Choroidal Vascularity Index in FM — negative result

One-paragraph summary

Ekici Zincirci et al ran a single-centre swept-source OCT case-control study comparing choroidal vascularity index (CVI) and choroidal thickness between FMS patients and healthy controls, with autonomic symptom burden (COMPASS-31), fibromyalgia impact (FIQ-R), and central sensitization (CSI) as exposure measures. The result is negative. CVI and choroidal thickness did not differ between FMS and controls (all p > 0.09), and CVI was not correlated with COMPASS-31, FIQ-R, or CSI within either group. Age was the only independent predictor of CVI in adjusted models. This is the first within-FM test of the choroidal-vascular substrate hypothesis and it fails to find a signal, which directly tempers B-Re-2 (choroidal MC mechanism extension) at the choroidal-thickness/vascularity endpoint and shifts the project's retinal-substrate priority toward inner-retinal (RNFL/GCL) rather than choroidal layers.

Claims as triples

Format: subject_id — predicate → object_id [evidence: figure/table; confidence: tier]

• choroidal_thickness — fails_to_differ_in → fm_central_only [evidence: between-group p = 0.097–0.136 (max/mean thickness); confidence: emerging]
• choroidal_vascularity_index — fails_to_differ_in → fm_central_only [evidence: between-group p = 0.124; confidence: emerging]
• choroidal_vascularity_index — fails_to_correlate_with → autonomic_dysregulation [evidence: Spearman correlations within both groups, multivariable regression with COMPASS-31 not significant; confidence: emerging]
• central_sensitization — elevated_in → fm_central_only [evidence: CSI score difference p < 0.001; confidence: established (replicates known finding)]
• autonomic_dysregulation — elevated_in → fm_central_only [evidence: COMPASS-31 difference p < 0.001; confidence: established (replicates known finding)]
• age — predicts → choroidal_vascularity_index [evidence: adjusted regression p < 0.001; confidence: emerging — non-FM-specific finding]

Methods note

Single-centre observational cross-sectional case-control study; adults 18-65; right eyes only; low-quality scans excluded. Swept-source OCT with AI-assisted segmentation for subfoveal max and mean choroidal thickness, and CVI as luminal-area / total-area ratio. Symptom measures: COMPASS-31 (autonomic), FIQ-R (FM impact), CSI (central sensitization). Statistical approach: Spearman correlations, multivariable linear regression. n not specified in abstract but characterized as single-centre observational (likely modest sample, ~30-60 per arm based on typical Medicina FM-OCT studies).

Limitations

• Self-reported autonomic symptom burden (COMPASS-31) rather than objective autonomic testing (HRV, tilt-table, sympathetic-skin-response). Authors explicitly note this and call for "studies incorporating objective autonomic testing and dynamic vascular imaging paradigms."
• Single time point — choroidal vascularity can vary with circadian phase, recent exercise, caffeine, autonomic state; cross-sectional snapshot may miss dynamic FM phenotype.
• Right-eye-only design; no inter-eye averaging; possible side-bias.
• Sample size not reported in abstract; null result interpretation depends on power.
• Did not measure inner-retinal layers (RNFL, GCL) — couldn't replicate Garcia-Martin 2016 finding in this cohort.
• Did not stratify by FM subtype (autoimmune vs central-only vs peripheral SFN) — choroidal substrate effects may be subtype-specific.

Open questions raised

• Q-Re-13 (new): Does the choroidal vascular substrate change in FM patients selected for autoimmune subtype (anti-SGC IgG positive, anti-GFAP IgG positive) rather than unselected FM? The Sanchez 2025 mechanism predicts choroidal MC degranulation should occur in FM-IgG+ patients specifically; unselected cohort may dilute the signal.
• Q-Re-14 (new): Does dynamic-vascular imaging (OCT-A flow-velocity, choroidal blood flow with laser speckle, choroidal pulsatility) show FM-related changes that static CVI and thickness miss?
• Q-Re-15 (new): Are RNFL / GCL / IPL inner-retinal-layer thinning (Garcia-Martin 2016) and choroidal-substrate status decorrelated within FM patients? If so, the retinal-substrate priority should partition into "inner-retinal" (works as biomarker) vs "choroidal" (does not work in unselected FM).

Triangulation notes

• Tempers B-Re-2 (Choroidal mast cells ↔ FM-MC mechanism extension): Shi 2025 established choroidal MC degranulation as causal for choroidal thinning in a lens-induced myopia mouse model with cromolyn rescue. This paper is the first within-FM test of whether that mechanism produces a measurable choroidal-substrate signature in FM patients. The negative result means the mechanism — if present in FM — is either subtype-restricted, requires dynamic imaging, or operates at scales smaller than current OCT can detect. B-Re-2 stays open but the static-CVI endpoint is no longer the preferred closing test.
• Tempers RE-1 query design at the choroidal layer: future RE-1 yield should be weighted toward inner-retinal (RNFL/GCL) papers since Garcia-Martin 2016 is FM-anchored at that layer; choroidal-layer FM papers now have a negative anchor.
• Reinforces priority of inner-retinal RNFL/GCL as the retinal-substrate biomarker: Garcia-Martin 2016 (RNFL/GCL thinning in FM, dual-device replication) remains the methodologically strongest FM-retinal-substrate finding; this paper does not contradict it but narrows the substrate-of-interest to inner-retinal layers.
• Supports the autoimmune-subtype stratification framing: the project's framing that FM heterogeneity may explain inconsistent biomarker findings predicts exactly this — unselected FM cohorts will dilute mechanism-driven signals. This paper adds another data point for stratification-by-subtype as the path forward.

Bridges

• B-Re-2 status update: stays open but with one negative anchor at the unselected-FM-cohort-static-CVI endpoint. Future closing path requires either (a) autoimmune-subtype-stratified cohort, (b) dynamic-vascular-imaging paradigm, or (c) within-patient cromolyn cross-over with paired choroidal imaging. Document in synthesis/bridges.md under B-Re-2.
• No new bridges raised by this paper.

Confidence-tier framing

The finding itself (CVI doesn't differ in unselected FM) is at emerging tier — single-centre, modest sample, negative result that needs replication before being elevated to established. The implication for B-Re-2 is at inferred tier — that the mechanism is subtype-restricted or dynamically expressed rather than absent is one interpretation, but a true-null interpretation (choroidal MC pathway doesn't matter in FM the way Shi 2025 predicts) is equally consistent with the data.