Optic Disc Features in Nonarteritic Anterior Ischemic Optic Neuropathy: Spatial Organization and Structure-Function Associations

To determine whether funduscopic features in non-arteritic anterior ischemic optic neuropathy (NAION) are spatially organized and associated with structural and functional measures at presentation and outcome.

Cross-sectional and longitudinal secondary analysis of the multicenter, QRK207 NAION treatment trial (NCT02341560).

Trial participants with symptomatic NAION and gradable color fundus photographs at enrollment (n=728) and Month 6 (M6; n=547).

We quantified hemorrhage, hyperemia, axoplasmic stasis (cotton wool spots/micro-opacities), pallid edema, and chronic changes via manual annotation. Each feature was analyzed both as presence versus absence (prespecified primary) and as burden standardized to disc area (secondary). Peripapillary swelling was graded 0-4 by degree of vessel obscuration. Spatial distribution was mapped using modified Garway-Heath sectors. We assessed associations with VF, OCT-derived swelling, and symptom duration.

Global and sectoral VF sensitivity (average total deviation; avgTD) and best-corrected visual acuity (BCVA) at enrollment and M6; OCT-derived peripapillary retinal nerve fiber layer thickness, peripapillary optic nerve head volume, and rate of ganglion cell-inner plexiform layer (GCIPL) thinning.

At enrollment, hyperemic swelling (88.9%) and hemorrhage (79.5%) predominated, and pallid edema was common (27.9%). Acute hyperemia clustered nasally. Hyperemic swelling area correlated with shorter symptom duration (r_s = -0.12, p = 0.004). The presence of pallid edema was associated with faster GCIPL thinning (-1.12 vs -0.37 µm/day, p < 0.001), worse enrollment acuity in multivariable models (β = -6.69 letters; p = 0.002), and modestly longer symptom duration (median 11 vs 10 days; p = 0.03). Enrollment features weakly associated with VF but did not predict M6 avgTD. Inferior peripapillary swelling mildly correlated with worse enrollment superior field deviation (r_s = -0.27, p < 0.001). At M6, pallor was most prevalent (86.7%), clustered temporally, and was independently associated with worse avgTD (Inferior ONH to superior VF: β=-2.07 dB; p= 0.007).

Funduscopic features in NAION exhibit distinct, topographically organized spatial and temporal patterns reflecting evolving tissue injury, but have limited standalone prognostic value for long-term visual outcomes. Notably, acute pallid edema is relatively common in NAION.