Please read this page if you are a patient interested in joining The MERLOT Study. The MERLOT Study investigates a new treatment for wet age-related macular degeneration (AMD), called epimacular brachytherapy. Epimacular brachytherapy involves an eye operation to deliver a targeted dose of radiation to the macula, the part of the eye that is damaged in AMD.

You can watch a SKY TV News Report on the MERLOT trial and epimacular brachytherapy by clicking the link. The Sky news report (and other media coverage of the MERLOT study) should not be used to decide whether or not you wish to join the study, but it may give you an overview of this new treatment.

Please note this is only a summary of the information which will be supplied to you at the Screening Visit at your local hospital. You will be supplied with the full Patient Information Sheet specific to the recruiting hospital you are attending.

If you have any questions, please locate the contact details for your nearest hospital from the Recruiting Centres listed on the other page or alternatively you may contact the lead site - King's College Hospital for an up to date list of actively recruiting centres.

Before you read the information below you may wish to answer the screening questions, to find out if you might be eligible to join the MERLOT study. The webpage with the screening questions also tells you how to seek referral, should you decide you want to try and join the MERLOT study.

Why am I being asked to volunteer?
Do I have to take part in this study?
How do I decide whether or not to participate?
What treatment alternatives do I have if I choose not to participate?
What is the purpose of this research study? & How long will it last?
What am I being asked to do?
What are the possible risks or discomforts?
What are the possible benefits of the study?
How does radiation work? & What amount is received during the procedure?
Who is organising and funding this research?
What if I have further questions about the study or treatment?

You are being invited to participate in a research study designed to evaluate a new device to treat wet age-related macular degeneration (AMD). You have been invited to participate in this research study because you have been diagnosed with wet AMD and have been previously treated with a drug to stop blood vessels from growing in your retina (Lucentis)®.

Your participation is voluntary which means you can choose whether or not you want to participate. If you choose not to participate, it will not affect the care you receive at your hospital in any way.                                                                                                       Back to Top

Before you make your decision, you will need to know what the study is about, the possible risks and benefits of being involved, and what you will have to do in this study. The research team will talk to you about the research study, and they will give you a Patient Information Sheet to read. You may also want to discuss it with your family, friends, regularly seen eye doctor, or family doctor. If you have problems with some of the medical language, please ask the study doctor and/or the research team to explain the medical language.

If you choose not to participate in this study your doctor will discuss treatment alternatives for your wet AMD. You do not have to take part in this study to receive treatment for your condition. To be eligible to join this study you will have already received treatment with a drug called ranibizumab (the trade name for this drug is Lucentis®). When given monthly, or at regular intervals, Lucentis® makes it less likely that you will lose vision.

Other therapies include treatment with laser photocoagulation (a surgical procedure involving the application of a hot laser to your retina), photodynamic therapy (a procedure that uses a non-thermal or cold laser with a light sensitive drug injected into an arm vein, verteporfin [Visudyne®]), and pegaptanib (Macugen®; a drug that is injected into the eye). Bevacizumab (Avastin®) is another drug, similar to Lucentis®, that is injected into the eye.  Other new treatments or combinations of treatment may become available. You may also choose to receive no treatment at all.                                                                         Back to Top

The purpose of this study is to determine whether a new treatment called epimacular brachytherapy, using a new surgical device (VIDION® System*), provides safe and more effective treatment for wet  AMD, compared to standard treatment. In particular, this study aims to find out if it reduces the burden of treatment, by reducing the need for such regular injections of Lucentis® into the eye. Details of this device a given later in this document.

You will be in this study for approximately three years. About 363 subjects with wet AMD will participate in this study. About 10 to 40 patients will be treated at each recruiting centrea as part of this UK-wide study.                                                                                           Back to Top

You will first come to the clinic for a Screening Visit to determine whether you are eligible to participate in the study. If you are eligible and you decide to participate in the study, you will be enrolled into the study.

Below is a summary of the treatment plan.  Most of the hospital visits shown below would occur as part of standard care, regardless of whether or not you enrol in this study, as patients with wet AMD require approximately monthly hospital appointments. 

Many of the tests below would also occur as part of standard care, although some additional tests are required for this study. The most important difference from standard care is the use of the epimacular brachytherapy (VIDION® System*) device.

Screening Visit During your first visit (the Screening Visit), you will have the following tests/procedures performed to determine if you can participate in the study. Only one eye (the “study eye”) will be treated if you are eligible. If you have AMD in both eyes, you may receive treatment in the eye that is not the “study-eye” with an approved therapy for AMD.

• You will be asked for your complete medical and surgical history, and the study personnel will discuss the requirements of the study with you. You will also be asked about any medications you are currently taking or any medications you may have taken within the last month.

• Patient Questionnaires.Two short questionnaires will be given to you to complete during your visit and will ask you some questions about how your vision affects your quality of life. This will be repeated at several points during the study to monitor how changes in your vision affect your quality of life and enable the health economics of the treatment to be assessed. They are short questionnaires with a series of set questions and multiple choice answers and should only take 5-10 minutes to complete.

• Slit Lamp Examination is an examination of your eye by the doctor using a special microscope that allows the doctor to see both the outside and the inside of your eye under magnification. The lens and back of your eye will also be examined after eye drops have been placed in your eyes to dilate your pupil.

• Indirect Ophthalmoscopic Examination The doctor will examine your retina with an ophthalmoscope (an instrument with a strong light and a magnifying lens).

• Intraocular Pressure is a measure of the pressure of the fluid inside your eye.

• Visual Acuity measurement uses letters on an screen (eye chart) to measure how well you can see at a specific distance.

• Fluorescein angiography is a test in which pictures of your retina are taken using a yellow dye (fluorescein). The dye will be injected into a vein (blood vessel) in your arm or hand. This dye will travel through your blood vessels to your eyes. The camera will then flash a special light into your eye and will take pictures of your retina. The pictures will show the amount of dye leaking out of the blood vessels into your retina.

• Fundus Photography Colour photographs of your retina will be taken. Eye drops will dilate your pupils, allowing the inside of your eye to be examined. A special camera will then be used to take photographs.

• Optical Coherence Tomography (OCT) uses a beam of light to measure the thickness of the retina. You will be asked to look into a machine at a pattern of flashing and rotating red and green lights.

1st Treatment (Baseline) Visit
If you are eligible to be in the study, you will be allocated randomly by a computer to receive the new treatment -epimacular brachytherapy (VIDION® System*), or to continue with Lucentis® treatment alone.  You will have a 2 out of 3 (67%) chance of  receiving epimacular brachytherapy and a one out of three (33%) chance of not receiving epimacular brachytherapy.  If you are allocated to epimacular brachytherapy this is called Arm A, or the Treatment Arm.  If you are allocated to continue with Lucentis® you are in Arm B, also called the Control Arm or Lucentis® monotherapy.  If you are allocated to undergo epimacular brachytherapy this will be performed within  approximately 3 weeks of your first (Screening) visit. 

• Epimacular Brachytherapy (VIDION® System)* You will have eye surgery to have the epimacular brachytherapy (VIDION® System*) device placed into your eye very close to your retina. Surgery can be done with you asleep (general anaesthetic), or awake but with an injection to numb the eye (local anaesthetic).  To deliver the treatment the surgeon will first remove the clear watery gel (vitreous) that fills the inner cavity of the eye, using very small openings into the eye. This operation is called a vitrectomy and is commonly used to treat a range of eye conditions.  In the second stage of the operation the surgeon delivers a dose of radiation into your retina. This will take about 3-5 minutes. After that, the device will be removed from your eye. Based on how active your AMD is at the time of surgery, you may also be given an injection of Lucentis®. The operation takes about 20-50 minutes and is usually done as a daycase procedure, meaning you go home the same day.  After the surgery you will be provided with several types of eye drops to use when you return home. The schedule for using these medications will be explained to you before you go home. You will come back for an appointment one day and one week after surgery to check the vision, measure the eye pressure, and to examine the eye.  If your disease remains active at subsequent visits you will still be able to receive further injections of Lucentis® as required.

• Lucentis® If you are allocated to continue with Lucentis® treatment (Arm B or Control Arm) you will receive Lucentis® as required, based on the activity of your disease.  Lucentis® injections will be familiar to you already, as you have been receiving these on a regular basis.  The way these injections will be given is similar to how you received them previously, although the criteria the doctors applies to decide whether or not you need an injection may be more precisely defined by being part of the study. 

Following the baseline visit you will have regular, monthly outpatient clinic appointments over the course of the 36 month study.  At most visits you will have visual acuity tested, your eye examined (slit lamp exam/ indirect ophthalmoscopic exam) and an OCT.  These tests would occur even if you weren’t part of the study. We may also ask you questions about your eye, your medications, and your general health at these visits and check your eye pressure.  You will require a fluorescein angiogram to monitor your eye disease at month 12 and 24.  Additional visits or tests may be necessary as required.                                         Back to Top

Most of the risks below would occur during standard care, regardless of whether or not you participate in this study, with the exception of epimacular brachytherapy (treatment with VIDION® System*).  You may also require more fluorescein angiograms that you might outside of this study.

Eye Examination and Dilation: As part of the eye exam, drops will be put in your eyes to dilate the pupils. These drops are used routinely in eye clinics. The drops may blur your vision and make you sensitive to light for several hours. There is a small risk of an allergic reaction to the drops. There is also a small risk that the drops could cause the eye pressure to rise. If this happens, it will be treated, but there is a very small risk of losing vision from the pressure rise.

Due to the blurring effect of your vision and possible light sensitivity, you will be advised not to drive until the drops have worn off and, if necessary, to have someone come with you who can drive after the exam.

Fluorescein Angiography: After the dye (fluorescein) is injected into your arm or hand, your skin may turn yellow for several hours. The yellow colour will disappear as your kidneys remove the dye from your body. Because the dye passes through your kidneys, you urine will turn dark orange for up to 24 hours after the procedure. You may have an upset stomach during the procedure, but this usually lasts only a few seconds. If the dye leaks out of your vein during the injection, some of the skin around the injection site may feel uncomfortable or become yellow. The discomfort usually lasts a few minutes, and the yellow colour goes away in a few days.

An allergic reaction to the dye is rare. If this does happen, you may have a rash or experience itching of your skin. This is usually treated by antihistamines that are given by mouth, or by injection if your symptoms are severe. A severe allergic reaction occurs very rarely (fewer than 1 in 1 million people) and may involve breathing and/or heart rhythm problems which can be life-threatening. Angiography is a routinely undertaken investigation in patients with AMD.

Fundus Photography: The bright flashes used to take the photographs may be annoying, but are not painful and cause no damage.

Optical Coherence Tomography: There are no known risks associated with this procedure.

Lucentis® Injection Procedure: Prior to injection of the drug into the eye to treat your AMD, your eye will be numbed with an eye drop and cleaned with betadine. You may experience redness or swelling of the eye or eyelid, or bleeding, tearing or watering of your eye. You may experience corneal abrasion (scratch on the clear front surface of the eye) if you rub your eye while numb. These events are likely to clear up quickly. You may experience allergy to the numbing drops, betadine or the Lucentis® itself.

Other events include some loss of vision, inflammation (infection) inside the eye, an increase in pressure inside the eye (possibly leading to glaucoma), bleeding inside the eye, detachment of the retina, blockage of blood vessels inside the eye, conjunctival haemorrhage (bleeding under the clear covering of the eye), eye pain, and vitreous floaters (when you can see objects floating in your field of vision).

Lucentis® drug: Lucentis® has been studied in humans in previously completed clinical trials and research studies. The following side effects have been observed:
•    temporary redness of the injected eye
•    minor bleeding at the injection site that resolves on its own (doesn't require treatment)
•    dull pain in the injected eye
•    sensitivity to light
•    mild and temporary burning and stinging
•    vision disturbances, including decrease in vision
•    bleeding inside the injected eye that resolves on its own
•    infection outside the treated eye
•    mild and self-resolving inflammation on the inside of the eye.

Less frequent side effects include:
•    Infection inside the eye (endophthalmitis)
•    Severe inflammation in the inside of the eye (uveitis)
•    Blockage of the blood flow in the main vein inside the eye (central retinal vein occlusion)
•    Temporary increase in the pressure inside the eye (intraocular pressure)
•    Damage to the lens inside the eye (cataract formation)
•    A tear through the retinal tissue in the eye (retinal tear/detachment)
•   A rip in the pigment cell layer that lies beneath and nourishes the retina (retinal pigment epithelial [RPE] tear) and inadequate response of the pupil to light entering the eye.

The complications listed above could lead to a mild, moderate or severe loss of vision that does not recover. Extremely rarely they may result in loss of the eye.

If you have a history of glaucoma, you may be at more risk for experiencing increased pressure within your eye after an injection of any substance, including Lucentis®. To participate in this study, it must be shown that your glaucoma is well controlled with medication and that you take your medication as it has been prescribed by your doctor.

There is a chance that your vision may worsen. Worsened vision could be due to progression of your AMD, to a side effect of Lucentis® injection, or for other reasons.

There is a chance that you will experience an allergic reaction to Lucentis®. Allergic reactions may be mild, such as skin rash or hives, or severe, such as breathing difficulties or shock. A severe allergic reaction would require immediate medical treatment and could result in permanent disability or death. An allergic reaction can also cause a red, dry or itchy eye. It is not possible to predict in advance if any of these problems will develop, but if they do, you will be promptly treated.

Tests have shown that low levels of Lucentis® can reach your blood stream after injection into the eye. The significance of this is not well understood. However, in one recent study, 1.2% of the people who took 0.5 mg of Lucentis® injected into the eye every 4 weeks developed stroke while only 0.3% of those who had an injection of a lower dose (0.3 mg) had a stroke. Among those people who had a history of prior stroke, the risk for another stroke was higher than among those with no prior stroke. The risk of having another side effect involving a body system other than the eye is unknown but is believed to be very small. As is true for any drug, unknown and potentially serious or life-threatening side effects could occur with Lucentis®. The effects of Lucentis® on a foetus (unborn child) are unknown and may be harmful; therefore, females who may become pregnant are not enrolled in this study. If you are female and have not yet been through the menopause you should explain this to the study doctors. If it is less than a year since you have been through the menopause you should also tell the study doctors.  It is not known if the radiation used in this treatment might damage the sperm of male patients with a risk of damage to any children that they father, but the low doses of radiation mean that this risk, if it exists, is very small. 

Epimacular Brachytherapy: The eye surgery required for use of the epimacular brachytherapy (VIDION® System*) device has two key components, the first is a well established operation called vitrectomy, as described earlier in this document.  The second involves the delivery of radiation (epimacular brachytherapy) using the VIDION® System* device. The VIDION® System* device being used in this study has a CE mark – this means it is approved for use in wet AMD. As such the use of this device is not experimental, but the study aims to determine how this new treatment compares to standard treatment with Lucentis® alone.

Both vitrectomy and epimacular brachytherapy have risks.

Serious risks of vitrectomy are small, but exact figures are difficult to determine.  The serious risks listed below probably occur in less than 5% of people:
•    Retinal detachment (this probably occurs in less than 3% of people)
•    Development of glaucoma (increased pressure in eye)
•  Serious bleeding and/or infection inside or outside of eye including endophthalmitis (approximately 0.2% or less)
•    Long term loss of depth perception and double vision
•    Swelling of the center of the retina (cystoid macular edema)
•    Loss of the eye (extremely rare)

Tearing of the retina can occur but in most cases this is detected at the time of surgery and treated, such that it does not cause a problem.  Studies of epimacular brachytherapy surgery reported one retinal tear in 60 cases (1.6%).

Cataract: If you have not previously undergone cataract surgery it is likely that you will develop a cataract as a result of vitrectomy (cataract is a cloudiness of the lens in your eye). Studies in patients who underwent vitrectomy and epimacular brachytherapy found that 25% of patients developed cataract by 18 months, and 42% by 24 months.  Other studies of vitrectomy suggest that cataract may be more likely than this, approximately 90% within two years. If you develop a cataract you may require surgery to have this treated, however cataract surgery is usually very effective and has a low risk of complications.  It is usually undertaken as a daycase procedure and takes about 10 to 20 minutes If you have previously had cataract surgery you will not be affected in this way.

Minor complications include a corneal abrasion (scratch on the outside of the eye), but in most patients this heals over 24-48 hours and does not cause lasting problems.

Since the radiation will be delivered directly to the retina there are risks, although preliminary experience using epimacular brachytherapy suggests that radiation damage is extremely rare.  Nonetheless, sight threatening side effects of radiation may include:
•   Damage to the optic nerve (the nerve that attaches the eye to the brain), retina, and    choroid (layer of retina that contains blood vessels)
•    Cataract (cloudiness of the lens in your eye)
•    Glaucoma (an increase in the pressure in the eye)
•    It is also possible that a condition known as “radiation retinopathy” (abnormal changes in       the retina) could occur.
•    There is a risk of cancer from exposure to radiation but the radiation doses to the body       as a whole are very low.

Minor side effects could include discomfort from the procedure.

The complications listed above could lead to a mild, moderate or severe loss of vision that does not recover. There may other side effects of radiation that are not known at present.

Until this trial is completed, it is not known if epimacular brachytherapy offers patients a better, similar, or worse treatment outcome than Lucentis® alone.

Other Risks: If you become pregnant during the study, the treatment may involve risks to the foetus. You should be aware that there may be additional risks that are currently unknown and unforeseeable. For example, the risks of Lucentis® therapy after radiation delivery to the eye are not known. Your condition may not improve, or may worsen while participating in the study. 

Surgery with the epimacular brachytherapy (VIDION® System*) device will involve a local anaesthetic to numb the eye or a general anaesthetic.  There is a very small risk that the local anaesthetic could damage the eye, or that you could have an allergic reaction to the numbing drug. There is an extremely small risk that the drug could enter the blood stream or space around the nerve behind the eye causing problems with your heart beat or breathing. These serious reactions are extremely rare and treatment would be immediately available.  The risk of general anaesthetic will depend on your general health condition, but for most people the risk of serious or life-threatening adverse reactions are very low. If your general health is poor the anaesthetist will discuss the risks of general anaesthesia with you, and it may be decided that a local anaesthetic is more appropriate.  Some patients have transient nausea after a general anaesthetic. 

It is not known if your enrolment in this study will alter your premium or entitlement to medical care paid for by medical insurance companies and you should discuss this with your insurer before agreeing to take part.

If you develop new visual symptoms or pain at any time during the study you should inform the study doctors immediately.                                                                                    Back to Top

It is anticipated that the epimacular brachytherapy (VIDION® System*) device will reduce the frequency of Lucentis® treatment that you require. By reducing the number of Lucentis® injections you receive you will have a less burdensome treatment routine. As each Lucentis® injection involves risks, reducing the number of injections would be expected to reduce your risk of Lucentis®-related complications. Some patients may need no further Lucentis® injections, or far fewer than they would have required without the epimacular brachytherapy (VIDION® System*) device.  It is also anticipated, but not proven, that your vision would be better with this treatment than with no treatment at all.  It is not known if your vision would be better, the same, or worse than with Lucentis® treatment alone, but it is possible that this device gives a better final vision than Lucentis® treatment. It may also be that the device slows the rate of vision loss. You may not benefit from participation in this study.

This study may help provide information on whether the epimacular brachytherapy (VIDION® System*) device is safe and effective for other people with wet AMD.  

Some patients find it reassuring to be part of a study as they feel that their clinical care is more closely monitored, and treatment often occurs in experienced research centres. Patients involved in research may have access to new treatments before they are widely available.                                                                                                                        Back to Top

The healthy eye contains several types of cell that allow you to see.  In wet AMD there are abnormal new cells cause loss of vision. These in include new blood vessels, scar cells, and inflammatory cells. Lucentis® works by suppressing the growth of new blood vessels. Radiation preferentially damages growing cells and therefore has the potential to kill the range of abnormal cells that cause vision loss. Because the abnormal cells are killed, rather than suppressed, radiation has the potential to produce a more long lasting effect. 

We are exposed to radiation every day of our lives from both natural (sun, earth, etc.) and manmade sources. For example, smoking a pack of cigarettes is equal to receiving about 2.5 units of radiation. The average radiation dose from natural and manmade sources is about 300 units per year (600 units for 2 years).

Although the local therapy dose to the retina and nearby locations within the eye will be high, the effective radiation dose to your whole body will be less than 1 unit. By comparison, the radiation dose you will receive as part of this study is approximately 1/200 times the annual amount received by the average person living in a developed nation, which is well below the levels thought to result in a significant risk of harmful effects. The radiation dose mentioned is what you will receive from the research and procedure components of this study only and does not include any exposure you may have received or will receive in the future from other tests outside of this study. A brochure outlining the use of radiation in the eye is available on request.                                                                                                                          Back to Top

Mr Tim Jackson is the clinician who leads this study. He is employed by King’s College Hospital.  Patients in this study are being treated within the NHS, which funds the treatment they receive. 

The study is receiving funding from the Department of Health's National Institute for Health Research (NIHR). The NIHR is part of the Government's strategy - Best Research for Best Health, (Jan 2006) in which the NHS supports leading edge research focused on the needs of patients and the public.

The  company that manufactures the new treatment device (NeoVista™), has also provided resources to support the research.

This research study has been reviewed and approved by the South West Research Ethics committee. It has also been scientifically reviewed and approved by the Research and Development department at King’s College Hospital.                                             Back to Top

You are encouraged to discuss these with the Principal Investigator at your local recruiting hospital whose details are listed on this website (Recruiting Centres).  You may also like to discuss participation with your friends, family, and your family doctor.                   Back to Top