Wet Amd: Symptoms, Types, Causes and Treatment

Wet age-related macular degeneration (wet AMD) is one of the most significant threats to vision in older adults, rapidly leading to central vision loss if untreated. As our population ages, understanding wet AMD—how it presents, why it occurs, and the latest in treatments—has never been more critical. This article explores the key symptoms, types, causes, and available therapies for wet AMD, synthesizing the latest clinical and scientific insights.

Symptoms of Wet AMD

Wet AMD often strikes quickly, making early recognition crucial. Unlike dry AMD, which can progress slowly and subtly, wet AMD causes rapid and sometimes dramatic changes in vision. Knowing the warning signs enables prompt medical attention and can help preserve sight.

Symptom	Description	Impact	Source
Blurred Vision	Loss of sharp central vision	Difficulty with detail	1 7 11
Metamorphopsia	Straight lines appear wavy	Distorted perception	7 11
Scotoma	Central dark/blank spots	Gaps in central vision	1 11
Rapid Progression	Sudden worsening over days/weeks	Accelerated vision loss	1 7

Table 1: Key Symptoms

Understanding Wet AMD Symptoms

Wet AMD affects the macula—the retina's central area responsible for detailed vision. The hallmark of wet AMD is the sudden onset and progression of symptoms compared to its dry counterpart.

Blurred or Distorted Vision

• Blurred Vision: One of the earliest and most common symptoms. Patients may notice reading or recognizing faces becomes challenging.
• Metamorphopsia: Straight lines (such as door frames or text lines) may appear wavy or distorted, a classic sign indicating fluid or blood under the macula 7 11.

Central Scotoma

• Scotoma: Central dark or empty spots in the field of vision can develop, making it difficult to see directly ahead 1 11.
• Impact: This particularly impairs activities like reading, driving, or recognizing people.

Rapid Vision Loss

• Wet AMD can progress alarmingly fast, sometimes causing significant vision loss within days or weeks 1 7.
• The abrupt change is in contrast to the slow progression of dry AMD, highlighting the need for urgent ophthalmic evaluation.

Additional Symptoms

• Color Perception Changes: Colors may appear less vivid.
• Difficulty Adapting to Low Light: Patients may have trouble seeing in dim lighting.

Recognizing these symptoms and seeking immediate care can dramatically affect prognosis, as early intervention is linked to better treatment outcomes 1 7 11.

Types of Wet AMD

Not all wet AMD is the same. Recent advances in imaging and research have shown that there are distinct subtypes, each with unique clinical features and implications for treatment and prognosis.

Type	Defining Feature	Clinical Importance	Source
Classic Neovascular AMD	Well-defined vessels	Rapid progression	2 7 10
Occult Neovascular AMD	Poorly defined vessels	Slower progression	2 7
Polypoidal Choroidal Vasculopathy (PCV)	Polyp-like vessels under retina	Different treatment response	2
Retinal Angiomatous Proliferation (RAP)	Abnormal vessels from retina	May resist standard therapy	10

Table 2: Wet AMD Types

Subtypes of Wet AMD

Classic vs. Occult Neovascular AMD

• Classic Neovascular AMD:
  • Characterized by well-demarcated areas of new, abnormal blood vessels (choroidal neovascularization or CNV) beneath the macula.
  • Rapid vision loss is common, and leakage or bleeding is easily detectable on imaging 2 7.
• Occult Neovascular AMD:
  • Features more diffuse, poorly defined vessels.
  • Progression is generally slower, and diagnosis can be more challenging without advanced imaging 2 7.

Polypoidal Choroidal Vasculopathy (PCV)

• PCV: A distinct form involving polyp-like outpouchings of blood vessels beneath the retina.
• Unique Features:
  • More common in Asian populations.
  • May require different management strategies compared to typical neovascular AMD 2.
  • Often presents with recurrent bleeding and serous (fluid) detachments.

Retinal Angiomatous Proliferation (RAP)

• RAP: Abnormal blood vessels arise from within the retina itself, rather than from the underlying choroid.
• Clinical Course:
  • Can be more resistant to standard anti-VEGF therapies.
  • Recognizing RAP is important for tailoring treatment, as switching medications may be necessary 10.

Importance of Subtyping

Identifying the specific type of wet AMD guides therapy choices and can influence prognosis. Advanced imaging techniques and artificial intelligence are enhancing our ability to distinguish these subtypes and personalize care 2.

Causes of Wet AMD

Why does wet AMD develop? The answer is multifactorial, involving a complex interplay of genetic predisposition, environmental triggers, and biological processes within the eye.

Cause	Mechanism	Risk Impact	Source
Age	Degeneration of macula	Primary risk factor	1 5 6 7
Smoking	Increases oxidative stress	Strong modifiable risk	1 5 6 7
Genetic Factors	Variants in HTRA1, ARMS2, CFH	Up to 10x risk increase	3 5 6 7
Oxidative Stress	Cell damage, inflammation	Promotes neovascularization	4 5 6 7
Chronic Inflammation	Sustained tissue injury	Drives disease progression	4 5 6 7
Vascular Growth Factors (VEGF)	Induces new blood vessels	Central to wet AMD pathology	1 4 5 7

Table 3: Main Causes and Risk Factors

The Multifactorial Nature of Wet AMD

Age and Lifestyle

• Age: The most significant risk factor; prevalence sharply rises after age 60 1 5 6 7.
• Smoking: Doubles the risk; one of the few modifiable risk factors. Smoking increases oxidative stress in the retina, accelerating damage 1 5 6 7.
• Other Factors: High blood pressure, obesity, poor diet, and heavy alcohol consumption may also contribute 6.

Genetic Susceptibility

• Key Genes:
  • HTRA1: A single nucleotide polymorphism (SNP) in the promoter region can increase the risk of wet AMD up to 10-fold 3 5.
  • ARMS2 and CFH: Associated with both dry and wet AMD; influence drusen formation and progression to advanced disease 5 7.
• Family History: A strong predictor, reflecting the contribution of inherited genetic variants 7.

Biological Mechanisms

• Oxidative Stress:
  • Accumulation of reactive oxygen species (ROS) damages retinal cells, leading to chronic inflammation and promoting abnormal blood vessel growth (angiogenesis) 4 5.
• Chronic Inflammation:
  • Sustained immune responses contribute to retinal degeneration and the breakdown of the blood-retina barrier 4 5.
• VEGF Overexpression:
  • The central pathological process in wet AMD is the upregulation of vascular endothelial growth factor (VEGF), which stimulates the growth of leaky, fragile new blood vessels under the macula 1 4 5 7.
• Endoplasmic Reticulum (ER) Stress:
  • Cellular stress responses (such as the unfolded protein response) can trigger VEGF production, linking various environmental and genetic insults to neovascularization 4.

The Role of Diet

• Protective Factors: Higher intake of vitamin K and other antioxidants may reduce risk 6.
• Supplements: Certain vitamins and minerals have shown some benefit in slowing progression, especially in early or intermediate stages 1 6.

Understanding these causes helps in both prevention—by modifying risk factors like smoking and diet—and in developing new treatments targeting the underlying mechanisms of disease.

Treatment of Wet AMD

The introduction of anti-VEGF therapies revolutionized the management of wet AMD. Today, a range of treatment options is available, each with its benefits and limitations. Ongoing research continues to expand and improve these therapies.

Treatment Type	Mechanism/Approach	Key Benefit	Source
Anti-VEGF Injections	Block VEGF, inhibit vessels	Preserve/improve vision	1 7 8 10 11
Photodynamic Therapy	Light-activated vessel closure	May complement anti-VEGF	8 9
Laser Photocoagulation	Destroy abnormal vessels	Used in select cases	9
Combination Therapy	Multiple agents (e.g., anti-VEGF + PDT)	Enhanced efficacy	8 11
Emerging Therapies	Novel drugs, longer-acting, gene therapy	Reduced injection burden	11
Lifestyle/Nutrition	Smoking cessation, vitamins	Slow disease progression	1 6 7

Table 4: Wet AMD Treatment Modalities

Standard Treatments

Anti-VEGF Injections

• Medications: Ranibizumab, aflibercept, and bevacizumab are the main agents used to block VEGF, halting the growth of abnormal blood vessels 1 7 8 10 11.
• Administration: Delivered via injection directly into the eye (intravitreal injection).
• Outcomes:
  • Can stabilize or even improve vision in most patients, especially if started early 1 8 10 11.
  • Cannot repair vision already lost but can prevent further deterioration.
• Dosing Regimens:
  • Monthly vs. PRN (as needed): Both approaches are effective. PRN regimens may reduce the number of injections while maintaining vision 8.
  • Switching Agents: Some patients who do not respond to one agent may benefit from switching to another (e.g., from ranibizumab to aflibercept) 10.

Photodynamic Therapy (PDT)

• How It Works: A light-activated drug (verteporfin) is injected and then activated with a laser to seal off abnormal vessels 8 9.
• Role: Now mostly used as an adjunct to anti-VEGF therapy in select cases, such as PCV or when patients do not respond fully to injections 8.

Laser Photocoagulation

• Mechanism: Destroys abnormal vessels with laser burns.
• Limitations: Less commonly used now due to risk of damaging healthy tissue and the superiority of anti-VEGF treatments 9.

Combination Therapy

• Approach: Combining anti-VEGF injections with PDT or other agents may offer additional benefits in certain subtypes (e.g., PCV) 8 11.

Emerging and Adjunctive Therapies

• Longer-Acting Drugs: New formulations aim to reduce injection frequency, improving patient convenience 11.
• Gene Therapy: Trials are ongoing for approaches that deliver genes to produce anti-VEGF proteins within the eye, potentially offering long-term control 11.
• Anti-HTRA1 Agents: Targeting upstream regulators like HTRA1 could offer alternatives or adjuncts to VEGF inhibition 5.

Lifestyle and Nutritional Interventions

• Smoking Cessation: Strongly advised for all patients 1 6 7.
• Nutrition: Diets rich in green leafy vegetables, antioxidants, and possibly vitamin K may help slow progression 1 6.
• Supplements: Evidence supports the use of certain vitamins (AREDS formula) in early/intermediate AMD, though less so in established wet AMD 1.

Limitations and Future Directions

• Treatment Burden: Frequent injections can be challenging for patients and healthcare systems 11.
• Cost: Anti-VEGF therapies are expensive, though cost-effectiveness analyses support their use, particularly for ranibizumab 9.
• Incomplete Cure: Current therapies halt progression but do not restore lost vision or cure the underlying disease process 1 11.

Research into novel drugs, improved delivery methods, and gene therapies holds promise for more durable and effective treatments in the near future 11.

Conclusion

Wet AMD remains a leading cause of vision loss, but advances in detection and treatment offer hope for preserving sight. Here’s a summary of key points:

• Symptoms: Rapid-onset blurred vision, distortion (metamorphopsia), central scotomas, and quick progression are classic for wet AMD 1 7 11.
• Types: Several subtypes exist, including classic, occult, PCV, and RAP, each with unique features and treatment implications 2 10.
• Causes: Wet AMD arises from a mix of age, genetics (notably HTRA1 and ARMS2), lifestyle (especially smoking), oxidative stress, inflammation, and VEGF-driven vessel growth 3 4 5 6 7.
• Treatment: Anti-VEGF injections are the mainstay, often complemented by PDT or combination therapies. New drugs and gene therapies promise to further improve outcomes 1 7 8 10 11.
• Prevention: Modifiable risk factors such as smoking and poor diet should be addressed to reduce risk and slow progression 1 6 7.

Early recognition and prompt treatment are vital. Ongoing research continues to improve the outlook for those diagnosed with wet AMD, offering new hope for maintaining vision and quality of life.