AMD and Geographic atrophy

Age-related macular degeneration (AMD) is divided into a “dry”, so far not treatable, and a “wet”, treatable form.
In dry AMD, metabolic products of the photoreceptor cells (drusen) are deposited in the center of the retina (macula), which is responsible for sharp vision and reading. Depending on the size and location of these drusen, this disease has a long-term effect on vision. At the same time, over many years, there is a decrease in the density and regularity of the retina’s pigment cells, which provide the energy for the sensory cells to function. This results in a deterioration of contrast vision and increased sensitivity to glare.

Geographic atrophy (GA) is a late form of dry AMD.
Here, cells in the outer retinal area lose their function, they degenerate (die) and eventually leave an empty, atrophic zone where light and image processing can no longer take place.
Such an area becomes recognizable in the form of a so-called scotoma, a spot, usually in the center of the central field of vision, or in the immediate vicinity of it. With the expansion of the atrophic area, the disturbing spot increases in size and the visual function in the corresponding field of vision decreases. Through the resulting defects, light hits the retina without attenuation, resulting in increased glare sensitivity and sensitivity to light.

AMD is now a fairly well researched group of diseases, but the exact pathogenesis, the direct cause of why GA may develop in some patients, is still not understood to the last detail. It is assumed that various factors favor the development.
Advancing age is known as one of the most important and unavoidable causes. In addition, lifestyle factors and a genetic predisposition are considerations in research discussions.

Common risk factors include:

  • Age
  • Family history
  • Smoking/former nicotine use
  • High blood pressure and obesity
  • Cardiovascular disease, high blood cholesterol levels
  • Some medications (e.g., hormones, antacids)

Except for a vitamin substitution according to the so-called AREDS 2 formula (lutein 10 mg, zeaxanthin 2 mg, vitamin E 180 mg, copper 2 mg, zinc 80 mg, vitamin C 500 mg and unsaturated fatty acids), which is not very effective even in the long term, there has been no therapy so far. Now, for the first time, new therapeutic options have been found for the treatment of dry AMD. An injection therapy for advanced geographic atrophy, is expected to be approved in 2024. There is also a light therapy as an alternative.

  • SYFOVRE® (Pegcetacoplan, Apellis) – injections against geographic atrophy

    Various therapies for the treatment of geographic atrophy are currently still being researched. Recently SYFOVRE® (active ingredient pegcetacoplan) has been approved as the first drug for this purpose in the USA, and is soon to be launched here in Switzerland. This slows the progression of GA when used every 1-2 months but does not improve visual function. Used over a 5-year period, it is expected to keep visual function stable for about 1 year or 18% longer than would be possible without treatment.
    The drug is also used in the treatment of rare blood disorders such as “nocturnal hemoglobinuria”. Now, when applied locally by injection into the eye, it has been shown to slow the development of GA.

    Functionality in the eye

    Injections of the drug into the eye, (initially monthly, later every two months) slow down the increase of GA and stabilize the disease. Using a fine needle, after local anesthesia and disinfection, the drug is injected into the eye under sterile conditions, largely painlessly. The treatment takes a few minutes, the injection itself only a few seconds.

    What is important to know, what should you expect?

    • Outlook
      • Time to vision deterioration will be prolonged.
      • Therapy is not a cure option for GA.
      • Improvement is not possible based on current research.
    • For whom is the therapy suitable?
      • Injections can be given unilaterally, in rare cases bilaterally.
      • Preference is given to eyes whose GA has NOT yet reached the fixation point and who still have usable vision, as improvement is not expected.
      • A simultaneous injection treatment against wet AMD may be necessary in the same eye.
    • Duration of therapy
      • The first three injections are given monthly.
      • Thereafter, injections are given approximately every 2 months.
      • If the patient tolerates the therapy well, it can be continued in the long term.
    • Costs
      • There are currently no prices for Switzerland, but it can be expected that the pure drug costs will amount to at least CHF 2000 per injection.

     

    Most common side effects:

    • Irritation of the ocular surface (10%)
    • Development of wet AMD (5-7%; doubling of risk compared to untreated eyes)
    • Vitreous opacities
    • Superficial hemorrhage around the injection site (not dangerous)

     

    Rare side effects (no more, than with conventional “macular injection”):

    • Intraocular infection (endophthalmitis) with risk of blindness (1:10000).
    • Inflammatory reaction to the injection or drug (1:100)
    • Short-term eye pressure derailment (too high or too low, about 2%)
    • Retinal detachment (1:100)

     

    If injections are not an option: Light therapy as an alternative?

  • Valeda Light Delivery System (LumiThera) – Photobiomodulation (PBM)

    If an eye has no or noncentral geographic atrophy but has age changes such as drusen and pigment irregularity, it does not qualify for injection therapy. In cases of large drusen, AREDS 2 preparations can have a positive effect on the course, although not very strong. Recently, however, there is also the possibility of light treatment (photobiomodulation).
    Photobiomodulation (PBM) is a non-invasive, largely risk-free, low-threshold light therapy that is already used in many medical fields, e.g., in sports to locally promote blood circulation and improve physical performance. The therapeutic effect in dry AMD and GA is also based on a similar effect. Light in the spectral range of near infrared light (590-850nm) is projected onto the diseased areas of the macula, stimulating the regeneration of cells affected by AMD.

    What is important to know, what should you expect?

    • Outlook
      • This therapy may not achieve a cure for dry AMD or GA.
      • The goal is to slow the progression of the disease.
    • For whom is the therapy appropriate?
      • Men and women ≥ 50 years of age with advanced dry AMD with reduced visual acuity with or without GA.
    • When should the therapy not be administered?
      • In the presence of or recently diagnosed wet AMD.
      • With GA present in the center and pre-existing loss of visual acuity.
      • Non-dilatable pupil (scar, suture, or adhesion).
      • Neurological diseases (migraine, epilepsy).
      • Sensitivity to intense light exposure (yellow, red, or near-infrared light).
    • Therapy duration
      • Therapy sessions are about 5-10 minutes per eye.
      • Nine therapy sessions over 3 weeks are required per treatment cycle, three sessions per week.
      • According to current knowledge, therapy must be repeated every 4-6 months to maintain a therapeutic effect.
    • Costs
      • The therapy costs amount to 1800 CHF (9 sessions) at the patients’ expense.
      • However, we are currently planning a study to investigate the effect of light therapy in everyday practice. In this context, we would like to offer our participants the treatment at cost price until February 26th, 2024. Are you interested in participating? In case of further clarification, your attending physician will be happy to inform you in more detail.

     

    Most common side effects:

    • Afterimages immediately after the therapy session
    • Blinding sensation

     

    Rare side effects:

    • No serious side effects have been reported to date.
  • In summary and important to know

    Neither of the two currently available therapies, intravitreal application of the drug SYFOVRE, nor PBM, can prevent the progression of AMD with age or the risk of transition from the dry to the wet form.

    Visual improvement is NOT expected. The goal of treatment is to stabilize vision as much as possible in the long term and thus delay deterioration.

  • What can you do yourself?

    The aging process at the center of the retina cannot be stopped, but it can possibly be slowed down. Depending on its severity, and through self-initiative, everyday life with the disease can be made more bearable through coping mechanisms.

    1. Wear sunglasses
      Not only will this reduce the damaging effects of UV light on the retina, but you will also experience relief from glare sensitivity. Consult a specialized optician to find out which lenses, individually adjusted to you, can optimize your vision.
    2. Nutritional adjustment
      Pay attention to a balanced, antioxidant-effective diet with

      • green, seasonal vegetables,
      • natural vitamin supplementation (fresh fruits and vegetables),
      • little to no animal fats.
    3. Dietary supplementation according to AREDS/AREDS2 (lutein, zeaxanthin, zinc, unsaturated fatty acids).
      This is a dietary supplement (not a drug, so it is not covered by health insurance) with antioxidant vitamins and trace elements that can benefit vision in dry AMD. AREDS2 is also suitable for (former) smokers.
    4. Daily life management strategies
      Get information from specialized groups and counseling centers. Exchange with patients in self-help groups how to overcome the hurdles of everyday life and make life with AMD easier.