1); the mean total peripapillary flow density (combined retinal and choroidal layers) was 64.3±2.4%, with a the highest average density in the temporal peripapillary sector (67.1±3.5%). In eyes with NAION, the same parameter was reduced (53.5±3.7%) by 17%, compared with normal control eyes (p<0.001) (table 2). Comparison of sector wise densities between NAION eyes and controls eyes showed decreased flow density in every peripapillary sector (table 2). On average, the temporal peripapillary sector was the most severely affected in patients with NAION, with a 24.1% reduction of the flow density (50.9±5.7%) compared with controls (67.1±3.5%).

Table 2

Peripapillary vascular flow density within different layers of 6 eyes with acute NAION and in 19 healthy control eyes

A dedicated analysis of the microvasculature within the choroid layer (defined as a layer located within the Bruch's membrane and a line situated 180 µm below) showed a total and sectorial reduction of choroidal flow density in eyes with NAION, compared with controls. The retinal layer analysis revealed marginally significant difference between the two groups (table 2). In patients with strictly unilateral involvement (patients 1, 2, 4 and 5), interocular comparisons at the choroidal level showed decreased mean peripapillary flow densities in affected NAION eyes (53.5±7.2%) versus normal, unaffected fellow eyes (68.5±2.3%; p<0.001). These unaffected fellow eyes had comparable mean choroidal peripapillary flow densities with those measured in healthy controls, 68.5±2.3% and 69.5±3.0%, respectively (p>0.5).

Typical clinical and OCT-A findings in a patient with NAION (patient 1) are shown in figure 2. In this patient, the inferior location of the peripapillary microvascular abnormalities detected with OCT-A matched the correspondent superior VF loss. In all included patients, OCT-A revealed the presence of vascular tortuosity at the acute stage, close to areas of decreased flow densities (figure 3). Those vascular tortuosities were less present during the asymptomatic, incipient phase than after visual loss (figure 4). In the three patients who underwent follow-up evaluations (at 4, 7 and 22 weeks), OCT-A demonstrated a spontaneous partial recovery of the peripapillary flow densities (figure 5). The reduced flow densities seen in patient 2 corresponded to late optic disc leakage on FA (see online supplementary figure S1).

Figure 2

Clinical and optical coherence tomography angiography (OCT-A) imaging findings at the acute stage of non-arteritic anterior ischaemic optic neuropathy, in patient 1 (OD). (A) Colour fundus photograph showing inferior sectorial optic disc swelling. (B) OCT-A en-face image with deviation map overlay showing decreased vascular density of the radial peripapillary capillaries, predominantly in the temporal and inferior peripapillary sectors. (C) Goldmann visual field displays superior and nasal field loss, corresponding to the inferior vascular dropout. (D) Colour-coded flow density map showing dark blue areas corresponding to areas of non-flow.

Figure 3

Evolution of clinical and optical coherence tomography angiography (OCT-A) imaging findings at the acute stage of non-arteritic anterior ischaemic optic neuropathy (baseline) and after resorption of the optic disc swelling, patient 3 (OS). (A) Colour fundus photograph showing severe optic disc oedema with haemorrhages in superonasal and inferior disc margins. (B) OCT-A en-face image with deviation map overlay shows global reduction in radial peripapillary capillaries (RPCs) flow densities. The tortuous vessels are indicated by yellow arrows. (C) Colour-coded flow density map shows diffuse areas of microvasculature abnormalities around the optic disc. (D) Colour fundus photograph during follow-up visit (4 weeks following the acute stage) showing a pale optic disk with distinct margins and resolved haemorrages. (E) Follow-up OCT-A, showing improvement in flow densities, compared with the acute stage and (F) decrease of previously non-perfused RPCs areas, in blue.

Figure 4

Optical coherence tomography angiography (OCT-A) findings in incipient non-arteritic anterior ischaemic optic neuropathy (NAION), evolving subsequently to clinically acute NAION, in patient 3 (OD). (A) Colour fundus photograph in an asymptomatic eye with incipient NAION. (B) At this stage, OCT-A en-face image with deviation map overlay discloses mild decrease in flow densities. (C) Colour-coded flow density map with areas of non-perfusion in blue. (D) Subsequently (4 weeks), the patient presented with acute NAION in the right eye and abrupt, severe visual loss. There was extensive disc oedema and haemorrhages. (E) OCT-A disclosed during the symptomatic phase further decrease of flow densities in the peripapillary sectors and larger areas of non-perfusion, visible on the colour-coded map (F).

Figure 5

Evolution of flow densities in three eyes of three patients (patients 3 OS, 4 and 5) with acute non-arteritic anterior ischaemic optic neuropathy (NAION), who underwent a longitudinal follow-up with optical coherence tomography angiography. The black horizontal line represents the average global peripapillary flow density in control eyes (64.3%) with the 95% CI (63.2% to 65.4%) in dotted red lines. All three patients with NAION showed improvement in the global mean peripapillary flow density at follow-up, without reaching comparable values with the controls in two of them (patients 3 and 5). The CI was calculated such as CI=average±1.96×σ/√n (where σ is the SD of the data and n is the number of data points).


In this pilot clinical study, we found that OCT-A is a useful tool for quantification of the peripapillary microvasculature in eyes with NAION, both at the acute stage and at follow-up, after resolution of the optic disc swelling. The main finding of this study is that OCT-A imaging in acute NAION reveals significant segmental and global reduction of the peripapillary vascular flow density, compared with the fellow, healthy eyes and with the age-matched control eyes. Furthermore, follow-up OCT-A scans disclosed spontaneous partial recovery of peripapillary vascular flow densities, in line with the partial improvement of the visual function.

These results are in agreement with previous studies that showed reduced ONH perfusion in NAION, explored with FA,7 indocyanine green angiography,25 laser Doppler flowmetry, velocimetry and colour Doppler imaging.26 ,27 Previous FA studies in NAION have shown significant delay in the filling of the ONH capillaries, but normal choroidal perfusion.7 A recent study has evaluated the ONH microvasculature in acute and chronic optic neuropathies of various causes, using swept-source OCT-A, showing less visible and more tortuous peripapillary and prelaminar microvessels, in affected eyes.16 Our study suggests reduced flow density in acute NAION eyes, when measured within the combined retina and choroid, as well as within the choroid alone. However, OCT-A did not disclose impaired microvasculature in the healthy unaffected eyes of patients, compared with controls. In healthy control eyes, the temporal sector had the highest flow density, a finding consistent with previous literature.28 In eyes with NAION, the temporal sectors were more affected than other peripapillary sectors, possibly due to damage of the watershed zone in this condition.29 Involvement of the temporal watershed zone in NAION might explain the observed increased prevalence of nasal VF defects in this condition.30 In the limited number of eyes with localised optic disc involvement, the clinical sectorial abnormality was associated with a spatially corresponding decrease in vascular flow density of the radial peripapillary capillaries (figure 2, see online supplementary figure S2 and S3). Interestingly, our OCT-A evaluation has also revealed at the acute stage presence of tortuous capillaries and telangectesia within or around regions of vascular dropout, a finding previously known as pseudoangiomatous hyperplasia, described in more than 50% of NAION cases.7 This finding could be consistent with the hypothesis of venous insufficiency in NAION.31 The current system used in our study provided automated estimation of vascular flow densities and serial comparisons using the same system. We have also found that OCT-A has a reduced variability of vascular flow measurements (3.8%), compared with laser Doppler flowmetry (18.5%–28.9%),26 velocimetry (7.9%–8.9%)27 and colour Doppler imaging (17.7%–25.9%).32 In a busy clinical setting, the speed of acquisition and reliability may be a useful feature of the OCT-A.

OCT-A is a non-invasive procedure allowing 3D visualisation of the peripapillary and ONH vasculature at various depths, with a rapid acquisition time of 3–4 s. Mainly used for exploration of retinal conditions, OCT-A has rarely been reported for evaluation of optic neuropathies, other than glaucoma.13 ,14 This study suggests that OCT-A may represent a valuable tool in NAION, but further studies are needed to understand its possible role for monitoring the disease. In our study, we were able to observe spontaneous restored perfusion and improvement in visual acuity in three NAION eyes. However, the peripapillary flow density remained reduced compared with controls in the follow-up visit in the involved peripapillary sectors (figures 3 and 5, see online supplementary figure S2 and S3). Indeed, spontaneous, albeit most often limited clinical improvement may occur in NAION, in up to 43% of patients.33 In contrast, we have also documented, using OCT-A, progression of NAION from its incipient to characterised, acute form, associated with visual loss. Additional OCT-A studies are needed to evaluate various types of optic disc swelling, in an attempt to identify microvascular features related to an ischaemic, versus an inflammatory or compressive causative event.

A dysfunctional vascular autoregulation in NAION may result in changes of the peripapillary choroidal thickness (PCT), a topic which has recently gained a high interest. Surprisingly, the few published studies have shown conflicting results, suggesting either thinning9 or, on the opposite, thickening of the PCT in NAION eyes,34 ,35 and sometimes in the healthy, opposite eyes, compared with controls. The choroid may be also thinner at the subfoveal level in eyes with NAION, compared with controls, after adjusting for age, optic disc diameter, gender and refractive error.8 It has been suggested that choroidal thinning may be a cause, rather a consequence of NAION, since it is also present in the contralateral, disease-free eyes in patients with NAION. Although we did not measure the choroidal thickness in our study, our results, suggesting reduced flow density at the choroid level in NAION, may be compatible with previously described reduced choroidal thickness in this condition. Further studies are needed to better delineate the phenotype and to understand the pathophysiology of NAION.

We recognise several limitations of our pilot clinical study, including its small sample size. In a post hoc power calculation, the sample size of 25 eyes (19 control eyes, 6 patient eyes) used in this study yielded more than 90% power to detect a difference in global peripapillary flow density in full, choroidal and retinal layers, with α=0.05. We acknowledge, however, that a larger sample size of patients (ie, a total of 10 NAION eyes) would have improved the statistical power of our findings (>80%) especially in the sectorial peripapillary analyses of the retinal layers. Given the scarcity of NAION in Singapore (1.08/100 000), the additional recruitment of four eligible patients proved to be challenging within the timeframe of the study.5 The reduction of the flow density measured by OCT-A may not reflect a primary ischaemic process, but rather be the result of compressive oedema, or could be due to signal attenuation secondary to shadowing effect of fluid (oedema, haemorrhage), creating artefacts. However, disappearance of the optic disc oedema at follow-up was still associated with reduced flow density in the involved peripapillary sectors of the three patients with a follow-up. It is possible, however, that the reduced flow density in the chronic phase was due to tissue loss and diminished metabolic needs. The reduction of flow density in the peripapillary choroidal layers could have been also due to segmentation errors, which could not be overcome with the current Angiovue system. The prototype software did not allow us to modulate the segmentation curve of the inner or outer limits to be adjusted; it only allowed movements up or down using the original automated segmentation line course, calculated automatically based on the contour of ILM. Despite all our efforts to perform an accurate segmentation, it is still possible that the current manual method may be associated with some errors, which may cause bias, especially in a small study. We believe that peripapillary oedema and haemorrhages could possibly account for some, but not all, of the reduced flow density observed in NAION. Additional OCT-A studies in patients with optic disc oedema and haemorrhages are essential to evaluate the impact of oedema on flow densities. Other potential limitations of our study are inherent to the current OCT-A technology: the relatively small field of view, potential image distortions and artefacts due to eye movements. Moreover, current OCT-A technology is also limited by signal saturation, which may be seen in large vessels with high velocities, or overestimation of actual vessel density in vessels where the OCT beam spot is larger than the diameter of the capillaries.36 Assessing the deeper choroid vasculature may also have been affected by either projection or masking artefacts from overlying retinal vasculature above the Bruch's membrane within the choroidal OCT-A scans, which may also have decorrelation signals in the choroidal stroma, especially in the Haller layer.37 Nevertheless, we were able to use the OCT-A to demonstrate microvascular abnormalities in eyes with NAION, using segmentation and quadrant comparison analysis, with good interobserver reliability.

In summary, OCT-A is useful for evaluating the peripapillary microvasculature in acute NAION, as well at later stages, showing global and regional vascular dropout. Further studies and larger sample sizes are needed to validate these preliminary findings, to distinguish ischaemic from other causes of optic disc swelling.


The authors thank Dr Lee Shu Yen for very valuable comments. They also thank Dr Benjamin Tan and Mr Mohanram SL, Dr David Goh and Dr Rahat Hussain (Singapore National Eye Centre), and Mr AW Kuang for their contribution to this study.


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  • Contributors SS collected, cleaned and analysed the data, drafted and revised the paper. MA contributed to the design and initiation of the project, designed data collection tools, monitored data collection, drafted and revised the paper. RPN contributed to the analysis and interpretation of data and drafted and revised the paper. CS and CC contributed to the interpretation of data, drafted and revised the paper. AVR analysed and revised the draft paper. LS contributed to the analysis and interpretation of data for the work and revised the draft paper. DM contributed to the design and initiation of the project, designed data collection tools, monitored data collection, contributed to the interpretation of data, drafted and revised the paper.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Sing Health Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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