Developments in the treatment of age-related macular degeneration

The macula is located in the centre of the retina and is defined in an area just 5.5mm in diameter.

It is a particularly sensitive area, as it contains a large number of light-sensitive nerve cells (photoreceptors), which receive visual information (light) and transfer it to the brain for processing through other nerve cells.

The macula is important for central, colour vision, as well as for recognising features such as a face. Any damage to the macula results in loss of central vision, which is usually immediately noticeable.

Age-related macular degeneration (AMD) is a degenerative condition that mainly affects people over the age of 50. The lesions it causes in the retina are mainly caused by the side effects of ultraviolet radiation, which strikes the eye and accumulates over the years.

EOH is distinguished in 2 forms: The dry type and the wet type. Dry-type IOP is characterized by extensive atrophy of melanin-containing cells that absorb light that is not bound by the retina (melancholic epithelium), but by photoreceptors. A typical picture of this type on ophthalmic examination (fundoscopy) is drusen (exudates) (Figure 1). Unfortunately, there is still no effective treatment for this type. Patients are recommended vitamin supplements rich in substances such as lutein, zeaxanthin and omega-3 fats. Also recommended is the consumption of green vegetables such as spinach.

Figure 1: Dry-type EEEO: Bottom with drusen

Wet-type IOP shows loss of central vision sooner than the previous type. On ophthalmoscopic examination there is fluid leakage and development of new abnormal vessels which are weak, resulting in rupture and bleeding (Figure 2). In the second stage, diffuse hemorrhages are seen in the fundus, while in the final stage of the condition there is scarring. There are various methods of treatment in the quiver of ophthalmic surgeons. Laser photocoagulation, which was the first therapeutic method, is applied with care around the central fovea. Photodynamic therapy in which an injection of dye is made that passes into the newly forming retinal cells and then laser-destroyed. Photodynamic therapy has now given way to treatment with anti-VEGF factors, which have been widely used in recent years, becoming the only treatment for most ophthalmologists. Anti-VEGF factors are administered by injection and reduce the leaks and neovascularisation that form in the retina. Of course, taking antioxidant-rich vitamins and avoiding smoking are also valid in this case.

Figure 2: Liquid-type EEEO: Bottom with bleeding in the macular region

However, despite the plethora of treatment methods, research continues to find new ways to treat and improve existing treatments.

The purpose of the methods of treatment of wet-type IOP is to stop the loss of vision and of course to improve it. Injection treatments, if taken at regular intervals (of about one month) in the affected eye, can stop the progressive decrease in vision and improve it.

However, there are many scientists around the world who argue that frequent injections can cause complications such as endophthalmitis, infection or bleeding within the eye, as well as an increase in intraocular pressure (IOP). In any case, intravitreal injections should be administered in a specially equipped room under aseptic conditions and by an ophthalmologist skilled in such injections.

In cases where we seek to improve vision through injection therapy, we recommend that patients receive 7-8 injections of antigenic agents per year when they are in the first year of treatment and at least 5-6 injections in the second year. We also recommend that the macular area be monitored via optical coherence tomography (OCT) at regular intervals, where we can compare the extent of the problem in detail between the retinal layers.
There are results of studies that correlate the number of injections given to a patient with the number of lines of vision gained on the control chart. Similarly, if the number of injections becomes fewer, then it seems difficult to maintain the improved visual acuity over a long period of time.

For this reason, new studies are being conducted, which aim to reduce the number of injections, while at the same time providing optimal benefit in terms of vision for patients with EEG.

The new data want researchers to turn to other types of treatments, which are applied to the back of the eye and will be effective for a long time, without the risk of complications that come with injectable treatments. A typical example is encapsulated cell therapy. This technique involves retinal cells that are rich in melanin (melanin-rich epithelium). Through genetic modification, therapeutic proteins and peptides can be produced by this technique (Figure 3).

Treatment with these cells has many advantages over other long-term treatments. In particular, it can support the continued production of therapeutic proteins within the vitreous, either individually or in combination with other therapies. Also, according to research results, it appears that encapsulated cell therapy can deliver proteins for 2-5 years treating a wide range of retinal diseases. Furthermore, the low dose of the drug within the vitreous reduces the risk of adverse effects that can occur with intravitreal injections.

Figure 3: Illustration of the operating principle of encapsulated cells

Research on the encapsulated cells continues with genetically modified human cells, which secrete therapeutic doses into the back of the eye to treat degenerative retinal diseases. Results of a recent pilot study in glaucoma patients showed improvement in visual field width, as well as retinal nerve fiber volume, within 1-18 months. To date, these cells remain safe with more than 1000 patients having received this treatment.

The studies continue to give impressive results, in terms of patients' visual acuity, as well as macular thickness, which appears to be reduced for at least 20 months after treatment with the encapsulated cells, combined of course with a lower frequency in the rate of injections.

Interestingly, a clinical study comparing the safety and efficacy of encapsulated cell therapy with that of endovascular injections of anti-VEGF factors was conducted. The study included patients who improved after at least three injections of anti-VEGF factors. Patients were randomly divided into two groups. Every eight weeks, one group was treated with inclusion cell therapy, while the other group received anti-VEGF factor. This study continues to this day and results are expected in early 2017. The effectiveness of the treatment will take into account the change in visual acuity, the change in retinal thickness and the rate of treatment failures.

The fact is that new research is emphasising not only young patients, but also those who have already been treated for some years. For this reason, it is necessary to consider not only the improvement in vision as a criterion for the effectiveness of a treatment, but also its durability in maintaining good levels of vision for a long time. This is where we expect these new encapsulating cells to play an important role. Essentially, their purpose is to produce many therapeutic proteins at stable levels for many years safely.

We believe that encapsulated cell therapy belongs to the new generation of treatments for chronic eye diseases. Results so far show improvements in the visual field of patients and corresponding improvements in nerve fiber anatomy, especially in glaucomatous cases.

In any case, we should not forget that the process of treating a retinal condition that requires injectable treatment, such as liquid-type IOP, is a marathon. It is also worth stressing the importance of repeating the injectable treatments at the intervals specified by the ophthalmologist in order to achieve the desired result of improving vision.

We can therefore understand that in these cases patience is necessary, both on the part of the surgeons-ophthalmologists and the patients, as there are cases where the treatment is long-term. The improvement in vision may be delayed in relation to the reduction of fluid or blood from the retinal area. It is also important to remind our patients that improvement is not only dependent on the treatment we carry out in our practice or clinic, but also on other factors such as regulating sugar levels, body weight and blood pressure.