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

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?

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.