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Choroidal Neovascularization - Causes, Clinical Features, Diagnosis, and Management

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Choroidal Neovascularization - Causes, Clinical Features, Diagnosis, and Management

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Choroidal neovascularization is the pathological formation of choroidal blood vessels invading the subretinal space. Read the full article below for more information.

Written by

Dr. A. Srividya

Medically reviewed by

Dr. Gargi Madhukar Apte

Published At July 21, 2022
Reviewed AtApril 20, 2023

Introduction

Choroidal neovascularization (CNV) is the excessive growth of blood vessels originating from the choriocapillaris complex. It invades the subretinal pigment epithelium or subretinal space. It is primarily responsible for blindness in developed countries and sequels to other ocular diseases.

What Causes CNV?

It occurs in association with other ocular and systemic diseases. The most consequential visual disorders contributing to CNV are:

  • Age-related macular degeneration or wet macular degeneration is characterized by endothelial dysfunction. The leaky blood vessels lead to the accumulation of fluid in the macula. Macular degeneration clinically results in loss of central vision.

  • Pathological myopia is characterized by reduced eyesight due to the degenerative change occurring in the back of the eye. Glasses do not correct eyesight loss.

Other systemic conditions promoting CNV are:

  • Pseudoxanthomas (deposition of calcium and minerals in the elastic fibers).

  • Paget’s disease (bone disorder affecting multiple bones).

  • Sickle cell anemias (blood disorder with defective red blood cells).

What Is the Mechanism Behind the Formation Of CNV?

There are several theories hypothesized for the development of CNV. These theories include:

  • Angiogenesis: The genesis of new blood vessels from the existing capillary network is one of the significant causes of the development of CNV. Various factors bring about angiogenesis in the choroid region -

    • Vascular endothelial growth factor (plays a predominant role in angiogenesis), other angiogenic factors include the fibroblast growth factors (FGF), matrix metalloproteins (MMP), and beta transforming growth factors.

  • Inflammation: Innate immunity plays a crucial role in the formation of CNV. The two main components of innate immunity are the monocytes and the complement system.

  1. Macrophages and monocytes promote the angiogenesis process and cause inflammatory damage to the retina.

  2. The complement system potentiates the process of neovascularization by activating the endothelial cells and recruiting macrophages.

  • Vasculogenesis: It is the repair process of the blood vessels by the bone marrow progenitor cells. In CNV, these progenitor cells contribute to endothelial and mesenchymal subsets in the CNV.

What Are the Different Types of CNV?

Neovascular lesions associated with age-related macular degeneration are of three types:

  • Type 1: CNV expands through the Bruch’s membrane into the retinal pigment epithelium.

  • Type 2: CNV extends into the subretinal space.

  • Type 3: Retinal proliferation of the blood vessels.

What Is the Clinical Picture of CNV?

CNV of pathological myopia is prevalent in younger patients. CNV linked to age-related macular degeneration is more prevalent in older individuals than CNV linked to pathological myopia. The most significant clinical presentation of CNV is painless, gradual vision loss accompanied by a black spot in the central vision.

Other manifestations include:

  • The size and color of the objects appear differently from different eyes.

  • Flickering of light in the central vision.

  • The presence of reddish circular structures around the retina suggests retinal hemorrhage.

  • Distorted vision.

  • Untreated CNV evolves into a fibrovascular band known as disciform scars.

How to Diagnose CNV?

The diagnosis of CNV is determined primarily by clinical imaging techniques:

  • Fluorescein angiography is a technique of injecting fluorescent dye into the body to detect the presence of choroidal membranes. It is the conventional technique for detecting CNV.

  • Combining fluorescein dye with indocyanine green dye helps in delineating the margins and branching of the neovascular capillaries of the eye.

  • Optical coherence tomography (OCT) is a non-invasive imaging technique that provides a cross-sectional image of the abnormal blood vessel. They are also used to determine the disease activity during the treatment.

What Are the Other Diseases That Mimic CNV?

Diseases That Mimic CNV

Other conditions that have similar findings to that of CNV are:

  • Angioid streaks are bilateral and irregular lines seen deep in the retina, causing a break in the Bruch’s membrane, resulting in blindness.

  • White dot syndromes are a group of retinal-choroidal diseases of unknown etiology clinically manifesting as blurred vision or loss of sight.

  • Choroidal neovascular membranes are the new damaged blood vessels growing beneath the retina. Draining blood vessels in the retina ultimately causes blindness.

  • Macular edema is an accumulation of fluid in the macula (an area in the center of the retina), promoting the thickening of macula and blurring of vision.

How to Manage CNV?

Different treatment modalities that treat CNV include:

  • Photodynamic Therapy (PDT) - It damages the unwanted mature blood vessels by using a photosensitizer drug and a low-power laser. It is used in age-related macular degeneration cases. There is a need for multiple doses of PDT.

  • Laser Photocoagulation - It is mainly used in juxtafoveal and extrafoveal CNV lesions. Lasers occlude the leaking blood vessels of CNV.

  • Thermal Laser Treatment - This high-energy laser is targeted at the blood vessels leading to the burning of the capillaries in that area. It prevents leaking, bleeding, and growth of blood vessels.

  • Anti Vascular Endothelial Growth Factors (anti-VEGF) - It is considered the treatment of choice for CNV. Anti-VEGF prevents the formation of new pathologic blood vessels and also reduces its permeability. Anti-VEGF has a few significant adverse effects, such as -

    • Prolonged use of anti-VEGF agents causes tachyphylaxis. In tachyphylaxis, the pharmacological agent loses its therapeutic effect upon repeated administration.

    • Prolonged use of anti-VEGF causes damage to normal blood vessels too.

    • It further promotes impairment of vision.

  • Corticosteroids - Corticosteroids have antiangiogenesis (the process of formation of new blood vessels) and antifibrotic properties. Thus it reduces the permeability of the blood vessels in CNV. It is injected peri-ocularly as an adjunct with PDT. Intraocular injections lead to increased intraocular pressure and cataract development.

  • Combination Therapy - CNV is a condition with multiple mechanisms of pathology; hence combination therapies are more beneficial.

    • PDT with steroids has a more profound inflammatory efficacy on CNV. Side effects consist of the transient increase in intraocular pressure and cataract development.

    • PDT with anti-VEGF has a synergistic effect. PDT helps destroy the mature blood vessels, while anti-VEGF prevents the formation of new blood vessels.

    • Anti VEGF and steroids decrease the macula thickness with improved vision.

    • Triple therapy includes the use of anti-VEGF, steroids, and PDT. It helps improve the vision by combining the synergistic aspects of all three treatment modalities.

What Is the Prognosis of CNV?

CNV overall does not have a poor prognosis. Extrafoveal CNV transforms itself into subfoveal CNV. Subfoveal CNV involutes or stabilizes spontaneously with time.

Conclusion

CNV is mainly a disorder of endothelial dysfunction. It is one of the principal causes of blindness in developed countries. It is associated with several ocular and systemic diseases. The application of appropriate therapies stabilizes the vision without further deterioration.

Frequently Asked Questions

1.

Is There a Cure for the Choroidal Neovascular Membrane?

The treatment options for choroidal neovascular membrane differ among individuals depending on the cause and severity of this condition. While it may not always be curable, various interventions such as anti-VEGF (vascular endothelial growth factor) injections, laser therapy, or photodynamic therapy can help to control this condition and prevent further vision loss.

2.

Is Blindness a Potential Consequence of Choroidal Neovascularization?

 
Choroidal neovascularization can potentially lead to vision loss and even blindness if left untreated. It is a prevalent pathological condition found in over 30 different eye diseases, leading to significant vision impairment and potential blindness. The primary cause of CNV among older individuals is age-related macular degeneration (AMD). However, in individuals below the age of 50, CNV can also arise due to various underlying factors, including pathologic myopia (PM), angioid streaks, trauma, and inflammatory or hereditary disorders.

3.

What Is the Most Effective Treatment for CNV?

The best treatment for choroidal neovascularization (CNV) often involves a combination of therapies tailored to the individual case. These may include anti-VEGF injections, laser photocoagulation, photodynamic therapy, or surgical options like vitrectomy. The majority of individuals affected by these conditions find relief through intravitreal injections of anti-VEGF medications such as Brolucizumab, Ranibizumab, or Aflibercept. VEGF plays a key role in promoting the growth and leakage of choroidal neovascularization (CNV) in most cases. Emerging studies are focusing on the development of longer-lasting anti-VEGF drugs like Brolucizumab, as well as exploring anti-VEGF gene therapy.

4.

What Methods Can Be Used to Prevent Choroidal Neovascularization?

Choroidal neovascularization can be prevented to a certain extent by managing the underlying conditions that contribute to its development. This may include controlling systemic factors like hypertension, diabetes, or high cholesterol through lifestyle modifications or medication. In some cases, targeted therapies or procedures targeting the specific site of neovascularization may be employed.

5.

Is Choroidal Neovascularization Considered a Serious Condition?

Yes, choroidal neovascularization is indeed a serious condition, as it can lead to significant vision impairment and impact the quality of life. CNV, a major contributor to vision impairment, arises from various conditions affecting the complex relationship between the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris. Among these conditions, age-related macular degeneration (AMD) is the primary cause of permanent and severe vision impairment in older individuals within developed countries.

6.

Can Choroidal Neovascularization Resolve on Its Own?

 
Choroidal neovascularization may not typically resolve on its own. However, in some cases, the growth and activity of the neovascularization may stabilize or diminish without intervention. The likelihood of spontaneous resolution depends on various factors, including the underlying cause, the stage of CNV, and individual factors. Timely and appropriate medical intervention, such as anti-VEGF injections or laser therapy, is often necessary to manage CNV effectively and prevent further vision loss.

7.

What Is the Duration of Corneal Neovascularization?

Neovascularization has been observed to manifest as soon as one day following a corneal infection caused by the herpes simplex virus (HSV). This vascularization process can persist for a duration of two to three weeks following the initial infection. It may last for weeks to months or even longer in some cases.

8.

At What Age Does Choroidal Neovascularization Typically Occur?

Choroidal neovascularization can occur at any age, but it is commonly associated with age-related macular degeneration (AMD), which predominantly affects individuals over the age of 50. Individuals who possess risk factors for various eye conditions or have experienced eye trauma may develop choroidal neovascularization at a relatively early age. The risk of getting this condition increases as one advances in age.

9.

Does Corneal Neovascularization Have Long-Term Effects?

Corneal neovascularization can be permanent if left untreated or if the underlying cause persists. In cases where neovascularization stems from inflammation in other ocular tissues or infection, with appropriate management and targeted interventions, it is possible to control and minimize the progression of neovascularization. After blood vessels have extended into the corneal tissue, they are unlikely to completely vanish. While enhancing oxygen supply to the cornea can halt their growth, residual vessels may persist. If the cornea experiences oxygen deprivation again, these vessels may refill and resume growing.

10.

What Are the Laser-Based Approaches for Managing CNV?

Photocoagulation and photodynamic therapy (PDT) are the two commonly used laser treatment approaches for choroidal neovascularization. 
- Photocoagulation involves using laser energy to selectively target and seal off abnormal blood vessels, preventing further leakage and reducing the progression of CNV. 
- PDT utilizes a photosensitizing agent that is injected intravenously and then activated by the laser light to selectively eliminate the abnormal blood vessels linked with CNV while minimizing damage to the surrounding healthy tissue. 
These treatments aim to control the growth and leakage of blood vessels in the choroid, thereby preserving vision and preventing further complications.
 
 

11.

What Factors Increase the Risk of Developing CNV?

Several risk factors associated with the development of CNV are listed below:
- Age-related macular degeneration (AMD).
- Myopia (nearsightedness).
- Hypertension (high blood pressure).
- Diabetes.
- Ocular inflammation.
-History of eye trauma.
- Certain hereditary disorders. 
Additionally, lifestyle factors such as smoking and prolonged sun exposure can contribute to the risk of CNV.

12.

Is Neovascularization Considered a Normal Physiological Process?

No, neovascularization is not considered a normal occurrence in healthy individuals. It is an abnormal response typically triggered by underlying conditions or pathological processes, such as tissue injury, inflammation, or vascular disorders.

13.

What Are the Potential Complications Associated With Choroidal Neovascularization?

Retinal hemorrhage accompanied by edema in the central macular region is a highly concerning complication associated with choroidal neovascularization. This particular complication significantly impacts an individual's visual acuity and can contribute to vision loss, ultimately leading to blindness in some cases. Other complications of choroidal neovascularization can include the following:
- Severe vision loss. 
- Central vision distortion or impairment. 
- Scarring of the macula.
- Retinal detachment.

14.

Can Neovascularization Result in Painful Sensations?

Neovascularization itself is typically not painful. However, underlying conditions or complications associated with neovascularization, such as inflammation or pressure on surrounding tissues, may cause discomfort or pain.  In cases of corneal vascularization, symptoms may not always be present, but if they do occur, they can include redness, excessive tearing, and ocular discomfort, or eye pain.

15.

What Are the Diagnostic Tests Used to Assess CNV?

 
The testing for choroidal neovascularization (CNV)  involves a comprehensive eye examination, which may include visual acuity tests, dilated fundus examination, optical coherence tomography (OCT), fluorescein angiography (FA), or indocyanine green angiography (ICGA). Fluorescein angiography (FA) can be a valuable tool in identifying choroidal neovascularization (CNV) associated with myopia. These tests help evaluate the presence, location, and extent of choroidal neovascularization and assist in determining the most appropriate treatment approach.

16.

Is There a Genetic Component to the Development of CNV?

Although certain genetic factors can be linked to choroidal neovascularization (CNV), it is not exclusively a genetic condition. The development of CNV is influenced by multiple factors, including age-related macular degeneration (AMD), other underlying conditions, environmental factors, and lifestyle choices. Genetic predisposition may be involved in some situations, but it is not the only thing that determines the occurrence of CNV.
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Dr. Gargi Madhukar Apte
Dr. Gargi Madhukar Apte

Ophthalmology (Eye Care)

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