Age-related macular degeneration (AMD) is the most common cause of blindness in the UK and the Western world.1 As discussed in the previous article there are two types; dry and wet. The majority of cases are the dry form associated with gradual vision deterioration in contrast to the sudden visual loss with distortion often associated with the wet type.
Although there are a number of potential options for treatment of wet AMD, this is not the case for the dry type. As discussed in detail in the previous article in this series it is thought that factors including causative genes, oxidative stress, an inappropriate immune response, deficiency of antioxidants and micronutrients have a role in AMD disease development.2 Patients with dry AMD may benefit from taking nutritional supplements.
The AREDs study found that a supplement comprising vitamin C, vitamin E, beta-carotene, zinc and copper significantly reduced the progression rate and extent of visual loss of individuals with intermediate or advanced AMD over a five-year time frame.2,3 It is important to check there are no contraindications.
An example is the link between high-dose beta-carotene and the increased chance of lung cancer development in smokers in which instance a supplement containing beta-carotene may not be advisable.3 However many manufacturers have taken this into account and excluded beta-carotene from their multi-supplement formulations. More recently the AREDS 2 study published its results. Based on the evidence of this trial, lutein, zeaxanthin and omega 3 fatty acids have been added to AREDS supplements without the beta carotene.4
The modified formulation is as follows: 500mg Vitamin C, 400 International units Vitamin E, 25 mg zinc, 2mg copper (cupric oxide), 10mg lutein, 2mg zeaxanthin and 1000 mg of omega-3 fatty acids, these comprising 350 mg docosahexaenoic acid (DHA) and 650 mg eicosapentaenoic acid (EPA).5 Smoking increases the risk of developing AMD by three times.6 Patients who smoke should be informed regarding smoking increasing the risk of AMD development and progression, though it is obviously their choice whether they reduce the number of cigarettes they smoke or stop altogether.
Clinical assessment
Photography
Fundus photography is useful in establishing a visible baseline in patients with dry AMD if available. Findings can be compared at future visits to determine if the condition is progressing more effectively than written records alone that are prone to subjective variation. Studies have shown that the likelihood of dry AMD progressing to wet over a five-year time frame is between 14 per cent and 20 per cent.7 Patients more at risk include those with moderate dry AMD according to the AREDs study classification (many medium-size drusen or one or more large drusen in one or both eyes) or individuals who have a history of wet AMD in the other eye.8 Figure 1 shows an image allowing drusen size and number to be evaluated.
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Autofluorescence
Autofluorescence imaging (photo) is a very useful way of monitoring the progression of dry AMD. It measures the re-emission of light by fluorophores (such as lipofuscin, a metabolic waste product) when they are subjected to light of a specific wavelength. Increased fluorescence can indicate lipofuscin accumulation in early-stage AMD, a predecessor of increased RPE and photoreceptor cell death (atrophy) indicating dry AMD progression.9 After extensive cell death (geographic atrophy in advanced AMD) the lipofuscin levels drop, resulting in reduced autofluorescence and a corresponding macular dark area on the retinal image – see Figure 2. The benefit of any potential future treatments could be monitored using this modality of imaging the fundus.
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A comprehensive examination should be performed on patients with signs of AMD. Wet AMD should be ruled out as much as possible by a slit lamp biomicroscopy with a 60, 66 or 78D lens. Binocular stereoscopic fundus examination can detect elevation of the retinal layers – see Figure 3 below.
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This may be due to active choroidal neovascularisation (CNV) resulting in intraretinal fluid accumulation (cystic changes) causing macular oedema, build up of subretinal fluid or leakage below the retinal pigment epithelium.10 Such changes in one eye may result in a uniocular hyperopic shift and the patient may report a recent acute onset of blurred central vision or metamorphopsia.11 On fundus examination CNV may present as a grey-green membrane situated beneath the retina see Figure 4. Exudates and/or haemorrhages (subretinal, intraretinal or retinal) may be present around the macula.
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Amsler
Monocular testing with the Amsler grid (using the patient’s reading prescription) may reveal areas of metamorphopsia and field loss (scotoma).3 However mild distortion of the Amsler grid may be observed that is due to the presence of drusen only.3 Individuals should also be asked about any changes in their vision and symptoms they are experiencing. A drop in visual acuity and an acute onset of visual distortion such as doorframes appearing bent would also raise suspicions regarding early wet AMD. The above clinical signs and symptoms in a new case of potential wet AMD would indicate the need for urgent referral.11
OCT
Ocular coherence tomography (OCT) can greatly aid differential diagnosis in practice if available. A macular scan can be performed which shows a cross-sectional image of the different retinal layers of the fovea and surrounding area due to their varied reflectance properties. The presence of fluid associated with leakage from neovascularisation in wet AMD can occur intraretinally, subretinally or below the RPE and present as dark (hyporeflective) areas.10
OCT also can help with the detection of subtle pigment epithelium detachments (PEDs), separation of the RPE from the underlying Bruch’s membrane. Although they are seen in a number of other conditions, including central serous chorioretinopathy and CNV due to other conditions such as angioid streaks, Figure 5, they are also associated with wet AMD. PED may be observed on a macula OCT scan as single or multiple RPE elevations.12 The RPE in these locations is hyper-reflective. If serous fluid has accumulated beneath, this presents as an optically empty space (serous PED). This may be due to serous exudation from new choroidal vessels in wet AMD.13 Alternatively a haemorrhagic PED results from the subretinal pooling of blood that tends to block hyper-reflective tissue. However in this type of PED the reflectance of the underlying choroid is reduced due to light scatter from the accumulated blood.14
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Fibrovascular and haemorrhagic PEDs are usually associated with various types of CNV.15 The former are thought to occur following the proliferation of CNV under the RPE (occult CNV) rather than growing through focal breaks in Bruch’s membrane, proliferating between the RPE and retina and subsequently leaking (classic CNV) – see Figure 6.16 The fibrovascular tissue can be viewed as a hyperreflective area below the RPE. Haemorrhagic PEDs are more characteristic of a subtype of wet AMD called polypodal choroidal vasculopathy where reddish orange aneurysmal dilatation as well branching vascular networks occur in the choroidal circulation resulting in exudation and subretinal haemorrhage.17
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Intraretinal haemorrhages can occur as a result of the initial neovascularisation occuring intraretinally as opposed to subretinally before establishing contacts with the choroidal circulation (chorioretinal anastomoses). This is known as retinal angiomatous proliferation (RAP) and comprises 10-15 per cent of cases of wet AMD and is commoner in females as well as very elderly patients.18 Drusenoid PEDs are comprised of confluent soft drusen and tend not to be homogenous in terms of hyperreflectivity on the OCT scan. PEDs are associated with a poorer prognosis with regards to AMD development.19 As many as 62 per cent of eyes with advanced AMD will demonstrate PEDs. Among those newly diagnosed with PED, half will have lost in excess of 3 lines of vision within a year.20 If there is any doubt regarding the presence of wet AMD in patients with PED they should be referred for further urgent ophthalmological investigation – see Figure 7.
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OCT is also helpful in distinguishing drusen from cotton-wools spots and hard exudates. Drusen appear as focal elevations of the hyper-reflective band of the RPE. Hyper-reflective cotton-wool spots are situated at the superficial nerve fibre layer. Exudates located in the middle outer plexiform layer.21 Exudates are a consequence of plasma leakage from vessels and, as well as being a characteristic of many vascular diseases such as diabetic and hypertensive retinopathy, they are also associated with CNVM development in wet AMD.1 OCT also enables monitoring of treatment effect with any change in retinal thickness from baseline.
Early treatment of wet AMD is associated with a better prognosis so urgent referral on diagnosis is mandatory. This varies in different areas. Birmingham has a fast track wet AMD service in place. A specialised referral form is completed and the service contacted prior to faxing them the referral. They subsequently contact the patients with an appointment for further assessment and treatment. Guidelines issued by the College of Optometrists and Royal College of Ophthalmologists recommend that treatment should take place within two weeks of the initial diagnosis.6 In the next article in this series we will discuss treatment options in more detail.
References
1 The Royal College of Ophthalmologists. Age-related macular degeneration: Guidelines for Management 2013.
2 Damico FM, Gasparin F, Scolari MR, Pedral LS, Takahashi BS. New approaches and potential treatments for dry age-related macular degeneration. Arq Bras Oftalmol, 2012;75(1):71-6.
3 Binns A. Assessment and Management of AMD. Optometry Today, 2011;p52 -56.
4 Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA,2013 May 15;309(19):2005-15
5 National Eye Institute. Age-Related Eye Disease Study 2 (2013).
6 The College of Optometrists. Commissioning better eye care. Clinical commissioning guidance from the College of Optometrists and the Royal College of Ophthalmologists. Age Related Macular Degeneration. Version1. 2013.
7 Gurwood AS, Hutchinson JK, Myers MD. AMD: Counteracting Conversion. Optometric Management 2011.
8 The AREDS system for classifying age-related macular degeneration from stereoscopic fundus photographs. AREDS Report No 6. Archives of Ophthalmology, 2001;132: 668-681.
9 Wu L. Use of Fundus Autofluorescence in AMD 2012. Retina Today.
10 Regatieri, CV, Branchini L, Duker JS. The Role of Spectral-Domain OCT in the Diagnosis and Management of Neovascular Age-Related Macular Degeneration. Ophthalmic Surg Lasers Imaging, 2011; 42(0): S56–S66.
11 Creer R, Parkes J, Charles S, Harper R. Optometric management of Age-related macular degeneration: Referral and Referral Refinement Pilot Surveys.Optometry in Practice, 2010;11:13-25.
12 Todorich B, Mruthyunjava P. Pigment Epithelial Detachments and Age-Related Macular Degeneration. 2014: 65.
13 Coscas F, Coscas G, Souied E, Tick S, Soubrane G. Optical coherence tomography identification of occult choroidal neovascularisation in age-related macular degeneration. Am J Ophthalmol, 2007;144:592-599.
14 Arevalo JF.Gracia RA. Chapter 13. Clinical Applications of Ocular Coherence Tomography in Age-related Macular Degeneration. In: Retinal Angiography and Ocular Coherence Tomography. Ed Gracia RA 2009 Springer p256.
15 Kanski JJ, Bowling B. Acquired macular disorders. Age-related macular degeneration. In: Synopsis of Clinical Ophthalmology, 3rd Ed. 2013 Elsevier Saunders p271.
16 Wachtlin J. 3.4 Classic Choroidal Neovascularisation. In: 3. Age-Related Macular Degeneration and Choroidal Neovascularisation of Other Etiologies. Heimann.
17 T H Lim, A Laude and C S H Tan. Polypoidal choroidal vasculopathy: an angiographic discussion. Eye, 2010;24: 483–490; doi:10.1038/eye.2009.323.
18 Heidelberg Engineering. Retinal Angiomatous Proliferation (RAP).
19 Talu SD. Optical Coherence Tomography in the Diagnosis and Monitoring of Retinal Diseases. Biomedical Imaging, 2013.
20 Todorich B, Pepple K, Mruthyunjaya P. Treatment of Pigment Epithelial Detachments in Age-related Macular Degeneration. A significant cause of visual morbidity in neovascular AMD, PEDs remain a treatment challenge 2012. Retinal Physician.
21 Zaharova E, Sherman J. The use of SD-OCT in the differential diagnosis of dots, spots and other white lesions. Eye and Brain, 2011.
Louise Stainer is a hospital optometrist at Optegra Eye Hospital, Birmingham where Salman Mirza is a consultant ophthalmologist
Model answers
(The correct answer is in bold text)
1. OCT would not be useful tool in which of the following?
A. Establishing a baseline regarding retinal thickness
B. Determining the anatomical success of treatment of wet AMD with regard to presence of fluid
C. Helping to distinguish wet AMD from other differential diagnosis
D. Assessing the origin of a pre-retinal haemorrhage
2. Fluorescein angiography gives information regarding all but one of the following. Which one?
A. characteristic leakage patterns of CNV
B. components of the CNV lesion
C. location of the CNV
D. whether drusen are discrete or ‘soft’
3. PEDs are due to
A. A split between the neurosensory retina
B. A split between the neurosensory retina and RPE
C. A split between Bruch’s membrane and RPE
D. A split between Bruch’s membrane and choriocapillaris
4. Fibrovascular PEDs are associated with
A. Occult CNV
B. Classic CNV
C. Disciform scarring
D. Drusen
5. What percentage of dry AMD patients develop wet AMD over a five year time frame?
A. 14-20%
B. 20-25%
C. 25-30%
D. over 35%
6. Which of the following statements about retinal angiomatous proliferation is true?
A. It has no gender bias
B. It is more common in the very elderly
C. It comprises 15 per cent of atrophic AMD
D. It originates in the choroid