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

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.

Automated summary

The purpose of this article is to provide a comprehensive review of non-arteritic anterior ischaemic optic neuropathy and its phenocopies, focusing on the current evidence for the different aetiopathogenic hypotheses. Due to limited responses of neural tissue and retinal structures, different mechanisms may result in a similar clinical picture. Clinicians must differentiate among similar pathologies affecting the optic nerve to avoid unnecessary diagnostic procedures.