What Is Neovascularization Of The Eye

Overview

Neovascularization of the eye is characterized as the abnormal formation of new blood vessels in the retina or other eye tissues.¹ This can be problematic as these newly formed vessels tend to be more fragile, increasing the risk of leaking, haemorrhages, and clouding of the visual field.^1,2 These effects can ultimately lead to impaired vision and even complete blindness in some cases.^1,2

Different types of neovascularization occur in the eyes, such as retinal, corneal, and choroidal angiogenesis.¹ Retinal neovascularization occurs in the retina and is typically associated with conditions like diabetic retinopathy or retinal vein occlusion.¹ Corneal neovascularization involves the growth of new blood vessels in the cornea.¹ This is often triggered by injury or inflammation, which can be the result of surgery, improper contact lens use or even certain infections.¹ Finally, choroidal neovascularization, which has a poor prognosis for blindness compared to other types of neovascularisation, develops beneath the retina and it is commonly associated with age-related macular degeneration.¹

The underlying causes of neovascularization are broad, and they are dependent on a wide range of factors. They can vary due to medical history, related areas of the eye, and even puberty.¹ Some of these causes include: 

• Ischemia: Lack of oxygen supply triggers a response to form new vessels.¹
• Inflammation: Certain eye diseases or injuries can stimulate the growth of abnormal blood vessels.¹
• Underlying diseases: These include diabetes, hypertension, or macular degeneration, which cause inflammatory symptoms that lead to angiogenesis and vision impairments.¹

Neovascularization profoundly impacts eye health since it is associated with many complications that can ultimately lead to vision loss.² This new vessel growth, or angiogenesis, often accompanies serious eye conditions like proliferative diabetic retinopathy, age-related macular degeneration or retinopathy of prematurity, exacerbating their severity and complicating treatment.² Managing neovascularization poses challenges due to the delicate nature of eye tissues and the need for targeted therapies to inhibit vessel growth without harming healthy parts of the eye.³ 

Causes and risk factors

Underlying conditions

It has been shown that in over 50% of cases, neovascularization results from complications caused by diabetes or retinal vein occlusion.¹ These pathologies are associated with ischemia in parts of the eye, which causes oxygen levels to decline, thus promoting the need for neovascularization.²

Diabetic retinopathy, which is a common complication of diabetes mellitus, is a major factor in the progression of neovascularization.¹ This is because long-term exposure to high sugar levels in the blood can damage retinal blood vessels causing inflammation.¹ Due to these inflammatory mechanisms as well as oxygen deficiency caused by damaged blood vessels, neovascularization occurs.¹

Retinal vein occlusion is also afflicted with neovascularization since it causes obstruction of retinal veins and can lead to retinal ischemia and reduced blood flow.¹ At the surface of the retina, neovascularization may cause vision impairment or even blindness if left untreated.¹ 

Injury or trauma to the eye

Injuries or surgeries may trigger corneal neovascularization due to the natural healing response in the eyes.¹ Abnormal vessel growth in the cornea compromises transparency and visual clarity.¹ Severe trauma can cause problems in the retina, one of which is ischemia, prompting abnormal vessel formation in the retina.¹ 

Uveitis is characterized by intraocular inflammation, resulting in the stimulation of neovascularization in the iris or retina.¹ The formation of new vessels can impair vision and lead to complications like glaucoma or retinal scarring.¹ Furthermore, infections like viral or bacterial keratitis can also induce inflammation, leading to corneal neovascularization, compromising the cornea's integrity, and affecting vision quality.¹

Mechanisms of neovascularization

Angiogenesis and vascular endothelial growth factor (VEGF)

Angiogenesis is the process by which new blood vessels are formed from pre-existing ones. Abnormal angiogenesis, or neovascularization of the eye, occurs in response to specific stimuli, leading to the growth of fragile and leaky vessels.⁴ One of these stimulating factors is VEGF, which is a critical signalling protein that stimulates angiogenesis.⁴ Overexpression and increased levels of VEGF promote the abnormal growth of blood vessels, particularly in conditions like diabetic retinopathy or age-related macular degeneration.⁴ Anti-VEGF treatments aim to inhibit excessive VEGF activity, curbing abnormal vessel growth and reducing defects in the eye.^2,4 There are also several other growth factors that can affect angiogenesis, such as fibroblast growth factor (FGF), which similarly to VEGF also has the potential to be a good target in treatment.²

Role of hypoxia and ischemia

Reduced oxygen levels, also known as hypoxia, stimulate the release of pro-angiogenic factors like VEGF, initiating and propagating neovascularization.^1,2,4 Tissues respond to the lack of oxygen by promoting vessel formation to enhance oxygen and nutrient delivery.4 Similarly, ischemia leads to tissue damage and triggers the release of signals, prompting the formation of new vessels.^1,2,4 Ischemic conditions can also be accompanied by inflammation, contributing to the development of abnormal vessels.^1,2,4 

Types and manifestations of eye neovascularization

Neovascular age-related macular degeneration (nAMD)

nAMD is a type of macular degeneration characterized by abnormal vessel growth beneath the macula, which is part of the retina.1 It is the leading cause of severe, irreversible vision loss, particularly associated with choroidal neovascularization that leads to fluid leakage and bleeding.1 If left untreated, nAMD can result in significant vision impairment, which affects tasks like reading or recognizing faces.¹

Retinal neovascularization

Diabetic Retinopathy is a common cause of retinal neovascularization due to insufficient oxygen supply.¹ Retinal Vein Occlusion is another cause of this type of neovascularization, which is caused by the obstruction of retinal veins, leading to retinal ischemia.¹ Severe cases may result in vitreous hemorrhage or tractional retinal detachment, but it can also cause bleeding and scarring ultimately leading to vision loss.¹

Corneal neovascularization

Neovascularization within the cornea often occurs in response to trauma, infections, or chronic inflammation.¹ Furthermore, prolonged use or improper hygiene with contact lenses may induce corneal neovascularization.¹ Corneal neovascularization affects visual clarity and increases the risk of corneal scarring.¹ Generally treatment is used to manage the underlying health concern, however, in some cases, procedures may be necessary to remove abnormal vessels or restore corneal clarity.¹

Diagnostic techniques

Key diagnostic techniques that are used in the assessment of neovascularization typically begin with simple ophthalmic examinations like fundoscopy.⁵ This can also be supplemented with the use of advanced imaging modalities such as optical coherence tomography (OCT) and indocyanine green angiography (ICGA).⁵ These are essential for accurate diagnosis and determining appropriate management techniques.⁵ 

Treatment approaches

Anti-VEGF therapy

Anti-VEGF therapies are heavily used in the treatment of neovascularization.³ Their mechanism of action is based on the inhibition of VEGF, which is a biological factor that promotes angiogenesis.³ One example is bevacizumab, which is an immunotherapy targeting VEGF, inhibit binding of VEGF to its receptor.³ The result is a reduction in abnormal blood vessel growth and inflammation.³ Bevacizumab is particularly effective when used in early treatments of patients with corneal neovascularization.³ Generally, anti-VEGF therapies help maintain vision by preventing further growth of abnormal blood vessels, especially in conditions like age-related macular degeneration and diabetic retinopathy.³

Laser and phototherapy treatment

High-energy laser beams, such as argon laser therapies, are used to target leaking or abnormal blood vessels in the retina.^1,3 It is effective in treating proliferative diabetic retinopathy by reducing neovascularization and preventing vision-threatening complications.¹ Despite this, laser therapy may cause scarring or damage to surrounding healthy tissues and not all patients are considered eligible for this form of treatment.¹

Surgical interventions (vitrectomy)

Vitrectomy involves removing the vitreous gel and any tractional forces causing retinal damage.² Successful vitrectomy can reduce, but not eliminate, severe visual loss in this disease progression.² This would typically be accompanied by medications to provide the best outcomes, assisting in the prevention of the onset or progression of neovascularization.

Conclusion

Neovascularization of the eye is characterized as abnormal blood vessel growth in ocular tissue. It is linked to conditions like diabetes, retinal vein occlusion, and also some infections that promote inflammatory processes. Suitable treatment approaches vary depending on the extent and location of the newly formed blood vessels, as well as any underlying health conditions. However, treatment typically includes anti-VEGF therapy, laser therapy, or surgical interventions like a vitrectomy.

Research into gene therapy, cell-based treatments, and innovative drug delivery systems may revolutionize neovascularization management. Future directions emphasize a holistic approach, integrating technology with patient education and personalized treatments to improve outcomes. These advancements hold the potential to reduce vision loss, prevent recurrence, and improve the quality of life for individuals affected by neovascularization whilst also educating them on disease causes and what symptoms to look out for.