• Study Purpose: Investigates whether PAMM and peripapillary intraretinal/subretinal fluid (IRF/SRF) on macular optical coherence tomography (OCT) can differentiate arteritic AION (A-AION) from nonarteritic AION (NA-AION) at an early stage.
• Design: Nested prospective cross-sectional diagnostic accuracy study using OCT data from 32 patients (8 A-AION, 24 NA-AION) at a single center in Denmark (2021–2023).
• Key Relevance: Early differentiation is critical as A-AION (linked to giant cell arteritis [GCA]) requires urgent corticosteroids, while NA-AION focuses on managing risk factors.
Study Design and Cohort
• Population: 8 A-AION (10 eyes) and 24 NA-AION (27 eyes) patients from two prospective studies (NCT05248906, NCT05305079).
• A-AION diagnosis: Based on expert interpretation of inflammatory markers (CRP, ESR, platelet count), temporal artery biopsy, and/or FDG PET/CT confirming GCA.
• NA-AION diagnosis: Confirmed neuro-ophthalmological diagnosis without A-AION suspicion; excluded optic disc drusen-associated cases.
• Mean Age: A-AION: 74.5 ± 7.9 years; NA-AION: 61.8 ± 12.5 years (P=.012).
• Sex: 62.5% female in both groups (P=1.00).
• OCT Timing: Initial scans at presentation (median 0 days); Heidelberg Spectralis OCT for PAMM (median 7 days A-AION, 20 days NA-AION).
• PAMM:
• Definition: Hyperreflective bands on OCT at the inner nuclear layer, indicating retinal ischemia.
• Prevalence: Present in 50% of A-AION (4/8 patients) vs 0% of NA-AION (P=.0019).
• Diagnostic Accuracy for A-AION:
• Sensitivity: 50% (95% CI: 16–84%).
• Specificity: 100% (95% CI: 86–100%).
• Positive Predictive Value (PPV): 100%.
• Negative Predictive Value (NPV): 86%.
• Notable: Bilateral PAMM observed in one unilateral A-AION case, suggesting systemic GCA-related retinal hypoperfusion.
• Definition: Peripapillary fluid extending toward the macula, assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (rings at 1, 3, 6 mm from fovea).
• Prevalence:
• Any IRF/SRF: 37.5% A-AION vs 96% NA-AION (P=.0015).
• Within ETDRS grid (≤3 mm from fovea): 0% A-AION vs 83% NA-AION (P=.000047).
• Within ring II (≤1.5 mm from fovea): 0% A-AION vs 33% NA-AION (P=.061).
• Diagnostic Accuracy for NA-AION:
• Any IRF/SRF: Sensitivity 96% (95% CI: 79–100%), Specificity 62% (95% CI: 24–91%), PPV 88%, NPV 83%.
• IRF/SRF in ring III: Sensitivity 83% (95% CI: 63–95%), Specificity 100% (95% CI: 63–100%), PPV 100%, NPV 67%.
• IRF/SRF in ring II: Sensitivity 33% (95% CI: 16–55%), Specificity 100% (95% CI: 63–100%), PPV 100%, NPV 33%.
• Association: IRF/SRF linked to tight optic disc in fellow eye or prior images (P=.0030), supporting NA-AION’s compartment syndrome hypothesis.
• PAMM presence + no IRF/SRF in ETDRS grid: 100% specific for A-AION (4/8 cases).
• No PAMM + IRF/SRF in ETDRS grid: 100% specific for NA-AION (20/24 cases).
• Classification: 75% of patients (24/32) correctly classified using these OCT findings; 100% in age-matched subgroup (>60 Rheum Dis. 2022;81(12):1647-1653.
Clinical Implications
• A-AION:
• PAMM is highly specific (100%) for A-AION, suggesting GCA. Its presence may justify initiating corticosteroids before biochemical results, pending confirmation (biopsy, ultrasound, PET/CT).
• Absence of IRF/SRF within the ETDRS grid further supports A-AION.
• NA-AION:
• IRF/SRF extending into the macula (≤3 mm from fovea) is highly specific (100%) for NA-AION, potentially avoiding unnecessary GCA workup in the absence of PAMM or GCA symptoms.
• IRF/SRF reflects local compartment syndrome, often associated with a crowded optic disc (“disc at risk”).
• Limitations:
• Small sample size (8 A-AION, 24 NA-AION).
• Age difference between groups (A-AION older), though age-matched subgroup analysis confirmed findings.
• Variable timing of OCT scans and potential subclinical GCA duration may affect biomarker detection.
• Retrospective use of different OCT machines (Heidelberg vs. TopCon) did not alter results.
Key Board Exam Pearls
• PAMM: Hyperreflective inner nuclear layer on OCT, linked to retinal ischemia, specific for A-AION (GCA-related).
• IRF/SRF: Peripapillary fluid extending to macula, specific for NA-AION, associated with tight optic disc.
• A-AION Management: Urgent high-dose corticosteroids, diagnostic workup (CRP, ESR, biopsy, PET/CT).
• NA-AION Management: Address modifiable risk factors (hypertension, diabetes, sleep apnea); no proven treatment.
• OCT Timing: Perform at initial presentation, as IRF/SRF may resolve within 1 month in NA-AION.
• Prognosis: PAMM may resolve without damage or lead to atrophy; visual prognosis generally good unless significant structural damage occurs.
Citation
Klefter ON, Hansen MS, Lykkebirk L, et al. Combining Paracentral Acute Middle Maculopathy and Peripapillary Fluid as Biomarkers in Anterior Ischemic Optic Neuropathy. *Am J Ophthalmol*. 2025;271:329-336. https://doi.org/10.1016/j.ajo.2024.12.001