# Assessing the Relationship between Foveal Cone Density, Outer Nuclear Layer Thickness and Foveal Morphology

**Authors:** Serena Zacharias, Joseph Kreis, Natalie Ungaretti, Emma Warr, Heather Heitkotter, Iniya Adhan, Ashleigh Walesa, Katherine Hemsworth, Jenna Grieshop, Joseph Carroll

PMC · DOI: 10.1016/j.xops.2025.100916 · Ophthalmology Science · 2025-08-18

## TL;DR

This study examines how foveal cone density, outer nuclear layer thickness, and foveal shape relate in people with normal vision.

## Contribution

The study reveals weak or negative correlations between foveal cone density and structural features, challenging the use of ONL thickness as a biomarker.

## Key findings

- Maximum ONL thickness weakly correlates with peak cone density (r = 0.23; P = 0.06).
- Peak cone density is significantly negatively correlated with foveal pit diameter (r = –0.54; P < 0.0001).
- Peak cone density is also negatively correlated with foveal pit volume (r = –0.39; P = 0.0011).

## Abstract

To assess the relationship between foveal cone topography, foveal outer nuclear layer (ONL) thickness, foveal morphology, and foveal avascular zone (FAZ) area in individuals with normal vision.

Retrospective cross-sectional study.

A total of 68 participants with normal vision were included (49 female; 19 male).

Directional OCT images were used to derive ONL thickness measurements. Images of the foveal cone mosaic were obtained using adaptive optics scanning light ophthalmoscopy, from which peak cone density (PCD) was measured. Foveal avascular zone area and foveal pit morphology were estimated using OCT angiography images and OCT macular thickness maps, respectively.

Foveal cone density metrics, foveal ONL thickness, foveal pit diameter and volume, and FAZ area.

There was a weak positive correlation between maximum ONL thickness and PCD in individuals with normal vision (r = 0.23; P = 0.06), and PCD was significantly negatively correlated with both foveal pit diameter (r = –0.54; P < 0.0001) and foveal pit volume (r = –0.39; P = 0.0011).

Findings suggest that foveal ONL thickness should be used with caution as a clinical biomarker of foveal cone density, at least when measured using current OCT technology. The relationship between foveal pit size and foveal cone density supports possible mechanistic links between the processes that establish these important features of foveal specialization.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

## Full-text entities

- **Diseases:** retinitis pigmentosa (MESH:D012174), visual impairment (MESH:D014786), cone dystrophy (MESH:D000077765), PCD (MESH:C564040), retinal and systemic diseases (MESH:D012164), pits (MESH:C536528), photoreceptor degeneration (MESH:D009410), albinism (MESH:D000417), inherited retinal degeneration (MESH:D012162), achromatopsia (MESH:D003117)
- **Chemicals:** tropicamide (MESH:D014331), cyclopentolate (MESH:D003519), phenylephrine hydrochloride (MESH:D010656), D (MESH:D003903), D-OCT (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** S192Y, R402Q

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12548097/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12548097/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12548097/full.md

---
Source: https://tomesphere.com/paper/PMC12548097