Macular degeneration – sight loss and treatment options
Age-related macular degeneration (AMD) is the most common cause of visual impairment in industrialised countries.
In Australia there are over 1 million people with the condition, accounting for 1 in 7 people over the age of 50. It is also the most common cause of blindness in Australia, accounting for 50% of all blindness.
The macula is the central and most sensitive part of the retina, and is responsible for central and fine detail vision. With AMD it is this particular part of the eye that is affected, and as the disease advances central vision becomes increasingly impaired. Many everyday activities such as reading, watching television and driving rely upon the macular functioning well therefore AMD can have significant effects on a person’s quality of life.
AMD can generally be classified into early and late stages, and whilst there is currently no cure for any particular type of AMD there are preventative measures and treatment available now (and potentially in the near future).
What is macular degeneration of the eye? Can wet macular degeneration cause blindness?
Early AMD involves the development of mounds of proteins and lipids (called ‘drusen’) which accumulate beneath the macula. At this stage, there is minimal to no effect on central vision, and lifestyle changes now (or even if you only have a family history of AMD) can be beneficial in preventing further progression of the condition.
The late stages of AMD can be divided into two categories: ‘dry’ AMD (geographic atrophy) and ‘wet’ (neovascular) AMD.
Dry AMD involves the atrophy (withering away) or loss of photoreceptors, the retinal pigment epithelium and underlying capillaries of the choroid (choriocapillaris). This condition generally develops slowly, but can cause progressive and significant impairment of central vision. There is currently no treatment publically available for this form of AMD, however I’ve been involved in a multi-centre worldwide trial of such a treatment at the Box Hill clinic, with preliminary results expected to become available in 2017.
Wet AMD is defined by the growth of abnormal new (neovascular) blood vessels beneath the macula. As these blood vessels are fragile and immature, they may leak fluid and bleed (leading to the term ‘wet’ AMD).
Whilst the symptoms are similar in both types of late stage AMD, severe vision loss in patients due to AMD is more often caused by the wet type (as opposed to dry). Without treatment, most patients with wet macular degeneration will become ‘legally blind’ in the affected eye. Fortunately, there is effective treatment available that significantly reduces the likelihood of vision loss, and has a good chance of improving sight.
What is the treatment of macular degeneration?
Vascular endothelial growth factor (VEGF) is a chemical that is normally present in all parts of the body, including the eye. Some conditions can cause there to be an excess of this ‘VEGF’ chemical, leading to leakiness of blood vessels or abnormal new blood vessel development. With wet AMD, it is the growth of these blood vessels beneath the macula, as well as their leakiness, that causes vision loss.
Treatment of wet macular degeneration involves anti-VEGF injections into the eye; these drugs are either complete or partial antibodies that block the action of VEGF.
There are currently three anti-VEGF drugs which are commonly used in Australia; current medical guidelines prevent me from listing them here. Whilst they are all very effective in treating wet AMD, subtle differences between each mean that the most appropriate drug (and treatment plan) could be different for each individual.
How effective are these injections? How long does it take to lose vision with macular degeneration?
The first anti-VEGF drug to receive PBS listing was introduced in 2006, prior to which there was significantly less effective treatment in the form of laser or photodynamic therapy (PDT) treatment.
Some of the early studies at the time showed that monthly injections were superior to these previous treatments, maintaining vision in approximately 90-95% of patients. Additionally, around 40% of patients had significant improvement in vision by 3 lines or more on a vision chart, compared with 5% with PDT.
Without effective treatment, 72-75% of patients with wet AMD would have severe vision loss, and would be classed as ‘legally blind’ in Australia.
A real world study in Denmark showed that legal blindness due to AMD dropped by 50%, and this was predominantly attributable to the introduction of anti-VEGF injections.
Whilst there have been no specific studies looking at the reduction of legally blind people in Australia, it is presumed that the introduction of anti-VEGF injections has had significant impact upon the vision of patients. It is estimated that monthly injections of anti-VEGF would reduce the risk of legal blindness by 72% compared with no treatment within 2 years, and lower the risk of visual impairment by 37%.
How often do I need treatment?
The early studies that looked at the effectiveness of anti-VEGF drugs in the treatment of wet AMD found that the drug was highly successful at preventing vision loss. Monthly injections were given in these studies for theoretical reasons and the pharmaceutical benefits scheme (PBS) in Australia allows anti-VEGFs for wet AMD be administered on a monthly basis.
With the release of the second major anti-VEGF drug in 2013 research for this new drug indicated that treatment could be given at a longer interval of 8 weeks (rather than 4). This theoretically meant that patients would require half as many injections.
In clinical practice finding the most effective drug, and how frequently it needs to be given, can vary between patients (and even between eyes in the same patient).
Some patients require monthly treatment, yet for others the anti-VEGF injections can last significantly longer.
Ongoing monthly injections and visits however are of significant burden to patients, so in order to alleviate this problem different treatment patterns (protocols) were devised; these aim to give as few injections as possible, whilst still maintaining sight. One such protocol involves giving injections in a ‘pro re nata’ method, or ‘as required’. For most patients, giving monthly injections will at some stage result in the resolution of fluid leakage from the abnormal blood vessels, with the wet AMD being termed ‘inactive’ at this point. Patients are then reviewed on a monthly basis, although treatment is only given when leakage is seen again (‘reactivation’ of the wet AMD).
Another treatment protocol, termed ‘treat and extend’, involves giving monthly injections until the wet AMD is inactive (no fluid leakage). Following this, the time between injections increases by two weeks between each visit as long as there is no reactivation. This extension of intervals generally continues until a maximum of 12 weeks is reached. If fluid leakage returns at any stage, then the time between injections is reduced to the last interval where the wet AMD was inactive.
The differences in approach to treating wet AMD using these two protocols result in varying (average) numbers of visits and injections for patients. The ‘as required’ protocol on average requires more frequent visits (monthly), though this is associated with fewer injections overall. By comparison, ‘treat and extend’ patients generally have less frequent visits, but a greater number of injections on average.
Research looking at the effectiveness of these two protocols have suggested that improvement in vision is greater with ‘treat and extend’, with these patients requiring treatment every 6-8 weeks on average. This protocol was also shown to be comparable to monthly treatment, which was demonstrated to be highly successful in the initial anti-VEGF studies.
Studies looking at the ‘as required’ patients showed that vision improved less on average, and that the degree of improvement was related to how frequently injections were given. Patients who received more frequent injections generally had greater improvements in vision, suggesting that this protocol potentially under-treats wet AMD. In one particular study, it was also noted that patients who switched to the ‘treat and extend’ regimen had significantly improved vision, even after receiving a prolonged ‘as required’ treatment approach.
This disparity in visual outcome could be related to the differing indicators for treatment between these regimens. ‘Treat and extend’ patients have a predictable treatment plan due to patients receiving an injection each visit, even if there is no reactivation of the wet AMD. This protocol aims to minimise any activity from the abnormal blood vessels by trying to maintain a state where the macula has no fluid leakage.
In contrast, ‘as required’ patients only receive treatment when there is fluid leakage and reactivation of the wet AMD; it is possible that in the short (and long term) allowing this fluid to continually return with fewer injections could impact negatively upon the vision of patients. Conversely, patients who have persistent fluid leakage at the macula (and thus usually require frequent monthly injections) were not shown to have negative long term visual outcomes.
What happens if I stop?
For patients that discontinue treatment for wet AMD, there is a significant risk of reactivation of wet AMD and associated potential visual repercussions.
In one particular study where patients discontinued treatment for more than 3 months, reactivation occurred in 91% of patients. This resulted in an average decline in vision of almost 2 lines at the time of recurrence.
Of these patients, 82% of recurrences were detected upon routine organised appointments, with only 18% returning sooner due to visual symptoms. This means that most patients who discontinue treatment are not seen immediately at the time of recurrence, leading to the potential for vision loss due to inadequate and delayed treatment.
9% of patients however did not show signs of reactivation associated with significant vision change over an average of 18 months of monitoring. This suggests that a small proportion of patients being treated under the ‘treat and extend’ regimen are receiving more frequent injections than is required, as generally the maximum interval allowable is 12 weeks.
There is currently no perfect solution for treatment protocols; inevitably there is a compromise in reducing the treatment load for patients, whilst still ensuring that vision remains unaffected by wet AMD. Research studies generally seek to identify trends in larger populations to establish conclusions and treatments that would benefit the majority of patients. There is the potential for individuals to react differently to treatment, meaning a one-size-fits-all approach is not always valid. Further research, along with greater personalisation of treatment, could potentially result in fewer injections on average in future without negative visual outcomes.
Given the likelihood for significant vision loss through inadequate or delayed treatment, and the potential permanency of these visual repercussions, erring on the side of caution may be the best approach.
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