Polypoidal choroidal vasculopathy is a disease affecting blood vessels in the choroid, the layer beneath the retina, that can cause sudden vision changes and bleeding in the eye. While it shares features with age-related macular degeneration, it requires specific diagnostic approaches and treatments to preserve sight.

Understanding Polypoidal Choroidal Vasculopathy

Polypoidal choroidal vasculopathy, often shortened to PCV, is a condition that primarily affects the vascular layer of blood vessels in the choroid, which is the layer of blood vessels located beneath the retina. This network of vessels normally supplies oxygen and nutrients to the outer portions of the retina, where the photoreceptor cells responsible for vision reside. When PCV develops, abnormally shaped blood vessels form in this layer, creating balloon-like structures that can leak fluid or blood, potentially damaging the overlying retina and causing vision loss.^[1]

The disease was first identified by Yannuzzi and colleagues at a meeting of the American Academy of Ophthalmology in 1982, where it was initially termed idiopathic polypoidal choroidal vasculopathy. In 1984, other researchers described a similar presentation in middle-aged Black women, calling it posterior uveal bleeding syndrome. Later, Yannuzzi and his team provided more detailed descriptions of PCV, establishing that it occurs across genders, various age groups, and different racial backgrounds.^[2]

What makes PCV distinctive is the presence of abnormal vessels with multiple small, polyp-shaped swellings, resembling tiny clusters of grapes. These polypoidal configurations develop due to defective vascular lining, with the vessel walls showing thinned out cells compared to normal blood vessels. These fragile structures are prone to leaking fluid and rupturing, which explains why patients often experience sudden bleeding under the retina.^[2]

How Common Is Polypoidal Choroidal Vasculopathy

Polypoidal choroidal vasculopathy is relatively uncommon in the general population. In Europe, studies estimate that only about 0.04% of the entire population is affected by this condition. However, the prevalence varies significantly among different ethnic groups, with much higher rates observed in Asian populations compared to Caucasian populations.^[2]

Among patients initially diagnosed with neovascular age-related macular degeneration, which is a condition causing new abnormal blood vessel growth, PCV is found much more frequently in certain populations. Studies have shown that PCV accounts for approximately 7.8% of such cases in white individuals. In contrast, the rates are dramatically higher in Asian populations, ranging from 23% to 54% in Japanese patients, 22.3% in Chinese patients, and 24.6% in Korean patients.^[2]

The condition tends to appear earlier in life than typical age-related macular degeneration, with most diagnoses occurring in people between 50 and 65 years old. While earlier studies suggested that middle-aged Black women were more frequently affected, recent research shows that PCV occurs in both men and women across diverse ethnic groups. Some studies indicate it may be more common in women, with one report suggesting it affects women about 4.7 times more often than men, though this finding continues to be studied.^[2][3]

What Causes Polypoidal Choroidal Vasculopathy

The exact causes of polypoidal choroidal vasculopathy remain incompletely understood, though researchers have identified several important features of the disease. The condition is characterized by abnormally shaped vessels in the choroid, but precisely why these abnormal vessels develop is still a mystery. What we do know is that these blood vessels have multiple, small, polyp-shaped swellings that form due to a defective vascular lining.^[1]

When examined closely, the abnormal vessels in PCV show structural differences from healthy blood vessels. They have thinned out endothelial cells, which are the cells that line the inside of blood vessels, and reduced numbers of pericytes, which are support cells that help maintain vessel structure and function. These structural weaknesses make the vessels more likely to leak or rupture.^[2]

One theory about how these polypoidal lesions develop involves the interaction between arteries and veins in the choroid. Researchers suggest that when a hardened small artery compresses a small vein at a crossing point, the resulting pressure can cause the vein to form polyp-like bulges. The compression slows blood flow in the vein, creating venous stasis, which leads to tissue breakdown and increased fragility. Over time, these degenerative changes result in the formation of polypoidal configurations that are prone to leakage and bursting.^[2]

The abnormal vessels in PCV cause vision loss when they leak fluid or blood into or under the retina. They may also cause scarring or loss of retinal tissue, sometimes called atrophy. Although PCV may initially appear to affect only one eye, it often progresses to involve both eyes over time, making regular monitoring essential.^[1]

Risk Factors for Developing PCV

Several factors appear to increase the risk of developing polypoidal choroidal vasculopathy. Age is one of the most significant risk factors, as the condition tends to occur in individuals over the age of 60, though it can develop in much younger people as well. The risk increases with advancing age, similar to other retinal vascular conditions.^[1]

Ethnicity plays a substantial role in PCV risk. The condition affects those of Asian and African descent significantly more than it affects Caucasians. This ethnic predisposition is one of the most striking features of the disease and suggests that genetic factors may contribute to its development, though specific genes have not yet been definitively identified.^[1]

Several medical conditions have been associated with polypoidal choroidal vasculopathy, though the exact relationships require further research. High blood pressure, or hypertension, has been linked to PCV in multiple studies. Raised plasma viscosity, which means thicker blood that flows less easily, and thrombocytopenia, which is a lower than normal number of platelets that help blood clot, have also been associated with the condition.^[2]

Some researchers have explored potential connections between PCV and other conditions such as sickle cell anemia and exposure to radiation, but these relationships remain uncertain and require additional investigation. The role of smoking and cholesterol levels, which are known risk factors for other retinal vascular diseases, is also being studied in relation to PCV.^[2]

Recognizing the Symptoms

Patients with polypoidal choroidal vasculopathy often experience blurred vision or notice a blind spot in or near the center of their vision in one or both eyes. These symptoms may appear suddenly rather than gradually, and they tend not to vary throughout the day, unlike symptoms of some other eye conditions. In some fortunate cases, a retina specialist may diagnose PCV early, before it has caused any noticeable symptoms, during a routine examination.^[1]

The most common presenting symptom is a decrease in vision quality. Other early signs can include distorted vision, where straight lines appear wavy or bent, a dark spot in the center of the visual field, and seeing floaters or small specks. People who report these symptoms within three months of onset usually have better initial vision compared to those who wait longer to seek care.^[2]

Patients may also show clinical signs of leakage or bleeding under the retina, even if they haven’t noticed symptoms yet. In more chronic cases, there might be signs of lipid accumulation or fluid-filled pockets within the retina itself, called intraretinal cysts. Interestingly, people with PCV often have better vision when first diagnosed compared to those with typical age-related macular degeneration. This may be because in some cases the affected area is located outside the very center of the retina, or because there is less widespread damage to the retinal tissue.^[2]

On examination, PCV usually presents with fluid under the retina and bleeding beneath the retina or within pigment epithelial detachments, which are raised pockets where the retinal pigment layer has lifted. Occasionally, orange-red structures representing the abnormal blood vessels themselves can be seen beneath the retina, particularly when associated with bleeding or fluid accumulation.^[4]

Prevention and Early Detection

While there are no proven methods to completely prevent polypoidal choroidal vasculopathy, managing overall health and addressing known risk factors may help reduce the likelihood of developing the condition or slow its progression. Controlling blood pressure through lifestyle changes and medication when necessary is important, given the association between hypertension and PCV.^[2]

Regular comprehensive eye examinations become increasingly important after age 50, particularly for individuals of Asian or African descent who have a higher risk of developing PCV. These examinations allow eye care professionals to detect subtle changes in the retina before symptoms appear, enabling earlier intervention that may preserve more vision.^[1]

Individuals with a family history of macular diseases should be especially vigilant about regular eye care. Maintaining healthy habits such as not smoking, eating a balanced diet rich in vegetables and fish, maintaining a healthy weight, and exercising regularly may contribute to overall retinal health, though specific preventive benefits for PCV have not been definitively proven.^[3]

Being aware of symptoms is crucial for early detection. Anyone who notices sudden blurred vision, distorted vision where straight lines appear wavy, a new blind spot in the center of vision, or sudden appearance of floaters should seek prompt evaluation by an eye care professional. Early diagnosis and treatment may restore vision and prevent further vision loss in some patients.^[1]

How the Disease Affects Normal Body Functions

To understand how polypoidal choroidal vasculopathy disrupts normal vision, it helps to understand the normal anatomy and function of the retina and choroid. The retina is the light-sensitive tissue at the back of the eye that converts light into electrical signals sent to the brain. The choroid is a rich network of blood vessels located between the retina and the white outer wall of the eye, called the sclera. The choroid’s primary job is to supply oxygen and nutrients to the outer layers of the retina.^[3]

In healthy eyes, the blood vessels of the choroid maintain their structure and remain beneath a layer called the retinal pigment epithelium, or RPE. This layer acts as a barrier and support system for the photoreceptor cells above it. The blood vessels function normally, delivering nutrients without leaking fluid or causing bleeding.^[1]

In PCV, this normal structure becomes disrupted. Abnormal blood vessels develop within the choroid, located between the RPE and a membrane called Bruch’s membrane. These vessels don’t maintain normal structure but instead develop balloon-like dilations at their ends, resembling clusters of polyps or grapes. Often these polyps connect to a branching network of abnormal vessels.^[4]

The walls of these abnormal vessels are structurally weak. The endothelial cells that line the vessels are abnormally thin, and there are fewer supporting pericyte cells than in healthy vessels. These structural defects make the vessels prone to leaking fluid through their walls. The leaked fluid accumulates under the retina, causing the retinal tissue to lift away from its normal position. This separation disrupts the normal flow of nutrients and oxygen to the photoreceptor cells.^[2]

The polypoidal dilations are particularly fragile and prone to rupture. When they break open, blood leaks into the space beneath the retina, causing sudden vision changes. The presence of blood and fluid under the retina interferes with the normal function of photoreceptor cells, which need to remain in close contact with the RPE layer to function properly. Over time, chronic leakage and bleeding can lead to permanent damage through scarring or atrophy of the retinal tissue.^[1]

The macula, which is the central portion of the retina responsible for detailed central vision needed for activities like reading and recognizing faces, is often affected in PCV. When fluid or blood accumulates in this critical area, it causes the distorted or blurred central vision that patients experience. The structural changes visible on imaging tests include raised areas where the RPE has lifted, accumulation of fluid in various layers, and sometimes blood that appears as darker areas on examination.^[4]

Diagnosis and Testing

The most important test used to diagnose polypoidal choroidal vasculopathy is a careful dilated eye examination by a retina specialist. During this examination, the doctor uses special instruments to view the inside of the eye and look for signs of abnormal blood vessels, fluid accumulation, or bleeding. However, additional specialized tests are typically needed to confirm the diagnosis and distinguish PCV from other similar conditions.^[1]

Indocyanine green angiography, or ICGA, is considered the essential test for definitively diagnosing PCV. This test involves injecting a special dye called indocyanine green into a vein, usually in the arm or hand, and then taking specialized photographs of the retina and choroid. The dye allows the doctor to see the abnormal blood vessels in the choroid in great detail. On ICGA images, the polypoidal lesions appear as areas of bright fluorescence, often with darker halos around them, while the branching vascular network connecting them can also be visualized.^[4]

Fluorescein angiography is another imaging test that may be useful. This test uses a different dye called fluorescein and helps create detailed images of the retinal blood vessels. While it can show leakage and some abnormalities, it typically doesn’t visualize the polypoidal structures as clearly as ICGA does. Both angiography tests require dye injection and multiple photographs taken over several minutes.^[1]

Optical coherence tomography, or OCT, scanning has become a routine and essential tool in diagnosing and monitoring PCV. This test uses light waves to create cross-sectional images of the retina, similar to how ultrasound creates images but with much higher resolution. OCT doesn’t require injections and is quick and painless. On OCT scans, the polyps of PCV appear as focal, sharply peaked elevations of the retinal pigment epithelium layer, shaped like an inverted U. The test can also show fluid accumulation beneath or within the retina and identify a characteristic appearance called the double-layer sign, which represents the branching vascular network.^[4]

Advanced OCT techniques can provide additional information. Enhanced-depth imaging OCT allows doctors to see deeper into the choroid and often shows that patients with PCV have a thicker choroid than normal. En face OCT, which is a viewing option available on most modern OCT devices, can display the abnormal vessels by creating images of specific layers beneath the retina. These images can show the polypoidal structures and branching networks without requiring dye injection, though ICGA remains the gold standard for diagnosis.^[4]

In the United States and many Western countries, ICGA is not routinely performed at the initial visit when patients present with bleeding or fluid in the macula. This practice contributes to underdiagnosis of PCV, as the condition may be mistaken for typical age-related macular degeneration. When ICGA is not available, careful evaluation of OCT features can suggest the diagnosis, but confirming it with ICGA when possible is important because PCV may respond better to certain specific treatments.^[4]

Treatment Options and Outlook

Unfortunately, some patients with polypoidal choroidal vasculopathy experience irreversible central vision loss in one or both eyes. However, early diagnosis and treatment may restore vision and prevent further vision loss in many patients. The approach to treating PCV has evolved over time, and current treatments have shown significant benefits for many people with the condition.^[1]

The most common treatments for PCV are intravitreal injections of anti-VEGF medication and photodynamic therapy, or PDT. These treatments may be used alone or in combination, depending on the specific characteristics of each case and how the disease responds to initial treatment.^[1]

Vascular endothelial growth factor, or VEGF, is a molecule naturally produced by the body that causes the abnormal vessels in PCV to leak fluid and bleed into and under the retina. Injections of anti-VEGF drugs into the eye block the activity of VEGF and often result in decreased fluid or blood caused by the abnormal vessels. These injections are given directly into the eye’s vitreous cavity, the gel-filled space in the center of the eye, using very fine needles after the eye has been thoroughly numbed.^[1]

Several anti-VEGF medications are used for treating PCV, including ranibizumab and bevacizumab. Studies have shown that anti-VEGF therapy can reduce leakage effectively in PCV and improve vision in many patients. However, these medications are less effective at causing the actual polypoidal lesions to regress or disappear. Research indicates that only about 30% of patients treated with anti-VEGF medication alone achieve complete regression of their polyps, though visual improvement can occur even when polyps persist, due to the medication’s strong effect at reducing leakage.^[8]

Successful treatment with anti-VEGF medication often requires repeat injections, sometimes as frequently as every 4 to 6 weeks, to prevent increased leakage or bleeding. The need for frequent ongoing treatment can be burdensome for patients, requiring regular office visits and repeated procedures.^[1]

Photodynamic therapy, or PDT, works differently from anti-VEGF treatment. This procedure involves an intravenous infusion of a special medication called verteporfin, which is injected over 10 minutes. This medication makes the abnormal blood vessels more sensitive to light. Approximately 15 minutes after the infusion, a special cold laser is applied to the retina and choroid in the treatment area. The laser activates the verteporfin, which then damages or destroys the abnormal blood vessels found in PCV.^[1]

PDT has shown excellent results in treating PCV, particularly in the short term. Studies have reported that complete polyp regression was achieved in 80% to 95% of cases, with resolution of fluid and bleeding and stabilization or improvement of vision at one-year follow-up. This makes PDT particularly effective at eliminating the polypoidal lesions themselves. However, PDT also has limitations. The branching vascular network often persists, and polyps can recur over time, with some studies showing recurrence in up to 77% of eyes at three years. Repeated PDT treatments may be needed, and there are concerns about potential damage to the choroid with multiple treatments.^[8]

Recognizing the strengths and limitations of each treatment approach, many specialists now use combination therapy for PCV. The EVEREST study, a major randomized clinical trial, compared PDT combined with ranibizumab, PDT alone, and ranibizumab alone. The study found that combination therapy resulted in better polyp regression rates than anti-VEGF medication alone and suggested advantages over either treatment used by itself. Combination therapy may reduce the number of PDT treatments needed, speed up fluid absorption, and potentially reduce bleeding events compared to PDT alone.^[8]

On rare occasions, surgical vitrectomy, which is a procedure to remove the eye’s vitreous gel, may be used to remove or move aside a large hemorrhage caused by PCV. This is typically reserved for severe cases where blood in the vitreous cavity is blocking vision and not clearing on its own.^[1]

The visual prognosis for PCV is variable. While it’s generally accepted that PCV may have a better visual prognosis than typical neovascular age-related macular degeneration, outcomes depend on many factors including how early treatment begins, the location and extent of the polypoidal lesions, initial visual acuity, and how well the condition responds to treatment. Some patients maintain good vision with ongoing treatment, while others experience gradual decline despite therapy. Regular monitoring and adjustments to treatment plans are essential for optimizing outcomes.^[8]