CET CONTINUING EDUCATION & TRAINING 1 FREE CET POINT Approved for: Optometrists 4 OT CET content supports Optometry Giving Sight Dispensing Opticians Having trouble signing in to take an exam? View CET FAQ Go to www.optometry.co.uk ✗ Dietary macular carotenoid supplements and drusen resolution 48 Course Code C-17541 O Shamina Asif, BSc (Hons), MCOptom, Dr John Nolan, BSc (Hons), PhD 09/12/11 CET If you have a patient whose visual acuity (VA) is decreasing year by year due Figure 1 The different types of free-radicals generated from oxygen15 lipid-containing residues of lysosomal digestion). Of note, the accumulation of to age-related macular degeneration (AMD) and the hospital eye service lipofuscin within the RPE cells increases (HES) has told them that ‘nothing can be done’, what advice would you give as a result of incomplete digestion of to the patient? In addition to discussing lifestyle changes such as smoking oxidatively cessation, ultraviolet (UV) protection and accessing low vision services, if appropriate, how many practitioners actively recommend the use of dietary supplements? Hopefully, by the end of this article, many more will understand the potential that nutritional supplements offer for this eye condition. AMD is now the leading cause of experiences with health professionals blindness world1 at the time of diagnosis because “they and its prevalence is likely to rise were not treated as a person”, making it as a consequence of increasing life more difficult to adapt to the condition. expectancy.2 Indeed, in 1933 just 6% of The the registered population in England and people were given more information Wales had ‘senile macular degeneration’ about the disease and the potential compared to nearly 50% in 1990.3 In the prevention/treatment options for AMD, UK, approximately 30,000 people are they would be more likely to adjust to registered blind or partially sighted every their situation, and it would enable year, half of whom will have AMD. With them to deal with the condition and respect to the visually consequential ultimately have a better quality of life. in the western stage of the disease, it has been estimated that 6-8% of people aged over 75 years suffer from visual problems due to AMD. If macular function is authors believe that if these What happens at the macula in AMD? damaged photoreceptor outer segment membranes. In turn, this yellow pigment then acts as a chromophore, a compound which, when irradiated with light of an appropriate wavelength, emits an electron, thereby generating reactive oxygen species (ROS). This provokes further oxidative injury. Of interest, ROS production (and, therefore, oxidative injury) peaks at the macula, where AMD manifests.4 Unfortunately there is no treatment that can restore vision in the dry, nonexudative form of AMD. For this reason there is a lot of interest in trying to prevent the disease from developing in the first place. Risk factors such as age, gender, family history (we now know the genes responsible for AMD), iris colour and refractive error are all examples of non-modifiable risk factors for AMD.6 However, there are degraded, The appearance of yellow-white lesions the ability to read, drive a car, and called drusen is usually the first clinical even recognise familiar faces can be manifestation lost. Many studies have shown that comprises a photoreceptor and axon- the quality of life of these patients is containing neurosensory layer with an significantly diminished, and patients underlying single-layer retinal pigment lose their social independence.4 Indeed, epithelium (RPE). The function of the RPE it was reported that over 60% of people is to nurture and remove waste products Macular pigment who were told ‘nothing can be done from the neurosensory retina. AMD is Macular pigment is yellow in colour and about your macular disease’ suffered characterised by loss of photoreceptors is housed in the fovea, where we have from anxiety and/or depression, and and by RPE cell dysfunction, the latter sharpest VA and colour appreciation 54 out of 1,421 people reported feeling being largely attributable to an age-related (it is found in the inner retinal layers suicidal.5 The same study found that accumulation (yellow- and the fibres of Henley).7,8 It is made most patients reported unsatisfactory brown pigment granules representing up of three carotenoids (from a total of of of AMD. The lipofuscin retina many modifiable risk factors that can be controlled, which forms the basis of preventative measures an individual can take. Importantly, smoking cessation and diet are two important modifiable risk factors for Find out when CET points will be uploaded to Vantage at www.optometry.co.uk/cet/vantage-dates AMD. 600 naturally occurring carotenoids) segments are rich in polyunsaturated fatty and these include lutein, zeaxanthin, acids (PUFAs), such as docosahexaenoic The correlation between AMD and carotenoids and meso- acid (DHA), compounds that represent an The investigators of the Eye Disease The density is at a ideal substrate for oxidative damage.11,16 Case Control Study23 found that the maximum at the centre of the fovea and The macular pigment serves to combat higher the levels of antioxidant micro- central zeaxanthin. 9,10 component blue nutrients, especially the carotenoids, and zeaxanthin cannot be synthesised light; it has peak absorption at 460nm the more protection there is against by the body and are therefore entirely and a broad spectrum, ranging from neovascular AMD. However, it was of dietary origin.12 Meso-zeaxanthin zero to about 560nm. The orientation a later study24 that discovered that is primarily formed in the retina of macular pigment is optimised to the highest correlation of disease following conversion from lutein, but enhance light absorption11 and because prevention was with the intake of is an important component of macular of the way the macular pigment is 6mg per day of lutein and zeaxanthin, pigment because of its unique central distributed which location. It is the strongest antioxidant cells, each cell screens other cells as of the macular carotenoids and allows well as itself. The macular pigment has for investigate which foods had the highest this decreases peripherally. 11 Lutein oxidative stress by absorbing 17 through photoreceptor resulted in a reduction in prevalence of AMD by 43%. The authors then went on to of damaging also been shown to have antioxidant (blue) light.13 capabilities, by itself donating electrons amount of lutein and zeaxanthin, Macular pigment is believed to have to free radicals in order to stabilise them and found that the consumption of and thus prevent damage to RPE cells. spinach in particular was associated optimal filtration short-wavelength a protective role in AMD mainly due 18 with a significantly reduced risk of to its light-filtering and antioxidant properties. 11,14 As the wavelength of light in the visible spectrum is reduced (i.e. shorter), retinal damage increases exponentially.14 In fact, 100x less energy is required to produce detectable damage at 440nm than at 590nm. This is known as the blue light hazard7 and retinal damage occurs due to the AMD. Subjects in the study group that Diet, plasma carotenoids and macular pigment Most studies19,20 have shown had the highest spinach consumption that increasing dietary intake of fruits and vegetables high in the carotenoids leads had an 86% lower chance of AMD as compared to the study group that had the lowest spinach consumption.24 to an increase in concentration of lutein in blood plasma. This relationship The AREDs trial is that In 2001, the Age-Related Eye Disease production of free-radicals (hydrogen measurements of such carotenoids in Study (AREDS) was published, having peroxide and singlet oxygen) (Figure 1). the plasma can be used as an indicator been conducted by the National Eye Free radicals have one or more of fruit and vegetable consumption and Institute (NEI). This was a double- unpaired electrons, making them have a vice versa. Furthermore, dietary intake masked, strong tendency to find and pair with an and serum carotenoid concentrations are controlled trial of 4,757 subjects over electron from substances such as lipids positively related to a person’s macular a period of five years. In brief, it was (known as lipid peroxidation), proteins, pigment level (this is not surprising shown that supplementation with carbohydrates and nucleic acid, resulting given that macular pigment is entirely vitamins C and E, beta-carotene, and in damage to biological molecules. Free of dietary origin).21 For example, in zinc in combination resulted in a radicals are also produced from oxygen subjects who took 30mg of lutein per 25% risk reduction of progression to metabolism, which is required for day for 140 days, the serum levels of advanced AMD. Of note, the AREDS normal cell function and life (i.e. free lutein increased from 0.13µg/ml to did not supplement with any of radical production cannot be avoided 0.93µg/ml within 20 days. The authors the macular carotenoids, primarily and is the “cost of living”). The retina also found that macular pigment in because these compounds were not is ideally suited for the production of the retina increased by 20-40%. As a available in supplement form at the free radicals, due to its high oxygen result, the authors calculated a 30-40% inception of that study. The study demand, exposure to light, metabolic reduction in blue light transmitted groups activities (such as RPE phagocytosis), to photoreceptors, antioxidants (vitamin C, vitamin E and its abundance of photosensitisers. Bruch’s membrane and RPE – the and beta-carotene), or antioxidants Furthermore, the photoreceptor outer tissues plus zinc, or zinc alone, or a placebo.25 strong the enough macular usually to suggest affected in AMD. 22 49 For the latest CET visit www.optometry.co.uk/cet randomised, were assigned placebo- to taking 09/12/11 CET its CET CONTINUING EDUCATION & TRAINING 1 FREE CET POINT Approved for: Optometrists 4 OT CET content supports Optometry Giving Sight Dispensing Opticians ✗ Having trouble signing in to take an exam? View CET FAQ Go to www.optometry.co.uk risk of developing this condition, with information of ways to help them reduce the risk of this condition progressing or developing. The case studies below are in support of such a notion. Case study one 50 A 64-year-old woman, who drove, did voluntary work at the local hospice, and enjoyed walking and gardening, was seen for a routine sight test for the Figure 2 Case study 1: macula appearance in September 2009 (see text for details) first time in five years on 13/02/2009. Her general health was good and the 09/12/11 CET only medication she was taking was cocodamol for hip problems. Her mother suffered from advanced (wet) AMD, so she had a confirmed family history. The patient used to smoke about 10 cigarettes per day from the age of 17 to the age of 55 years, but gave up once her husband stopped smoking. The patient reported that her diet had always been good. On examination, she was found to have soft confluent drusen at the macula in both eyes (Figure 2). Figure 3 Case study 1: macula appearance in March 2010 (see text for details) Her best corrected vision at this stage was RE: 6/6- and LE: 6/6+, whilst there was corresponding distortion on Amsler chart investigation. As a result, this patient was referred to the HES, who later confirmed that she had dry AMD; she was discharged without treatment or any recommendations on lifestyle or nutrition to help prevent the disease progressing. The patient conducted research on the Internet and read may help that taking to stabilise supplements the AMD. Since September 2009, this woman Figure 4 Case study 1: macula appearance in March 2011 after intake of dietary supplements (see text for details) had been taking a dietary supplement The AREDS 2 is an ongoing multi- the outcome of AREDS 2 (expected (commercially known as Macushield). centre trial at the end of 2012) and other clinical On the 02/03/2010 this woman was designed to evaluate the effect of trials studying the macular carotenoids, seen for a follow-up sight test at which supplemental lutein and zeaxanthin the authors feel that it is important there was evidence of drusen resolution (and/or omega-3) with respect to the that eye care professionals furnish (Figure 3). Importantly, the patient’s progression of AMD. While we await patients with AMD, and individuals at best corrected vision at this examination randomised controlled containing zeaxanthin the and carotenoids lutein, meso-zeaxanthin Find out when CET points will be uploaded to Vantage at www.optometry.co.uk/cet/vantage-dates was RE: 6/6 and LE: 6/6, and there was no distortion reported on Amsler chart investigation. At the most recent eye examination on 08/03/2011, the patient’s best corrected vision was RE: 6/5 and LE: 6/5, and the drusen has resolved further, as shown in Figure 4. The 51 patient herself felt that her “vision had noticeably improved”. In this particular case, the only variable that had changed in the past two years was the intake of supplementation every day. Case study two Figure 5 Case study 2: macula appearance in 2008 (see text for details) 09/12/11 CET dietary This 64-year-old woman who was a retired classroom assistant had always had good general health, had never smoked and had not been on any longterm medication. She was diagnosed with dry AMD in 2004. She then presented for a sight test in 2008, and was referred to the HES for suspected wet AMD in the LE (Figure 5). Her VA was RE: 6/10 and LE: 6/10. The HES planned to administer Lucentis injections. However, by the time the patient was allocated an appointment, they noted that the exudation had ceased and the Figure 6 Case study 2: macula appearance in March 2011 after intake of dietary supplements (see text for details) patient was therefore discharged. At this moment in time the patient decided to Discussion start taking 20mg of lutein every day. In both of the cases reported here, the the Prior to this, the patient had been taking drusen was initially of the soft confluent carotenoids against AMD. These case generic supplements. type, which is more likely to progress studies, combined with findings emerging multi-vitamin are consistent with research that suggests potential protection of macular In January 2010 her VA in her right to advanced AMD. Since taking dietary in the past two years, contribute to the eye had improved to 6/7.5 and there supplements containing the macular evidence around AMD and carotenoids. was a further improvement to 6/6- carotenoids over a relatively short time However, the results of gold standard 1 when she was reviewed again in period (18-24 months), there are notable clinical studies are required, and are March 2011; there was a corresponding areas of the macula where the drusen has awaited, in order to gain further support reduction in macular drusen too, as completely resolved, whilst in other areas for the use of dietary supplements for shown in Figure 6. The LE VA has not it has become discrete and hard, which is AMD, but there is growing evidence and improved even though there is drusen less likely to progress to advanced AMD. it is, perhaps, only a matter of time. At resolution. This woman had herself Many optometrists will be familiar with present, eye care professionals have a noticed that her vision iwas getting fundus images showing progression duty to make informed recommendations better, and she reported that she could of AMD but discovering two cases of for patients at risk of AMD, regarding the now do cross stitching again. She also AMD getting better is quite remarkable! use of appropriate dietary supplements always made an effort to wear sunglasses for AMD (e.g. a supplement containing when outdoors and would continue to Conclusion the macular carotenoids), along with take macular carotenoid supplements. The case studies reported in this article positive lifestyle changes (e.g. smoking For the latest CET visit www.optometry.co.uk/cet CET CONTINUING EDUCATION & TRAINING 1 FREE CET POINT Approved for: Optometrists Having trouble signing in to take an exam? View CET FAQ Go to www.optometry.co.uk ✗ is also Chair of the Dudley LOC and Howard Fellowship by the Howard protection). So the next time you a council member for the College of Foundation at Cambridge University, see a patient with AMD, will you Optometrists, representing the West UK. He is a key opinion leader on the consider and weight control authors and carotenoids Midlands. Dr John Nolan is a senior subject of macular pigment and AMD, supplementation? scientist and director of the Institute and has been invited to speak at over certainly of Vision Research and the Macular 40 international scientific conferences Pigment Research Group (MPRG). His and has published over 30 scientific PhD study, entitled “Determinants of peer-reviewed publications on the topic. recommending dietary These 09/12/11 CET Dispensing Opticians UV cessation, 52 4 OT CET content supports Optometry Giving Sight will. About the authors Shamina Asif is an optometrist working macular pigment in healthy subjects”, at the Merry Hill Centre, Dudley. She was the largest cross-sectional study References was awarded an academic prize for of its type in the world. Dr Nolan See the best mark in her Elective Studies was awarded a Fulbright scholarship clinical/index. Click on the article title looking at AMD and nutrition. She and in May 2010 he was awarded a and then download “references”. Module questions http://www.optometry.co.uk PLEASE NOTE There is only one correct answer. All CET is now FREE. Enter online. Please complete online by midnight on January 6, 2012 – You will be unable to submit exams after this date – answers to the module will be published on www.optometry.co.uk. CET points for these exams will be uploaded to Vantage on January 16, 2012. Course code: C-17541 O 1. Which of the following foods has the highest amount of lutein/ zeaxanthin? a) Broccoli b) Brussel sprouts c) Spinach d) Coriander 2. Why were lutein and zeaxanthin not included in the AREDS trial? a) There was no known link between lutein/zeaxanthin and AMD prevention b) They were too expensive to use c) Lutein and zeaxanthin had not been discovered at the time d) They were not readily available in supplement form 3. The peak wavelength of absorption of macula pigment is: a) 460nm b) 490nm c) 520nm d) 560nm 4. Which of the following is NOT a non-modifiable risk factor for AMD? a) Iris colour b) Age c) Gender d) Diet 5. How does the macula pigment protect against AMD? a) It causes lipid peroxidation b) It stabilises free radicals by donating electrons c) It reduces oxygen consumption in the retina, reducing free radical production d) Its absorption spectrum peaks at 560nm hence absorbing the blue light hazard 6. What does the macula pigment consist of? a) Lutein and meso-zeaxanthin b) Beta-carotene, lutein and zeaxanthin c) Lutein, zeaxanthin and meso-zeaxanthin d) Meso-zeaxanthin, lutein and beta-carotene Find out when CET points will be uploaded to Vantage at www.optometry.co.uk/cet/vantage-dates