Choroidal neovascularisation is a serious eye condition where abnormal blood vessels grow beneath the retina, potentially threatening central vision. When these fragile vessels leak fluid or blood, they can damage the delicate light-sensing cells in the eye, leading to distorted or blurred vision. Understanding the available treatment approaches and the promising therapies being tested in clinical trials can help patients and their doctors make informed decisions about managing this sight-threatening condition.

How Treatment Aims to Preserve Your Vision

The primary goal when treating choroidal neovascularisation is to stop or slow down the growth of these abnormal blood vessels that threaten your eyesight. Treatment focuses on reducing fluid leakage, preventing further damage to the light-sensing cells in your retina, and ultimately preserving as much of your central vision as possible. In some cases, treatment can even restore some vision that has already been lost, though this is not guaranteed for every patient.^[1]

The choice of treatment depends heavily on the underlying cause of the neovascularisation, the location and size of the abnormal vessels, and how quickly the condition was detected. Age-related macular degeneration (often shortened to AMD) is the most common cause of choroidal neovascularisation in older adults, while extreme nearsightedness (called high myopia) is a more common cause in younger patients. Other conditions like inflammatory eye diseases or injury can also trigger this abnormal vessel growth.^[2][3]

Time is critical when treating choroidal neovascularisation. The sooner treatment begins after symptoms appear, the better the chances of preventing permanent vision loss. This is because the fluid leaking from these abnormal vessels can quickly damage or kill the photoreceptors, which are the specialised cells that capture light and allow you to see. Once these cells die, they cannot be replaced, and the resulting vision loss becomes permanent.^[1]

Standard Treatments Used Today

Anti-VEGF Injections: The Current Gold Standard

The most widely used treatment for choroidal neovascularisation today involves injecting drugs called anti-VEGF agents directly into the eye. VEGF stands for vascular endothelial growth factor, which is a protein that signals the body to grow new blood vessels. In people with choroidal neovascularisation, the retina produces too much of this protein, causing the abnormal vessel growth. Anti-VEGF drugs work by blocking this protein, which stops new vessels from forming and reduces leakage from existing ones.^[1][4]

Common anti-VEGF medications include ranibizumab, bevacizumab, and pegaptanib. These drugs are delivered through an injection into the white part of the eye in a procedure called intravitreal injection. While the idea of an eye injection may sound uncomfortable, the procedure is performed in an outpatient setting with numbing drops, and most patients report only mild discomfort. The actual injection takes only seconds.^[4][8]

Most patients require multiple injections over time because the effect of each dose gradually wears off. In the initial treatment phase, injections might be given monthly. As the condition stabilises, the frequency may be reduced based on how the eye responds. Some people need repeated treatments over many months or even years to maintain the benefits. Regular monitoring with imaging tests helps doctors determine when additional injections are needed.^[4][10]

Anti-VEGF therapy has been shown to significantly improve visual outcomes for many patients. Clinical studies have demonstrated that these medications can slow or stop the formation of new blood vessels, reduce fluid accumulation beneath the retina, and in many cases improve vision compared to baseline. However, not all patients respond equally well. Some people experience little improvement, while others may gradually become less responsive to treatment after repeated injections.^[10][16]

Common side effects of anti-VEGF injections include temporary eye redness, mild discomfort, and the sensation of having something in the eye. More serious but rare complications include infection inside the eye (called endophthalmitis), bleeding, increased eye pressure, and retinal detachment. Your eye doctor will discuss these risks before treatment and monitor you carefully afterwards.^[1]

Treatment Resistance: A Significant Challenge

One of the major limitations of anti-VEGF treatment is that up to one-quarter of patients show little or no response to these drugs from the start. Additionally, about one-third of patients who initially respond well may develop resistance over time, meaning the injections gradually become less effective even when given more frequently. This phenomenon has been particularly challenging for both patients and doctors because it means some people continue to lose vision despite receiving treatment.^[10][19]

Several theories have been proposed to explain why some people become resistant to anti-VEGF therapy. The body may develop antibodies that neutralise the medication, or other growth factors besides VEGF may start driving the vessel growth. The structure of the abnormal vessels may also change over time, becoming more mature and less dependent on VEGF. Understanding these mechanisms is an active area of research, as finding ways to overcome resistance could help many more patients preserve their vision.^[10]

Photodynamic Therapy: A Laser-Based Approach

Before anti-VEGF drugs became available, photodynamic therapy (often abbreviated as PDT) was a common treatment for choroidal neovascularisation. This approach uses a light-activated drug called verteporfin combined with a special low-power laser. The drug is injected into a vein in your arm and travels through your bloodstream until it reaches the abnormal blood vessels in your eye.^[4][13]

Once the drug has accumulated in the target vessels, the eye doctor shines a specific wavelength of laser light onto the affected area. This activates the drug, causing it to produce substances that damage the unwanted blood vessels and cause them to close off. The surrounding healthy tissue is generally spared because the drug preferentially accumulates in the abnormal vessels.^[4]

Today, photodynamic therapy is used much less frequently than anti-VEGF injections because studies have shown that anti-VEGF drugs alone are more effective for most patients. However, PDT may still be considered for patients who do not respond to anti-VEGF treatment or as part of combination therapy approaches. Multiple treatment sessions are often necessary, and the procedure may need to be repeated if new vessel growth occurs.^[10][13]

Thermal Laser Treatment: The Historical Approach

Thermal laser treatment, also called laser photocoagulation, was the first proven treatment for choroidal neovascularisation. This method uses a high-energy laser to destroy the abnormal blood vessels by burning them. While this can effectively seal off the leaking vessels, it also destroys surrounding healthy retinal tissue, which creates a permanent blind spot.^[4][13]

Because of the damage it causes to healthy tissue, thermal laser treatment is now rarely used for treating choroidal neovascularisation beneath the central part of the retina. It may still be considered for abnormal vessels located away from the centre of vision, where the resulting scar would not affect the most critical part of your eyesight. Additionally, the abnormal vessels often regrow after thermal laser treatment, requiring repeated procedures.^[13]

Promising Therapies Being Tested in Clinical Trials

Targeting Multiple Pathways: Beyond VEGF

Researchers have recognised that relying on VEGF inhibition alone may not be sufficient for all patients. Clinical trials are now exploring drugs that target additional pathways involved in abnormal blood vessel growth. One particularly promising approach involves blocking angiopoietin-2 (often shortened to Ang-2), a protein that works alongside VEGF to promote vessel formation and vascular instability.^[10]

Studies have shown that levels of angiopoietin-2 are elevated in eyes with choroidal neovascularisation. When abnormal vessels form, angiopoietin-2 makes them more permeable and unstable, contributing to fluid leakage. Blocking both VEGF and angiopoietin-2 simultaneously might provide better control of the disease than targeting VEGF alone. This dual-targeting strategy is being tested in clinical trials to determine whether it can help patients who have developed resistance to standard anti-VEGF therapy.^[10]

Novel Combination Approaches to Overcome Resistance

An innovative strategy being explored in research involves combining anti-VEGF drugs with a protein called apolipoprotein A-I binding protein (AIBP). This approach is based on observations that abnormal cholesterol accumulation in certain immune cells called macrophages may contribute to the development and persistence of choroidal neovascularisation. AIBP helps remove excess cholesterol from these cells and from the cells lining blood vessels.^[19]

Preclinical research using animal models has demonstrated that combining AIBP with anti-VEGF treatment can overcome resistance to anti-VEGF drugs alone and more effectively suppress the growth of abnormal vessels. The mechanism appears to involve reducing cholesterol accumulation in macrophages, which in turn reduces their contribution to vessel growth and inflammation. While this approach is still in the early stages of development, it represents a promising new direction for treating patients who do not respond adequately to current therapies.^[19]

Light-Activated Nanoparticles: A Non-Invasive Delivery System

One of the major drawbacks of current treatment is the need for repeated injections directly into the eye, which are uncomfortable for patients and carry risks of complications like infection. Researchers have developed an experimental system using specially designed nanoparticles that can be given intravenously (through a vein in the arm) and then activated with light directed at the eye.^[14]

These nanoparticles are engineered with a light-sensitive chemical group that keeps them inactive as they circulate through the bloodstream. When blue light is shone onto the affected area of the eye, it triggers a change in the nanoparticles, activating a cell-penetrating peptide on their surface. This allows the nanoparticles to specifically enter cells in the diseased tissue while sparing healthy areas that are not exposed to light.^[14]

In experimental studies using mice with laser-induced choroidal neovascularisation, these light-activated nanoparticles were shown to accumulate specifically in the abnormal vessel areas after intravenous injection combined with light exposure to the eye. When loaded with an anti-cancer drug called doxorubicin, the targeted nanoparticles significantly reduced the size of the neovascular lesions. While this technology is still in the research phase, it could potentially offer a less invasive way to deliver treatment in the future.^[14]

Understanding the Cellular Mechanisms: New Drug Targets

Recent research has focused on understanding the cellular and molecular events that lead to choroidal neovascularisation, particularly looking beyond VEGF-dependent mechanisms. Studies have shown that dysfunction in the cells lining blood vessels (called endothelial cells) plays a central role in the disease process. These cells respond to various signals in their environment, including inflammation, oxidative stress, and mechanical forces.^[6]

Researchers are investigating how factors like genetic variations, systemic health conditions, and ageing affect endothelial function in the eye. Understanding these mechanisms may reveal new targets for drug development. For example, therapies that improve endothelial barrier function or reduce inflammation independent of VEGF might help patients who are resistant to current treatments. While specific drug candidates are still being identified, this research is laying the groundwork for the next generation of therapies.^[6]

Clinical Trial Phases and What They Mean

When new treatments are being developed, they must go through several phases of clinical trials before they can be approved for general use. Phase I trials focus primarily on safety, testing the new drug or approach in a small group of people to determine safe dosing and identify any serious side effects. Phase II trials involve more participants and evaluate whether the treatment shows evidence of effectiveness while continuing to monitor safety. Phase III trials are large studies that compare the new treatment to the current standard of care to determine if it offers advantages in terms of effectiveness or fewer side effects.^[2]

Patients participating in clinical trials for choroidal neovascularisation treatments may have access to promising new therapies before they become widely available. However, participation also involves uncertainty about whether the new treatment will work and requires careful monitoring. Clinical trials are typically conducted at specialised centres in locations such as the United States, Europe, and other regions with advanced ophthalmology research programmes. Eligibility criteria vary depending on the specific trial but generally require a confirmed diagnosis, specific disease characteristics, and willingness to follow the study protocol.^[2]

Most Common Treatment Methods

• Anti-VEGF Therapy
  • Intravitreal injections of drugs like ranibizumab, bevacizumab, or pegaptanib that block vascular endothelial growth factor
  • Reduces growth and leakage from abnormal blood vessels
  • Requires multiple injections over time, often monthly initially
  • Has been shown to improve vision or slow vision loss in many patients
  • Current gold standard treatment for choroidal neovascularisation
• Photodynamic Therapy
  • Uses light-activated drug verteporfin combined with low-power laser
  • Drug is injected into arm vein and activated by laser light in the eye
  • Causes damage to abnormal blood vessels while sparing surrounding tissue
  • May require multiple treatment sessions
  • Less commonly used now but may be considered for anti-VEGF resistant cases
• Thermal Laser Photocoagulation
  • High-energy laser burns and destroys abnormal blood vessels
  • Also damages surrounding healthy tissue, creating permanent blind spot
  • Was the first proven treatment but rarely used now for central lesions
  • May still be used for vessels away from centre of vision
  • Re-treatment often needed as vessels may regrow
• Combination Therapies (Experimental)
  • Dual targeting of VEGF and angiopoietin-2 pathways
  • Combination of anti-VEGF with apolipoprotein A-I binding protein
  • Anti-VEGF combined with photodynamic therapy
  • Strategies to overcome resistance to standard treatments
  • Being tested in various phases of clinical trials
• Novel Drug Delivery Systems (Research Stage)
  • Light-activated nanoparticles administered intravenously
  • Targeted specifically to diseased tissue using external light
  • Potential to reduce need for repeated eye injections
  • Still in preclinical and early clinical development

Living with Treatment and Monitoring

Managing choroidal neovascularisation is typically a long-term commitment that requires regular follow-up appointments and ongoing monitoring. Your eye doctor will use various imaging techniques to track how the abnormal vessels are responding to treatment and to detect any new vessel growth early. The most common monitoring tool is optical coherence tomography (OCT), a painless scan that creates detailed cross-sectional images of your retina, showing fluid accumulation and structural changes.^[2]

In addition to professional monitoring, you can play an active role in detecting changes by performing simple vision checks at home. One useful tool is the Amsler grid, a pattern of straight lines arranged in a grid. By looking at this grid regularly, you can notice if the lines appear wavy, distorted, or if any dark spots develop in your vision—all signs that may indicate active disease or the need for treatment adjustment.^[1]

The frequency of treatment and monitoring visits varies depending on how your condition responds. During the initial treatment phase, you might need monthly visits for injections and assessment. As the condition stabilises, the interval between treatments may be extended based on your individual response. Some patients are managed with a “treat and extend” approach, where the time between injections is gradually increased as long as the eye remains stable.^[10]

Many people with choroidal neovascularisation benefit from low vision aids and rehabilitation services, especially if some permanent vision loss has occurred. These might include magnifying devices, special lighting, large-print materials, and adaptive technology. Occupational therapists and low vision specialists can help you maintain independence and continue daily activities despite vision challenges.^[18]