AusPharm CPD Age related Macular degeneration 5/11/2015

Transcription

1 Age-related Macular degeneration Age-related macular degeneration (AMD) is a degenerative disorder affecting the central part of the retina responsible for central sight. It affects the ability to read, drive, recognise faces and perform activities requiring detailed vision. AMD can occur in one eye or both. A patient can have early AMD in one eye and late AMD in another. The presence of late AMD in one eye increases the risk of late AMD developing in the other. AMD affects one in seven Australians older than 50 years of age, about one million people, and is the leading cause of vision loss in Australia. The prevalence is expected to double with the ageing of the population. Learning objectives After completing this activity, pharmacists should be able to: Describe the incidence of macular degeneration List risk factors for macular degeneration Describe the differences between dry and wet macular degeneration Assess the role of antioxidant vitamins in the management of dry macular degeneration Discuss the pharmacological treatments available for the management of wet macular degeneration. Successful completion of this activity is demonstrated by answering eight of the ten multiple choice questions correctly. Accreditation number: A1511AP1. This activity has been accredited for 1 hour of Group 1 CPD (or 1 CPD credits) suitable for inclusion in an individual pharmacist s CPD plan which can be converted to 1 hour of Group 2 CPD (or 2 CPD credits) upon successful completion of relevant assessment activities. The 2010 Competency Standards addressed by this activity include (but may not be limited to): 4.1, 4.2, 7.1, 7.2, 7.3, 8.1 Author: Jenny Gowan PhD, Grad Dip Comm Pharm, PhC, FACPP, FPS, AACPA, MSHPA Jenny, is a practicing consultant pharmacist, MediCom Medication Management Services, a Teaching Associate in the Faculty of Pharmacy & Pharmaceutical Sciences, Monash University and Australian Pharmacist of the year, She originally trained in New Zealand and completed her PhD at Monash University Her areas of interest include: aged care, asthma, arthritis, drugs and driving, new drugs and guidelines, non-prescription medicines, primary health care, medication management, medical and pharmacy education. She has presented hundreds of lectures, in Victoria, Australia and internationally. She has published over 280 papers and educational articles, one book, and three book chapters. AusPharm gratefully acknowledges the financial support provided by the sponsors of our CE program, MIMS.

2 Introduction Age-related macular degeneration (AMD) is a degenerative disorder affecting the central part of the retina responsible for central sight. (1, 2) It affects the ability to read, drive, recognise faces and perform activities requiring detailed vision. AMD can occur in one eye or both. A patient can have early AMD in one eye and late AMD in another. The presence of late AMD in one eye increases the risk of late AMD developing in the other. AMD affects one in seven Australians older than 50 years of age (about one million people) and is the leading cause of vision loss in Australia. (1) The prevalence is expected to double with the ageing of the population.( 2) Most patients suffer from dry macular degeneration (MD), resulting in a gradual decline of central visual function over many years. About 15% will suffer from wet, or exudative macular degeneration in which vision loss can occur suddenly due to bleeding within the macula. If untreated, this exudation leads to distortion and loss of the central vision. Up until five years ago, wet AMD had limited treatment options with 75% of patients being classified as legally blind three years after diagnosis.( 2) In older persons visual impairment combined with other co-morbidities leads to increased falls, hip fractures, a need for increased community support and aged care home placements and increased mortality. Risk factors Age: The rate of MD increases dramatically with age however MD is not an inevitable consequence of ageing Family history: There is a 50% risk of developing MD if a family history is present. Up to 70% of cases have a genetic link Smoking: The risk of developing MD is increased 3 to 4 times in smokers. Smokers get MD 5 to 10 years earlier, on average but 20 years after quitting, an ex-smoker s risk is the same as someone who has never smoked. (1) Other risk factors include excessive alcohol, obesity, lack of exercise and other cardiovascular risk factors.( 1) Aspirin and AMD A recent study reported an apparent association between long term aspirin use and the development of age-related macular degeneration (AMD). (3) This was a prospective population-based cohort study involving 2,389 people, of whom 257 were identified as regular aspirin users. Participants were followed over 15 years, during which time 63 individuals out of the 2389 in the cohort had developed incident wet AMD. Results showed a small increase in risk for AMD in the regular aspirin users relative to non-regular users. However, due to various study characteristics, conclusive findings have not been drawn from this association. The evidence is not considered strong enough to recommend a change in current clinical practice in relation to aspirin use for the secondary prevention of cardiovascular disease. (4) Pathogenesis There are several theories surrounding the pathogenesis of AMD, including vascular, inflammatory and immune insults on the retina. The cause remains multifactorial and elusive, with studies suggesting a complex interplay of environmental and genetic factors.( 2) Family history of AMD is a strong risk factor and has been shown to be present in more than 20 per cent of cases. (2)

3 Genetic factors: The Centre for Eye Research in Australia (CERA), Macular Research Unit, centred at Melbourne University has a strong interest and track history in genetic studies related to AMD. The current studies into AMD genetics include: 1. Genetic analysis in age-related macular degeneration, including genetic associations with AMD and the risk of progression to advanced disease. 2. The influence of genes on treatment outcomes for neovascular AMD 3. The interaction between genetics and environment in AMD. (5) The LEAD trial (Laser intervention in Early Age-related Macular Degeneration) is the first, multicentered, randomised, controlled trial of nanosecond laser intervention in high-risk, early AMD to delay progression. (5) Types of AMD There are three stages of AMD early, intermediate or late. The stages are defined in part by the size and number of drusen under the retina. (6) Drusen are discrete white-yellow spots on the macular formed by accumulation of cellular debris after photoreceptor turnover. The clearance of the debris is impaired with age but vision at this point may not be affected. With time, the macula drusen deposits gradually become more extensive and cause thinning of the adjacent retinal pigment epithelium (RPE) layer. This layer nourishes the photoreceptors. Over decades, the thinning continues to become a patch of RPE loss at the macula, termed geographic atrophy and results in visual loss and legal blindness.( 2) It is possible to have AMD in one eye only, or to have one eye with a later stage of AMD than the other. Not everyone with early AMD will develop late AMD. For people who have early AMD in one eye and no signs of AMD in the other eye, about five percent will develop advanced AMD after 10 years. For people who have early AMD in both eyes, about 14 percent will develop late AMD in at least one eye after 10 years. Early referral is important Early AMD. Early AMD is diagnosed by the presence of medium-sized drusen, which are about the width of an average human hair. People with early AMD typically do not have vision loss. Intermediate AMD. People with intermediate AMD typically have large drusen, pigment changes in the retina, or both. Again, these changes can only be detected during an eye exam. Intermediate AMD may cause some vision loss, but most people will not experience any symptoms. Late AMD. In addition to drusen, people with late AMD have vision loss from damage to the macula (6) There are two types of late AMD dry and wet. Dry macular degeneration accounts for about 90 per cent of all cases of macular degeneration in Australia. It is not readily treated. Wet macular degeneration accounts for the other 10 percent of cases and is responsible for 90% of legal (1, 6) blindness. 1. Dry, or non-exudative, (also known as atrophic, or drusenoid) AMD is thought to arise from immune-mediated damage to the retinal pigment epithelium and the oxidative stress related to the highly metabolic process of light absorption. This forms the rationale for the use of antioxidants to slow the rate of dry AMD progression. 2. Neovascular, exudative, or wet, AMD is characterised by new blood vessel growth from the choroidal circulation of the retina. The blood vessels bleed and exude fluid to disrupt the layers of the retina causing rapid and extensive loss of central sight over days to weeks

4 Subsequent macular fibrosis results in severe and permanent vision loss, resulting in legal blindness. (2) When undetected or left untreated, rapid and severe loss of central vision can occur within a short period of time. Previous treatments included thermal and non-thermal lasers to target and cauterise the new choroidal vessels but results were poor. Recently, vascular endothelial growth factor (VEGF) has been identified to play a role in this abnormal angiogenesis. (a physiological process through which new blood vessels form from pre-existing vessels). VEGF also causes retinal arteriolar dilatation, leading to macular oedema. (2) The VEGF protein is targeted with anti-vegf drugs to stop neovascularisation and exudation. Anti- VEGF drugs including ranibizumab (Lucentis ) and aflibercept (Eylea ) have been shown in large clinical trials to effectively preserve and improve vision.( 7-9) Diagnosis The Amsler Grid is used to detect early changes in vision (Figure one). (10) It is used to test for and monitor symptoms of MD but should not be depended upon for diagnosis. The Amsler Grid should be used daily as per instructions to test for symptoms of MD which can include one or more of the following: Distortion where straight lines appear wavy or bent Dark patches or empty spaces appearing in the centre of your vision In addition, key symptoms may also include: Distinguishing faces becomes a problem Difficulty with reading or any other activity that requires fine vision Increased need for illumination, sensitivity to glare, decreased night vision or poor colour sensitivity. Normal Amsler Grid Possible AMD Instructions: 1. Do not remove glasses or contact lenses normally used for reading. 2.Hold grid at eye level approximately 33cm away in a well lit room 3.Cover one eye and focus on the centre dot with the uncovered eye (make sure the eye is fully covered) If the grid lines are wavy, broken or distorted, or if there are blurred or missing patches, this may be a symptom of AMD. Immediate referral to an optometrist or ophthalmologist is critical. Figure 1: The Amsler Grid (10)

5 Symptoms that may suggest MD include central visual distortion, central scotoma (partial alteration in the field of vision), difficulty reading and a problem with coordinating both eyes together. Many patients with early MD may not have any visual symptoms and are often diagnosed incidentally on eye examination. The signs of MD are detectable on clinical examination using an ophthalmoscope or a retinal camera. Drusen deposits appear as whitish-yellow spots of varying size and haemorrhage and retinal oedema indicate the presence of choroidal neovascularisation. The evaluation of a patient with AMD may include fluorescein angiography using a specialised retinal camera or use of an optical coherence tomography (OCT) scan. (2) Treatment and management of dry AMD The Age-Related Eye Disease Study (AREDS) was a major clinical trial sponsored by the Australian National Eye Institute (NEI).( 11) The AREDS was designed to learn more about the natural history and risk factors of AMD and cataracts and to evaluate the effect of high doses of vitamin C, vitamin E, beta-carotene and zinc on the progression of AMD and cataracts. Results from the AREDS in 2001, showed that high levels of antioxidants and zinc significantly reduced the risk of advanced AMD and its associated vision loss. These same nutrients had no effect on cataracts. There have been concerns that the high zinc dose in AREDS could cause gastrointestinal side effects.( 11) Drug interactions also need to be considered particularly with high dose zinc. In May 2013, the NEI completed the Age-Related Eye Disease Study 2 (AREDS-2) which tested several changes to the formulation.( 12,13) The researchers added omega-3 fatty acids. Reduced the dose of zinc and substituted lutein and zeaxanthin for beta-carotene. Previous studies had associated betacarotene with an increased risk of lung cancer in smokers. The study found that while omega-3 fatty acids had no effect on the formulation, lutein and zeaxanthin together appeared to be a safe and effective alternative to beta-carotene. Benefits were shown for patients at high risk of developing advanced or neovascular AMD. (14-17) The Macular Degeneration consumer website recommends that patients discuss the use of nutritional supplements such as Macuvision, and/or Luteinvision with their eye specialist before commencing products and check the dose and product/s required. (1) Smokers are advised to use a product where beta- carotene has been replaced with lutein and zeaxanthin. (1) The effectiveness of eating foods rich in the macular pigments (carotenoids, e.g. lutein and zeaxanthin found in green leafy vegetables) in reducing the risk of AMD is uncertain, but may delay progress of dry MD. Studies on the use of statins and omega- 3 fatty acids to delay the progress of AMD have not shown evidence.( 18,19) Treatment and management of wet AMD In neovascular (wet or exudative) AMD excessive growth of blood vessels causes bleeding, leakage and scarring under the retina. This may cause retinal thickening and oedema. Vascular endothelial growth factor A (VEGF-A) and placental growth factor (PGF) are angiogenic factors that have been identified. VEGF acts via binding to VEGFR-1 and VEGFR-2, which are present on the surface of endothelial cells. PGF binds to VEGFR-1, which is also present on the surface of leucocytes. Pathological neovascularisation and excessive vascular permeability can result from excessive activation of VEGFR-1 and VEGFR-2 by VEGF-A, and PGF can act synergistically with VEGF-A in these processes. PGF also promotes the infiltration of leucocytes and vascular inflammation. (2,7,20)

6 Current options for treatment of wet AMD include: treatment with injections, photodynamic therapy (PDT) and laser photocoagulation. (1) 1. Treatment with injections. Anti- vascular endothelial growth factor (anti-vegf) agents act as soluble decoy receptors that bind to VEGF-A and PGF (with higher affinity than their natural receptors), thus preventing the binding and subsequent activation of VEGF receptors. VEGF blockade is now the standard of care for patients with wet AMD. In Australia, two drugs used principally for the treatment of wet AMD are ranibizumab and aflibercept. (2) There are other anti-vegf drugs used for treatment of certain cancers eg bevacizumab (Avastin ) but these are not TGA approved for AMD. (2,7) Anti-VEGF agents: Ranibizumab (Lucentis ) is an antibody fragment. It binds to and inhibits the activity of human VEGF-A. It is administered monthly by intravitreal injection and is PBS authority listed Aflibercept (Eylea ) is a decoy receptor binding to VEGF with a stronger affinity compared to previous drugs. (7) Additionally, it targets and blocks another pro-angiogenic molecule in placental growth factor (PGF). Many patients will receive an intravitreal injection on a two-monthly basis, also under PBS authority if approved. (20) The injection is given under aseptic conditions with local anaesthesia in a clinic procedure room or an operating room environment. A 30-gauge needle is passed through the sclera into the vitreous cavity to deliver a small amount (0.05mL) of drug. For PBS supply both medications require diagnosis by fluorescein angiography and must be prescribed and administered by an ophthalmologist experienced in administering intravitreal injections. This usually occurs in the specialists rooms although some patients may be treated in a day stay unit. Bevacizumab (Avastin ) is another monoclonal anti-vegf treatment which was originally developed and registered for the treatment of certain cancers. It is neither Therapeutic Goods Administration (TGA) approved nor PBS listed for ophthalmic indications and therefore its use is 'offlabel' when treating patients with wet macular degeneration. In Australia, Avastin is typically used for people who are not eligible to receive the approved drugs Lucentis or Eylea via PBS. (1,7) Patients with neovascular AMD who have a poor initial response to an anti-vegf agent may still respond to treatment with the same drug over time, without being switched to an alternative agent, the Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) study suggests. (21) These agents are also used for diabetic macular oedema, and retinal vein occlusion. Practice tips for aflibercept (Eylea ) and ranibizumab (Lucentis ) used for wet AMD (2,7,20,22-25) Contraindications: Treatment with aflibercept and ranibizumab is contraindicated in the presence of ocular, periocular infection and active, severe intraocular inflammation, stroke or TIA, pregnancy (Category D), breastfeeding, or children or adolescents Precautions: Intraocular pressure should be checked prior to injection and for one hour after the injection. It should be used with caution in patients with glaucoma. Concomitant administration to both eyes has not been studied

7 Adverse Reactions: Adverse reactions include transient post injection ocular pain (10-15% of patients), cataracts, intraocular inflammation associated with intraocular infection (endophthalmitis), increased intraocular pressure, arterial thromboembolic events. non ocular haemorrhage. Patients should be advised to contact the ophthalmologist immediately if there are any signs of inflammation and/or infection of the eye eg conjunctival haemorrhage redness of the eye eye pain light sensitivity vision changes seeing flashes of light with floaters loss of sight blurred vision Any signs of sore throat, headache, joint pain, flu-like symptoms, fatigue, general feeling of being unwell, anxiety, cough, nausea, and or allergic reactions (rash, urticaria itching, redness of the skin) should be immediately reported to the doctor. As patients may experience temporary visual disturbances after an intravitreal injection with Eylea or Lucentis and the associated eye examinations they should not drive or use machinery until visual function has recovered. Drug Interactions: No formal interaction studies have been done for either drug and no interactions have been reported in the studies to date Administration: Eylea and Lucentis can only be administered by an ophthalmologist as an injection into the eye under local anaesthesia. Antimicrobial eye drops are to be instilled used four times a day for three days before and after each injection to prevent any possible eye infection. Make up should not be worn on the day of the injections. The interval between two doses should not be shorter than one month. For ranibizumab for patients treated for wet AMD the injection is given once a month. If given less frequently, the full benefit may not be obtained or benefits already obtained might be lost For aflibercept the injection is given monthly for three months then one injection every two months. Only one eye should be treated at a time Storage: It is unlikely that community pharmacists or patients will have to store Lucentis or Eylea, however if necessary: Keep it in a refrigerator (2 C to 8 C). Do not freeze. Keep the vial in the outer carton in order to protect it from light. Follow-up and adherence: It is often difficult for patients and carers to adhere to a rigorous monthly treatment schedule. Significant barriers include travel time and medical and indirect costs to both the patient and carers. To maintain control of the disease injections must usually be continued on an indefinite basis. The interval between injections is determined on an individualised basis by the eye specialist in consultation with the patient. Vision should continue to be monitored every day using an Amsler grid, one eye at a time Intravitreal injections of Lucentis, Eylea are sight-saving therapies for patients with wet AMD. Reading sight can be restored in many patients. The effectiveness of these drugs is best when given early in the course of wet AMD. Monthly or bimonthly injections may be required to best maintain

8 the central sight. The View 1 and View 2 studies show little difference between the two agents with the advantage of less frequent injections with Aflibercept and consequent cost reduction.( 7,26-7) A recent study shows that visual acuity remains stable or continues to improve over 5 years in most patients treated with ranibizumab for neovascular age-related macular degeneration under "real-life" conditions but the main challenge is ongoing compliance with therapy with advancing age and comorbidities. (27) Other dose forms for anti-vegf products eg eye drops are under development. (28) 2. Photodynamic Therapy Unlike with anti-vegf drugs, with which the vision is usually maintained, patients having photodynamic therapy (PDT) normally continue to lose vision in the first six months. Their vision then generally stabilises so that the eye does not progress to severe vision loss. PDT therefore is now rarely used to treat ordinary AMD. It is sometimes used in conjunction with an anti-vegf drug in people with a type of macular degeneration called polypoidal choroidal vasculopathy as some of these cases do not settle completely with anti-vegfs. PDT is a two-step process combining verteporfin (Visudyne ), a light-activated drug with the light from a cold laser. The laser is directed on to the abnormal retinal area to seal and halt or slow down the progression of abnormal retinal blood vessels. It is necessary to avoid sunlight for 24 to 48 hours after the drug has been infused. (1) 3. Laser photocoagulation This treatment consists of a laser directed on to the retina to destroy and seal the leaky blood vessels. As it also destroys the retina adjacent to the new vessel it is primarily used for treating new vessels that are not under the central vision. This represents only a small percentage of patients. There is a 50% recurrence rate. (1) Patients with AMD require close follow-up and monitoring, as the disease is unpredictable. Wet changes develop in the second eye of about 10 per cent of patients each year cumulatively. In these patients there is a potential for a significant loss of function and independence. Vision Australia offers many products to help patients with their activities of daily living. (29) Pharmacists have a role to play in early referral and encouraging persistence with therapy. Table 2 lists an Eye health check list provided by the Macular Degeneration Foundation. (1) Table 2: Eye health check list (1) Have your eyes tested and macula checked Do not smoke Keep a healthy lifestyle, control your weight and exercise regularly Eat fish 2 to 3 times a week Eat dark green leafy vegetables and fresh fruit daily Choose low glycaemic index carbohydrates Eat a handful of nuts a week Consider a suitable supplement in consultation with your doctor Protect your eyes from the sun Use an Amsler grid for checking for symptoms of macular degeneration Seek immediate attention from an eye care professional if there are any sudden changes in vision

9 References: Chew J, Change A. Macular degeneration. Medical Observer March accessed 10 October Liew G, Mitchell P, Wong TY, et al. The association of aspirin use with age-related macular degeneration. JAMA Intern Med 2013; 173: Ranibizumab (Lucentis) and aflibercept (Eylea). NPS RADAR; April 2015: Rosenfeld PJ, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355: Heier JS, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012; 119: AREDS study: AREDS AREDS2 Research Group. Lutein/Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration. The Age-Related Eye Disease Study 2 (AREDS2) Controlled Randomized Clinical Trial. JAMA 2013 May 15;309(19): Chew et al. Long-Term Effects of Vitamins C, E, Beta-Carotene and Zinc on Age-Related Macular Degeneration. Ophthalmology, published online April 11, Ma L, Dou HL, Wu YQ, Huang YM, Huang YB, Xu XR, Zou ZY, Lin XM.Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis. Br J Nutr Feb;107(3): Ma L, Hao ZX, Liu RR, Yu RB, Shi Q, Pan JP. A dose-response meta-analysis of dietary lutein and zeaxanthin intake in relation to risk of age-related cataract. Graefes Arch Clin Exp Ophthalmol Jan; 252(1): doi: /s Epub 2013 Oct The Age-Related Eye Disease Study 2 (AREDS2) Research Group Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration. JAMA. 2013; 309(19): doi: /jama accessed 10 Oct accessed 10 Oct emims CMP Medical Australia, October Ying G, Maguire M, Ebenezer D et al. Association of Baseline Characteristics and Early Vision Response with 2-Year Vision Outcomes in the Comparison of AMD Treatments Trials (CATT) Rossi S (Ed), Australian Medicines Handbook, 2015 Australian Medicines Handbook Pty Ltd Adelaide Bicopoulos D (Ed). AUS-DI Lucentis. Consumer Medicines Information. Available from emims 25. Eylea. Consumer Medicines Information. Available from emims 26. Verner-Cole EA, Davis SJ, Lauer AK. Aflibercept for the treatment of neovascular age-related macular degeneration. Drugs Today (Barc) May;48(5): Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology Jan;121(1): Fonseca C. European Society of Retina Specialists 15th EURETINA Congress. Presented September 17,

10 AusPharm CPD MCQs Questions based on the above article: Please answer the following questions: (only one answer per question is correct). Successful completion of this activity is demonstrated by answering eight of the ten multiple choice questions correctly. 1. In relation to macular degeneration (MD) which one of the following statements is INCORRECT? (a) Age-related macular degeneration (AMD) affects one in seven Australians older than 50 years (b) Most people suffer from dry macular degeneration which comes on suddenly usually in older people. (c) There is no cure for AMD wet or dry (d) The prevalence of AMD increases with age. (e) Without treatment seventy five percent of people diagnosed with wet AMD will be classified as legally blind at three years after diagnosis. 2. Indicate which one of the following statements is INCORRECT? (a) Family history is a strong risk factor for the development of AMD. (b) Environmental factors and genetic factors may play a role in the development of MD (c) Smoking has been shown to be a risk factor for the development of AMD. (d) Low dose aspirin has been shown to have a causal link to AMD. (e) A diet risk in carotenoids eg green leafy vegetables may delay the progress of AMD 3. Indicate which one of the following statements is INCORRECT? (a) Dry or non- exudative AMD is thought to arise from immune-mediated damage to the retinal pigment epithelium and the oxidative stress related to light absorption. (b)with early intervention dry AMD can be cured by the use of antioxidant supplements which counteract the oxidative stress. (c) In dry AMD small white- yellow spots (known as drusen) on the macular accumulate from cellular debris after photoreceptor turnover. (d) The clearance of cellular debris is impaired by age in dry AMD. (e) Thinning of the retinal pigment epithelium causes a loss at the macula which results in visual loss and legal blindness. 4. Indicate which one of the following statements is INCORRECT? (a) Wet AMD is also known as neovascular or exudative AMD (b) Wet AMD is characterised by new blood vessel growth from the choroidal circulation of the retina (c) The blood vessels bleed and exude fluid to disrupt the layers of the retina causing rapid and extensive loss of central sight over days to weeks. (d) Cauterisation of the leaky blood vessels by laser has about a 50% reoccurrence rate (e) The use of vascular endothelial growth factors (VEGF) have been shown to prevent the abnormal angiogenesis.

11 5 Indicate which one of the following statements is INCORRECT? (a) Many patients with early AMD may not have any visual symptoms. (b) Common changes using the Amsler grid include distortion where straight lines appear wavy or bent (c) Common changes using the Amsler grid include dark patches or empty spaces appearing in the centre of vision (d) The Amsler Grid is used to diagnose AMD. (e) Clinical examination using an ophthalmoscope or a retinal camera will show drusen deposits or haemorrhage and retinal oedema from choroidal neovascularisation. 6 Indicate which one of the following statements is INCORRECT? (a) Results from the AREDS showed that high levels of antioxidants and zinc significantly reduce the risk of advanced AMD and its associated vision loss. (b) Betacarotene has been associated with increased risk of lung cancer in smokers. (c) In the AREDS-2 study lutein and zeaxanthin appear to be a safe and effective alternative to beta-carotene (d) The AREDS 2 study showed an additional beneficial effect in the progression of AMD by adding omega-3 fatty acids and substituting lutein and zeaxanthin for betacarotene. (e) High dose zinc may cause gastrointestinal side effects 7 Indicate which one of the following statements is INCORRECT? (a) Vascular endothelial growth factor A (VEGF-A) and placental growth factor (PGF) are angiogenic factors that have been identified in causing the excessive growth of blood vessels causing neovascular AMD (b) Anti-VEGF agents act as soluble decoy receptors that bind to VEGF-A and PGF (with higher affinity than their natural receptors), thus preventing the binding and subsequent activation of VEGF receptors. (c) Ranibizumab inhibits the activity of VEGFA (d) Aflibercept acts as a decoy receptor and also blocks placenta growth factor (e) Anti-VEGF agents currently approved for the treatment of neovascular AMD are all given via the intravenous route. 8 Indicate which one of the following statements is INCORRECT? (a) Ranibizumab is category D for pregnancy (b) Aflibercept should be used with caution in people who have glaucoma (c) Antibiotic eye drops should not be used prior to the use of anti-vegf agents. (d) The injection should be stored in the fridge between 2 and 8 degrees prior to use. (e) Only one eye should be treated at a time with aflibercept even although both eyes may be affected

12 9 Indicate which one of the following statements is INCORRECT? (a) Patients meeting the PBS criteria for anti-vegf agents will only need to use them for three years. (b) Patients should be advised not to drive after anti-vegf injections until visual function has revered. (if they are still permitted to drive ) (c) Any patient suffering flu- like symptoms after the use of ranibizumab or aflibercept should be urgently referred to a doctor (d) The interval between the injections of ranibizumab must not be shorter than one month. (e) Post injection ocular pain may occur in up to 15% of patients following anti-vegf injections. 10 Indicate which one of the following statements is INCORRECT? (a) People with AMD should be assessed for falls risk and may require home modification. (b) People with AMD should check that cardiovascular risk factors are reduced (c) The use of omega- 3 fatty acids has not been shown to delay the progress of AMD (d) Once people with AMD are having intravitreal injections there is no need to check the Amsler grid. (e) Bevacizumab is another anti-vegf treatment but is not TGA or PBS approved however it is used off label for treatment of people with wet AMD.