Nonproliferative Diabetic Retinopathy: Early Detection Matters
Understanding Nonproliferative Diabetic Retinopathy
Diabetic retinopathy is a microvascular complication of diabetes mellitus. This means diabetes harms the smallest blood vessels in the retina over time. NPDR is the earlier, less advanced stage of this disease. In NPDR, damaged retinal capillaries begin to leak blood, fluid, and cholesterol into the surrounding retinal tissue.
The leaking blood causes tiny hemorrhages in the retina. Leaking fluid can cause the retina to swell, a condition known as edema. Leaking cholesterol forms yellowish deposits called hard exudates. These changes may be subtle at first. They are often detected only during a dilated eye exam.
NPDR is distinguished from proliferative diabetic retinopathy (PDR), which is the more advanced stage. In PDR, the retina becomes so damaged that abnormal new blood vessels grow on its surface. These vessels also extend into the vitreous cavity (the gel-filled space inside the eye). These fragile new vessels can bleed and cause severe vision loss.
In NPDR, this abnormal blood vessel growth has not yet occurred. The damage is limited to changes within the existing retinal blood vessels. Identifying and managing NPDR before it progresses to PDR is one of the most important goals in diabetic eye care.
The changes seen in diabetic retinopathy can be grouped into three main categories. The first is retinal neurodegeneration, where the nerve cells of the retina begin to deteriorate. The second involves a breakdown of the blood-retinal barrier, which normally prevents fluid from leaking out of blood vessels. The third results from ischemia, a lack of adequate blood flow to parts of the retina.
In NPDR, a retina specialist may observe several characteristic findings during an exam:
- Microaneurysms: tiny bulges in weakened blood vessel walls
- Small dot and blot hemorrhages within the retina
- Hard exudates: yellowish deposits from leaking cholesterol
- Cotton-wool spots: pale patches caused by poor blood flow to small areas of the retina
NPDR is classified into mild, moderate, and severe stages based on the number and type of abnormalities found. Mild NPDR involves only a few microaneurysms. Moderate NPDR shows more widespread hemorrhages, microaneurysms, and possibly cotton-wool spots. Severe NPDR is defined by extensive hemorrhages and vascular abnormalities throughout the retina.
The stage of NPDR matters because it predicts the risk of progression. Patients with severe NPDR have a 52% risk of developing PDR within one year (Modern OD, 2019). This places them at high risk for serious vision loss. Retina specialists use the Diabetic Retinopathy Severity Scale (DRSS) to classify and monitor these stages.
Who Is Affected and Risk Factors
Diabetic retinopathy affects a very large number of people. In 2021, an estimated 9.60 million people in the United States were living with diabetic retinopathy (Lundeen et al., 2023). This corresponds to a prevalence rate of roughly one in four people with diabetes (Lundeen et al., 2023). Diabetic retinopathy affects more people in the United States than age-related macular degeneration and glaucoma combined.
The duration of diabetes is one of the strongest predictors of developing NPDR. Research has found that NPDR was present in 25% of patients five years after diagnosis. That rate rose to 60% at ten years and 80% at fifteen years (Modern OD, 2019). The longer a person has diabetes, the more likely they are to develop retinal changes.
The level of blood sugar control also plays a central role. Consistently elevated blood glucose accelerates damage to retinal blood vessels. Maintaining blood sugar levels as close to target as possible is one of the most effective ways to slow or prevent NPDR progression.
Beyond blood sugar, several other modifiable risk factors influence NPDR. High blood pressure (hypertension) is a major contributor. It places additional stress on already weakened retinal blood vessels. Elevated triglyceride levels, higher body mass index, and smoking are also linked to greater risk.
Diabetic peripheral neuropathy, a condition involving nerve damage in the hands and feet, shares the same cardiometabolic risk factors. Patients who have neuropathy are often more likely to have advanced retinal changes. Patients with severe NPDR are most likely experiencing neuropathy elsewhere in their body (Modern OD, 2019).
Both type 1 and type 2 diabetes can lead to diabetic retinopathy. Age is a risk factor because older adults have typically lived with diabetes for longer. However, younger patients with type 1 diabetes can also develop significant retinal damage. This is especially true if blood sugar control has been difficult to maintain.
Signs and Symptoms
One of the most important facts about NPDR is that it frequently causes no noticeable symptoms. This is especially true in its early stages. Many people with mild or moderate NPDR see normally and feel no eye discomfort. The damage happens inside the retina at a microscopic level, where you cannot detect it without special equipment.
This lack of symptoms is precisely what makes regular dilated eye exams so essential. By the time a person notices vision changes, the disease may have already progressed to a more advanced stage.
When NPDR does affect vision, it is usually because of diabetic macular edema (DME) or macular ischemia. DME occurs when fluid leaks into the macula, the central part of the retina responsible for sharp vision. This can cause blurred or distorted central vision. Macular ischemia occurs when blood flow to the macula is reduced.
Some patients may notice that colors appear faded. Reading and recognizing faces may become more difficult. These changes tend to develop gradually rather than suddenly.
While NPDR itself may not cause sudden symptoms, any person with diabetes should know the warning signs of progression. The following symptoms require immediate evaluation by a retina specialist or a visit to the emergency room:
- A sudden increase in floaters (spots or strings drifting across your vision)
- Flashes of light in one or both eyes
- A shadow or curtain appearing over part of your visual field
- Sudden loss of vision in one eye
Diagnosis and Testing
The most fundamental test for detecting NPDR is a comprehensive dilated eye exam. During this exam, drops are placed in the eyes to widen the pupils. This allows a retina specialist to view the retina directly. The specialist looks for microaneurysms, hemorrhages, exudates, and cotton-wool spots.
Optical coherence tomography (OCT) is a noninvasive imaging test that creates detailed cross-sectional images of the retina. OCT can detect fluid within or beneath the retina, measure retinal thickness, and identify early macular edema. It is a quick, painless scan that provides critical information about macular health.
Fluorescein angiography involves injecting a special dye into a vein in the arm. As the dye circulates through the retinal blood vessels, photographs are taken. These images reveal areas of leakage, poor blood flow, or microaneurysms. This test helps a retina specialist determine the severity of NPDR.
Ultra-widefield retinal photography captures detailed images of a large portion of the retina in a single photograph. These images help track changes over time. They can be compared at each visit to determine whether NPDR is stable or progressing.
Treatment Options
For many patients with mild to moderate NPDR, the primary approach is careful observation combined with tight systemic health control. This is based on findings from the Early Treatment Diabetic Retinopathy Study (ETDRS).
Key systemic management strategies include:
- Maintaining blood sugar (hemoglobin A1c) as close to target as your doctor recommends
- Controlling blood pressure to reduce stress on retinal blood vessels
- Managing cholesterol and triglyceride levels
- Quitting smoking
- Maintaining a healthy weight
Anti-VEGF agents block vascular endothelial growth factor, a protein that drives abnormal blood vessel growth and leakage. Eylea (aflibercept) was approved in 2019 for all forms of diabetic retinopathy. Lucentis (ranibizumab) received the same approval in 2017. These medications are delivered as intravitreal injections (injections directly into the eye).
The PANORAMA and Protocol W trials showed that early treatment with Eylea in eyes with moderately severe to severe NPDR led to significant improvement in DRSS scores. These trials also showed reduced risk of vision-threatening complications.
It is important to understand the full picture of current research. Four-year results from Protocol W confirmed that early anti-VEGF treatment improved disease severity scores. However, it did not provide a long-term visual acuity benefit compared to observation alone in patients without center-involved DME. For many patients with NPDR who do not yet have macular edema, careful monitoring may still be preferred.
A retina specialist will weigh the severity of NPDR, the presence or absence of macular edema, and overall health when recommending treatment or continued observation.
Avastin (bevacizumab) is also widely used to treat diabetic retinopathy. Avastin is FDA-approved for the treatment of certain cancers and is used off-label for eye conditions. Despite this off-label status, it has well-documented results in retinal care. Vabysmo (faricimab), a bispecific antibody targeting both VEGF and Ang-2, is another option approved for DME.
Scatter laser photocoagulation (also called panretinal photocoagulation or PRP) uses thermal laser energy to treat ischemic areas of the retina. While laser treatment is more commonly associated with PDR, selected cases of severe NPDR may also benefit. This approach is based on findings from the ETDRS. Laser treatment does not improve vision but aims to reduce the risk of progression.
Research from the FIELD study has suggested that fenofibrate, a medication typically used to lower triglycerides, may help slow diabetic retinopathy progression. This protective effect appeared most pronounced in participants with mild NPDR at baseline. A retina specialist or primary care physician may discuss whether fenofibrate is appropriate for you.
What to Expect
If you are diagnosed with mild NPDR, a retina specialist may recommend follow-up exams every six to twelve months. Moderate NPDR typically requires visits every three to six months. Severe NPDR may call for follow-up every two to four months because of the high risk of progression.
Your monitoring schedule may change based on how your condition responds to management and whether new findings appear on imaging.
At each visit, a retina specialist will perform a dilated exam and often obtain OCT imaging. You may be asked about changes in your vision, your most recent blood sugar readings, and any medication changes.
These visits are designed to catch progression early. If NPDR worsens or if DME develops, treatment can be started promptly.
If your retina specialist determines that treatment is needed, intravitreal injections are the most common first approach when macular edema is present. Initial treatment typically involves injections given every four to eight weeks. Over time, the interval between injections may be extended based on how the eye responds.
Living With Nonproliferative Diabetic Retinopathy
Living with NPDR places a strong emphasis on managing diabetes and related conditions. Keeping blood sugar, blood pressure, and cholesterol under good control are the most impactful steps you can take. Work closely with your primary care physician or endocrinologist to set appropriate targets.
Regular physical activity, a balanced diet, maintaining a healthy weight, and not smoking all contribute to better outcomes. These factors affect blood vessel health throughout the body, including the retina. Even modest improvements can make a meaningful difference over time.
Being diagnosed with a condition that can affect your eyesight can cause worry and stress. It can help to know that mild to moderate NPDR often remains stable for years with proper management. Many people with NPDR maintain good vision throughout their lives. Staying informed, attending all scheduled eye exams, and following your treatment plan are the most effective ways to maintain control.
If you notice any changes in your vision between appointments, contact a retina specialist promptly.
When to See a Retina Specialist
All people with diabetes should have a comprehensive dilated eye exam at least once a year. Screening should begin within five years of a type 1 diabetes diagnosis and at the time of a type 2 diabetes diagnosis. Pregnant women with diabetes should have an eye exam during the first trimester.
Beyond routine screenings, see a retina specialist promptly if you experience blurred or distorted central vision, difficulty reading, or a change in color perception. A sudden increase in floaters, flashes of light, a curtain or shadow over your vision, or sudden vision loss in one eye requires immediate evaluation. See a retina specialist or go to the emergency room right away. These may be signs that diabetic retinopathy has progressed.
Questions and Answers
Clinical trials such as PANORAMA have shown that anti-VEGF treatment can improve the DRSS score. This means the visible signs of NPDR can be reduced. However, this is not the same as a complete reversal of all underlying damage. The most effective way to slow or limit NPDR is through tight control of blood sugar, blood pressure, and other systemic factors.
Not all patients with NPDR require injections. Many cases of mild to moderate NPDR are managed with observation and systemic health control alone. Injections are typically recommended when DME develops or when NPDR is severe. Four-year data from Protocol W showed that early anti-VEGF treatment for NPDR without center-involved macular edema did not provide a long-term visual acuity benefit. The decision to treat is individualized.
The rate of progression varies from person to person. Patients with mild NPDR who maintain good blood sugar and blood pressure control may remain stable for many years. In contrast, patients with severe NPDR have a 52% chance of progressing to PDR within one year (Modern OD, 2019). The stage of NPDR, the duration of diabetes, and how well risk factors are managed all influence the speed of progression.
A diagnosis of NPDR does not mean you will lose your vision. Many people with NPDR, especially mild or moderate forms, maintain good vision for years or even decades. Vision loss from diabetic retinopathy is most commonly associated with untreated DME or progression to advanced proliferative disease. Regular monitoring and proactive management of diabetes significantly reduce the risk of serious vision loss.
There is no strong clinical evidence that any over-the-counter supplement can prevent or treat diabetic retinopathy. Some studies have explored the role of antioxidants and omega-3 fatty acids, but results have not been conclusive. The most reliable approaches remain blood sugar control, blood pressure management, and regular monitoring by a retina specialist.