Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) is the most common of these disorders, mainly affecting people over the age of 60. It is the most frequent cause of blindness in western countries like the US, Europe and Australia, and is one of the top three causes of blindness in Asia, including Singapore. For those aged 60 and above, the incidence of AMD is 12.5%, but at age 80 and beyond, this rate increases to 33%

AMD is an eye disease that primarily affects the central portion of the retina known as the macula. The macula is the central portion of the back of retina, the film that lines the inside of the eyeball. It is responsible for reading, colour perception and face recognition.

The risk for developing macular degeneration increases with age. By the age of 75, about 1 in 3 persons will suffer from some form AMD. Other risk factors include: a family history of the disease, cigarette smoking, diet low in antioxidant and high in fat, excessive sunlight exposure, hypertension and cardiovascular disease.

In the early stages of macular degeneration, the transport of nutrients and wastes by the RPE slows down. As waste products accumulate under the retina, they form yellowish deposits called drusen. Most people with drusen do not lose vision.

A portion of people with drusen may begin to experience mild visual loss. At this point, macular degeneration may progress in one of two ways. These two types of degeneration are known as the dry (atrophic) and wet (exudative) forms of the disease.

Dry (atrophic) AMD

Dry AMD is the gradual process of thinning of the macula due to wear and tear. Dry macular degeneration alone rarely causes severe visual impairment or blindness.

Occasionally, a large region of cells may be lost. This is called “geographic atrophy” and produces a blind spot in the central portion of vision. This blind spot is called a scotoma.

Wet AMD

In the wet form of macular degeneration, new blood vessels called choroidal neovascularisation, or CNV begin to grow underneath the retina. These new vessels may leak blood or fluid under the retina, causing the retinal surface to become uneven. As a result, objects in that portion of your visual field may appear wavy or distorted. The neovascularization may even break through some of the retinal layers. Blind spots may appear in your vision if portions of the retina become damaged by the CNV.

What are the most common symptoms of wet AMD?

Often the first sign of fluid under the retina is distortion of straight lines. Early signs of vision loss from AMD include shadowy areas in your central vision or unusually fuzzy or distorted vision. An Amsler grid consists of straight lines, with a reference dot in the centre. Someone with macular degeneration may see some of the lines as wavy or blurred, with some dark areas at the centre.

‘Asian’ type of wet AMD

In Asia, about 40-50% of CNV have a peculiar pattern like grapes hanging from the end of branches. This pattern is known as polypoidal disease (polypoidal choroidal vasculopathy, PCV) and can result in extensive bleeding and scarring under the retina.

What if wet AMD is not treated?

Without treatment, neovascularization and leakage often lead to scarring of the macula and permanent blindness.

It is important to realise that this entire process occurs only in the macula, and affects only central, or detail vision. Peripheral, or side vision is rarely affected by macular degeneration. While macular degeneration is the leading cause of legal blindness, it rarely leads to total blindness.

Dry AMD

Vitamin therapy, sunlight protection with UV sunglasses, healthy lifestyle e.g. stop smoking, regular exercise, diet rich in colourful fruits and vegetables. Trials are ongoing to find a drug that can slow down or stop and degeneration. Brimonidine eye drops is one such potential treatment. It has been successfully used in slowing down optic nerve degeneration in glaucoma. In the future, retinal stem cell therapy may be able to replace the atrophic tissue.

Wet AMD

To date, 3 drugs, Lucentis (2006), Eylea (2008) and Beovu (2019) have been approved by the US FDA (Food & Drug Administration), EMA (European Medicines Agency), MHRA (Medicines and Healthcare products Regulatory Agency) of the United Kingdom (UK) and Australia’s TGA (Therapeutic Goods Administration). Most countries in Asia including Japan, China, South Korea, Taiwan and Singapore have also approved these drugs.

These drugs are administered into the eye via an intravitreal injection procedure. The inside of the eye is filled with a jelly-like fluid (vitreous). During this procedure, your health care provider injects medicine into the vitreous, near the retina at the back of the eye. The medicine can treat certain eye problems and help protect your vision. This method is most often used to get a higher level of medicine to the retina.

Treatment Plan

The strategy is to inject once a month for the first three months (known as the loading phase) and then re-evaluate. If we’ve suppressed the disease activity, we can gradually extend the interval between shots during the maintenance phase. This approach, used by most ophthalmologists around the world, is called “treat and extend”. Another alternative is to give the injection only when needed (i.e. when the disease becomes active again), but this usually means monthly visits to monitor for recurrence of disease activity, at least within the first year.

How many injections will I need?

On average, up to 8 injections may be required in the first year of treatment, depending on the severity of the condition and type of wet AMD. However, the number of treatments decreases over the next 2 years to an average of 3-5 injections per year. Some patients may require continuous treatment for life.

What is the purpose of treatment of wet AMD?

The goal of injections is to render the disease inactive or dormant. By this we mean:

• Vision and symptoms are improved or stable
• There’s no fluid leakage;
• There’s no bleeding;
• The blood vessel underneath the retina is not getting bigger.

What is the result of treating wet AMD?

When treated in a timely fashion, most patients respond to treatment. Over 90% of treated patients avoid losing significant vision (defined as 3 lines or more); 70% do not lose any vision at all, and about 40% experience significant gain of vision. About 50% of patients can expect to retain vision good enough for driving and operating machinery (usually defined as 6/12 or better)

When can I stop having injections?

It is difficult to stop treatments indefinitely, but rather to suspend treatments during long periods of disease inactivity. Treatment will have to be re-started again if the disease flares up again. It is not possible to predict when or why these episodes occur.

I’m terrified of pain – how painful are injections into the eye?

Adequate numbing drops will be applied to ensure that the procedure is fast and painless. Typically, patients feel pressure, with little or no pain during the injection. You may also feel a slight burning sensation that is related to the antiseptic used to clean the surface of the eye. The entire process takes about 10 to 15 minutes.

What are the possible complications of the procedure?

Severe complications are very rare with intravitreal injections. The major risks are:

• Infection in the eye or endophthalmitis
• Inflammation in the eye
• Bleeding into the vitreous gel (vitreous hemorrhage)
• Retinal detachment
• Sometimes there may be a small bleed or subconjunctival hemorrhage on the surface of the eye where the needle enters; this usually heals within a week.
• Temporary rise in eye pressure that usually returns to baseline in a few minutes. If excessively high, your doctor may perform a minor procedure called paracentesis to draw a small amount of fluid from the eye to relieve the pressure quickly.

What steps can I take to avoid infection after the procedure?

It is important to avoid rubbing the eye as the most common source of infection is from skin bacteria. You should also try to keep the eye as dry as possible especially when taking a shower. You should not swim for at least a week after injection. Besides these, you may return to normal activities after 1-2 days, including driving, reading, watching television and light exercise.

What should I look out for after the injection?

You might notice a few floaters or small bubbles appearing in the corner of your vision after the injection. These are normal and will disappear within 2-3 days.

However, you should contact your ophthalmologist if you experience signs and symptoms of complications, such as:

• Eye pain
• Decreased vision
• Seeing many floaters after the first day
• Increased sensitivity to light

I would like to know what are the new drugs coming for treating wet AMD

Additional drugs for wet AMD that target VEGF and could last even longer than brolucizumab are in the pipeline. The port delivery system is a device implanted into the wall of the eye in the operating room that can store, and slowly release, Lucentis. It can be refilled during an office visit. Abicipar is another drug that is injected into the eye to target VEGF. A phase II trial shows it can last as long as 12 weeks. RGX-314 is an anti-VEGF treatment delivered by gene therapy. It has the potential to block VEGF for years following a surgical procedure in which a harmless virus, called adeno-associated virus (AAV), carrying the anti-VEGF gene, is injected under the retina.

Photodynamic Therapy - ‘Cold laser’ treatment?

Also known as photodynamic therapy (PDT), cold laser treatment is used to seal leaking blood vessels without burning and damaging tissue. It involves injecting a medicine (Visudyne, verteporfin) that reacts to light is injected into your bloodstream. When the medicine reaches the retina, a cold laser (light) is used to activate the medicine and close the leaking blood vessels. This procedure may need to be repeated 3 or more months later.

When is PDT used?

Before intravitreal anti-VEGF drugs became available, PDT was the only approved therapy for wet AMD. Since then, it has been used less frequently because the results with anti-VEGF therapy is better than with PDT alone. However, for a group of wet AMD with grape-like abnormal vessels called ‘polyps’, using PDT together with anti-VEGF therapy has been shown to be very effective.