Neovascularization is the growth of new blood vessels, a natural process that becomes destructive when it occurs abnormally in the eye. This uncontrolled proliferation of new vessels within the retina or choroid is a leading cause of severe, permanent vision loss. These new vessels are inherently fragile and defective, severely disrupting the delicate structure of the eye’s light-sensing tissues. Understanding the biological signals and underlying conditions that trigger this process is essential for modern eye care.
The Biological Mechanism of Abnormal Vessel Growth
The primary trigger for neovascularization is oxygen deprivation, known as ischemia, affecting the retina or the tissue layers beneath it. When the existing blood supply is insufficient to meet the metabolic demands of the eye’s cells, the tissue attempts to compensate. This compensatory response involves the release of specific chemical messengers to stimulate the growth of a new blood supply.
The most potent signal is Vascular Endothelial Growth Factor (VEGF), a protein that stimulates blood vessel formation. Cells within the oxygen-starved retina, such as the retinal pigment epithelium (RPE), increase their production of VEGF. This surge binds to receptors on existing endothelial cells, which line blood vessels. This binding initiates a cascade causing these cells to multiply, migrate, and form new, aberrant vascular structures.
The new vessels created under the influence of high VEGF are structurally flawed and do not resemble healthy capillaries. They lack the normal tight junctions between their endothelial cells, making them porous and leaky. The balance between pro-angiogenic factors like VEGF and anti-angiogenic factors, such as Pigment Epithelium-Derived Factor (PEDF), is disrupted, favoring destructive vessel growth.
Key Conditions Associated with Eye Neovascularization
Neovascularization is the hallmark of several major sight-threatening diseases, appearing in different locations depending on the pathology. In Age-Related Macular Degeneration (AMD), the abnormal vessels originate in the choroid, the layer beneath the retina, a condition called Choroidal Neovascularization (CNV). These vessels push through the Bruch’s membrane into the space beneath the retina, often causing an elevation that distorts central vision. CNV defines the “wet” form of AMD, which accounts for most severe vision loss from the disease.
Neovascularization caused by diabetes affects the retina itself, a complication called Proliferative Diabetic Retinopathy (PDR). Chronic high blood sugar damages existing retinal vessels, leading to widespread blockages and subsequent ischemia. The resulting high levels of VEGF stimulate the growth of new vessels directly on the surface of the retina or the optic nerve head, known as Retinal Neovascularization (RNV).
Other conditions also lead to this destructive process, sharing the common mechanism of retinal ischemia. Retinal vein occlusions, where a major vein becomes blocked, cause an immediate lack of oxygen in the drained area, leading to RNV. Retinopathy of Prematurity (ROP) in infants is another disorder where abnormal oxygen levels cause a surge in VEGF, resulting in disorganized new vessels in the developing retina.
Immediate and Long-Term Impact on Vision
The immediate threat stems from the fragility and permeability of the newly formed vessels. These vessels are prone to rupture, resulting in hemorrhage or bleeding into the vitreous gel or beneath the retina. Bleeding into the vitreous, the clear gel that fills the eye, causes sudden vision loss, often perceived as floating spots or a dense shadow.
The vessels also leak fluid and blood components, known as edema, causing retinal tissue to swell. When this leakage occurs in the macula, the central area responsible for sharp vision, it compromises visual acuity. This leads to distorted central vision, known as metamorphopsia. Fluid pooling beneath the retina can lift the light-sensitive photoreceptor cells away from their nutrient supply, causing them to cease functioning.
In the longer term, the persistent presence of abnormal vessels and inflammation leads to the formation of scar tissue, or fibrosis. This fibrovascular membrane contracts over time, pulling on the retina and causing tractional retinal detachment, which results in irreversible blindness. This scar tissue formation is a common final pathway for vision loss in advanced neovascular diseases, as the opaque material permanently blocks light from reaching the photoreceptors.
Current Treatment Strategies
The modern approach focuses on neutralizing the underlying biological signal driving neovascularization. Anti-VEGF therapy involves injecting specialized drugs directly into the vitreous cavity. These medications, such as ranibizumab, bevacizumab, and aflibercept, bind to the excess VEGF protein, effectively blocking its ability to stimulate abnormal vessel growth and leakage.
By inhibiting VEGF, these injections cause the new, fragile vessels to shrink and regress, reducing fluid leakage and hemorrhage. This therapeutic approach has revolutionized the treatment of wet AMD and PDR, transforming previously untreatable conditions into manageable chronic diseases. Patients often require repeated injections, typically administered monthly or every few months, to maintain vessel regression and prevent recurrence.
Laser Photocoagulation
For extensive retinal neovascularization, particularly in PDR, laser photocoagulation remains an important treatment option. This procedure uses a laser to deliberately destroy areas of oxygen-starved peripheral retina. Ablating these ischemic areas reduces the tissue’s overall oxygen demand, lowering VEGF production and allowing abnormal vessels to regress. While effective at preserving central vision, this scatter laser treatment can result in some loss of peripheral vision and reduced night vision.
Photodynamic Therapy (PDT)
Photodynamic Therapy (PDT) is a less common, older treatment used in select cases of CNV, often combined with anti-VEGF agents. This technique involves injecting a light-sensitive drug, verteporfin, into the bloodstream. The drug is then activated by a non-thermal laser shined onto the affected area. The activated drug selectively damages the abnormal neovascular tissue, causing it to close down and stop leaking.