Choroidal Neovascularisation

Choroidal neovascularisation is a serious eye condition where abnormal blood vessels grow beneath the retina, potentially leading to vision loss if left untreated.

Table of contents

• What is Choroidal Neovascularisation?
• Causes and Risk Factors
• Symptoms and Warning Signs
• How is Choroidal Neovascularisation Diagnosed?
• Treatment Options
• Related Eye Conditions

What is Choroidal Neovascularisation?

Choroidal neovascularisation (CNV) involves the growth of new blood vessels that originate from the choroid through a break in the Bruch membrane into the area beneath the retinal pigment epithelium or the space under the retina^[1][2]. The choroid is a layer of tissue in the eye located between the retina and sclera that is filled with blood vessels^[3].

The term “neovascularisation” means “new blood vessels.” These new, abnormal blood vessels originate in the choroid, a vessel-containing layer under the retina^[1]. The retina is the part of the eye that converts light into electrical signals that travel to the brain^[3].

The new blood vessels that form are different from normal vessels. They are fragile and leaky, allowing fluid from the blood, and sometimes even red blood cells, to enter the retina^[1][3]. This fluid can immediately distort vision because it forms a “blister” in the retina, which is normally flat. Over the course of days to months, this fluid can damage the retina, killing the light-sensing cells called photoreceptors^[1].

CNV, choroid neovascularization

• Choroid
• Retina
• Retinal pigment epithelium
• Bruch membrane

Causes and Risk Factors

CNV is a major cause of visual loss^[2]. The most common cause of CNV is age-related macular degeneration (AMD). Some patients with dry age-related macular degeneration eventually develop wet AMD, in which abnormal blood vessels grow into the retina and leak fluid^[1].

When the retinas of people with AMD produce too much vascular endothelial growth factor (VEGF), new blood vessels sprout from the choroid, then grow into the retina^[1]. Experts believe high levels of VEGF made by the retina in someone with AMD cause CNV^[3].

In younger patients, CNV occurs primarily in the presence of cracks within the retinal macular tissue known as lacquer cracks when associated with myopic degeneration and extreme myopia (nearsightedness)^[4]. Extreme nearsightedness can stretch and thin the eye’s layers, including the choroid, making the eye more susceptible to CNV^[3].

Virtually any pathologic process that involves the retinal pigment epithelium and damages the Bruch membrane can be complicated by CNV^[7]. Other causes include inflammatory or infectious conditions such as histoplasmosis, sarcoidosis, and multifocal choroiditis^[7]. Eye injury, including choroidal rupture and laser photocoagulation, can also lead to CNV^[7].

Additional risk factors include advanced age, a history of smoking, high blood pressure, and a family history of the condition^[23]. Certain medical conditions, such as diabetes or cardiovascular disease, can also increase the risk^[23].

Symptoms and Warning Signs

CNV can create a sudden deterioration of central vision, noticeable within a few weeks^[8]. Patients with CNV describe painless loss of vision^[2][7].

The symptoms of CNV include a distortion or waviness of central vision or a gray, black, or void spot in the central vision^[1]. Straight lines may appear wavy or distorted, a condition known as metamorphopsia^[2][4]. This symptom is particularly concerning because it indicates that fluid is affecting the normally flat structure of the retina.

Other symptoms include:^[4]

• Colors lose their brightness or appear differently in each eye
• Loss of vision without pain
• Apparent change in image size
• Flashes of light or flickering in central vision

A paracentral or central scotoma may develop, which is an island of relative or absolute vision loss in the center or near the center of vision^[4][7]. Hemorrhaging of the new blood vessels can accelerate the onset of symptoms^[8].

If you notice any of these symptoms, you should call an ophthalmologist right away to get a priority emergency visit. The ophthalmologist can halt the growth and leakage of the blood vessels by injecting a drug blocking VEGF into the eye, but only if they can deliver the drug as soon as possible, within hours or days from the time you notice the change in vision. Time lost is vision lost^[1].

How is Choroidal Neovascularisation Diagnosed?

The ophthalmologist can detect CNV using a combination of techniques. Clinical examination is the first step, followed by specialized imaging studies^[4].

Clinical Examination

During the dilated eye exam, the doctor may see a blister of fluid or bleeding in the retina^[1]. Physical findings in patients with CNV include subretinal blood, subretinal fluid, lipid exudation, retinal pigment epithelial detachment, and subretinal fibrosis^[2][7].

Fluorescein Angiography

Fluorescein angiography (FA) was once an essential tool in diagnosing and managing CNV^[2]. In this test, a special dye is injected into the arm, and as it circulates through the bloodstream to the blood vessels in the eyes, images are captured that clearly show areas where there is leakage from abnormal blood vessels^[21].

Different patterns can be seen on angiography. A lesion that shows increased brightness in the early phases of the angiogram, maintains well-defined borders, and leaks late is called classic CNV. A lesion whose borders cannot be determined is called occult CNV^[2].

Optical Coherence Tomography

Spectral domain optical coherence tomography (OCT) is now the imaging modality of choice^[2]. It is a painless imaging procedure that produces high-quality, three-dimensional cross-sectional images of the retina^[21]. Unlike fluorescein angiography, OCT does not require any injections. It uses light waves to capture detailed images of the retinal layers, highlighting any abnormalities such as the presence of new blood vessels^[21].

Indocyanine Green Angiography

Indocyanine green angiography (ICG) uses a dye with peak absorption and fluorescence in the near infrared range, which allows visualization of choroidal pathology through overlying fluid, pigment, or a thin layer of hemorrhage that usually blocks visualization during fluorescein angiography^[2].

Treatment Options

The treatment of choice for CNV is intravitreal anti-VEGF therapy^[10]. Current knowledge of molecular events in the development of CNV has allowed it to be targeted with very specific antiangiogenic factors^[10].

Anti-VEGF Treatment

Vascular endothelial growth factor (VEGF) causes abnormal blood vessels to grow under the retina. With anti-VEGF treatment, a drug is used to block VEGF, which reduces the growth of CNV, slows leakage, and helps to improve vision or stop vision loss^[4].

Anti-VEGF is administered directly into the eye in an outpatient procedure. Multiple injections may be given over the course of many months, and repeat anti-VEGF treatments may be needed for continued benefit^[4]. Targeting VEGF allows a two-hit strategy: antiangiogenesis and antipermeability. VEGF is 50,000 times more potent than histamine in inducing vascular permeability^[10].

The effectiveness of angiogenesis inhibitors has been shown to significantly improve visual prognosis with CNV^[8]. These inhibitors slow or stop the formation of new blood vessels, typically by binding to or deactivating the transmission of VEGF^[8].

The major limitation of anti-VEGF treatment is the injection burden. Most patients require multiple injections^[10]. Up to one-fourth of all treated patients are unresponsive to this treatment, and about one-third of the responders become resistant to it after repeated administration over time^[19].

Photodynamic Therapy

Photodynamic therapy (PDT) uses a laser and a combination of a photosensitizer (light-activated drug) and a special low-power, or cool, laser to target the CNV^[4]. The photosensitive drug reaches the abnormal vessels by being injected into a vein in the arm. The low-power laser light activates the photosensitive drug to cause damage to the unwanted blood vessels^[4].

Multiple treatments may be necessary. PDT may be done in patients that are unresponsive to anti-VEGF injections^[4]. However, PDT has fallen out of favor since randomized clinical trials have shown no added benefit to anti-VEGF monotherapy^[10].

Thermal Laser Treatment

Thermal laser treatment is used to destroy the abnormal blood vessels, prevent further leakage, bleeding and growth. Although the abnormal blood vessels are destroyed using laser treatment, re-treatment may be needed^[4]. This was the first proven treatment but inevitably destroys retinal tissue^[1].

Combination Approaches

A number of different protocols are looking at combining photodynamic therapy, corticosteroids, and anti-VEGF drugs^[10]. Recently, the angiopoietin-Tie2 pathway has been implicated in the pathogenesis of CNV. Increased levels of Angiopoietin-2 have been shown to be elevated in eyes with CNV. Targeting this pathway may provide added benefits^[10].

Related Eye Conditions

CNV is closely associated with several other eye conditions that share similar mechanisms or risk factors:

• Age-related macular degeneration
• Wet age-related macular degeneration
• Dry age-related macular degeneration
• Myopia
• Myopic degeneration
• Histoplasmosis
• Sarcoidosis
• Multifocal choroiditis