Early Inflammation Markers Could Transform How We Detect Diabetic Retinopathy

A Silent Eye Disease That Starts Early

Diabetic retinopathy is one of the main causes of preventable blindness in adults, yet it often progresses quietly for years without any symptoms. Many people only learn they have it when vision starts to blur or when scans reveal clear damage to the retina.

The new work suggests the disease begins much earlier than our current tests can show. At a microscopic level, low‑grade inflammation and subtle changes in tiny blood vessels may already be underway while the retina still looks normal in routine check‑ups.

How the Study Was Carried Out

The research was driven by the Ophthalmology Research Unit “Santiago Grisolía” at FISABIO, together with Spain’s Network of Inflammatory Diseases. Instead of starting with retinal images, the team looked at the fluid that bathes the front part of the eye, known as the aqueous humour.

They examined samples from three sets of people: those with early non‑proliferative diabetic retinopathy, individuals with diabetes but no detectable retinopathy, and people who do not have diabetes. This allowed them to tease out which biological signals were specifically linked to the earliest stage of retinal damage caused by diabetes.

The analysis revealed a clear pattern of inflammatory and vascular molecules in patients who already had early retinopathy, even when the back of the eye still appeared healthy on clinical examination.

Inflammation Before Visible Retinal Damage

A key message from the study is that the eyes of people with early diabetic retinopathy are already in an inflamed, stressed state, even if their retinal scans look unchanged. The disease process does not begin with visible haemorrhages or obvious lesions, but with a prolonged, subtle disruption of the eye’s internal environment.

This “silent” phase is driven by chronic exposure to high blood sugar, which affects small vessels and triggers immune responses inside the eye. By the time classic signs appear on a retina photograph, this underlying process may have been active for a long time.

The Molecular Signature: What Changes in the Eye

The team identified a group of molecules that together form a distinctive early signature of diabetic retinopathy. Many of them are already familiar from other inflammatory and vascular diseases but had not been so clearly mapped to the earliest retinopathy stages.

Among the most notable molecules were:

• Inflammatory interleukins such as IL‑1β and IL‑6, which act as chemical messengers that amplify immune responses and chronic inflammation.
• VEGF (vascular endothelial growth factor), a protein known to encourage new vessel growth and increase leakiness of existing vessels in the retina.
• GM‑CSF, a factor that supports the survival and activity of certain white blood cells, helping sustain inflammatory reactions.
• Chemokines including MCP‑1 and IP‑10, which work like “chemical beacons” that call immune cells into the eye’s tissues.

Higher levels of these molecules were found in people with early retinopathy compared with diabetics without retinopathy and non‑diabetic participants, suggesting a specific link with the first stages of disease.

New Opportunities for Early Detection

Because these molecular changes occur before structural damage is visible, they could form the basis of new tools to detect risk much sooner. In future, measuring selected biomarkers in the eye might help doctors identify which people with diabetes are on the path towards retinopathy, even when standard tests look reassuring.

This kind of information would make it easier to decide who needs closer monitoring and who can safely be seen less often. It could also support decisions about when to intensify treatment, for example by tightening metabolic control or introducing new therapies that calm inflammation and protect the microvasculature.

Instead of waiting until blood vessels are clearly damaged, eye care could become more proactive and tailored to each patient’s molecular risk profile.

Aqueous Humour as a “Liquid Window” Into the Eye

One practical advantage is that the aqueous humour samples used in the study can be taken during routine operations such as cataract or glaucoma surgery. This means researchers and clinicians can access detailed biological information about the eye without subjecting patients to extra procedures purely for testing.

Looking ahead, measuring selected biomarkers in this fluid during planned surgery might become a useful add‑on for people with diabetes. It could help reveal early disease activity, estimate the likelihood of progression and guide how intensively a person should be followed up after surgery.

The concept is similar to blood tests in other fields: the eye’s own fluid becomes a directly accessible source of information about what is happening deeper inside the retinal tissue.

Rethinking What Diabetic Retinopathy Really Is

Historically, diabetic retinopathy has been described as a complication of small blood vessels: high blood sugar damages capillaries, they leak or close, and the retina suffers. The new data adds another layer to this picture by placing inflammation and immune activation at centre stage from very early on.

A persistent inflammatory environment can destabilise blood vessels, damage retinal cells and encourage the development of fluid build‑up or fragile new vessels later in the disease course. Recognising this early inflammatory phase encourages a broader treatment strategy that goes beyond purely mechanical vessel damage.

What This Could Mean for Future Treatments

Current eye treatments for diabetic retinopathy are mostly reserved for moderate or advanced disease. They include laser procedures and injections aimed at blocking VEGF to limit abnormal vessel growth and leakage. By the time these interventions are used, damage is often well established.

The new findings suggest that tomorrow’s treatment landscape might look different. Therapies could be aimed not only at VEGF and visible vessel abnormalities but also at the inflammatory mediators that appear earlier in the process. Targeting specific interleukins or chemokines, for example, might help “cool down” the inflammatory environment before major structural damage accumulates.

Combined with strict control of blood sugar, blood pressure and cholesterol, this more comprehensive approach could slow or even prevent progression to the stages where vision is at serious risk.

Key Takeaways for People Living With Diabetes

For anyone with diabetes, this research reinforces several important points. First, eye damage can begin long before you notice any change in your vision. That is why regular eye checks, including retinal examinations, are so important even when you see clearly and feel well.

Second, keeping blood sugar, blood pressure and cholesterol under good control remains the foundation of protecting your eyes and other organs. These new findings do not replace that advice; they strengthen the case for taking it seriously.

Finally, the study hints at a future in which eye care is more personalised. Instead of treating everyone in the same way, doctors may one day use molecular markers to identify who is at greatest risk and who might benefit most from early, targeted therapies. The long‑term aim is simple: to keep people with diabetes seeing clearly for as many years as possible.