1. Overview of the Review

This systematic review and meta‑analysis synthesized 63 studies involving 7316 participants.
It evaluated how CVI differs across 12 physiological and disease conditions, using OCT‑derived measurements.
Most studies used Spectral‑Domain OCT, focused on the subfoveal region, and were judged to have low risk of bias.
The goal was to determine whether CVI can serve as a reliable biomarker of ocular and systemic vascular health.

2. Understanding SMD (Standardized Mean Difference)

CVI values differ across studies because of variations in imaging devices, segmentation methods, and regions of interest.
To compare them meaningfully, the authors used SMD, which expresses the difference between groups in standardized units.

How to interpret SMD values

SMD Value	Interpretation of Effect Size
~0	No meaningful difference
±0.2	Small effect
±0.5	Moderate effect
±0.8 or more	Large effect

Positive SMD → CVI is higher in the condition group than controls.
Negative SMD → CVI is lower in the condition group than controls.

This interpretation is essential for understanding the magnitude of CVI changes across diseases.

**3. Conditions With Increased CVI**

These conditions showed higher vascular proportion in the choroid, often reflecting vascular engorgement, inflammation, or transient hemodynamic shifts.

Physiological

First‑trimester pregnancy: SMD ≈ +0.93 (large increase)
Valsalva maneuver: SMD ≈ +0.55 (moderate increase)

Ocular inflammatory disease

Active panuveitis: SMD ≈ +2.38 (extremely large increase)
Active anterior uveitis – fellow eye: SMD ≈ +0.30 (small increase)
Inactive thyroid eye disease (TED): SMD ≈ +0.57 (moderate increase)

Interpretation:
Inflammation and increased venous pressure expand the luminal (vascular) component of the choroid, raising CVI.

**4. Conditions With Reduced CVI**

These conditions showed lower vascular proportion, typically indicating microvascular loss, ischemia, or stromal expansion.

Systemic disease

Diabetes mellitus without DR: SMD ≈ –0.61 (moderate reduction)
Mild–moderate NPDR: SMD ≈ –1.02 (large reduction)

Ocular disease

Early dry AMD: SMD ≈ –0.74 (moderate–large reduction)
Wet AMD: SMD ≈ –0.72 (moderate–large reduction)
Hyperopic amblyopia: SMD ≈ –0.93 (large reduction)

Interpretation:
These patterns suggest microvascular dropout, choroidal ischemia, or increased stromal volume relative to vascular area.

5. Conditions With No Significant CVI Change

Acute or chronic CSCR (affected eyes)
- Only fellow eyes in acute CSCR showed increased CVI.
Several uveitis subtypes (depending on activity)
Many inherited retinal diseases (high heterogeneity limited conclusions)

6. Mechanistic Insights

The review synthesizes several biological explanations for CVI changes:

Inflammation

Cytokine‑driven vascular permeability → higher CVI (e.g., panuveitis).

Ischemia / Hypoxia

Microvascular damage → lower CVI (e.g., diabetes, AMD).

Compensatory Remodeling

Autoregulation, neovascularization, or fibrosis can raise or lower CVI depending on disease stage.

Aging

Vascular sclerosis and endothelial dysfunction → lower CVI.

Hormonal influences

Pregnancy hormones increase vascular permeability → higher CVI.

Transient physiological stress

Valsalva increases venous pressure → higher CVI.

7. Methodological Considerations

Only 13 of 35 meta‑analyses had low heterogeneity (I² < 40%).
Major sources of variability:
- OCT device type (SD‑OCT vs SS‑OCT)
- Region of interest (subfoveal vs wider scans)
- Binarization/segmentation protocols (Sonoda vs Agrawal)
- Geographic differences in study populations

This variability underscores the need for standardized CVI acquisition and analysis protocols.

8. Clinical Implications

CVI is a promising biomarker for:
- Differentiating disease states
- Monitoring inflammatory activity
- Understanding systemic vascular health
- Tracking treatment response (e.g., anti‑VEGF, acetazolamide)
However, lack of standardization currently limits widespread clinical adoption.

9. Authors’ Conclusions

CVI shows distinct, condition‑specific patterns across ocular and systemic diseases.
It may serve as a non‑invasive indicator of microvascular health.
Standardized imaging protocols and longitudinal studies are needed before CVI can be used routinely in clinical practice.

Choroidal Vascularity Index (CVI) Changes Across Physiological and Disease Conditions
Increased CVI
Physiological	• First‑trimester pregnancy — SMD ≈ +0.93 (large increase) • Valsalva maneuver — SMD ≈ +0.55 (moderate increase)
Ocular Inflammatory Disease	• Active panuveitis — SMD ≈ +2.38 (very large increase) • Active anterior uveitis (fellow eye) — SMD ≈ +0.30 (small increase) • Inactive thyroid eye disease (TED) — SMD ≈ +0.57 (moderate increase)
Decreased CVI
Systemic Disease	• Diabetes mellitus without DR — SMD ≈ –0.61 (moderate reduction) • Mild–moderate NPDR — SMD ≈ –1.02 (large reduction)
Ocular Disease	• Early dry AMD — SMD ≈ –0.74 (moderate–large reduction) • Wet AMD — SMD ≈ –0.72 (moderate–large reduction) • Hyperopic amblyopia — SMD ≈ –0.93 (large reduction)
No Significant CVI Change
• Acute CSCR (affected eye) • Chronic CSCR (affected eye) • Several uveitis subtypes (activity‑dependent) • Many inherited retinal diseases (heterogeneous findings)

Reference:

Loh NC, Rojas‑Carabali W, Lim YH, Bong JE, Villabona‑Martinez V, Cifuentes‑Gonzalez C, et al. Choroidal vascularity index as a marker of health and disease: systematic review and meta‑analyses. Surv Ophthalmol. 2026;71:35‑52. doi:10.1016/j.survophthal.2025.09.003.