# Skin Melanin Content and the Foveal Avascular Zone Correlation in a Healthy White Population

**Authors:** Valentina Folegani, Mariano Cozzi, Andrea Menghi, Salvatore Parrulli, Francesco Romano, Alessandro Invernizzi, Giovanni Staurenghi

PMC · DOI: 10.1167/iovs.67.3.43 · Investigative Ophthalmology & Visual Science · 2026-03-18

## TL;DR

This study found a link between skin melanin levels and the size of a blood vessel-free area in the eye's fovea among healthy white individuals.

## Contribution

The study is the first to show a direct correlation between skin melanin content and foveal avascular zone dimensions in a healthy white population.

## Key findings

- Higher skin melanin index was significantly correlated with larger foveal avascular zone area.
- Lower melanin index was associated with persistent foveal inner retinal layers and increased central foveal thickness.
- Age, sex, and axial length did not significantly influence foveal avascular zone dimensions.

## Abstract

This study aimed to investigate the correlation between skin melanin content and foveal avascular zone (FAZ) characteristics in healthy White subjects and to determine whether melanin expression influences foveal morphology.

In this cross-sectional study, 154 eyes from healthy volunteers 18 to 55 years old underwent comprehensive ophthalmic examinations including optical coherence tomography angiography (OCTA) imaging. The FAZ area was manually delineated from OCTA images. Skin melanin content was measured using a colorimeter at three anatomical sites to obtain a melanin index. Pearson’s correlation and multivariable linear regression analyses were performed to assess associations among the melanin index, FAZ area, axial length (AL), central foveal thickness (CFT), and the presence of persistent foveal inner retinal layers.

A statistically significant positive correlation was observed between the melanin index and FAZ area (r = 0.394, P < 0.001). Multivariable analysis revealed that each 100-unit increase in the melanin index was associated with a 0.12-mm2 increase in FAZ area (P < 0.001), whereas age, sex, and AL were not found to be associated with FAZ. Furthermore, a lower melanin index was significantly associated with the likelihood of foveal inner retinal layer persistence (odds ratio = 0.98) and higher CFT (β = −0.11, P = 0.02).

These findings suggest that physiological variations in cutaneous melanin may be associated with FAZ dimensions and foveal architecture in healthy White individuals. Melanin-related pathways appear to play a regulatory role in retinal development, highlighting the need to consider pigmentation when using FAZ measurements as biomarkers in ocular and systemic diseases.

## Full-text entities

- **Genes:** TYRP1 (tyrosinase related protein 1) [NCBI Gene 7306] {aka CAS2, CATB, GP75, OCA3, TRP, TRP1}, TYR (tyrosinase) [NCBI Gene 7299] {aka ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3}, GPR143 (G protein-coupled receptor 143) [NCBI Gene 4935] {aka NYS6, OA1}, NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}, MC1R (melanocortin 1 receptor) [NCBI Gene 4157] {aka CMM5, MSH-R, SHEP2}, SERPINF1 (serpin family F member 1) [NCBI Gene 5176] {aka EPC-1, OI12, OI6, PEDF, PIG35}, SLC45A2 (solute carrier family 45 member 2) [NCBI Gene 51151] {aka 1A1, AIM1, MATP, OCA4, SHEP5}, DCT (dopachrome tautomerase) [NCBI Gene 1638] {aka OCA8, TRP-2, TYRP2}, HERC2 (HECT and RLD domain containing E3 ubiquitin protein ligase 2) [NCBI Gene 8924] {aka D15F37S1, MRT38, SHEP1, jdf2, p528}, OCA2 (OCA2 melanosomal transmembrane protein) [NCBI Gene 4948] {aka BEY, BEY1, BEY2, BOCA, D15S12, EYCL}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** retinal ischemic (MESH:D012173), CFT (MESH:C537858), depression (MESH:D003866), Diabetic Retinopathy (MESH:D003930), media opacities (MESH:D003318), CMT (MESH:D008268), prematurity (MESH:C536271), retinal diseases (MESH:D012164), albinism (MESH:D000417), ocular pigmentation (MESH:D010859), AL (MESH:C537791), genetic disorders (MESH:D030342), skin (MESH:D012871), ocular and systemic diseases (MESH:D034721)
- **Chemicals:** AL (-), dopaquinone (MESH:C035157), Melanin (MESH:D008543), l-tyrosine (MESH:D014443), l-DOPA (MESH:D007980)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** S192Y, R402Q
- **Cell lines:** RPE — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_IQ82)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13007563/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC13007563/full.md

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Source: https://tomesphere.com/paper/PMC13007563