AGE-RELATED MACULAR DEGENERATION (AMD)

Age-related Macular Degeneration (AMD) is a common eye disorder that affects the central part of the vision. AMD can affect one or both eyes. AMD is the most common cause of severe loss of vision in patients over the age of 50.

AMD affects the macula. The macula is the central area of the retina. The retina is a thin membrane located in the inside of the eye and that acts like the film of a camera, capturing the image that will be transmitted to the brain through the optic nerve. We use the macula to see details, colours, read small print and discriminate faces, between others.

There are two types of AMD: dry or atrophic and wet or exudative.

In dry AMD there is loss of photoreceptors; the retinal cells that capture the image.

In the wet form of AMD abnormal blood vessels grow underneath the macula. These abnormal blood vessels can lead to the formation of a blister or retinal pigment epithelium detachment (PED), leakage of serum or fluid or bleeding under and/or inside the macula. These changes usually lead to the development of a scar in the macula and the consequent reduction of vision.

It is important to remember that AMD does not cause complete blindness equivalent to being in total darkness; affected patients usually maintain their peripheral or roundabout vision as the retina surrounding the macula continues to function normally. We must note that the peripheral retina is normally used only for navigation purposes as it is not capable of picking up small details or objects as the macula is.

AMD can make it difficult for affected patients to read, recognise people, drive, or perform tasks that require the use of accurate central vision.

Common symptoms of AMD are reduction of vision, blurring or distortion of central vision.

Without treatment, vision loss may be quick, severe and irreversible.

It is sometimes necessary to carry out investigations both initially and at regular intervals to determine whether you present the dry or the wet form of AMD, whether the lesions are active or not and treatable or not. The most commonly requested tests are fundus fluorescein angiography (FFA) and Optical Coherence Tomography (OCT).

During FFA a dye injected into a vein in the patient's arm and flash photographs are obtained through dilated pupils. FFA provides a detailed view of the macular blood vessels.

OCT is a non-contact test that is analogous to ultrasound but uses light instead of sound to images the macula by means of cross-sectional images similar to a histopathological microscope section. OCT can be very useful to determine the presence or absence of fluid, objectively determine the retinal thickness and response to treatment.

Treatments for wet AMD most commonly include Photodynamic Therapy (PDT) and/or the intraocular injection of anti-vascular endothelial growth factors (anti-VEGF). The two treatment modalities can be carried out independently or in combination. Mr Stanga will discuss with you the best option for you.

Click here for more information on Age-Related Macular Degeneration

PHOTODYNAMIC THERAPY (PDT)
During PDT a special dye called Vysudine® is injected into a vein of the arm during 10 minutes. Mr Stanga or a member of his team numbs the eye to be treated with eyedrops and a contact lens is placed on the eye. A special non-thermal red laser is applied to the eye 5 minutes later during 83 seconds. The laser activates the dye within the macular abnormal blood vessels with the aim of thrombosing (occluding) them. As a non-thermal laser is used, there is no heating or burning. At the end of the treatment the patient is given a green bracelet to wear for the first 48 hours. This is a precaution and is intended to remind you and other health care professionals that you have received PDT as it will cause your skin and eyes to become more sensitive to light. You must therefore avoid direct sunlight and bright lights for 48 hours immediately after treatment. To reduce this sensitivity please bring with you or wear the following: wide-brimmed hat, dark sun-glasses, clothing that will fully cover your arms and legs, socks and shoes.

You do not necessarily need to stay in the dark after PDT. In fact, exposing your skin to indoor light helps to inactivate any remaining drug in the skin.

You may have some blurring of eyesight in the 48 hours following treatment, but this is usually short lived.

PDT may need to be repeated. The aim of PDT is to reduce the potential for loss of central vision caused by wet AMD. PDT on its own can slow or stop the progression of wet AMD with stabilisation of vision in some cases. In clinical trials, 6 out of 10 patients experience stabilisation of vision over 2 years while some patients (16%) actually experience an improvement in vision.

All treatments have risks. It can be possible, though unlikely, to experience adverse reactions to PDT and these can include: injection-site reactions such as pain, swelling, inflammation, leakage into the area surrounding the vein, bleeding at the injection site and hypersensitivity to the drug or severe anaphylactic shock, blurred vision and other visual disturbances, back pain during infusion (around 2.2% of patients reported back pain). Severe vision decrease (occurred in l%-4% of patients).

If you have had a severe reaction to previous intravenous injections or if you have a strong allergic history, porphyria or severe liver disease please bring this to the attention of Mr Stanga.
If you think you might have a sensitivity (allergy) to any component of PDT or if you feel there is any reason why you should not be treated with PDT, do not hesitate to discuss these matters thoroughly Mr Stanga.

Click here for more information on Photodynamic Therapy (PDT)

LUCENTIS OR AVASTIN (ANTI-VEGF DRUGS)

The goal of treatment with these drugs is to prevent further loss of vision.  Although some patients have regained vision, the medication may not restore vision that has already been lost, and may not ultimately prevent further loss of vision caused by the disease.  After the pupil is dilated and the eye is numbed with anaesthesia, the medication is injected into the vitreous, or jelly-like substance in the middle of the eye.

Mr Stanga is currently indicating either Lucentis® or Avastin® as anti-VEGF drugs. These drugs restrict the growth of blood vessels.  These drugs can slow or stop the progression of wet AMD with improvement of vision in some cases.

Possible benefits of Avastin® and Lucentis and “Off-Label” status of Avastin®

Avastin® was not initially developed to treat AMD.  Based upon the results of clinical trials that demonstrated its safety and effectiveness, Avastin® was approved by the Food and Drug Administration (FDA) in the United States of America (USA) for the treatment of metastatic colorectal cancer.  As a condition of approval, the manufacturer produced a “label” explaining the indications, risks, and benefits.  The label explains that Avastin® works by blocking a substance known as VEGF.  Blocking or inhibiting VEGF helps prevent further growth of the blood vessels that the cancer needs to continue growing. 

Once a device or medication is approved by the FDA, physicians in the USA may use it “off-label” for other purposes if they are well-informed about the product, base its use on firm scientific method and sound medical evidence, and maintain records of its use and effects.  Ophthalmologists are using Avastin® “off-label” to treat AMD and similar conditions since research indicates that VEGF is one of the causes for the growth of the abnormal vessels that cause these conditions.  Some patients treated with Avastin® had less fluid and more normal-appearing maculas, and their vision improved.  Avastin® is also used, therefore, to treat macular oedema, or swelling of the macula. 

Recently, a medication similar in function and designed for intravitreal administration Lucentis®, was approved by the FDA in the USA for the treatment of AMD and is currently licensed in the United Kingdom (UK) for the treatment of AMD via intravitreal injections.

Possible limitations and administration

Avastin® is administered by an injection into your eye as needed at regular intervals (about every four to six weeks); Mr Stanga or his team will tell you how often you will receive the injection, and for how long.

Lucentis® is administered by an injection into your eye every four weeks for three months and from then on as required; Mr Stanga or his team will tell you how often you will receive the injection, and for how long

Some patients may be eligible for Combination Therapy: Photodynamic Therapy (PDT) followed by an intravitreal injection of Avastin® or Lucentis®. As PDT and Avastin® or Lucentis® works in different ways, some Ophthalmologist believe the effect of the combined therapies could be complementary, potentially reducing the number of treatment sessions required.  We must point out this has yet to be proven scientifically and studies are underway to test this hypothesis.

Complications from the medication and injection

Complications when Avastin® is given to patients with cancer
When Avastin® is given to patients with metastatic colorectal cancer, some patients experienced serious and sometimes life-threatening complications, such as gastrointestinal perforations or wound healing complications, hemorrhage, arterial thromboembolic events (such as stroke or heart attack), hypertension, proteinuria, and congestive heart failure. 

Patients who experienced these complications not only had metastatic colon cancer, but were also given 400 times the dose you would be given, at more frequent intervals, and in a way (through an intravenous infusion) that spread the drug throughout their bodies.

Complications following Lucentis®
The prescribing information for intravitreal Lucentis® contains a warning about arterial thromboembolic events:  “Although there was a low rate (<4%) of arterial thromboembolic events observed in the LUCENTIS clinical trials, there is a theoretical risk of arterial thromboembolic events following intravitreal use of inhibitors of VEGF.

Genentech, the company that manufactures bot Avastin® and Lucentis®, has advised ophthalmologists “of a higher incidence in one LUCENTIS study of strokes in the 0.5-mg dose group compared with the 0.3-mg dose group (1.2% versus 0.3%, respectively; P=0.02).”

One study showed that patients who have had a stroke are at greater risk of having one again. The causal relationship between Lucentis and strokes is unclear, and patients with AMD are already at risk for stroke.

It must be noted that whenever a medication is used in a large number of patients, a small number of coincidental life-threatening problems may occur that may have no relationship to the treatment. 

Risk when Avastin® or Lucentis® is given to treat patients with eye conditions

Ophthalmologists believe that the risk of these complications for patients with eye conditions is low.  Patients receiving Avastin® for eye conditions are healthier than the cancer patients, and receive a significantly small dose, delivered only to the cavity of their eye.  While there are no randomised controlled trials about the use of Avastin® in the eye that prove it is safe and effective, Lucentis®, a similar drug, was recently licensed for AMD. One study of patients who received Avastin® through an intravenous infusion reported only a mild elevation in blood pressure.  Another study of patients treated like you will be with intravitreal Avastin® (that is, Avastin® injected into the eye) did not have these elevations or the other serious problems seen in the patients with cancer. 

However, the benefits and risks of intravitreal Avastin® or Lucentis® for eye conditions are not yet fully known.  In addition, whenever a medication is used in a large number of patients, a small number of coincidental life-threatening problems may occur that have no relationship to the treatment.  For example, patients with diabetes are already at increased risk for heart attacks and strokes.  If one of these patients being treated with Avastin® or Lucentis® suffers a heart attack or stroke, it may be caused by the diabetes and not the Avastin® treatment. There is the risk that Avastin® reduce even further the blood supply in eyes suffering from conditions where the blood supply is already compromised, such as diabetic retinopathy or central or branch retinal vein occlusion.

Known risks of intravitreal eye injections

Your condition may not get better or may become worse.  Any or all of these complications may cause decreased vision and/or have a possibility of causing blindness.  Additional procedures may be needed to treat these complications.  During the follow up visits or phone calls, you will be checked for possible side effects and the results will be discussed with you.

Possible complications and side effects of the procedure and administration of Avastin® include but are not limited to retinal detachment, cataract formation (clouding of the lens of the eye), glaucoma (increased pressure in the eye), hypotony (reduced pressure in the eye), damage to the retina or cornea (structures of the eye), and bleeding.  There is also the possibility of an infection inside the eye infection (endophthalmitis).  You will receive eyedrops with instructions on when to use them to reduce the possibility of this occurring.  Any of these rare complications may lead to severe, permanent loss of vision or blindness and in extreme cases, even loss of the eyeball. You may require to be admitted into hospital for treatment that could include, between others, further injections into the eye or surgery. The prognosis in such event is usually guarded.

Patients receiving an injection of Avastin® or Lucentis® may experience less severe side effects related to the pre-injection preparation procedure (eyelid speculum, anaesthetic drops, dilating drops, antibiotic drops, povidone-iodine drops and the injection of the anaesthetic).  These side effects may include eye pain, subconjunctival haemorrhage (bloodshot eye), vitreous floaters, irregularity or swelling of the cornea, inflammation of the eye, and visual disturbances.

ALTERNATIVES

You do not have to receive treatment for your condition if you do not want so, although without treatment, these diseases can lead to further vision loss and blindness, sometimes very quickly.

Other forms of treatment are available.  At present, the standard National Health System (British NHS) treatment for some subtypes of AMD is photodynamic therapy (PDT). Although this treatment has been proven to slow down the rate of visual loss, most people do not get back better vision. 
The alternatives to PDT are Avastin®, Lucentis® and Macugen®; on their own or in combination with PDT.

Some ophthalmologists use intravitreal Kenalog® (steroid: Triamcinolone) - a long-acting cortisone-like drug—“off-label” to treat eye conditions like yours.

Mr Stanga will discuss with you the benefits and risks associated with these other choices of treatment.

DRY AMD

There is still no treatment for dry AMD thought plenty of research in this area is being carried out. Low visual aids (LVA) can often be very helpful in dry or inactive AMD by forcing the peripheral retina to perform many of the tasks normally undertaken by the macula. Mr Stanga can organise assessment and assistance with LVA.

Vitamin supplements may be of help for some subtypes of AMD; please remember to ask Mr Stanga about this.

Mr Stanga always recommends patients to quit smoking as it has been shown to be a contributing factor to the development of this condition.

Regular testing of each eye separately using an Amsler Grid (please ask Mr Stanga for a copy) can help to detect early changes.

The Amsler Grid test is a simple test that may help locate vision problems that might be related to macular disease:
1.   Hold the grid about 12 inches (30 cm) from the eye.
2.   Wear your reading glasses or bifocals.
3.   Test one eye at a time.
4.   While looking at the centre dot ask yourself the following questions;
a) Can you see all four corners of the grid?
b) Are any of the lines: blurry? bent? wavy? missing?
5. Use the grid once a week
6. If you note any changes in how you see the grid, please consult Ms Stanga urgently.

PATIENT RESPONSIBILITIES WHEN UNDERGOING TREATMENT

You must immediately contact Mr Stanga or his team if any of the following signs of infection or other complications develop: pain, blurry or decreased vision, sensitivity to light, redness of the eye (compared to immediately after the injection), or discharge from the eye. You should not rub my eyes or swim for three days after each injection. Please keep all post-injection appointments or scheduled telephone calls so that Mr Stanga or his team can check for complications. 

Although the likelihood of serious complications affecting other organs of your body is low, you should immediately contact your GP doctor or go to the Accidents and Emergency Room if you experience abdominal pain associated with constipation and vomiting, abnormal bleeding, chest pain, severe headache, slurred speech, or weakness on one side of the body.

As informed by Mr Stanga and his team, symptoms of stroke include sudden changes in vision; sudden numbness or weakness of the face, arm, or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble walking, dizziness, loss of balance or co-ordination; sudden, severe headache with no known cause.

Please notify Mr Stanga or his team about any of these problems. 

Please inform Mr Stanga or his team if you need to have any surgery or if you are on a medication that needs to be stopped before you can have treatment for AMD. Please do inform any other surgeon, including dentists, of the treatment for AMD that you have had or are undergoing.