Age-Related Macular Degeneration Management

Last updated: 17 March 2026
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Principles of Therapy

In initiating pharmacological therapy, it is important to explain to both the patient and the family that medications will not cure dementia and may not work for everyone. Symptomatic treatment, even with improvement of symptoms, will stop disease progression and cognitive decline will continue even with therapy. It is important to note that response to medications should be monitored to assess cognitive, behavioral and functional benefits. If necessary, dose titration and change of medication should be done. Lastly, severity of the disease should be assessed prior to starting medications.

Pharmacological Therapy for Cognitive Symptoms

Cholinesterase Inhibitors

This group of drugs should be considered in patients in all stages of AD. All inhibit the enzyme cholinesterase in the synaptic cleft, thereby enhancing central cholinergic function. Donepezil inhibits acetylcholinesterase, Galantamine inhibits acetylcholinesterase while providing allosteric modulation of nicotinic receptors, and Rivastigmine inhibits both acetylcholinesterase and butyrylcholinesterase. Cholinesterase inhibitors improve cognition, behavioral and functional measures in AD. These drugs may also be given in patients with DLB. Both Donepezil and Galantamine have shown modest efficacy in treating cognitive impairment in patients with vascular dementia or mixed dementia. However, they should be used with caution. Cholinesterase inhibitors are generally well tolerated but a common side effect is gastrointestinal (GI) disturbances like nausea, vomiting, and diarrhea. These drugs are not recommended for the treatment of FTD and MCI.

Donepezil

This drug showed significant effects in cognitive function as evaluated by cognitive subscale of the AD assessment scale. Studies have shown the efficacy of Donepezil in reducing a few behavioral problems and psychotic symptoms in patients with mild to moderate dementia. It is used for the treatment of mild to moderate AD and has been approved for the use in more severe forms of AD and DLB.

Galantamine

Galantamine has been shown to improve functional ability and may also provide significant effects on behavior in patients with AD. It is used in patients with mild to moderate DLB that cannot tolerate Donepezil and Rivastigmine. Higher doses are more efficacious than lower doses, but doses >24 mg/day have showed no additional benefit. Slow dose escalation of Galantamine appears to improve tolerability. It is important to note that there is evidence of some benefit in cognition in patients with mixed AD and cerebrovascular disease.

Rivastigmine

This drug showed significant effects in cognitive and global function in patients with mild to moderately severe AD. Meta-analysis results show that Rivastigmine may provide benefit in AD patients experiencing rapid symptom progression compared to those with slow progression. It has also been found to be effective in managing cognitive decline among patients with DLB. Additionally, a transdermal patch preparation has been shown to have the advantage of causing less GI side effects, better 24-hour drug profile, and the ease of administration in patients. This transdermal patch has been approved for treatment in all stages of AD. Rivastigmine is also used in patients with mild to moderate dementia associated with Parkinson’s disease and severe DLB.

“Please see Parkinson’s Disease and Parkinson’s Disease Dementia disease management chart for further information.”

Donanemab and Lecanemab

These are amyloid β- directed antibodies for the treatment of AD with confirmed amyloid pathology. Studies have shown significant dose- and time-dependent reduction of amyloid β plaques compared to placebo. In a study, Donanemab-treated patients demonstrated statistically significant reduction in clinical decline compared to placebo in standardized assessment scales for Alzheimer’s disease. Lecanemab was approved under accelerated approval by the United States Food and Drug Administration (US FDA) to be initiated in patients with mild cognitive impairment or mild dementia stage of AD. However, there is no safety or effectiveness data yet on initiating treatment at earlier or later stages of the disease.

Memantine

Memantine is a noncompetitive NMDA-receptor antagonist given in patients with moderate to severe AD. This drug may be given to patients with mild to moderate AD as a monotherapy if cholinesterase inhibitor is contraindicated, not tolerated or in cases of disease progression despite an adequate trial of cholinesterase inhibitors. Current available data on this drug suggest that combination with cholinesterase inhibitor increases the likelihood of delaying symptom progression compared to cholinesterase inhibitor alone in moderate to severe cases of established AD. Studies suggest that there is improvement of cognition at all levels of AD severity, but effects on behavior, ADL, and global outcome were more significant for moderate to severe AD.

Other Agents Used to Treat Cognitive Symptoms

Pharmacological therapy

Intravitreal Anti-Vascular Endothelial (VEGF) Injection Therapy  

Intravitreal anti-VEGF injection therapy is the recommended first-line treatment for patients with neovascular or late or wet AMD. Its use exhibited improved visual and anatomic outcomes compared to other therapies. It controls the progression of exudative AMD and stabilizes or reverses visual loss. Notably, there are no clinically significant differences in the effectiveness and safety between different anti-VEGF agents. 



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Aflibercept  

Aflibercept is a pan-VEGF and placental growth factor (PGF) inhibitor. It is a recommended treatment option for patients with neovascular or wet or AMD with macular CNV.  

Bevacizumab  

Bevacizumab is a recombinant monoclonal antibody that binds to all isoforms of VEGF. It has been used off-label in the treatment of neovascular AMD. Improved in visual acuity and decreased retinal thickness has been observed following intravitreal treatment.  

Brolucizumab  

Brolucizumab is a humanized single-chain antibody fragment that inhibits all forms of VEGF-A. It is a treatment option for patients with neovascular AMD with macular CNV.  

Pegaptanib Sodium  

Pegaptanib sodium is an RNA oligonucleotide that is a selective VEGF antagonist which binds to the 165 isoform of VEGF-A. It is indicated for all subtypes of neovascular AMD.

Ranibizumab  

Ranibizumab is a recombinant humanized immunoglobulin that binds and inhibits the action of all isoforms of VEGF-A. It is a recommended treatment option for all subtypes of neovascular AMD. It is indicated for active subfoveal CNV as shown by studies as it improves visual acuity and prevents leakage and progression of neovascularization.

Complement Pathway Inhibitors  

Example drugs: Avacinaptad pegol, Pegcetacoplan  

Complement pathway inhibitors have been recently approved by the US Food and Drug Administration (US FDA) for the treatment of geographical atrophy with or without subfoveal involvement. Avacinaptad pegol inhibits the cleavage of C5 which prevents the formation of the membrane attack complex. It has been demonstrated to show a significant reduction in the mean rate of lesion growth by 14.3% compared to placebo at 12 months. On the other hand, Pegcetacoplan is a pegylated complement C3 inhibitor peptide that demonstrated a significant reduction in lesion growth over a 24-month period in a phase III study. However, trials have shown no improvement of visual acuity. There were also reports of serious vasculitis and significant vision loss after Pegcetacoplan approval. 

Vitamin and Mineral Supplements (Antioxidant)  

Vitamin and mineral supplements have been indicated in patients with either intermediate AMD or advanced AMD in one eye. A daily dose of combination of 500 mg Vitamin C, 400 IU Vitamin E, 80 mg Zinc, 2 mg Copper, 10 mg Lutein, and 2 mg Zeaxanthin was found to reduce the risk of progression to advanced AMD. Beta-carotene is replaced with Lutein and Zeaxanthin because it is associated with increased risk for lung cancer in smokers and those who recently quit smoking.  

Photodynamic Therapy (PDT) with Verteporfin  

Verteporfin is a photosensitizing dye given by IV before laser light administration in PDT for predominantly classic, subfoveal neovascular AMD. It is a less commonly used treatment option for patients with neovascular AMD with new or recurrent macular CNV, where the classic component is >50% of the lesion and the entire lesion is ≤5400 µm in greatest liner diameter. It may be used for neovascular AMD with occult CNV with vision <20/50 or if the vision is >20/50 but the CNV is <4 macular photocoagulation studies (MPS) disc areas in size. PDT has minimal damage to the overlying retina than laser photocoagulation therapy because the energy from the laser is taken up by the Verteporfin causing damage vascular endothelial cells and thrombotic occlusion of the blood vessels within the CNV lesion. It also reduced the risk of moderate to severe visual loss. It must be noted that most patients will still have loss of vision, and that visual improvements are unusual.

Nonpharmacological

Observation  

Observation is a treatment option for patients with non-neovascular early AMD (AREDS category 2) or advanced AMD with bilateral subfoveal geographic atrophy or disciform scars. It may also be considered in patients with late AMD if disease appears stable without giving anti-VEGF therapy.  

Patient Education  

It is important to instruct patients with AMD on how to test their vision daily or at least weekly, while patients with exudative AMD or have had laser treatment should be instructed on how to monitor the size of their blind spots or the appearance of new ones. High risk patients (eg with early AMD and/or with family history of AMD) are encouraged to have regular dilated eye exams for the early detection of the intermediate stage of AMD. Patients at very high risk (eg presence of advanced AMD in one eye and large drusen with RPE changes in the fellow eye) should be examined every 6 to 12 months to detect asymptomatic CNV at a treatable stage. For low-risk patients, it is recommended to have a comprehensive eye evaluation as follows: For patients 40 to 54 years old, examination is every 2 to 4 years. For patients 55 to 64 years old, examination is done every 1 to 3 years. Patients ≥65 years old, examination is done every 1 to 2 years. Patients should be informed about the symptoms of progressing CNV (eg progressive decrease in central vision) and counseled on the need for prompt consultation with an ophthalmologist. Smoking cessation should be done as this is the main modifiable risk factor for AMD. Diet that includes leafy green vegetables, fresh fruits, and fishes rich in omega-3 fatty acids may help decrease the risk for AMD. The ideal body weight should be maintained. It is noted that increased body mass index (BMI) and abdominal obesity have increased risk for AMD. In bight environments, sunglasses with 100% protection against UVA and UVB should be worn. Lastly, blood pressure should be monitored and controlled. 



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Rehabilitation  

Vision rehabilitation is useful in heightening the patient's functional ability. Low vision rehabilitation by using magnifiers and low vision aids is recommended for advanced non-neovascular AMD patients.

Surgery

Laser Photocoagulation  

Laser photocoagulation is indicated in patients with extrafoveal classic CNV. It may be used as treatment option for patients with juxtapapillary CNV. It destroys the neovascular complex with heavy confluent laser and thereby decreases further loss of vision. Monitoring should be done as it can cause scotoma and recurrences that usually appear a year after therapy. Complications include severe vision loss which may be permanent following treatment and rupture of Bruch’s membrane with subretinal or vitreous hemorrhage.