Macular degeneration treatment options

Once AMD has been diagnosed, it is important to commence appropriate management immediately. This is usually directed by an ophthalmologist (eye specialist), but can be supported by your optometrist.

As previously noted, [insert link to previous post], dry AMD is the more common of the two AMD subtypes and it is characterised by retinal drusen, pigmentation, and atrophy. Neovascular AMD (wet AMD) is less common but is imminently vision-threatening. Wet AMD presents with retinal fluid leakage and bleeding.Vitamin C tablets for age related macular degeneration

Treatment for Dry AMD

Currently, there are no prescription medications or surgery that can stop or reverse dry macular degeneration. However, there is some evidence that vitamin supplementation can slow down progression of dry AMD in certain subgroups of patients.

For most people, taking vitamins supplements isn’t necessary for eye health. Even though certain vitamin deficiencies can cause eye disease, these deficiencies are very rare in individuals with normal digestive function. Most healthy people get all the nutrients that their eyes need through a normal diet.

However, patients who have been diagnosed with AMD often ask their ophthalmologist if they should take vitamin supplements. The appropriate answer depends upon the severity of their AMD. For patients with very mild dry AMD, taking supplements does not appear to be of benefit, whereas supplements can help those with more established forms of AMD. Stopping smoking is also critically important.

Vitamins and supplementsvitamins for age related macular degeneration

The underlying pathophysiology of AMD is complex and involves the interplay of multiple factors. The role of oxidative stress as an element of the cascade underpins the rationale behind vitamin and antioxidant supplementation.

Some studies were undertaken in the United States of America, which examined this exact problem: can vitamin supplements slow down the progression of the disease, and, if so, which would be most effective?  These studies were called the Age-related Eye Disease Studies (AREDS). Two series of AREDS were undertaken: in 2001 and 2006.

These were randomised controlled trials that investigated a concoction of vitamins and antioxidants to slow the progression of AMD (7-9) in people with intermediate or advanced AMD. They found that those who took specific supplement combinations reduced their risk of AMD progression by 10 to 25%.

AREDS1

AREDS1 categorized a large number of AMD patients according to their disease severity at baseline and then randomized them to receive either vitamin supplements or placebo.

This trial found that a combination of daily zinc 80mg, copper 2mg, vitamin C 500mg, vitamin E 400IU, and b-carotene 15mg reduced the progression to advanced AMD in select populations.

AREDS2

In the second AREDS trial (AREDS2), the formula was changed slightly.  Zinc was reduced to 25mg and b-carotene was replaced with lutein 10mg and zeaxanthin 2mg. Zinc was reduced due to the risk of Zinc induced anaemia, and b-carotene was omitted due to an increased risk of lung cancer in smokers.zinc tablets for age related macular degeneration

Baseline characteristics of AREDS patients

It is important to recognize the baseline characteristics of the patients in AREDS in order to determine whether its benefits are applicable to practice. In the AREDS1 and AREDS2 population, the majority of participants were Caucasian and concurrently took multivitamins (Centrum) throughout the study.

In the AREDS2 population, the effects of additional supplementation were minimized as participants ceased any supplements which contained any components of the AREDS2 formulation.

The following patients were excluded from the AREDS trials: patients outside the ages of 55 to 80 years, those with significant co-morbid ocular or systemic disease, previous ocular surgery other than cataract extraction, consumption of medications with ocular toxicity, prior prolonged use of lutein/zeaxanthin/omega-3 fatty acids, intraocular pressure >26mmHg, cataract surgery within 3 months, or YAG laser capsulotomy within six weeks. These exclusions should be kept in mind in determining whether supplementation with the AREDS2 formulation is likely to benefit a specific patient.

AREDS Results

The results showed that only individuals in Category 3 or 4 (Table 2) who were randomized to receive vitamin supplements experienced a significantly reduced progression to advanced AMD (central GA or neovascular AMD) (11).

When Category 3 and 4 were grouped together, these patients experienced a 25% relative risk reduction in progression to advanced AMD at 7 years. The absolute risk reduction was 8%, meaning that 12 patients in Category 3 or 4 would need to be treated with vitamin supplements for 7 years in order to expect one to be spared from progression to advanced AMD (number needed to treat = 12).

Interestingly, supplements reduced the risk of neovascular AMD (OR 0.66) but did not reduce the risk of central geographic atrophy (OR 1.02) (12).

Individuals with only small drusen or less than 20 medium drusen did not experience a significant benefit from vitamin supplements.

AREDS2 optimized the supplement ingredients, but this study did not have a placebo arm, therefore it is difficult to know how the improvements to the supplement could expand the patient group that derives benefit.

TABLE 2:

AREDS CategoryCharacteristicsBenefit from supplementation
Category 1Small or no drusen, no pigment abnormalities

Other eye same

No
Category 2Small to intermediate drusen with or without pigment abnormalities OR

Pigment abnormalities without drusen

Other eye same, or category eye

No
Category 31+ large drusen OR

>~20 medium indistinct drusen OR

medium hard drusen +/- pigment +/- extra-foveal GA

VA >6/9

Other eye same, or category 1-2

Yes
Category 4One eye advanced AMD (central GA or CNVM)

AND

Vision <6/9

Other eye category 1-3

Yes

Analysis of the AREDS findings

Combining the population groups of the two AREDS trials revealed an association between high dietary nutrient intake and a reduced risk of progression to late dry AMD.

But AREDS reported that only select patient populations are likely to benefit from vitamin and antioxidant supplementation.

The benefit of AREDS2 supplementation in those who already have bilateral advanced AMD is unclear as these patients were not included in AREDS. Similarly, AREDS2 supplementation is not expected to benefit individuals without signs of AMD. This is supported by recent meta-analyses, which have found no significant benefit of vitamin supplementation in the prevention of AMD in patients with normal eyes (7, 13).

The formula supported by the AREDS2 trial is:

10 mg lutein.

500 mg vitamin C.

400 IU vitamin E.

80 mg zinc (as zinc oxide);

2 mg copper (as cupric oxide);

2 mg zeaxanthin.

Commentary

Vitamins C and E are essential micronutrients. They are antioxidants which are effective in providing protection against free radical and antioxidant damage to the retina.

Carotenoids (lutein and zeaxanthin) are present in the retina and tend to concentrate in the macula. These macular pigments offer retinal protection through minimising oxidative stress.

While AREDS1 suggested that beta carotene be included in this combination, the AREDS2 study determined that dry AMD benefitted more from cutting beta carotene out of the diet as much as possible, as b-carotene is associated with an increased risk of lung cancer in smokers.

So, lutein and zeaxanthin were the carotenoids chosen for the AREDS2 formula (16).  However, eating fruits and vegetables containing beta carotene before AMD develops can ward off the disease for several years or reduce your risk of developing it.

Conclusions

Not everyone needs to take these nutritional supplements. If you don’t have AMD at all, or if you only have very early signs of AMD, then there is no evidence to indicate that taking macular vitamin supplements help your eyes. Those who will benefit most are people at high risk for developing advanced age-related macular degeneration. They typically already meet one of these two conditions:

  • Intermediate AMD in one or both eyes
  • Advanced AMD in only one eye.

Treatments for wet AMD

Vitamin supplements are not associated with slowing down the progression of wet AMD once it develops. Wet AMD progresses much faster than dry AMD, and it is more likely to lead to blindness. Fortunately, there are some highly effective medical interventions to treat wet AMD.

Anti-vascular endothelial growth factor (anti-VEGF) drugs

The current standard treatment for wet AMD is anti-VEGF drugs. Your body relies on chemical signals to trigger blood vessel development. When those signals are present, the body starts building. When they are not, the body rests.

A protein molecule found in your eye is called vascular endothelial growth factor (VEGF), is such a chemical signal. VEGF is critical for the growth of abnormal blood vessels under the retina in macular degeneration.

Blocking this molecule with an anti-VEGF drug causes the abnormal vessels to regress. The drug causes the abnormal vessels to shrink and also be less permeable. The result is that fluid leakage into the retina is reduced, if not stopped. As the retinal swelling resolves, vision improves.

Injections of anti-VEGF drugs into the vitreous humour (back of the eye) have been developed to treat wet AMD. They are tremendously effective and are usually the first line of treatment for individuals with wet AMD.

intravitreal anti-vegf injection to treat age related macular degenerationIntravitreal Anti-VEGF injections

Anti-VEGF treatments are delivered by injections that go directly into the eye.

The ophthalmologist will first numb the eye with eyedrops, to minimise any discomfort. After your eye is anesthetised, the treatment is injected into the white portion of your eye using a very fine needle. Injections are given at one-month intervals, but this interval is extended as your eye health improves. Some patients can be extended to only needing an injection every three months, but it is rare to ever extend the treatment interval beyond this.

AMD is an area of intensive research. The discovery of VEGF as an important driver of wet AMD, and its treatment through use of anti-VEGF drugs, has been an important medical breakthrough.

Investigations are continuing into port delivery systems, in which a small device could be implanted in your eye that would slowly deliver the anti-VEGF drug over several months.  This would obviate the need for frequent injections.

Top of Form

photodynamic therapy for age related macular degenerationPhotodynamic therapy (PDT):

In this treatment, a light sensitive drug (verteporfin), is injected into a vein in your eye and the dye accumulates in the abnormal vessels beneath your retina. A special low-powered laser is then aimed at the abnormal blood vessels in your macula. This laser triggers a photochemical reaction that results in the release of oxygen free radicals to destroy the abnormal blood vessels. PDT is used infrequently in the treatment of AMD, due to a small risk of causing permanent damage to central vision

Laser photocoagulation

Here, a laser is used to thermally destroy the abnormal blood vessels. Unfortunately, laser also permanently destroys the retina overlying these vessels. Laser was, until recently, the only treatment for wet AMD. It is now seldom used, as anti-VEGF therapy is safer and more effective.photocoagulation as treatment for age related macular degeneration

Conclusions

Various lifestyle changes, such as quitting smoking, maintaining a healthy weight, and lowering blood pressure, cholesterol, and blood sugar may all slow down progression of AMD. Vitamin supplements based on the AREDS2 formula have been shown to benefit patients with certain severities of the disease. If wet AMD develops, then intravitreal injections of an anti-VEGF drug by an ophthalmologist is required urgently, in order to save your vision.

For all appointments and enquiries, please contact

Sight Specialists, Gold Coast.

Dr Nick Andrew

Ophthalmologist and Eye Surgeon Gold Coast

Sight Specialists, Level 2, 95 Nerang St, Southport QLD 4215

Medical disclaimer

This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician.

All readers/viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions.

Neither Dr. Andrew nor the publisher of this content takes responsibility for possible health consequences of any person or persons reading or following the information in this educational content.

All viewers of this content, especially those taking prescription or over-the-counter medications, should consult their physicians before beginning any nutrition, supplement or lifestyle program.