NAION or not NAION? A literature review of pathogenesis and differential diagnosis of anterior ischaemic optic neuropathies

Abstract

Purpose: To offer a comprehensive review of the available data regarding non-arteritic anterior ischaemic optic neuropathy and its phenocopies, focusing on the current evidence to support the different existing aetiopathogenic hypotheses for the development of these conditions.

Conclusions and importance: Due to the limited array of responses of the neural tissue and other retinal structures, different aetiopathogenic mechanisms may result in a similar clinical picture. Moreover, when the insult occurs within a confined space, such as the optic nerve or the optic nerve head, in which different tissues (neural, glial, vascular) are highly interconnected and packed together, determining the primary noxa can be challenging and may lead to misdiagnosis. Anterior ischaemic optic neuropathy is a condition most clinicians will face during their everyday work, and it is important to correctly differentiate among resembling pathologies affecting the optic nerve to avoid unnecessary diagnostic procedures. Combining a good clinical history and multimodal imaging can assist diagnosis in most cases. The key remains to combine demographic data (e.g. age), with ophthalmic data (e.g. refractive error), systemic data (e.g. comorbidities and medication), imaging data (e.g. retinal OCT) with topographic signs (e.g. focal neurology).

Methodology: Papers relevant for this work were obtained from the MEDLINE and Embase databases by using the PubMed search engine. One author (MPMG) performed the search and selected only publications with relevant information about the aetiology, pathogenic mechanisms, risk factors as well as clinical characteristics of phenocopies (such as vitreopapillary traction, intrapapillary haemorrhage with adjacent peripapillary subretinal haemorrhage or diabetic papillopathy) of non-arteritic anterior ischaemic optic neuropathy (NAION). The terms "non-arteritic ischaemic optic neuropathy/NAION", "vitreopapillary traction", "vitreopapillary traction AND non-arteritic ischaemic optic neuropathy/NAION", "posterior vitreous detachment AND non-arteritic ischaemic optic neuropathy/NAION", "central retinal vein occlusion AND non-arteritic ischaemic optic neuropathy/NAION", "disc oedema/disc oedema", "diabetes mellitus AND non-arteritic ischaemic optic neuropathy/NAION" and "diabetic papillopathy" were searched on PubMed. From each of these searches, publications were selected based on their title, obtaining a total of 115 papers. All papers not written in English were then excluded, and those whose abstracts were not deemed relevant for our review, according to the aforementioned criteria. Subsequent scrutiny of the main text of the remaining publications led us (MPMG, AP, ZS) to include references which had not been selected during our first search, as their titles did not contain the previously mentioned MeSH terms, due to their significantly relevant contents for our work. A total of 62 publications were finally consulted for our review. The literature review was last updated on 24-Aug-2022.

Fig. 1. This diagram depicts the proposed site of occlusion of the short posterior ciliary arteries (SPCAs) as the most widely accepted cause of ischaemia in non-arteritic anterior optic neuropathy (NAION).

The location of the suggested occlusion would be distal to the bifurcation of SCPAs into paraoptic and choroidal branches. The reason to propose that occlusion occurs at this level is the delay of prelaminar optic disc filling (whose blood supply mainly depends on the paraoptic branches of the SCPAs) and the lack of choroidal filling delay on fluorescein angiography (FA), which suggests normal perfusion from the choroidal branches of the SCPAs. It is important, however, to remark that histopathological evidence for this hypothesis is lacking.

Fig. 2. Flowchart depicting the venous aetiology for ischemia in NAION as proposed by Levin et al.

Prolonged hypotension, nocturnal hypotension, shock and/or PED-5 inhibitors would be the primary causes that would lead to a sequential cascade of events resulting in delayed filling in fluorescein angiography and, finally, NAION.

Fig. 3. OCT Spectralis scans through the right optic disc of an 86-year-old female.

The patient presented with haemorrhages obscuring the superior quadrant of her right optic disc, associated with central retinal vein occlusion (CRVO). The images exhibit sequential cuts through the optic disc, superiorly to inferiorly from top to bottom. A–D There is significant swelling of the optic disc, more markedly superonasally. Note the hypereflective vitreous bands, vertically oriented, and the beginning of a vitreous detachment in the more superior cut. The hyperreflective dots overlying the optic disc head represent vitreous haemorrhage. E Repeat optic disc scans over the subsequent 5 months demonstrated sectoral optic disc atrophy consistent with a diagnosis of NAION, whilst the vitreopapillary adhesions remained unchanged (note the fine hipereflective vitreous bands, vertically oriented, in a similar disposition as in previous OCT scans).

Fig. 4. Multimodal imaging of a 22-year-old female, who was diagnosed with intrapapillary haemorrhage with adjacent peripapillary subretinal haemorrhage (IHAPSH) in her right eye.

The patient was myopic and of Asian descent; she had few symptoms and denied any recent Valsalva manoeuvres. Complete resolution of the haemorrhage was observed 10 weeks after presentation. A, B Spectralis OCT through her right optic disc. Note the tilted disc and the subretinal haemorrhage (white arrow) adjacent to the optic disc on its supero-nasal quadrant. C Fundus pseudocolour image of the patient´s right eye. The intrapapillary haemorrhage in the supero-nasal quadrant of the optic disc is evident.

Fig. 5. Fundus pseudocolour image of the right eye of an 86-year-old female diagnosed with non-arteritic anterior optic neuropathy (NAION).

This is the same patient as in Fig. 3. Note the intra- and peripapillary haemorrhages obscuring most of the optic disc. Cotton wool spots can be seen on the superior quadrant of the optic disc. Intraretinal haemorrhages in all 4 quadrants and vitreous haemorrhage could be consistent with a diagnosis of central retinal vein occlusion (CRVO), although venous tortuosity and dilation were not evident. We hypothesise that swelling of the optic disc secondary to NAION may have led to secondary venous congestion in the central retinal vein.

Fig. 6. Flowchart exemplifying management of patients diagnosed with anterior vasculopathic optic neuropathy in our clinic.

Note that for some entities, especially those in which a surgical treatment is not needed, management may be similar.