# Frequency tagged multifocal pupillary response fields identify age-related macular degeneration and diabetic retinopathy

**Authors:** Laure Trinquet, Thierry David, Frédéric Chavane, Jean Lorenceau, Fréderic Matonti

PMC · DOI: 10.3389/fnins.2025.1653938 · Frontiers in Neuroscience · 2026-02-10

## TL;DR

This study uses a new method to detect eye diseases like AMD and DR by analyzing how the pupil responds to light patterns.

## Contribution

The study introduces frequency tagged multifocal pupillary response fields as a novel, objective biomarker for retinal diseases.

## Key findings

- mPRF showed decreased power in central and paracentral sectors for AMD patients.
- DR patients exhibited diffuse defects in pupillary response fields.
- mPRF features achieved high sensitivity and specificity in classifying patients from healthy controls.

## Abstract

To quickly characterize multifocal Pupillary Response Fields (mPRF) using frequency tagging and to identify pupillary biomarkers of age-related macular degeneration (AMD) and diabetic retinopathy (DR).

Participants with AMD (N = 74), DR (N = 56), and healthy controls (HP, N = 62) underwent standard ophthalmologic assessments together with a multifocal Pupillary Frequency Tagging test (mPFT). The mPFT test comprised 9 retinal regions whose luminance were sinusoidally modulated at incommensurate temporal frequencies so as to elicit sustained pupillary oscillations over 45 s of fixation.

The recorded pupillary traces were corrected for blinks and transient artifacts. Features of pupillary dynamics and eye-movements, − eye instability during fixation, pupil light reflex, and spectral components of pupil oscillations - were compared across groups. Statistical analyses were performed for each feature separately using Student t-tests and Cohen’s d. The Area under the Curve (AUC) of the Receiver Operating Characteristics (ROC) was computed for different combinations of the extracted features. Pearson’s correlation was used to compare spectral power with other functional measures.

Multifocal Pupillary Response Fields (mPRF) derived from regional spectral power and phase distributions differed significantly between patients and controls, in accordance with the characteristics of each pathology: decreased power for central and paracentral sectors in AMD, diffuse defects in DR. AUCs of ROC performed with relevant features achieved excellent sensitivity (>0.9) and specificity (>0.9) in classifying patients from healthy subjects.

Fast, objective, and easily recorded, mPRF assessments evaluate the functional integrity of retino-pupillary circuits, providing spatiotemporal bio-signatures selective for maculopathies and retinopathies.

## Linked entities

- **Diseases:** age-related macular degeneration (MONDO:0005150), diabetic retinopathy (MONDO:0005266)

## Full-text entities

- **Genes:** SLC7A2 (solute carrier family 7 member 2) [NCBI Gene 6542] {aka ATRC2, CAT-2A, CAT-2B, CAT2, HCAT2, SLC7A2A}, TRPV6 (transient receptor potential cation channel subfamily V member 6) [NCBI Gene 55503] {aka ABP/ZF, CAT1, CATL, ECAC2, HRPTTN, HSA277909}
- **Diseases:** diabetic microangiopathy (MESH:D003925), glaucoma (MESH:D005901), uveitis (MESH:D014605), mPFT (MESH:D013736), fatigue (MESH:D005221), retinal damage (MESH:D012164), retinopathies (MESH:D058437), Cataract (MESH:D002386), asymmetrical damage (MESH:C567658), retinitis pigmentosa (MESH:D012174), TD (MESH:D004409), Stargardt disease (MESH:D000080362), structural (MESH:D020914), blindness (MESH:D001766), neuropathies (MESH:D009422), ischemia (MESH:D007511), migraine (MESH:D008881), HP (MESH:D000067329), Ophthalmic diseases (MESH:C535922), visual defects (MESH:D014786), drusen (MESH:D015593), photophobia (MESH:D020795), pupillary (MESH:D011681), pupillary and eye movements (MESH:D015835), glare sensitivity (MESH:D003807), diseases (MESH:D004194), ocular trauma (MESH:D014947), optic neuropathies (MESH:D009901), Age-Related Maculopathy (MESH:D008268), atrophy (MESH:D001284), atrophic (MESH:D020966), diabetic macular oedema (MESH:D008269), Leber's hereditary optic neuropathy (MESH:D029242), PDR (MESH:C564461), retinal dystrophies (MESH:D058499), DR (MESH:D003930), photoreceptor (MESH:D012173), Diabetic (MESH:D003920)
- **Chemicals:** GW2486TC (-)
- **Species:** Hepacivirus P (species) [taxon 2202225], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929433/full.md

## References

67 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929433/full.md

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Source: https://tomesphere.com/paper/PMC12929433