The Hidden Role of the Choroid in Vitelliform Maculopathies

The Hidden Role of the Choroid in Vitelliform Maculopathies

Vitelliform lesions are yellowish, oval deposits in the macula composed of photoreceptor debris and lipofuscin resulting from impaired phagocytosis by the retinal pigment epithelium (RPE). While these lesions often look similar, advances in Enhanced-depth imaging OCT (EDI-OCT) have revealed that the underlying choroidal thickness (CT) varies significantly across different disorders, serving as a critical indicator of pathophysiology.

Hereditary Vitelliform Dystrophies

In genetic conditions, choroidal changes often reflect a secondary response to RPE stress:

• Adult-onset Foveomacular Vitelliform Dystrophy (AOFVD): Subfoveal CT is significantly increased during early and vitelliruptive stages. This thickening is thought to be a compensatory vascular response to RPE damage. Conversely, decreasing CT is associated with progression toward macular atrophy and poorer visual outcomes.
• Best Disease: This autosomal dominant disorder shows increased CT during active vitelliform stages, but characteristically progresses to choroidal thinning in atrophic and cicatricial phases.
• Autosomal Recessive Bestrophinopathy (ARB): Unlike the dominant form, ARB frequently presents with diffuse choroidal thickening (found in 60–75% of cases), often associated with hyperopia.

Acquired Vitelliform Lesions in AMD

Choroidal thickness helps differentiate between types of vitelliform lesions in age-related macular degeneration:

• Standard AVLs in AMD: These eyes typically show a thicker choroid and a higher frequency of pachyvessels compared to AMD eyes without vitelliform material.
• Leptovitelliform Maculopathy (LVM): A recently defined entity, LVM is characterized by diffusely thin (lepto) choroid associated with subretinal drusenoid deposits (SDD). These patients tend to be older and are more prone to rapid progression toward macular atrophy.

The Pachychoroid Disease Spectrum (PDS)

In PDS, choroidal abnormalities are considered a primary driver of disease:

• Pachyvitelliform Maculopathy (PVM): This variant features markedly increased CT and choroidal vascular hyperpermeability (CVH). The prognosis is often poor due to high rates of central atrophy.
• Central Serous Chorioretinopathy (CSCR) and PPE: Both conditions involve thickened choroids that contribute to RPE dysfunction and the subsequent accumulation of subretinal hyperreflective material.
• Peripapillary Pachychoroid Syndrome (PPS): This syndrome shows unique nasal or peripapillary choroidal thickening, with vitelliform lesions resolving as choroidal congestion stabilizes.

Miscellaneous and Tractional Disorders

• Angioid Streaks (AS): Vitelliform lesions in AS are associated with a progressive reduction in CT over time, which parallels a decline in visual acuity.
• Toxicities and Systemic Disease: Disorders like Pentosan polysulfate toxicity or immunogammopathies (e.g., multiple myeloma) can also manifest with vitelliform lesions and associated choroidal thickening or pachyvessels.
• Tractional Disorders: In conditions like vitreomacular traction, vitelliform-like lesions are driven by mechanical forces rather than primary choroidal or RPE dysfunction.

Clinical Implications

Evaluating choroidal thickness is no longer just a research tool; it is a vital clinical biomarker. While thickening may indicate a primary driver in pachychoroid diseases, it often represents a secondary metabolic response in hereditary dystrophies. Understanding these distinctions is essential for accurate diagnosis and monitoring disease progression toward atrophy or fibrosis.

Reference: Eye (2026) 40:12–23; https://doi.org/10.1038/s41433-025-04103-7