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Age-related macular degeneration
Consultant Ophthalmologist, Southampton Eye Hospital, Hampshire, UK
Executive Editor, InnovAiT
E-mail: one{at}rbnewsom.plus.com
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Abstract |
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 TOP Abstract The GP curriculum and...Presentation of macular...Classification of AMDTreatment of AMDFuture developments in treatmentReferences |
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Age-related macular degeneration (AMD) is the most common cause of blindness in the UK accounting for 16 000 registrations of blindness every year. One in fifty people over the age of 65 in the UK are blind in one or both eyes due to AMD. Macular degeneration is always a bilateral disease but one eye is usually more severely affected than the other. Smoking is the most important risk factor for development of AMD. The risk of developing AMD is 3.6 times greater for smokers and former smokers than those who have never smoked.
Rather oddly, in view of its importance as a major cause of blindness in the UK, age-related macular degeneration (AMD) is not listed as an important topic within the knowledge base of statement 15.5 of the GP curriculum (Eye problems). However, principles of management of any patient with eye disease presenting to primary care apply. GPs must be able to:
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Presentation of macular degeneration |
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TOPAbstractThe GP curriculum and...Presentation of macular...Classification of AMDTreatment of AMDFuture developments in treatmentReferences |
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Macular degeneration is difficult for GPs to detect in primary care as symptoms and signs are non-specific and often subtle in the early stages.
Around 25% of 75 year olds will have early signs—drusen and pigmentation of the macular. This is called age-related maculopathy or ARM. Around 10% of those patients then go on to develop macular degeneration which may be defined as ARM with visual symptoms. In all types of macular degeneration, there is deterioration and distortion of central vision. This affects reading and face recognition first and is worse with changes in lighting. A dark patch that rapidly fades may be noticed on waking. This is often interpreted as ‘seeing a shadowy figure’ and can be very frightening. With severe visual loss, patients may see visual hallucinations, usually of faces or stars. These can also be very frightening.
On examination, there is reduced acuity. This may be picked up during a routine optometrist examination. In severe cases, there may also be an afferent pupil defect and/or decompensated squint. Macular examination can be difficult, particularly within the confines of primary care where hand-held ophthalmoscopes are the norm and it is difficult to dilate the pupil. Even in ideal settings, there may be minimal signs. Look for macular drusen (yellow/white spots seen on the retina), pigment and subretinal haemorrhage (with or without oedema). The disc should look normal. Have a low threshold to refer any patient with recent loss in visual acuity for an ophthalmology review.
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Classification of AMD |
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TOPAbstractThe GP curriculum and...Presentation of macular...Classification of AMDTreatment of AMDFuture developments in treatmentReferences |
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AMD is a degenerative condition of the macula in patients over the age of 55 years, characterized by drusen and areas of retinal pigmentation.
All patients start with the ‘dry’ (or ‘geographic’ form)—Fig. 1. This is caused by atrophy of the neuroretina. The cells of the macula begin to break down causing yellowish white lipid deposits, or drusen, to begin forming beneath the retina. As the number and size of the drusen increase, there is gradual distortion and loss of central vision.
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About 1% of patients over the age of 75 develop ‘wet’ (or ‘neovascular’) AMD—Fig. 2. A ‘choroidal neovascular membrane’ (CNV) is formed as a result of relative ischaemia of the retinal pigment epithelium (RPE). The drusen lift the RPE off the choroid which contains its blood supply. As a result, vascular endothelial growth factor (VEGF) is released which causes blood vessels to grow out from the choroid under the RPE (Fig. 3). This may result in bleeding and scar tissue formation under the retina. Without treatment, most patients with CNV will go on to develop a ‘disciform scar’ in this way, resulting in severe and irreversible central visual loss—Fig. 2b. Wet AMD accounts for 50% of registrations of blindness due to AMD.
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Treatment of AMD |
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TOPAbstractThe GP curriculum and...Presentation of macular...Classification of AMDTreatment of AMDFuture developments in treatmentReferences |
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General measures
Although there is no effective treatment for dry AMD and disciform scar as a result of wet AMD is irreversible, treatment of other coexisting eye conditions, such as cataract or glaucoma, may help. Provision of visual aids, registration of blindness and social support are also important.
Registration of blindness is voluntary in the UK. Blindness is defined as inability to perform any work for which eyesight is essential—not the total absence of sight. In practice, this means:
- acuity of less than 3/60 or
- acuity better than 3/60 but worse than 6/60 with a very restricted visual field
Refer patients with low vision for assessment. Application is made by a consultant ophthalmologist to social services. Social services should offer every patient registered blind an assessment of needs. In addition, registration entitles the patient to benefits such as a disabled parking badge, reduced price television license and access to special educational facilities and visual rehabilitation programmes. Box 1 lists sources of information and support for patients.
| Box 1. Sources of information and support for patients with AMD Macular Disease Society, Information and support; Tel: 0845 241 2041, Website: www.maculardisease.org.uk Eye Care Trust, Patient information; Website: www.eye-care.org.uk Royal College of Ophthalmologists, Patient information; Website: www.rcophth.ac.uk Moorfields Eye Hospital, Patient information; Website: www.moorfields.org.uk/EyeHealth Royal National Institute for the Blind, Information and talking book service; Tel: 0207 388 1266, Website: www.rnib.org.uk Partially Sighted Society; Tel: 01302 323 132. Association for education, training and support of blind and partially sighted people; Tel: 0121 428 5037, Website: www.opsis.org.uk Department of work and pensions, Information on benefits and support available for blindness & partial sight; Tel: 0800 88 22 00, Website: www.direct.gov.uk/disability
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Treatment of wet AMD
In general, treatment is only offered to patients with active lesions and visual symptoms. Effectiveness of treatment is measured in terms of recurrence of CNV and visual loss on special vision assessment charts (Logmar charts).
Over the past 3 years, a flurry of new treatments for wet AMD have appeared on the market. These are taking over from more traditional treatments and show great promise in halting and even reversing visual loss.
Ranibizumab (Lucentis)—is a humanized mouse monoclonal antibody to all isoforms of VEGF. Initially, injections are given into the eye monthly for 3 months. Then the patient's visual acuity is monitored monthly. A further injection is given if there has been a drop in visual acuity of one Snellen line equivalent or greater. The MARINA trial (Fig. 4) showed that, at 12 months, 95% of patients had the same or better vision compared to 62.2% of controls. Of those treated with ranibizumab, one in four had significantly improved vision compared with 1 in 20 in the control group.
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Although ranibizumab is now the gold standard treatment of wet AMD, it has only recently been approved by NICE for NHS use in the UK. This is because of its cost. However, a landmark agreement has been struck between the Department of Health and the pharmaceutical company Novartis, so that Lucentis will be provided free of charge to the NHS to any patient after the first 14 injections.
Bevacizumab (Avastin)—is a humanized mouse monoclonal antibody to VEGF usually used for treatment of bowel cancer. Results of trials show that bevacizumab is of similar efficacy to ranibizumab in treatment of CNV. It is given either intravenously or as intraocular injections every 4–12 weeks depending on activity of the CNV. A head-to-head trial of ranibizumab and bevacizumab is underway.
Both these drugs may also be useful for patients with other retinovascular diseases such as central retinal vein occlusion and diabetic retinopathy. Trials are underway.
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Future developments in treatment |
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TOPAbstractThe GP curriculum and...Presentation of macular...Classification of AMDTreatment of AMDFuture developments in treatmentReferences |
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There are several trials underway looking at systemic therapy for wet AMD, thus reducing the risks from repeated intraocular injections. Most are assessing the role of other anticancer drugs in suppressing neovascularization.
Epi-Rads treatment is an exciting new treatment for wet AMD. The patient undergoes a vitrectomy. Following this, low-dose radiotherapy with Strontium 90 is delivered to the macular area together with a single dose of ranibizumab. Initial trials have shown that most patients have an improvement in vision at least as great as that seen with serial ranibizumab injections alone, and less than 1 in 10 having Epi-Rads treatment require further injections of ranibizumab thus saving 70% of the cost of treatment.
Key points
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References |
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TOPAbstractThe GP curriculum and...Presentation of macular...Classification of AMDTreatment of AMDFuture developments in treatmentReferences |
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Bird AC, et al. An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Survey of Ophthalmology (1995) 39(5):367–74.[Web of Science][Medline]
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Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, Venkatraman AS. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. Ophthalmology (2005) 112(6):1035–47.[CrossRef][Web of Science][Medline]
NICE. Macular degeneration (age-related)—ranibizumab and pegaptanib (2008) Accessed via www.nice.org.uk/nicemedia/pdf/TA155guidance.pdf [date last accessed 03.09.2008].
Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. In: New England Journal of Medicine (2006)) 355:1419–31. Accessed via http://content.nejm.org/cgi/content/full/355/14/1419 [date last accessed 24.09.2008].
Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surgery Lasers Imaging (2005) 36(4):336–39.
Nguyen QD, Shah S, Tatlipinar S, Do DV, Anden EV, Campochiaro PA. Bevacizumab suppresses choroidal neovascularisation caused by pathological myopia. British Journal of Ophthalmology (2005) 89:e1. Accessed via bjo.bmj.com/cgi/reprint/89/6/e1.pdf [date last accessed 24.08.2008].
RCGP. The GP Curriculum Statement 15.5—Eye problems. (2008) Accessed via www.rcgp-curriculum.org.uk/PDF/curr_15_5_Eye_problems.pdf [date last accessed 03.09.2008].
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