What is the difference between wet and dry Age-related Macular Degeneration (AMD)?

Difference Between Wet and Dry Macular Degeneration

Dry AMD is the more common form (85-90% of cases) characterized by drusen deposits and retinal pigment epithelial atrophy that progresses slowly, while wet AMD is less common but more severe, characterized by abnormal blood vessel growth (choroidal neovascularization) that causes rapid vision loss. 1, 2

Pathophysiology and Classification

Dry (Non-Exudative) AMD

• Dry AMD involves progressive deterioration of the retina with atrophy of retinal layers and retinal pigment epithelial cells 1
• Characterized by the accumulation of drusen (waste materials) under the retina as old cells die without being replaced 3
• Accounts for approximately 85-90% of all AMD cases 2
• Progresses more slowly than wet AMD but can eventually lead to geographic atrophy and central vision loss 1, 2

Wet (Neovascular) AMD

• Wet AMD is associated with the development of abnormal blood vessels in the choroid layer underneath the retina 1
• These new vessels are fragile and leak fluid or blood, causing rapid damage to the macula 3
• Represents a more severe form with faster progression and greater vision loss 2
• Often develops in patients who already have dry AMD, as the body attempts to compensate for retinal damage 3

Clinical Presentation and Progression

Symptom Differences

• Early dry AMD is typically asymptomatic, while wet AMD causes more acute symptoms 2
• Both forms can cause blurred central vision and central vision loss, but wet AMD progresses much more rapidly 2
• Metamorphopsia (distorted vision, such as straight lines appearing wavy) is particularly characteristic of wet AMD and can be monitored using an Amsler grid 2

Risk of Vision Loss

• Wet AMD can lead to vision loss much more quickly than dry AMD 3
• Dry AMD causes gradual vision impairment over years, while wet AMD can cause significant vision loss within weeks to months if untreated 3
• Both forms may progress to macular atrophy, which causes irreversible vision loss 4

Treatment Approaches: The Critical Distinction

Dry AMD Treatment

• Currently, there are no FDA-approved treatments to reverse or halt dry AMD progression 2, 3
• The AREDS2 formulation (vitamin C, vitamin E, zinc, copper, lutein 10mg, zeaxanthin 2mg) is the only proven intervention to slow progression, reducing risk by up to 36% over 10 years in patients with intermediate or advanced dry AMD 1, 2
• Antioxidant multivitamins combined with zinc reduced the risk of progression to late AMD (OR 0.72) and visual acuity loss of more than 3 lines (OR 0.77) 1
• Important caveat: Beta-carotene in the original AREDS formulation was associated with increased lung cancer risk in former smokers (2.0% vs 0.9%, P=0.04), leading to its replacement with lutein and zeaxanthin in AREDS2 1, 2

Wet AMD Treatment

• Anti-VEGF (vascular endothelial growth factor) therapy is the primary treatment for wet AMD and must be initiated immediately upon diagnosis 2, 3
• Treatment protocol consists of three loading doses at 4-week intervals using aflibercept, ranibizumab, or bevacizumab 2
• Early treatment within 2 years of diagnosis significantly reduces legal blindness and visual impairment 2
• VEGF inhibitors proved effective in improving visual acuity outcomes, including likelihood of visual acuity gain ≥15 letters (RR 2.92) and preventing visual acuity loss (RR 1.46) 1
• Maintenance regimens include aflibercept every 8 weeks, treat-and-extend protocols, PRN (as-needed), or monthly injections 2

Treatment-Related Harms

Dry AMD Treatment Risks

• Zinc supplementation at 80mg was associated with increased risk of hospitalization due to genitourinary causes 1, 2
• Antioxidants were associated with increased risk of yellowing skin 1
• No association with withdrawal due to gastrointestinal symptoms in pooled data 1

Wet AMD Treatment Risks

• Intravitreal anti-VEGF injections carry risks of endophthalmitis, ocular hemorrhage, and retinal detachment, though these occurred at similar rates to sham treatment 1
• Serious ocular and cardiovascular adverse events were infrequent and similar between aflibercept and ranibizumab 1
• Emerging concern: Recent evidence suggests that excessive anti-VEGF blockade may accelerate the development of macular atrophy, particularly in patients with type III macular neovascularization 4

Clinical Implications

The fundamental clinical distinction is that wet AMD is treatable with anti-VEGF therapy that can preserve and even improve vision if caught early, while dry AMD can only be slowed with nutritional supplementation. 2, 3 This makes early detection through regular comprehensive eye examinations crucial, as patients with dry AMD remain at risk for conversion to wet AMD and require ongoing monitoring 2.