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Blood-Derived Systemic Inflammatory Biomarkers and Intraocular Pressure in a Routine Health Examination Population

In a cross-sectional study of 1,840 routine health examination participants, higher levels of systemic inflammatory biomarkers—specifically the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI)—were found to be independently and positively associated with elevated intraocular pressure, suggesting a link between systemic inflammation and IOP regulation.

Original authors: Hu Li, Qian Xie, Chunmao Jiang, Jie Wan, Xia Gao, Liang Huang, Yan Long, Xiaotong Hu

Published 2026-07-01

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CC BY 4.0

Original authors: Hu Li, Qian Xie, Chunmao Jiang, Jie Wan, Xia Gao, Liang Huang, Yan Long, Xiaotong Hu

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

The Big Picture: A Check-Up for Your Eyes and Your "Internal Fire"

Imagine your body is like a busy city. Sometimes, this city gets a little bit of "smog" or "rust" building up inside. In medical terms, we call this systemic inflammation. It's a low-level, silent fire that can happen when you have high blood pressure, extra weight, or just general wear and tear on your body.

Usually, doctors check for this "smog" by looking at your blood. They count specific types of white blood cells (like the city's police and firefighters) to see if the city is under attack.

This study asked a simple question: Does the amount of "smog" in your blood have anything to do with the pressure inside your eyes?

High pressure inside the eye (called Intraocular Pressure or IOP) is a major risk factor for glaucoma, a disease that can damage your vision. While we know that high blood pressure in your body can affect your eyes, scientists wanted to know if this "internal fire" (inflammation) also pushes up the pressure inside your eye.

The Experiment: A Snapshot of 1,840 People

The researchers took a "snapshot" (a cross-sectional study) of 1,840 healthy adults who came in for routine health check-ups. They didn't pick people who already had eye diseases; they picked regular folks to see if there was a hidden link.

They measured two main things:

The Eye Pressure: They used a special machine that puffs a tiny bit of air at the eye to measure how hard it is to push the eye's surface in. They averaged the pressure from both eyes.
The "Fire" Indicators: They looked at blood tests to calculate five different "scores" that measure inflammation. Think of these scores as different types of thermometers for the body's fire:
- NLR: The ratio of "attackers" (neutrophils) to "regulators" (lymphocytes).
- SII: A complex score mixing attackers, "messengers" (platelets), and regulators.
- SIRI: A score mixing attackers, "clean-up crew" (monocytes), and regulators.
- (They also checked PLR and MLR, but those didn't show a strong link).

What They Found: The "Smog" and the "Pressure"

The researchers found a clear, though modest, connection.

The Analogy: Imagine the eye is a balloon. The fluid inside the balloon needs to drain out through a tiny filter (the drainage system). If the "smog" (inflammation) in the body gets too thick, it might clog that filter slightly, making it harder for the fluid to escape. This causes the pressure inside the balloon to rise.

The Results:

People with the highest levels of inflammation (the top 25% of the group) had higher eye pressure than those with the lowest levels.
Specifically, three "thermometers" showed this link: NLR, SII, and SIRI.
The difference wasn't huge. The people with the most inflammation had eye pressures that were about 0.5 to 0.7 mm Hg higher than those with the least inflammation.
- Think of it like this: If your eye pressure was 15, the "high inflammation" group was around 15.6 or 15.7. It's a small bump, but statistically, it's a real trend.
The other two scores (PLR and MLR) didn't show a clear link.

The Shape of the Link:
The researchers checked if this relationship was a straight line or a curve. They found it was mostly a straight line. This means that as the inflammation gets a little higher, the eye pressure tends to get a little higher, too. It's not a sudden explosion; it's a steady, gradual climb.

What This Means (and What It Doesn't)

What the paper claims:

There is a real, independent link between blood inflammation and eye pressure in healthy people. Even after adjusting for age, weight, blood pressure, and cholesterol, the inflammation scores still mattered.
This suggests that the body's "internal fire" might play a small role in how the eye manages its fluid pressure.

What the paper does NOT claim:

It's not a diagnosis tool: The authors explicitly state that because the difference in pressure is so small (less than 1 point), you cannot use these blood tests to diagnose high eye pressure in a single patient. You still need an eye exam.
It's not a cause-and-effect proof: Because this was a "snapshot" study (looking at data from one moment in time), we don't know which came first. Did the inflammation cause the high pressure? Or did the high pressure cause the inflammation? Or did a third factor (like a bad diet) cause both? The study cannot answer that.
It's not a cure: The paper does not suggest that taking anti-inflammatory drugs will lower your eye pressure. That is a future question, not a finding of this study.

The Bottom Line

Think of your body's inflammation as a slow leak in a tire. This study found that people with a bigger leak (higher inflammation) tend to have slightly higher pressure in their "eye tires."

While this doesn't mean you should panic if your blood shows a little inflammation, it adds a new piece to the puzzle. It suggests that keeping your body's "internal fire" low—through a healthy lifestyle—might be one of many small ways to help keep your eye pressure in a healthy range. However, for now, this is just an interesting clue for scientists, not a new rule for doctors.

Technical Summary: Blood-Derived Systemic Inflammatory Biomarkers and Intraocular Pressure

Problem Statement
Glaucoma is a leading cause of irreversible blindness, with elevated intraocular pressure (IOP) serving as the most established and modifiable risk factor for its development and progression. While anatomical abnormalities and impaired aqueous humor outflow are known mechanisms of IOP elevation, the role of systemic factors remains under-investigated. Chronic low-grade inflammation is increasingly recognized as a systemic process linked to metabolic and cardiovascular disorders, yet evidence regarding the specific relationship between systemic inflammatory status and IOP levels in a general population is limited. Previous studies have focused on established ocular diseases (e.g., glaucoma, cataracts) rather than IOP as a continuous physiological parameter. This study addresses the gap in understanding whether blood-derived systemic inflammatory biomarkers are independently associated with IOP in a routine health examination population.

Methodology
This cross-sectional study analyzed data from 1,840 participants (median age 41 years, 51.4% female) who underwent routine health examinations at the Army Medical Center between September 2024 and May 2026.

Data Collection: Mean IOP was defined as the average of bilateral non-contact tonometry measurements. Systemic inflammatory biomarkers were calculated from peripheral blood cell counts: Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocyte-to-Lymphocyte Ratio (MLR), Systemic Immune-Inflammation Index (SII), and Systemic Inflammation Response Index (SIRI).
Exclusion Criteria: Participants with a history of glaucoma, current corticosteroid use, missing key variables, or implausible IOP values (<5 or >30 mm Hg) were excluded.
Statistical Analysis: Multivariable linear regression was employed to examine associations between inflammatory biomarkers and mean IOP. Three models were used: unadjusted, adjusted for age/sex/BMI, and fully adjusted for systolic/diastolic blood pressure, fasting plasma glucose, lipid profiles, and estimated glomerular filtration rate (eGFR). Significant biomarkers were further analyzed by quartiles and via restricted cubic spline (RCS) analyses to assess dose-response patterns and linearity.

Key Results
Among the five biomarkers evaluated, NLR, SII, and SIRI demonstrated independent positive associations with mean IOP, while PLR and MLR showed no significant association.

Multivariable Regression: In the fully adjusted model, higher levels of NLR, SII, and SIRI were significantly associated with higher IOP.
Quartile Analysis: Compared to the lowest quartile (Q1), the highest quartile (Q4) of these biomarkers was associated with increased IOP:
- NLR (Q4): Adjusted $\beta$ = 0.479 mm Hg (95% CI: 0.095–0.863; $P$ =0.014).
- SII (Q4): Adjusted $\beta$ = 0.661 mm Hg (95% CI: 0.275–1.047; $P$ <0.001).
- SIRI (Q4): Adjusted $\beta$ = 0.619 mm Hg (95% CI: 0.227–1.011; $P$ =0.002).
Trends and Linearity: Significant trends across quartiles were observed for all three biomarkers ( $P$ for trend <0.05). Restricted cubic spline analyses confirmed significant overall associations for ln(NLR), ln(SII), and ln(SIRI) with IOP, with no evidence of significant non-linearity, suggesting an approximately linear relationship within the observed range.

Significance and Claims
The authors claim that in a routine health examination population, higher levels of NLR, SII, and SIRI are modestly but independently associated with higher IOP. These findings suggest that systemic inflammatory burden may be related to the regulation of ocular pressure.

The study emphasizes several points regarding its significance and limitations:

Epidemiological Association: The results provide epidemiological evidence linking systemic inflammation to IOP, a continuous and modifiable ocular parameter, distinct from studies focusing on established glaucoma.
Biological Plausibility: The authors note that systemic inflammation may influence IOP through pathways involving oxidative stress, vascular endothelial dysfunction, and extracellular matrix remodeling in the trabecular meshwork, potentially increasing outflow resistance.
Clinical Utility: The authors explicitly state that the observed magnitude of difference (approx. 0.5–0.7 mm Hg between quartiles) is too small to serve as an independent diagnostic tool for screening elevated IOP in individual clinical practice. Instead, the potential value lies in population-level risk assessment and mechanistic exploration.
Limitations: The study acknowledges that the cross-sectional design precludes causal inference. It does not establish whether inflammation causes IOP elevation or vice versa, nor does it account for unmeasured confounders such as recent infections, smoking, or specific ocular parameters like central corneal thickness.

In conclusion, the paper posits that systemic inflammatory biomarkers derived from routine blood tests may serve as indicators of systemic inflammatory burden that correlates with IOP regulation, warranting further longitudinal investigation to clarify causal mechanisms.