A patient with advanced AMD will have central distortion and a scotoma (dark spot) in their vision. Photo by Garo/Phanie/Rex Features
In his latest Clinical Update, Gary Culliton examines recent developments in the treatment of age-related macular degeneration (AMD), which is thought to affect one Irish person in 10, over the age of 50.
Leading cause of permanent eye impairment
Visual impairment has a huge negative effect on patients’ quality of life. It is associated with increased rates of depression, hip fractures, premature death and premature admission to nursing homes, due to loss of independence.
Age-related macular degeneration (AMD) is a degenerative retinal disease. It can cause central visual loss and lead to legal blindness. There are almost 14 million people affected.
There were almost two million people affected in 2000 in the USA and this is expected to increase to three million in the next eight years.
AMD gives rise to wide direct and indirect costs and is the leading cause of permanent visual impairment among those over 50 years old in the Western world. Risk factors for AMD include age, a poor diet (with a lack of anti-oxidants) and genetics.
Smoking is associated with a three-fold risk of developing advanced AMD.
Huge difficulties
A large study of elderly patients with AMD found the vast majority of them had huge difficulties compared to their peers, with shopping, managing money, housework, using the telephone and meal preparation. Consultant Ophthalmic Surgeon Ms Brid Morris spoke about pathology, treatment and prognosis in the area of AMD at St Vincent’s Private Hospital’s recent GP Education Evening.
Ms Morris described macular anatomy. The macula is the central part of the retina; the reason it is so important is that it contains the highest concentration of cone photoreceptors, which are responsible for fine vision. In AMD, Bruch’s membrane, the layer between the choroid and retina, thickens. This leads to the accumulation of lipids and extra-cellular material.
There are two types of AMD. In dry AMD, the accumulation of material leads to atrophy of the central retina.
In wet AMD, there is an increased expression of vascular endothelial growth factor (VEGF) in the eye. Blood vessels develop and break through the retina, bleed and cause distortion of vision.
Central distortion
A patient with advanced AMD will have central distortion and a scotoma (dark spot) in their vision. Dry AMD accounts for 90 per cent of all AMD but only accounts for about 10 per cent of serious visual loss. Generally, patients will not present acutely or sub-acutely, as it is very gradual in onset.
Dry AMD is characterised by drusen or yellow dots in the retina, as well as thinning and atrophy of the central retina. Wet AMD accounts for only 10 per cent of the disease but it is responsible for 90 per cent of severe visual loss in this condition. Patients present acutely or sub-acutely with distortion or decreased central vision due to the presence of fluid or blood.
Patients are examined on the slit lamp and further investigations include fluorescein angiography and Optical Coherence Tomography (OCT) tests. A fluorescein angiogram involves an injection of bolus dye, usually into an arm vein. Photographs are taken of the eye as the dye passes through the retinal circulation.
Fluid pooling
Any abnormalities due to breakdowns in the blood retinal barrier or other pathology are evident. A late-phase fluorescein angiogram may indicate obvious hyperfluorescence in the macula due to fluid pooling.
From the patient’s point of view, an OCT involves placing the chin on a chin-rest. The test takes a very short time and a laser scanning ray is used. A very fine cross-section of the retina is imaged; all the retinal layers and any pathology can be seen.
Recently, diabetic patients have received intra-ocular injections of anti-vascular endothelial growth factor (anti-VEGF) medicines. Anti-VEGF therapy has been hailed as possibly the greatest advance in the last decade in ophthalmology.
Anti-VEGF medications are administered via intravitreal injections under sterile conditions as a day-case procedure. Anti-VEGF works by binding the VEGF-A molecule and angiogenesis of the new abnormal vessels also decreases.
The sooner patients get the injection, the better, said Ms Morris. “Patients start losing vision from baseline. The gold standard would be to get them into the clinic and investigated with a fluorescein angiogram, OCT test and treated within a two-week period,” she said.
The natural history of wet AMD is for fibrosis and scarring to develop. The sooner the disease can be treated, to limit the scarring and dry up the fluids, the better for vision.
Infection is uncommon and occurs in about one case per thousand. Less common adverse events include inflammation, retinal damage and lens damage. Systemically, headaches, nasopharyngitis and arthralgia are sometimes reported.
Caution
Caution is however advised in administering such treatment in patients who have had a recent cerebrovascular or myocardial ischaemic event.
Prognosis for these patients is generally good — 90 per cent of patients who get injections will retain vision. Only 40 per cent of patients will improve vision significantly.
Vision is stabilised in AMD cases
Ms Morris cited the case of a man diagnosed with wet AMD in his left eye who was treated with anti-VEGF therapy. This was administered as seven individual injections to the left eye. His vision improved dramatically over a seven-month period, from counting fingers, to 6/18 (four lines on the Snellen chart).
A second case cited by Ms Morris was that of a 72-year-old female. She presented at a GP’s surgery with decreased vision in her right eye for one week. On examination, she could see 6/18 with the right eye and 6/6 with the left eye. She had tests, including a fluorescein angiogram. There was fluid under the retina and the diagnosis was wet AMD.
A course of five intravitreal anti-VEGF injections were given to the right eye. The patient dramatically improved from 6/18 (four lines of the Snellen chart) to normal vision and seeing all the way down the chart. The patient’s right eye remained stable.
However in January of this year, she re-presented with a two-line decrease in vision in her left eye. There was fluid present in her left eye and she is now undergoing a course of treatment to the left eye. While AMD may often be bilateral, the presentation may be asymmetrical.
Amsler grid
Patients are given an Amsler grid, involving lines and squares. The grid works for central vision but it has limitations and it is common for patients to have false positives using it. Many of the patients who use the grid will have some form of dry AMD and some impairment of central vision.
It is very important that patients recognise the symptoms, present early and are referred early. By and large, patients may only keep the vision they present with. Early treatment is thus important.
It is also important to explain to families that they may need maintenance and multiple injections for a period anywhere between one and three years.
Lose three lines
Studies looking at the natural history of AMD show that over a two-year period, untreated patients lose on average three lines of the chart. With treatment, they will either gain a little or retain vision.
“GPs should advise AMD patients and their families not to smoke (the biggest risk factor that may be addressed),” Ms Morris stressed.
A good diet with brightly-coloured and green vegetables, as well as oily fish twice a week, is very beneficial. Patients with intermediate or advanced AMD will generally commence on vitamin supplements in the eye clinic. Beta-carotene supplements would be avoided in former smokers.
Patients should be told they will not go blind, even if they get advanced AMD in both eyes. They will lose central vision but will always have peripheral vision. They will be able to navigate and find their way around. Those who still want to read should have a good reading light that comes right down to the print.
The eye clinic at St Vincent’s Hospital puts patients in touch with the National Council of the Blind of Ireland (NCBI)early, even though initially for some patients, there is some resistance to this.
The NCBI offers huge emotional and practical support.
Driving is not an option for many of these patients and they are told this and it is important that relatives back this up.
