Acute Optic Neuropathy in Older Adults: Differentiating Between MOGAD Optic Neuritis and Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease optic neuritis (MOGAD-ON) and nonarteritic anterior ischemic optic neuropathy (NAION) can cause acute optic neuropathy in older adults but have different managements. We aimed to determine differentiating factors between MOGAD-ON and NAION and the frequency of serum MOG-IgG false positivity among patients with NAION. METHODS: In this international, multicenter, case-control study at tertiary neuro-ophthalmology centers, patients with MOGAD presenting with unilateral optic neuritis as their first attack at age 45 years or older and age-matched and sex-matched patients with NAION were included. Comorbidities, clinical presentations, acute optic disc findings, optical coherence tomography (OCT) findings, and outcomes were compared between MOGAD-ON and NAION. Multivariate analysis was performed to find statistically significant predictors of MOGAD-ON. A separate review of consecutive NAION patients seen at Mayo Clinic, Rochester, from 2018 to 2022, was conducted to estimate the frequency of false-positive MOG-IgG in this population. RESULTS: Sixty-four patients with unilateral MOGAD-ON were compared with 64 patients with NAION. Among patients with MOGAD-ON, the median age at onset was 56 (interquartile range [IQR] 50-61) years, 70% were female, and 78% were White. Multivariate analysis showed that eye pain was strongly associated with MOGAD-ON (OR 32.905; 95% CI 2.299-473.181), while crowded optic disc (OR 0.033; 95% CI 0.002-0.492) and altitudinal visual field defect (OR 0.028; 95% CI 0.002-0.521) were strongly associated with NAION. On OCT, peripapillary retinal nerve fiber layer (pRNFL) thickness in unilateral MOGAD-ON was lower than in NAION (median 114 vs 201 µm, p < 0.001; median pRNFL thickening 25 vs 102 µm, p < 0.001). MOGAD-ON had more severe vision loss at nadir (median logMAR 1.0 vs 0.3, p < 0.001), but better recovery (median logMAR 0.1 vs 0.3, p = 0.002). In the cohort of consecutive NAION patients, 66/212 (31%) patients with NAION were tested for MOG-IgG and 8% (95% CI 1%-14%) of those had false-positive serum MOG-IgG at low titers. DISCUSSION: Acute unilateral optic neuropathy with optic disc edema in older adults can be caused by either MOGAD-ON or NAION. Detailed history, the degree of pRNFL swelling on OCT, and visual outcomes can help differentiate the entities and prevent indiscriminate serum MOG-IgG testing in all patients with acute optic neuropathy.

Nonarteritic anterior ischemic optic neuropathy and incidence of Parkinson's disease based on a nationwide population based study.

This study aimed to investigate the association between nonarteritic anterior ischemic optic neuropathy (NAION) and Parkinson's disease (PD) using a retrospective, nationwide, population-based cohort in South Korea. This study utilized data from the Korean National Health Insurance database, including 43,960 NAION patients and 219,800 age- and sex-matched controls. Cox proportional hazards regression models were used to assess the risk of developing PD in the NAION group compared to the control group after adjusting for various confounding factors. Subgroup analyses were conducted based on sex, age, and comorbidities. The incidence rate of PD was higher in the NAION group (1.326 per 1000 person-years) than in the control group (0.859 per 1000 person-years). After adjusting for confounding factors, the risk of developing PD was significantly higher in the NAION group (adjusted hazard ratio [aHR] 1.516, 95% confidence interval [CI] 1.300-1.769). Subgroup analyses did not reveal a significant difference in the risk of PD development based on sex, age, or comorbidities. This retrospective, nationwide, population-based cohort study revealed a significant association between NAION and an increased risk of developing PD in a South Korean population. The incidence rate of PD was observed to be higher in individuals diagnosed with NAION than in age- and sex-matched controls even after adjusting for potential confounding variables, with the risk being approximately 51.6% higher in the NAION group. Further research is necessary to elucidate the underlying pathophysiological mechanisms linking NAION to PD and to determine whether similar associations exist in other ethnic and geographical populations.

Anterior and posterior ischemic optic neuropathy in a child with focal segmental glomerulosclerosis on hemodialysis.

BACKGROUND: Ischemic optic neuropathy (ION) is exceedingly rare in children on dialysis, resulting from poor perfusion of the optic nerve, and presents as sudden acute painless vision loss. CASE-DIAGNOSIS/TREATMENT: We report the case of a 3-year-old male with stage 5 chronic kidney disease (CKD 5) due to focal segmental glomerulosclerosis (FSGS) status post-bilateral nephrectomy on chronic hemodialysis who had acute loss of vision several hours after a hemodialysis session. Earlier that day, he had a drop in blood pressure intra-dialysis to 89/67 mmHg, with at home blood pressures ranging 90/60 to 150/100 mmHg. The patient was treated with tight blood pressure control to maintain blood flow and prevent blood pressure lability, received high-dose corticosteroids with a corticosteroid taper, and placed on high-dose erythropoietin for neuroprotective effect. He regained partial vision beginning approximately 1 month after presentation. CONCLUSIONS: The exact cause of our patient's simultaneous bilateral anterior and posterior ION, confirmed via MRI and fundoscopic examination, is unclear; however, is likely secondary to a combination of fluctuating blood pressure, anemia, anephric status, and hemodialysis. This highlights the need for close blood pressure monitoring, management of anemia, and more diligent ophthalmologic screening in pediatric patients on chronic hemodialysis.

Differentiating Ischemic Optic Neuropathy from Glaucoma Using Diagnostic Tests.

INTRODUCTION: Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize differences in diagnostic tests that can help perform a correct diagnosis. METHODS: The search strategy was performed according to the PRISMA 2009 guidelines, and four databases were used: MEDLINE, Embase, Web of Science, and Cochrane. Totally, 772 references were eligible; 39 were included after screening with respect to inclusion criteria that included English language and published in the 20 years before search date. RESULTS: Ninety percent (n = 35) of included studies used optical coherence tomography (OCT). Glaucomatous eyes had a significantly greater cup area, volume and depth, cup-to-disk ratio, a lower rim volume and area, and a thinner Bruch's membrane opening-minimum rim width. Retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes occurred primarily at the superotemporal, inferotemporal, and inferonasal sectors, while AION eyes demonstrated mostly superonasal thinning. Glaucoma eyes showed greater macular ganglion cell layer thickness, except at the inferotemporal sector. OCT angiography measurements demonstrated a significant decrease in superficial and deep macular vessel density (VD) in glaucoma compared to AION with similar degree of visual field damage; the parapapillary choroidal VD was spared in AION eyes compared to glaucomatous eyes. CONCLUSION: By use of OCT imaging, optic nerve head parameters seem most informative to distinguish between glaucoma and AION. Although both diseases affect the RNFL thickness, it seems to do so in different sectors. Differences in structure and vascularity of the macula can also help in making the differential diagnosis.

Features of Peripapillary Hyperreflective Ovoid Mass-Like Structures in Nonarteritic Anterior Ischemic Optic Neuropathy Patients and Normal Controls.

Purpose: To determine the characteristics of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and in normal adults. Methods: A total of 406 included eyes were divided into four groups: acute NAION group, chronic NAION group, unaffected group, and normal eyes group. PHOMS were detected on optical coherence tomography slices from optical coherence tomography angiography scans centered on the optic nerve head (ONH). The differences in age, sex, and ONH parameters were investigated between eyes with PHOMS and eyes without PHOMS among groups. Results: The prevalence of PHOMS in acute eyes (43.48%) and fellow eyes (28.20%) was significantly higher than that in normal eyes (11.76%) (acute vs. normal, P < 0.001; fellow vs. normal, P = 0.014). In the acute group, the PHOMS score of size was negatively correlated with age in acute eyes (r = -0.486, P = 0.03). The size of PHOMS was negatively correlated with age and cup/disc ratio and positively correlated with retinal nerve fiber layer thickness in the nasal and inferior sectors in the normal groups. No differences in age, sex, ONH parameters, or visual field defects were found between eyes with PHOMS and eyes without PHOMS. Conclusions: The prevalence of PHOMS increased significantly in acute nonoptic disc drusen (NODD)-NAION eyes and fellow eyes. PHOMS could also be found among normal adults. PHOMS may be a nonspecific sign secondary to ONH edema and axoplasmic stasis. Translational Relevance: The high prevalence of PHOMS in acute NODD-NAION eyes may indicate axoplasmic stasis secondary to tissue edema.

Papillary vitreous detachment as a possible accomplice in non-arteritic anterior ischaemic optic neuropathy.

AIM: To evaluate the role of papillary vitreous detachment in the pathogenesis of non-arteritic anterior ischaemic optic neuropathy (NAION) by comparing the features of vitreopapillary interface between NAION patients and normal individuals. METHODS: This study included 22 acute NAION patients (25 eyes), 21 non-acute NAION patients (23 eyes) and 23 normal individuals (34 eyes). All study participants underwent swept-source optical coherence tomography to assess the vitreopapillary interface, peripapillary wrinkles and peripapillary superficial vessel protrusion. The statistical correlations between peripapillary superficial vessel protrusion measurements and NAION were analysed. Two NAION patients underwent standard pars plana vitrectomy. RESULTS: Incomplete papillary vitreous detachment was noted in all acute NAION patients. The prevalence of peripapillary wrinkles was 68% (17/25), 30% (7/23) and 0% (0/34), and the prevalence of peripapillary superficial vessel protrusion was 44% (11/25), 91% (21/23) and 0% (0/34) in the acute, non-acute NAION and control groups, respectively. The prevalence of peripapillary superficial vessel protrusion was 88.9% in the eyes without retinal nerve fibre layer thinning. Furthermore, the number of peripapillary superficial vessel protrusions in the superior quadrant was significantly higher than that in the other quadrants in eyes with NAION, consistent with the more damaged visual field defect regions. Peripapillary wrinkles and visual field defects in two patients with NAION were significantly attenuated within 1 week and 1 month after the release of vitreous connections, respectively. CONCLUSION: Peripapillary wrinkles and superficial vessel protrusion may be signs of papillary vitreous detachment-related traction in NAION. Papillary vitreous detachment may play an important role in NAION pathogenesis.

Ocular manifestations of obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: The association of obstructive sleep apnea (OSA) with development of eye diseases is unclear. This current systematic review and meta-analysis attempts to summarize and analyze associations between OSA and ocular disorders in the literature. METHODS: PubMed, EMBASE, Google Scholar, Web Of Science, and Scopus databases were searched from 1901 to July 2022 in accordance with the Preferred Reporting in Systematic Review & Meta-Analysis (PRISMA). Our primary outcome assessed the association between OSA and the odds of developing floppy eyelid syndrome (FES), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), retinal vein occlusion (RVO), keratoconus (KC), idiopathic intracranial hypertension (IIH), age-related macular degeneration (AMD), and central serous chorioretinopathy (CSR) through odds ratio calculated at the 95% confidence interval. RESULTS: Forty-nine studies were included for systematic review and meta-analysis. The pooled OR estimate was highest for NAION [3.98 (95% CI 2.38, 6.66)], followed by FES [3.68 (95% CI 2.18, 6.20)], RVO [2.71(95% CI 1.83, 4.00)], CSR [2.28 (95% CI 0.65, 7.97)], KC [1.87 (95% CI 1.16, 2.99)], glaucoma [1.49 (95% CI 1.16, 1.91)], IIH [1.29 (95% CI 0.33, 5.01)], and AMD [0.92 [95% CI 0.24, 3.58] All observed associations were significant (p < 0.001) aside from IIH and AMD. CONCLUSION: OSA is significantly associated with NAION, FES, RVO, CSR, KC, and glaucoma. Clinicians should be informed of these associations so early recognition, diagnosis, and treatment of eye disorders can be addressed in at-risk groups, and early referral to ophthalmic services is made to prevent vision disturbances. Similarly, ophthalmologists seeing patients with any of these conditions should consider screening and referring patients for assessment of possible OSA.

A Successfully Treated Case of Posterior Ischemic Optic Neuropathy That Developed during Antihypertensive Therapy for Hypertensive Emergency.

A 33-year-old woman developed hypertensive emergency (268/168 mmHg) with renal failure and hypertensive retinopathy. Four hours after the initiation of antihypertensive therapy with the continuous infusion of nicardipine, her blood pressure (BP) decreased to 168/84 mmHg; however, the patient developed blindness. She was diagnosed with posterior ischemic optic neuropathy (PION). Her BP was maintained at approximately 175/90 mmHg until her vision improved. Olmesartan was initiated on day 13, and her BP decreased to approximately 135/95 mmHg without the re-exacerbation of vision loss. Although the prognosis of PION is poor, its early diagnosis and gradual antihypertensive therapy may help preserve the patient's vision.

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.

Vessel Density Features of Optical Coherence Tomography Angiography for Classification of Optic Neuropathies Using Machine Learning.

BACKGROUND: To evaluate the classification performance of machine learning based on the 4 vessel density features of peripapillary optical coherence tomography angiography (OCT-A) for classifying healthy, nonarteritic anterior ischemic optic neuropathy (NAION), and optic neuritis (ON) eyes. METHODS: Forty-five eyes of 45 NAION patients, 32 eyes of 32 ON patients, and 76 eyes of 76 healthy individuals with optic nerve head OCT-A were included. Four vessel density features of OCT-A images were developed using a threshold-based segmentation method and were integrated in 3 models of machine learning classifiers. Classification performances of support vector machine (SVM), random forest, and Gaussian Naive Bayes (GNB) models were evaluated with the area under the receiver-operating-characteristic curve (AUC) and accuracy. RESULTS: We divided 121 images into a 70% training set and 30% test set. For ON-NAION classification, best results were achieved with 50% threshold, in which 3 classifiers (SVM, RF, and GNB) discriminated ON from NAION with an AUC of 1 and accuracy of 1. For ON-Normal classification, with 100% threshold, SVM and RF classifiers were able to discriminate normal from ON with AUCs of 1 and accuracies of 1. For NAION-normal classification, with 50% threshold, the SVM and RF classified the NAION from normal with AUC and accuracy of 1. CONCLUSIONS: ML based on the combined peripapillary vessel density features of total vessels and capillaries in the whole image and ring image could provide excellent performance for NAION and ON distinction.