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EXCIMER Ophtalmologic Clinics
ophtalmologic clinic
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EXCIMER Ophtalmologic Clinics Ophtalmologic clinic
Moscow St. Petersburg Novosibirsk Nizhny Novgorod Rostov-on-Don
Рус Eng Version for visually impaired
офтальмологическая клиника
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EXCIMER Ophtalmologic Clinics Ophtalmologic clinic
Moscow St. Petersburg Novosibirsk Nizhny Novgorod Rostov-on-Don

Management of age-related macular degeneration

According to World Health Organization, age-related macular degeneration is one of the most frequent causes of blindness and extreme vision reduction in senior citizens. Age-related macular degeneration is a chronic degenerative condition that mostly affects people above 50. According to the official data of WHO Center for Prevention of Avoidable Blindness, this condition affects 300 people of every 100 thousand of population. AMD in developed countries is the third most frequent ocular pathology causing vision reduction after glaucoma and diabetic retinopathy. 10% of US nationals aged 65 to 75 and 30% of US nationals aged above 75 lost their central vision to AMD. 1,7% of all people above 50 and 18% of all people aged 85 have AMD in the terminal stage (blindness). The incidence of AMD in Russia is 15 per 1000 of population.

AMD manifests itself as progressing worsening of central vision and irreversible macular deterioration. Macular dystrophy is a bilateral condition (both eyes are affected in about 60% of all cases), however, the condition is more evident and develops more rapidly in one of the eyes, while the second eye may develop AMD only 5 to 8 years later. Often patients fail to notice the onset of the condition, because the eye with better vision takes up all visual load.

important! If you notice that your far-range and close-range vision worsens or if you encounter difficulties while reading and writing, find that you require more intense lighting, notice a semitransparent fixed spot before one or both eyes, or find that the shapes, colors and contrasts are distorted, consult an ophthalmologist immediately. Only a doctor can diagnose macular dystrophy. However, self-testing using Amsler grid is also useful.
Amsler grid (normal)Amsler grid (AMD)

Development and varieties of age-related macular degenerations (AMD)

Development and varieties of age-related macular degenerations (AMD)

  • The macula is several layers of retinal pigment epithelium; below lies a thin Bruch's membrane that separates the upper layers from the vessels (choriocapillars) that provide the macula with oxygen and nutrients.
  • Development and varieties of age-related macular degenerations (AMD)

  • As the eye ages, cell metabolism by-products accumulate to form drusen, or yellowish thick masses under the retinal pigment epithelium. A multitude of small drusen or one (or more than one) large druse is the first sign of an early stage of «dry» AMD form. A «dry» (non-exudative) form is the most frequent (about 90% of all cases).
  • Development and varieties of age-related macular degenerations (AMD)

  • As they grow in size and number, the drusen may inflame and bring about the production of vascular endothelial grows factor (VEGF), or a protein that facilitates growth of new blood vessels in the eye. New pathological blood vessel growth is called angiogenesis.
  • Development and varieties of age-related macular degenerations (AMD)

  • These new blood vessels grow through the Bruch’s membrane. As these new vessels are, by nature, a pathology, blood plasma and even blood itself percolate through their walls to penetrate inside the macular layers.
  • Development and varieties of age-related macular degenerations (AMD)Механизм развития ВМД

  • From then on AMD comes to the progressing phase and takes a more aggressive , or «wet» form. Fluid accumulating between the Bruch’s membrane and the photoreceptor layer attacks the vulnerable nerves responsible for healthy vision. Unless this process is arrested, hemorrhages will lead to separations and cicatrization, which, in turn, may bring about irreversible loss of central vision.
    «Wet» (exudative) form is much rarer than the «dry» form (about one or two cases per 10), however, it is much more dangerous as it progresses rapidly, and vision deteriorates very quickly.
  • Symptoms of «wet» AMD

    • Rapid deterioration of visual acuity, no improvement when corrected with glasses.
    • Blurry vision, reduced contrast sensitivity.
    • Loss of individual letters or curvy lines while reading.
    • Distorted objects (metamorphopsia).
    • Dark spot before the eyes (scotoma).

    Objective of AMD management

    Age-related macular degeneration is manageable. However, until recently, there was only one way to arrest the “leakage” of the vessels associated with wet AMD – laser coagulation. This method did not eliminate the root cause of vessel pathology and was a temporary measure only.

    In early 2000s, a more effective method called «target therapy» was developed. This approach is based on using substance medication to target VEGF protein.

    Target therapy

    Anti-VEGF therapy has completely revolutionized AMD management and helped preserve vision and maintain quality of life in millions of people around the world. Anti-VEGF therapy can slow down the progression of AMD and sometimes even reverse it. This method of management is effective, but only before cicatrization and irreversible loss of vision.

    Intravitreal injections — Anti-VEGF therapy

    Anti-neovascularization medications must be introduced directly inside the vitreous body to be efficacious for the macula. The procedure is performed in a sterile operation room by an experienced ophthalmologist.

    Intravitreal injections

    The injection takes several minutes and causes no pain. As the anti-VEGF medication percolates through the macular tissues, it reduces the activity of the protein. As a result, neovascularization stops, the newly formed vessels start deteriorating and regressing. If this procedure is repeated for several times, pathological fluid also dissipates.

    Angiogenesis and edema control helps stabilize vision and prevent progression of the macular damage. Clinical data show that approximately 30% of the patients who received anti-VEGF therapy for wet AMD recovered some of their vision after the treatment.

    Medications for age-related macular degeneration management – Lucentis and Eylea

    The first anti-VEGF medication for intravenous injections certified for use in Russia was Lucentis, a medication which revolutionized AMD management to become a «gold standard». In June 2006, it was approved by Federal Drug Administration (FDA) as a unique medication for age-related macular degeneration, and in 2008 it was registered in Russia. Excimer eye clinics have been using Lucentis in clinical practice since 2009.

    Research was continued to obtain a medication similar to Lucentis as to its efficacy, but with more prolonged action. In November 2011 Eylea, a new medication for age-related macular degeneration was approved in the US. It has been registered in Russia since March 2016 and has been in use by Excimer ever since.

    Effect of Lucentis and Eylea

    Before the emergence of the above medications, cancer drugs were used for the purpose of anti-VEGF therapy. Lucentis (and later Eylea) were designed for ophthalmology application, therefore, they are more efficacious and much safer.

    The active component of Lucentis is ranibizumab that acts to reduce overstimulated angiogenesis (neovascularization) in patients with age-related macular degeneration and normalize the thickness of the retina. Lucentis is quickly distributed into all retinal layers to reduce the macular edema and arrests the progression of damage, vascularization and new hemorrhages.

    The active component of Eylea is aflibercept. Its molecules acts as a trap by way of attaching themselves to vascular endothelial grows factor (VEGF) and placental growth factor (PIFG). Eylea has a more lasting intraocular effect which allows to extend the interval between injections. This medication can also be used in patients with vision reduction due to diabetes-induced macular edema or macular edema caused by retinal vein occlusion.

    Evidence of research data

    Clinical efficacy and safety of these medications were proven by a number of large-scale international research projects. The results are impressive: most of the patients showed significant improvement in visual acuity, in addition the arrested progression of the condition.

    Treatment results
    Thickness of the central retina before and after the treatment

    • Anti-VEGF medications demonstrated significant improvement in visual acuity in comparison with laser methods (photodynamic therapy): injection therapy resulted in ~8,5-11,4 symbols (ETDRS chart) by month 6 against 2,5 symbols in a group which received laser therapy. By week 52, the group which received anti-VEGF therapy gained 9,7 to 13,1 symbols, while the group which received laser therapy lost 1 symbol.
    • At the end of week 52, the percentage of patients who retained visual acuity and received Lucentis and Eylea was 94,4% and 95,3%, respectively.
    • The percentage of patients with visual acuity improved by ≥15 ETDRS symbols is 30,6% with Eylea and 30,9 % with Lucentis; average visual acuity improvement rate was 7,9 symbols and 8,1 symbols with Eylea and Lucentis, respectively.
    • Average central retina thickness change rate: -128,5 μm (Eylea) and -116,8 μm (Lucentis).

    Frequency and dosage

    The dosage of Lucentis injected in the vitreous body is 0,5 mg (0,05 mL). First 3 Lucentis injections are made consecutively each month (stabilization phase), later the number of injections shall be determined by the attending ophthalmologist depending on the condition of visual functions and progression of the disease (maintenance phase). The interval between injections is at least 1 month. After stabilization, the injections are suspended, however, the patients’ visual status has to be screened 2 to 3 times per year.

    Eylea regimen starts with three consecutive injections into the vitreous body (dosage 2 mg); the interval between later injections is 2 months. No additional control checkups between injections are required. After stabilization, the interval between injections may be increased by the attending ophthalmologist based on the visual acuity data and anatomic measurements.

    Management of age-related macular degeneration
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