The research, conducted at HOCH Health Ostschweiz in St. Gallen and published in Frontiers in Neuroimaging, revisited a retrospective series of seven consecutive patients diagnosed with AZOOR between 2005 and 2025. The team, led by Scott Tschuppert, Christophe Valmaggia, and Margarita G. Todorova, combined the full arsenal of modern retinal diagnostics—optical coherence tomography, fundus autofluorescence, near-infrared reflectance, fluorescein angiography, visual field testing, and two forms of electroretinography—with a technique called retinal oximetry. The goal was ambitious: to see whether AZOOR leaves a measurable metabolic fingerprint that could distinguish it from retinitis pigmentosa, a hereditary disease it can superficially mimic.

The cohort itself reflects the typical face of AZOOR. Five of the seven patients were women, with a median age of just 28 years and a range spanning 20 to 53. Six patients had symptoms in only one eye at presentation. Their complaints ranged from scotomas and photopsias to reduced visual acuity and color desaturation. Diagnostic delay varied widely, from as little as eight days to as long as 180 days, underscoring how easily this condition slips past initial examination. One patient had a preceding flu-like illness, another later developed thoracic herpes zoster, and one had bilateral congenital aniridia, with AZOOR assigned clinically to a single presenting eye.

On structural imaging, the disease left its mark consistently. Spectral-domain optical coherence tomography revealed disruption or irregularity of the ellipsoid zone—the thin band corresponding to the inner segments of photoreceptors—in every affected eye. Fundus autofluorescence showed patchy hyperautofluorescence, and near-infrared reflectance imaging displayed the trizonal patterns that have become a hallmark of the disorder. Multifocal electroretinography, which maps macular function point by point, detected macular dysfunction in six of seven patients. Full-field electroretinography, by contrast, was abnormal in only five patients and entirely normal in others, confirming that AZOOR is fundamentally a focal, zonal process rather than a uniform degeneration.

The real novelty lay in the oximetry data. The technique relies on a simple physical principle: oxygenated and deoxygenated hemoglobin absorb light differently at different wavelengths. The Oxymap T1 oximeter mounted on a fundus camera captures images simultaneously at 586 nanometers, where absorption is insensitive to oxygen, and at 605 nanometers, where it is oxygen-sensitive. Software then calculates the optical density ratio for each vessel segment, yielding an estimate of hemoglobin oxygen saturation. Measurements were taken in a predefined peripapillary zone, between concentric circles of two and three optic-disc diameters centered on the optic nerve. Complete arterial and venous data were available for eight eye-level measurements from four AZOOR patients, which were compared against an existing institutional dataset of 22 eyes from 15 healthy controls and 42 eyes from 21 retinitis pigmentosa patients.

The numbers told a striking story. Across the AZOOR measurements, mean arteriolar oxygen saturation was 95.2 percent, noticeably below the 99.1 percent seen in healthy controls and the 101.3 percent recorded in the retinitis pigmentosa group. Meanwhile, venular saturation was unremarkable at 67.3 percent, and consequently the arteriovenous difference—a surrogate for how much oxygen the retina actually consumes—was compressed to 27.9 percent, versus roughly 34 to 36 percent in the other groups. Kruskal–Wallis testing across all three groups confirmed significant intergroup differences for arteriolar saturation and the arteriovenous difference, while exploratory pairwise Mann–Whitney comparisons showed that AZOOR was significantly lower than both controls and retinitis pigmentosa on both parameters. Venous saturation, intriguingly, did not differ among the groups at all.

Why does this matter? The comparison with retinitis pigmentosa is the intellectually satisfying part. In that degenerative disease, photoreceptors—especially oxygen-hungry rods—die off progressively. When the tissue’s metabolic demand collapses, less oxygen is extracted from the blood, so vessels carry away oxygen they never delivered, and measured saturation rises. Some retinitis pigmentosa values even exceed 100 percent, a recognized calibration artifact of altered vessel caliber and changed retinal optics rather than true supersaturation. AZOOR shows the opposite pattern: lower arterial saturation despite outer retinal damage. Reduced oxygen consumption alone cannot explain this, because dying photoreceptors should push saturation up, not down. Something else is going on—possibly vascular dysregulation, inflammation-associated vascular change, or disease-related optical effects, though the authors are careful to label all such explanations hypothetical.

This metabolic profile is biologically plausible in the context of an inflammatory disease. In uveitic conditions such as Vogt-Koyanagi-Harada disease and Behçet disease, retinal oxygen metabolism and vascular parameters shift measurably, and occlusive vasculitis can be documented with angiography and optical coherence tomography angiography. The AZOOR pattern is compatible with localized inflammatory or vascular dysregulation—though oximetry measures saturation, not blood flow, so it cannot by itself prove occlusion or reduced perfusion. The researchers emphasize that because oximetry was performed at wildly different disease stages, roughly 15 days after symptom onset in one patient and up to 120 months in another, these findings represent a disease-associated pattern observed during routine follow-up, not evidence of acute inflammatory activity.

The caveats deserve honest acknowledgment. AZOOR is rare, and seven patients is a small sample by any standard; oximetry was available in only four of them because the instrument arrived at the clinic after several patients had completed care. Both eyes of the same individual were analyzed when available, violating statistical independence, and the exploratory comparisons were not corrected for multiple testing. The retinitis pigmentosa and control data came from a separate institutional dataset without a standardized severity classification. The authors themselves frame the p-values as hypothesis-generating rather than confirmatory. A sensitivity analysis excluding the patient with congenital aniridia left the direction of all findings unchanged, which strengthens the signal somewhat, but nobody is claiming a diagnostic threshold yet.

Still, the conceptual advance is real. By adding a metabolic vascular parameter to a phenotyping workflow traditionally built on structure and electrophysiology, the St. Gallen team has sketched what a complete multimodal assessment of AZOOR could look like: arterial, venous, and arteriovenous oxygen metrics layered onto OCT segmentation, wide-field autofluorescence mapping, OCT angiography, adaptive optics imaging, and longitudinal visual field and ERG outcomes. If prospective studies confirm that AZOOR’s low arterial saturation and reduced oxygen extraction persist or evolve in a characteristic way, retinal oximetry could become a practical biomarker for monitoring disease activity and, eventually, for testing treatments in a condition where no controlled therapeutic trial has ever been completed. For a disease discovered more than thirty years ago and still lacking a known cause, a new window on its metabolism is a genuinely exciting development.

Subject of Research: Retinal oxygen saturation measured with oximetry in acute zonal occult outer retinopathy compared with retinitis pigmentosa and healthy controls

Article Title: Distinct retinal oxygenation patterns in acute zonal occult outer retinopathy assessed by multimodal imaging

Article References: Tschuppert, S., Valmaggia, C., & Todorova, M. G. (2026). Distinct retinal oxygenation patterns in acute zonal occult outer retinopathy assessed by multimodal imaging. Frontiers in Neuroimaging, 5, Article 1902215. https://doi.org/10.3389/fnimg.2026.1902215

Image Credits: AI Generated

DOI: 10.3389/fnimg.2026.1902215

Keywords: AZOOR, retinal oximetry, retinitis pigmentosa, oxygen saturation, multimodal imaging, ellipsoid zone, electroretinography, optical coherence tomography, outer retinopathy, retinal metabolism, ophthalmic imaging, autofluorescence