Introduction: Who Should Undergo Diagnostics

If you start noticing blurred vision or a dark spot appearing in or near the center of your vision in one or both eyes, you should consider seeking diagnostic testing for polypoidal choroidal vasculopathy. These symptoms may come on suddenly and typically don’t change much throughout the day. The vision changes can appear out of nowhere, which is why paying attention to any shifts in how you see is so important.^[1]

You may also notice that straight lines appear wavy or distorted, a symptom called metamorphopsia. Some people see small floating spots or specks in their vision. Early diagnosis matters because your retina specialist may even be able to detect PCV before it has caused any noticeable symptoms at all. This means that people who are at higher risk should have regular eye examinations even when they feel their vision is fine.^[1]

Certain groups of people should be especially vigilant about eye examinations and diagnostic testing. PCV tends to occur in individuals over the age of 60, although it can develop much earlier in some cases. If you are of Asian or African descent, your risk is higher compared to Caucasians. The condition affects people between 50 and 65 years old most commonly, and while earlier studies suggested it was more frequent in middle-aged Black women, more recent research shows it affects both men and women across diverse ethnic groups.^[1][2]

If you have conditions like high blood pressure, increased blood thickness, or a lower than normal number of platelets (the cells that help your blood clot), you may also be at increased risk for developing PCV. Additionally, if anyone in your family has had macular disease, you should make sure to have your eyes checked regularly. People who smoke, have high cholesterol, or have a family history of macular problems should also consider more frequent monitoring, as these factors can increase your likelihood of developing the condition.^[2][6]

Diagnostic Methods: Classic Testing to Identify the Disease

The most important first step in diagnosing polypoidal choroidal vasculopathy is a careful dilated eye examination performed by your retina specialist. During this examination, your doctor will use special drops to widen (dilate) your pupils, allowing them to see the back of your eye more clearly. This lets them look at your retina and the blood vessels beneath it to spot any abnormalities. On direct examination, PCV usually shows up as fluid under the retina and bleeding under the retina or as a hemorrhagic pigment epithelial detachment (a pocket where fluid or blood has lifted the layer beneath the retina). Sometimes, doctors can see orange-red colored structures beneath the retina that are associated with the bleeding or fluid.^[1][4]

However, the appearance of PCV during a basic eye examination can be very difficult to distinguish from another common eye condition called neovascular age-related macular degeneration, or wet AMD. This is why additional specialized imaging tests are essential for making an accurate diagnosis. The treatments for PCV may differ from those for wet AMD, so knowing exactly which condition you have can make a real difference in how well your treatment works and how much treatment you need over time.^[4]

Indocyanine Green Angiography (ICGA)

The essential diagnostic tool for confirming PCV is a test called indocyanine green angiography, or ICGA. This test is considered the gold standard because it can clearly show the characteristic abnormal blood vessels that define polypoidal choroidal vasculopathy. During ICGA, a special dye called indocyanine green is injected into a vein, usually in your arm or hand. This dye travels through your bloodstream to the blood vessels in your eye. Then, your doctor takes a series of photographs of the back of your eye using a special camera that can detect the dye.^[1][4]

On ICGA images, PCV appears as an abnormal network of blood vessels beneath the retina, often with a branching vascular network (BVN) and distinctive balloon-like swellings at the ends of these vessels. These balloon-like structures are called polypoidal dilations or “polyps,” and they show up as bright spots with a dark ring around them. In rare cases, these lesions can even be seen pulsating, which means they’re actively moving with each heartbeat. ICGA is particularly good at showing these structures because the indocyanine green dye is better at highlighting the blood vessels in the choroid (the vascular layer beneath the retina) than other types of dyes.^[4][8]

One challenge is that ICGA is not routinely ordered in many parts of the world, especially in the United States, when patients first present with signs of bleeding or fluid in the macula. This means that PCV may be underdiagnosed in places where this test isn’t readily available or isn’t part of standard practice. If your eye doctor suspects you might have PCV but ICGA isn’t available at your location, they may refer you to a specialized center where this test can be performed.^[4]

Fluorescein Angiography (FA)

Another angiography test that may be performed is called fluorescein angiography, or FA. Like ICGA, this test involves injecting a dye into a vein in your arm or hand, but the dye used is fluorescein instead of indocyanine green. Fluorescein angiography creates detailed images of the blood vessels in the retina itself, rather than focusing on the choroid layer beneath it. Both fluorescein angiography and indocyanine green angiography may be useful in helping your retina specialist identify important abnormalities and distinguish PCV from other similar conditions.^[1]

On fluorescein angiography, PCV often shows an occult choroidal neovascularization pattern, meaning the leakage doesn’t have clear, well-defined borders. However, some eyes diagnosed with PCV can show what’s called “classic type leakage” on fluorescein angiography, which appears as a well-defined area of bright leakage. This finding suggests that some abnormal vessels may have grown above the layer beneath the retina and into the space directly under the retina itself. The presence of classic type leakage may influence treatment planning and outcomes.^[10]

Optical Coherence Tomography (OCT)

Optical coherence tomography, or OCT, is another routinely used imaging test that provides detailed cross-sectional images of your retina and the layers beneath it. OCT works somewhat like an ultrasound, but instead of sound waves, it uses light waves to create highly detailed pictures of the different layers of tissue at the back of your eye. This test is non-invasive, which means nothing touches your eye and no injections are needed.^[1][4]

On OCT scans, the polypoidal lesions of PCV appear as sharply peaked elevations of the retinal pigment epithelium (RPE), the layer that sits just beneath the light-sensing cells of your retina. These elevations are shaped like an upside-down letter U. Additionally, OCT often shows fluid collections under the retina, and the abnormal branching vascular network has a characteristic appearance on OCT called the “double-layer sign,” which shows up as two bright lines running parallel to each other.^[4]

Certain findings on OCT can help your doctor suspect PCV rather than typical wet AMD. For example, PCV tends to cause more frequent and taller pockets of fluid under the retina, and there is often less swelling within the retina itself compared to wet AMD. Another feature that suggests PCV is a thicker choroid layer when measured using a special type of OCT called enhanced-depth imaging OCT.^[4]

En Face OCT and OCT Angiography

Newer imaging technologies are being used to diagnose PCV when ICGA isn’t available. En face OCT is a way of viewing OCT data that creates a “face-on” image of the layers beneath the retina, rather than a cross-sectional slice. To image the PCV complex using en face OCT, the software focuses on the space between the retinal pigment epithelium and the layer called Bruch’s membrane, using very thin slices of tissue. On these images, the abnormal vessels appear as dilated structures with bright borders. Studies have shown good correlation between what’s seen on en face OCT and what’s visible on ICGA.^[4]

OCT angiography (OCTA) is another non-invasive imaging method that can show blood flow in the vessels without requiring any dye injection. It works by taking multiple OCT scans of the same area very quickly and comparing them to detect movement, which indicates blood flow. OCTA can help identify the abnormal vascular networks and polypoidal lesions characteristic of PCV. However, while these newer technologies are promising and helpful when ICGA isn’t available, ICGA remains the most definitive test for diagnosing PCV.^[4]

What Else Could It Be?

Because PCV can look very similar to wet age-related macular degeneration during a basic examination, distinguishing between the two conditions is one of the main diagnostic challenges. People with PCV usually have better vision when the condition is first discovered compared to those with typical wet AMD. This may be because the abnormal vessels in PCV are often located outside the very center of the retina, and because fluid pockets in PCV tend to stay beneath rather than within the retina itself.^[6][12]

Your doctor may also need to rule out other conditions that can cause similar symptoms, such as central serous retinopathy (CSR), which also causes fluid to collect under the retina. In one documented case, a patient was initially diagnosed with central serous retinopathy and treated with oral medications for several months without improvement. It wasn’t until indocyanine green angiography was performed more than a year later that the correct diagnosis of PCV was made. This highlights how important specialized testing is when initial treatments don’t work as expected.^[5]

Diagnostics for Clinical Trial Qualification

If you’re considering participating in a clinical trial for polypoidal choroidal vasculopathy, you’ll need to undergo specific diagnostic tests to determine whether you qualify. Clinical trials have strict criteria about who can participate, and these criteria are designed to ensure that the study results are reliable and that participants are as safe as possible. The diagnostic tests used to qualify patients for clinical trials are similar to those used in regular clinical practice, but they may be performed more frequently or with specific protocols.^[7]

Most clinical trials for PCV require confirmation of the diagnosis using indocyanine green angiography. This is because ICGA provides the most definitive evidence of the characteristic polypoidal lesions and branching vascular networks. Trials may use specific criteria for what constitutes a polypoidal lesion versus an “uncertain polyp,” which can affect whether you’re eligible to participate. Different studies have used slightly different definitions, which is one reason why reported rates of PCV vary across research studies.^[8]

Optical coherence tomography is also routinely used in clinical trials to measure the thickness of your retina and to track changes in fluid accumulation over time. Trials typically measure something called central macular thickness (CMT) or central retinal thickness (CRT), which tells researchers how much swelling is present in the very center of your macula. These measurements help determine whether a treatment is working and are taken at regular intervals throughout the study period.^[15]

Fluorescein angiography may also be required as part of the baseline testing for clinical trials. This test helps researchers document the pattern of leakage from the abnormal vessels and provides information about whether there’s a branching vascular network present. Some trials specifically look at whether the polypoidal lesions are located directly under the fovea (the very center of your macula) or in other areas, as this can affect treatment outcomes.^[8]

Visual acuity testing is a standard requirement for all clinical trials involving eye diseases. Your best-corrected visual acuity (BCVA) will be measured using standardized eye charts, often using a scale called the logarithm of the minimum angle of resolution, or LogMAR. This measurement is more precise than the typical “20/20” notation you might be familiar with, and it allows researchers to detect even small changes in vision over time. Clinical trials may have specific requirements about your starting vision level, such as requiring that your vision be better than or worse than certain thresholds.^[10][15]

Some clinical trials may also require specialized tests to measure the size and location of the abnormal blood vessel complex. This might involve using software to trace the area of the lesion on ICGA or OCT images. The presence or absence of bleeding is another factor that trials often document, as bleeding from polypoidal lesions can affect both symptoms and treatment outcomes.^[8]

Clinical trials often repeat these diagnostic tests at regular intervals throughout the study to monitor how well the treatment is working. You might have OCT scans at every visit, ICGA at specific time points (such as at 6 months, 12 months, and 24 months), and fluorescein angiography at certain milestones. The frequency of testing is usually much higher in clinical trials than in routine care, which helps researchers gather detailed information about how the disease and treatment response progress over time.^[7]

One important thing to understand about clinical trials is that the diagnostic criteria used in research studies may be stricter than what’s used in everyday practice. For example, a clinical trial might require that you have a certain number of polypoidal lesions visible on ICGA, or that the lesions be a certain distance from the center of your macula. These specific criteria help ensure that all participants in the trial have similar characteristics, which makes it easier to tell whether differences in outcomes are due to the treatment rather than differences in the patients themselves.^[8]