Wet age-related macular degeneration (wet AMD) is caused by abnormal blood vessels growing beneath the retina and leaking fluid or blood into the macula, the part of your eye responsible for sharp central vision. Only 10% to 15% of people with AMD develop this wet form, but without treatment, 79% to 90% of affected eyes eventually reach legal blindness. Understanding what triggers this shift from normal aging to active disease involves genetics, lifestyle, and a chain of structural failures inside the eye.
How Normal Eye Structures Break Down
Your retina sits on top of a thin layer of support cells called the retinal pigment epithelium (RPE), which in turn rests on Bruch’s membrane, a five-layered barrier separating the retina from the blood-vessel-rich choroid beneath it. In a healthy eye, Bruch’s membrane and the RPE act as a physical and chemical wall that prevents choroidal blood vessels from invading the retina.
With age, waste products accumulate under the RPE and Bruch’s membrane thickens, cracks, or weakens. Once that barrier is compromised, blood vessels from the choroid can push through the gaps. Animal studies confirm this directly: experimentally breaching Bruch’s membrane reliably triggers the same type of abnormal vessel growth seen in wet AMD. Certain enzymes produced in higher-than-normal amounts can also degrade the membrane’s structure, opening a path for choroidal blood vessels to infiltrate.
The Role of VEGF in New Blood Vessel Growth
The central driver of wet AMD is a signaling protein called vascular endothelial growth factor, or VEGF. In normal conditions, VEGF helps maintain existing blood vessels and supports wound healing. In wet AMD, VEGF production goes into overdrive, and the consequences cascade quickly.
VEGF does three things that make wet AMD destructive. First, it stimulates the lining cells of blood vessels to multiply, generating entirely new vessels that weren’t supposed to be there. Second, it makes those new vessels excessively leaky, allowing plasma proteins and fluid to seep out into the surrounding tissue. That leaked fluid is what distorts and damages the macula. Third, VEGF triggers the release of enzymes that break down the tissue between cells, helping the new vessels invade deeper into the retina.
VEGF also recruits immune cells to the area, which adds inflammation on top of the physical damage. The combination of leaking vessels, tissue invasion, and inflammation is what makes wet AMD progress so rapidly compared to the dry form. Left unchecked, the abnormal vessels can bleed, scar, and permanently destroy central vision within weeks to months.
Genetic Risk Factors
Two gene regions carry the strongest known genetic risk for developing wet AMD: complement factor H (CFH) and ARMS2. These aren’t rare mutations. They’re common genetic variants that a significant portion of the population carries.
CFH is part of the complement system, a branch of the immune system that clears damaged cells. Variants in CFH can cause this system to overreact, driving chronic inflammation in the retina. People carrying two high-risk CFH variants have a 72% higher rate of progressing to the wet form compared to those with lower-risk versions. ARMS2 variants carry an even steeper risk: those with one or two high-risk copies have a 2.76-fold higher rate of developing wet AMD.
These risks compound. A person with high-risk versions of both CFH and ARMS2 faces substantially greater odds than someone with just one. Researchers have grouped patients into four genetic risk tiers based on their combination of CFH and ARMS2 variants, and the highest tier progresses to wet AMD far more often and more quickly than the lowest. You can’t change your genes, but knowing your family history of AMD gives you useful information about how aggressively to monitor your eyes.
Smoking and Oxidative Damage
Smoking is the single most modifiable risk factor for wet AMD. It increases the likelihood of developing the wet form by two to four times, and it reduces how well anti-VEGF treatments work once the disease is present.
The retina is one of the most metabolically active tissues in the body, making it especially vulnerable to oxidative stress. Cigarette smoke floods the body with free radicals that damage retinal cells and the delicate structures supporting them. Recent research has identified a more specific mechanism: compounds in cigarette smoke activate a signaling pathway involving support cells that wrap around blood vessels (pericytes). When these cells are abnormally activated, they destabilize the normal blood vessel architecture, promoting the chaotic new vessel growth that defines wet AMD.
The damage from smoking is dose-dependent and cumulative. Former smokers carry elevated risk for years after quitting, though the risk does gradually decline over time.
Progression From Dry to Wet AMD
Wet AMD almost always begins as dry AMD. The dry form involves the gradual buildup of deposits (drusen) under the retina and slow thinning of the RPE. Most people with dry AMD will never convert to the wet form, but a meaningful percentage do.
Annual conversion rates depend on how advanced the dry disease is. People with early dry AMD convert at about 2% per year. Those with intermediate dry AMD convert at roughly 6.1% per year, and those with advanced dry AMD (geographic atrophy) convert at about 6.7% per year. These numbers mean that over a five-year period, someone with intermediate dry AMD has roughly a one-in-three chance of developing the wet form in at least one eye.
The conversion can happen suddenly. One day straight lines look straight; the next day they appear wavy or bent. This visual distortion, called metamorphopsia, is often the first sign that fluid has started leaking under the macula. Objects may also appear larger or smaller than they actually are, or your central vision may develop a dark or blurry spot. Because the macula handles fine detail and color, even small amounts of fluid there produce noticeable changes.
How Wet AMD Is Detected
Optical coherence tomography (OCT) is the primary imaging tool used to confirm wet AMD. It creates cross-sectional images of the retina detailed enough to show pockets of fluid that are invisible on a standard eye exam.
On OCT, wet AMD shows up as fluid trapped in two locations: within the retina itself (intraretinal fluid) and beneath the retina (subretinal fluid). Active new blood vessels appear as a well-defined, spindle-shaped thickening between the RPE and Bruch’s membrane, often with steep edges and a crater-like shape. Inactive or “occult” lesions look flatter and less defined. The scan can also reveal detachments of the RPE layer, where fluid has pushed the support cells away from the membrane below.
An Amsler grid, a simple chart of horizontal and vertical lines, is a practical home-monitoring tool. If straight lines start looking wavy, distorted, or missing, that change warrants prompt evaluation. Early detection matters enormously with wet AMD because treatment is far more effective when started before significant scarring has occurred.