What are the treatment options for Age-related Macular Degeneration (AMD)?

Treatment Options for Age-Related Macular Degeneration

For neovascular (wet) AMD, initiate intravitreal anti-VEGF therapy immediately with three loading doses at 4-week intervals using aflibercept, ranibizumab, or bevacizumab; for dry AMD with intermediate or advanced disease, prescribe AREDS2 supplementation to reduce progression risk. 1, 2

Neovascular (Wet) AMD Treatment

First-Line Anti-VEGF Therapy

Anti-VEGF therapy is the gold standard treatment for wet AMD and must be started as soon as diagnosis is confirmed. 2

• Administer three loading doses at exactly 4-week intervals with one of the following agents: aflibercept, ranibizumab, or bevacizumab 1, 2
• Early treatment within 2 years of diagnosis significantly reduces legal blindness and visual impairment 2
• Monthly anti-VEGF injections result in 94.6% of patients experiencing less than 15-letter visual acuity loss at 12 months compared to 62.2% receiving sham treatment 3

Maintenance Regimens

After the loading phase, choose from these evidence-based maintenance protocols 1, 2:

• Aflibercept every 8 weeks (fixed interval)
• Treat-and-extend regimen (individualized dosing that extends intervals based on disease activity)
• PRN (as-needed) dosing based on OCT findings
• Monthly injections (continuous fixed dosing)

Important caveat: PRN regimens using ranibizumab have comparable efficacy and safety to fixed monthly regimens over 1 year, but do not maintain initial visual gains with longer follow-up 1. Exercise caution with PRN bevacizumab, as it may be slightly less effective than other monthly anti-VEGF regimens 1.

The treat-and-extend approach is frequently used in clinical practice, with prospective studies (LUCAS) showing similar efficacy between monthly and treat-and-extend protocols for both bevacizumab and ranibizumab 1.

Safety Considerations for Anti-VEGF Therapy

All three anti-VEGF agents have comparable safety profiles at 1 year, with no statistically significant differences in death, arteriothrombotic events, or venous thrombotic events between ranibizumab and aflibercept. 1

Ocular complications include 1:

• Endophthalmitis (cumulative ≤1.0% over 1 year for aflibercept and ranibizumab; 0.16% per injection for bevacizumab)
• Retinal detachment (0.02-0.16%)
• Vitreous hemorrhage (0.16%)
• Noninfectious inflammation

Critical distinction: The CATT study found a higher rate of serious systemic events with bevacizumab compared to ranibizumab (24% vs. 19%; P=0.04), including arteriothrombotic events, venous thrombosis, and gastrointestinal hemorrhage, persistent at 2 years 1. However, bevacizumab remains widely used off-label due to cost-effectiveness 1.

Inform patients about bevacizumab's off-label status and obtain appropriate informed consent 1.

Dry (Non-Exudative) AMD Treatment

AREDS2 Supplementation

For patients with intermediate AMD or advanced AMD in one eye, prescribe AREDS2 formulation to reduce progression risk by up to 36% over 10 years. 2

The recommended AREDS2 formulation includes 2:

• Vitamin C
• Vitamin E
• Zinc 25mg (not 80mg, as 25mg shows equivalent efficacy with fewer adverse effects)
• Copper (necessary to prevent copper-deficiency anemia from zinc)
• Lutein 10mg
• Zeaxanthin 2mg

Critical formulation change: Beta-carotene was eliminated from AREDS2 due to an 18% increased cumulative incidence of lung cancer in current and former smokers (relative risk 1.28) 2. Lutein and zeaxanthin serve as safer carotenoid substitutes 1, 2.

Safety Concerns with AREDS2

• Zinc at 80mg was associated with increased hospitalizations for genitourinary causes 2
• Coordinate with primary care physicians before initiating long-term AREDS2 supplementation due to potential adverse effects 2
• Never use beta-carotene-containing formulations in current or former smokers 2

No FDA-Approved Therapies for Geographic Atrophy

Currently, no FDA-approved therapies exist to slow geographic atrophy progression, though multiple agents are under investigation in clinical trials 2. AREDS2 supplementation remains the only proven intervention to slow progression of dry AMD 2.

Lifestyle Modifications

Smoking Cessation

Smoking cessation is mandatory and non-negotiable, as cigarette smoking is the key modifiable risk factor for AMD progression. 1, 2

• Smoking increases AMD progression risk proportional to pack-years smoked 2
• Long-term prospective studies show significantly higher AMD incidence in people who smoke more than 20 cigarettes per day 3

Additional Risk Factor Management

Address modifiable risk factors including 4, 3:

• Obesity
• Dyslipidemia
• Cardiovascular disease
• Poor dietary intake of carotenoids

Vision Rehabilitation

Refer patients with reduced visual function to vision rehabilitation services immediately. 1, 2

Available interventions include 1, 2:

• Optical or electronic magnifying devices
• Bright lights
• Electronic reading aids
• Implantable Miniature Telescope (IMT) for screened, phakic, motivated patients with end-stage AMD

Set realistic expectations: Vision rehabilitation optimizes existing visual function rather than restoring lost vision 1, 2. Patients can read more effectively with aids, but not as well as before AMD onset 1.

Patient Education and Monitoring

Reassure patients that while central visual loss is common, total visual loss is extremely rare. 1, 2

• Peripheral vision is typically preserved 2
• There is no harm in using eyes for normal visual tasks 1
• Screen for depression and Charles Bonnet syndrome (visual hallucinations), which frequently accompany severe central vision loss 1, 2

High-Risk Fellow Eye Monitoring

For patients with wet AMD in one eye, the fellow eye remains at exceptionally high risk and requires aggressive monitoring every 6-12 months even without symptoms. 2, 5

• Patients with advanced AMD in one eye and large drusen with RPE changes in the fellow eye represent the highest risk group 2
• AREDS2 supplements can lower fellow eye risk by 36% over 10 years 2
• Instruct patients to monitor vision with Amsler grid and return promptly with new symptoms 2

Common Pitfalls to Avoid

• Do not delay anti-VEGF therapy once wet AMD is diagnosed—early treatment within 2 years significantly impacts outcomes 2
• Do not continue anti-VEGF injections if OCT confirms absence of active exudation with only fibrotic scarring or geographic atrophy present 5
• Do not use PRN bevacizumab as first-line without understanding its slightly reduced efficacy compared to other regimens 1
• Do not prescribe beta-carotene to current or former smokers due to documented lung cancer risk 2
• Do not use 80mg zinc formulations when 25mg provides equivalent efficacy with better safety profile 2