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Age-related macular degeneration (AMD)
When we discuss Vision 2020,1 we think of the developing world where even a simple pair of spectacles is not an option for most of the population. However, in the UK it is the increased ageing population that poses the largest risk to 'the right to sight'. Also it appears that more effort and expense is put into glaucoma (at 4.7 per cent prevalence2) compared with AMD (at up to 27 per cent prevalence), both for over 65 years patient groups.3 When you talk to many patients in the later stage of the disease they often feel more could have been done, communication was poor and depression and anxiety have developed.4
So can we become better at identifying this disease in the early stages? There have been many risk factors identified and the most significant of those which are modifiable are cigarette smoking,5 blue light hazard6 and low macular pigment.7 Of those which are non-modifiable the most significant are increasing age, drusen and family history.8 How can we use this information? Regarding the modifiable, most optometrists in the past have been resistant to discuss lifestyle. However, if we are to be seen as healthcare professionals instead of simply spectacle sellers we must change our approach.
In Scotland I have sent a significant number of patients from my AMD clinic to my local pharmacist to discuss smoking cessation clinics which are free as part of a 'healthier Scotland' initiative, prior to introducing supplements. Interestingly, patients feel they should not pay for NHS nicotine patches as it is an addiction.
The so-called 'blue light hazard' has increased with the onset of the government initiative to reduce falls due to poor vision and provide fast-track cataract surgery to all suitable patients.9 Most of the IOLs do not contain a yellow filter to absorb UV as they can affect circadian photoreception and may be associated with sleep disturbance in patients after surgery.10 Combine this with an older patient base and the advancement of surgical procedures under local anaesthesia allowing nearly all patients a choice of surgery, we get an increase of oxidative damage to the retina.
Low macular pigment (MP) can be identified in practice either objectively using single wave fundus reflectometry (Zeiss Visucam11) or subjectively using heterochromic flicker (Topcon MPOD12). At this time the Zeiss instrument has no normative patient database and may be unable to measure MP in moderate to severe cataract patients. The Topcon instrument has a large normative database and, in my practice, gives valid and repeatable results in the hands of an experienced assistant similar to results obtained when measuring visual fields. Regarding non-modifiable risk factors, age and a positive family history in first-degree relatives are notable risk factors, and can increase the risk of developing AMD four-fold.13
Drusen have been shown to reduce in size with supplementation. More importantly we have to change our thinking that they are simply a benign consequence of ageing as we now know even the first drusen represents an inflammatory bio-marker which, if within the central arcades and in combination with other risk factors, may result in a cascade of the disease process.14
Research
It is now more than 10 years since the publication of AREDS 115 where it was shown that the use of general antioxidants vitamins C, E and beta carotene in combination with zinc reduced the progression of AMD in patients with extensive intermediate size drusen, at least one large drusen, non-central geographic atrophy in one or both eyes, or advanced AMD or vision loss due to AMD in one eye.
Following on from this was research into the retinal carotenoids lutein, zeaxanthin and meso-zeaxanthin, which constitute the MP. This is distributed centrally and decreases para-centrally being concentrated in the fibres of Henlé and outer axon segments of the photoreceptors. MP has a characteristic absorption peak at 460nm and is able to absorb high-energy blue light (400-500nm). MP is a powerful antioxidant, free radical scavenger and reduces chromatic aberration being entirely of dietary origin such as leafy green vegetables, yellow/orange fruits, and egg yolks. Meso-zeaxanthin is an isomer of zeaxanthin and is formed in the retinal tissue from lutein.16 While we await publication of AREDS 2 (which is investigating four sub-groups placebo; lutein and zeaxanthin; omega 3; lutein/zeaxanthin/omega 3) we already know of the benefits of these powerful anti-oxidants individually and it may be the case that the third group will show the best results of protection from a cumulative effect (www.areds2.org).
Case studies
Patient 1: Female, aged 76, positive family history, non-smoker; drusen seen peripherally on the fundus. An OCT scan captured an elevation in the RPE within the central arcades (Figure 1). Macular pigment measurement using an MPOD was performed and revealed an initial score of 0.30 (Figure 2). This is below the average of all patients who have had a MPOD measurements of mean 0.36 SD 0.17 (Figure 3) which compares favourably with a large published study of MPOD measurements mean 0.30 SD.12 Six months later the supplementation had improved the MPOD score to 0.45 (Figure 2) - VA stable, fundus appearance the same. Now one might say one drusen, grade 1 AREDS, why bother? However, drusen is not a dormant sign to be ignored. These are focal deposits of debris external to the RPE basal lamina and internal to the collagenous layer of Bruch's membrane. They contain acute phase reactants and are inflammatory markers as a result of oxidative injury and are the pathogenesis of AMD. They represent loss of photoreceptors, RPE cell dysfunction and reduced foveolar choroidal circulation. Again thinking about glaucoma this is like measuring the first subtle signs such as nerve fibre loss before a visual field defect occurs. This patient will be kept on the supplement and reviewed every 12 months.
Patient 2: Female aged 67, no family history, non-smoker; drusen seen on the fundus (Figure 4). Macular pigment measurement was performed using an MPOD and revealed her score was 0.46 within the range 0.2-0.5 and may require supplements. After informed consent macular supplementation was commenced using Nutrof Total. Thirteen months later the supplementation had improved the MP score to 0.64, VA improved from 6/9 to 6/6, fundus appearance revealed less drusen (Figure 5). Drusen can be seen to apparently resolve spontaneously,17 but this can be due to RPE atrophy (ie the drusen are still there but now hidden from view with a fundus camera/ophthalmoscope but not an OCT) and the VA may decrease. In this case the drusen disappeared centrally but VA and MP density increased. Also coalescent soft drusen can convert to isolated soft drusen or hard drusen, which represents less risk to central vision. This patient will be kept on the supplement and reviewed every 12 months.
Discussion
There is no magic tablet that will cure dry AMD. There are many supplements on the market, but this is a multi-factorial disease and advice about lifestyle changes, eg smoking, diet, exercise and UV protection, should also be considered. The case studies reveal improved macular pigmentation optical density (MPOD), decreased drusen and improved and stable VA with supplementation. However, this is not always the case and I have some patients who have lost VA on supplementation, often when the patient presented with more advanced disease. The question arises over what the VA would be now if I had not started supplementation. This is an evolving science but the fact is that the rise of the supplements is here to stay and I would urge fellow optometrists to start looking at this disease in a different light knowing that our direct influence could potentially improve a patient's quality of life significantly. ?
References
1 Foster A, Resnikoff S. The impact of vision 2020 on global blindness; Eye, 2005; 19, 1133-1135.
2 Klein BE, Klein R et al. Prevalence of Glaucoma - The Beaver Dam Eye Study; Ophthalmology, 1992; 99(10), 1499-504.
3 Lee PP, Zachary W et al. Longitudinal Prevalence of Major Eye Diseases; Archives of Ophthalmology, 2003; 121, 1303-1310.
4 Rovner BW, Casten RJ. Activity loss and depression in age-related macular degeneration. American Journal Geriatic Psychiatry, 2002; 10(3), 305-310.
5 Khan JC, Thurlby DA, et al. Smoking and age related macular degeneration: the number of packs of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation; Br J Ophthalmol, 2006; 90, 75-80.
6 Lu L, Hackett SF, Mincey A, et al. Effect of different types of oxidative stress in RPE Cells; J Cell Physiol, 2006; 206, 119-25.
7 Nolan JM, Stack J, et al. Risk factors for age-related maculopathy are associated with a relative lack of macular pigment. Exp Eye Res, 2007; 84(1), 61-74.
8 Smith W, Mitchell P. Family history and age-related maculopathy: blue mountains eye study. Clin and Exp Ophthalmol, 1998; 26(3), 203-206.
9 Harwood RH, Foss AJE, et al. Falls and Health status in elderly women following first eye cataract surgery; a randomised controlled trial; Br J Ophthalmol, 2005; 89, 53-59.
10 Mainster MA, Turner PL. Blue-blocking IOLs decrease photoreception without providing significant photo protection; Surv Ophthalmol, 2010; 55(3), 272-283.
11 Ivins P, McArthur C. Technology on test; Optician, 2011; 01.04.11, 18-22.
12 Van Der Veen RLP, Berendschot TTJM, et al. A new desktop instrument for measuring macular pigment optical density based on a novel technique for setting flicker thresholds; Ophthal Physiol Opt, 2009; 29, 127-137.
13 Klaver CC, Wolfs RC, et al. Genetic risk of age-related maculopathy. Population-based familial aggregation study. Arch Ophthalmol 1998; 116(12), 1646-51.
14 Hollyfield JG, Bonilha VL, et al. Oxidative damage-induced inflammation initiates age-related maculopathy. Nat Med, 2008; 14(2), 194-198.
15 AREDS Report No 8. A randomised, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene and zinc for age-related macular degeneration and vision loss; Arch Ophthalmol, 2001; 119, 1417-1436.
16 Sommerburg O, Keunen JEE, et al. Fruits and vegetables that are sources of lutein and zeaxanthin:the macular pigment in human eyes. Br J Ophthalmol, 1998; 82(8), 907-910.
17 Bressler NM, Munoz B, et al. 5-year incidence and disappearance of drusen and retinal-pigment epithelial abnormalities. Arch Ophthalmol, 1995; 113(3), 301-308.
? Spectrum Thea, Andy Clark's Practice Building and Topcon are holding an interactive AMD learning day on June 20; for bookings email emily.jones@spectrum-thea.co.uk or phone 0845 521 1290.
? Dr Scott W Mackie is an industry consultant and has his own practices in Glasgow