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Wet Macular Degeneration Treatments Comparison

Eyes | July 8, 2014 | Author: The Super Pharmacist

Macular, degeneration, macular degeneration, MD, wet

Wet Macular Degeneration Treatments Comparison

Exudative macular degeneration is a condition caused by neovascularisation (abnormal blood vessel growth) in the choroid. This lies between the sclera (outer structure) and retina (which contains the cells that allow visual perception) of the human eye, and contains capillaries (small blood vessels) that supply nutrients to these structures.

Neovascularisation of these may damage the nearby macula, or the area within the eye where central vision is processed. This may occur through bleeding or scar tissue formation, which damages the layers of photoreceptors (light-processing molecules) in the macula, ultimately leading to specific types of vision loss.

Exudative macular degeneration is one of two main types of macular degeneration (MD), and is also known as 'wet' MD. Approximately 2.5 million people suffer from this variant of the condition.

Wet Macular Degeneration Treatments ComparisonBoth types of macular degeneration are associated with many risk factors

  • Age: Advanced age is associated with the risk of developing both wet and dry MD.
  • Genetic factors: MD may be hereditary. In addition, mutations in certain genes may be associated with an increased risk of developing the disorder.
  • Diabetes
  • High blood pressure
  • Smoking (tobacco)

The condition is associated with high levels of vascular epithelial growth factor (VEGF), a protein that plays a central role in blood vessel development.

Signs and Symptoms

Wet MD is characterised by certain signs and symptoms. These include:

  • Sudden onset. MD of this type often presents without warning and progresses rapidly.
  • Visual disturbances; for example, straight lines may appear to waver or be crooked, regular shapes (such as rectangles) may seem distorted, and objects may be perceived to be farther away than they are in reality.
  • Deterioration of central vision
  • Deterioration of colour and light perception
  • Definitive blurs or blind spots in the field of vision
  • Advanced AMD may be associated with false perceptions, including hallucinations.

‚ÄčTreatments available

There are a number of drugs in use to treat wet MD. These include:

  • Pegaptanib
  • Bevacizumab
  • Ranibizumab
  • Aflibercept

Comparing Ranibizumab and Aflibercept

Ranibizumab and aflibercept are particularly effective anti-VEGF drugs. These are similar in action, but have some differences which may affect the decision to use one or the other when addressing a case of wet MD.

Mechanism of Action

Both aflibercept and ranibizumab inhibit VEGF by attaching themselves to the protein before it can bind to its receptor in the choroid. Therefore, the shape of VEGF is changed to such an extent that the receptor will no longer recognise it, and thus new vessel growth will be avoided.

Comparing Ranibizumab and AfliberceptBoth drugs may significantly reduce or even halt the progressive vision loss associated with MD.

This type of drug action is particularly associated with specific molecules designed to identify and bind to corresponding proteins, known as monoclonal antibodies. Ranibizumab is one such antibody that has been developed to bind to the A subunit of VEGF (VEGF-A) with significant affinity.

Aflibercept is not an antibody, but rather recombinant (replicated in a lab) subunits of both subtypes (one of each) of the VEGF receptor itself, bound to a 'foundation' protein. Ranibizumab is partially synthetic (i.e. not found in humans) whereas aflibercept mimics aspects of both human VEGF receptor subtypes exactly. Therefore, the affinity of aflibercept may be superior to ranibizumab. Both ranibizumab and aflibercept are administered intra-vitreally, i.e. they must be administered by injection into the eye.

Efficacy

Ranibizumab is associated with significant VEGF binding and retention of visual ability. However, a seven-year multicentre study into the long-term outcomes of therapy with this drug showed that a third of patients documented had declines in visual acuity after treatment. On the other hand, more frequent injections of ranibizumab (i.e. 11 or more over a 3-4 year period compared to 7 or less) were associated with significant improvements.

Aflibercept, approved by the FDA in 2011, has demonstrated very similar efficacy and vision improvement profiles in comparison with ranibizumab. However, there is evidence to suggest that the newer drug maintains its effects for longer, indicating that it requires fewer injections per year than ranibizumab to achieve the same therapeutic gain. In other words, a monthly ranibizumab injection will be necessary to treat wet MD, in comparison with approximately four injections of aflibercept per year. Monthly treatments are required for both drugs in the first year of treatment, however. 

Risks and Side-effects

The more common side-effects of ranibizumab include:

  • Conjunctival haemorrhaging
  • Ocular inflammation
  • Ocular hypertension
  • Eye pain

More serious and unusual adverse events include:

  • Tearing of the retinal pigmented epithelium (RPE; a layer of cells that protect the photoreceptors). This is particularly associated with cases of wet MD in which the RPE has dissociated from the choroid (a complication of this condition). A recent study revealed that this occurred in 24% of 401 documented patients treated with the drug.
  • Increased risk of scar tissue formation as the condition progresses 
  • Inflammation of the inner layers of the eye in rare cases
  • Increased risk of a stroke or cerebrovascular accident

In contrast, aflibercept is not strongly associated with these severe side effects. However, this may be due to its status as a relatively new drug, and the concomitant lack of independent long-term studies on the outcomes and adverse reactions of aflibercept treatment. On the other hand, it is also associated with the typical side-effects of VEGF inhibition, such as ocular hypertension, eye pain and haemorrhaging. Both aflibercept and ranibizumab may also cause a dangerous increase in intraocular pressure, in rare cases.

Summary

Comparing Ranibizumab and AfliberceptWet macular degeneration is a disease than can significantly affect the visual capacity of patients.

It is caused by abnormal blood vessel proliferation in the choroidal capillaries of the eye. If this impinges on the macula, it may result in the loss of central vision.

This condition is mainly associated with advancing age and genetic risk factors.

It is thought to be caused by high levels of VEGF in the affected eye(s). This is a protein known as a growth factor that contributes to blood vessel development.

Wet macular degeneration is treated by drugs that bind VEGF before it can bind to its receptor, which stimulates blood vessel growth.

Prominent VEGF inhibitors include ranibizumab, a monoclonal humanized antibody, and aflibercept, a recombinant human protein.

Comparative studies indicate that these drugs are equally effective, although aflibercept may have greater affinity to VEGF. However, ranibizumab may have a shorter duration of effect than aflibercept; in other words, treatment with this drug may require more frequent doses.

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