AMD - Student Slides PDF

AMD Age-Related Macular Degeneration Sarah Larose, BSc Pharm Instructor, Dalhousie College of Pharmacy Disclaimer This lecture was prepared for PHAR 1051 in the 2024-2025 academic year. It is as complete and accurate as possible, based on available resources at the time o...

AMD Age-Related Macular Degeneration Sarah Larose, BSc Pharm Instructor, Dalhousie College of Pharmacy Disclaimer This lecture was prepared for PHAR 1051 in the 2024-2025 academic year. It is as complete and accurate as possible, based on available resources at the time of preparation When read alone, these slides may give the reader an incomplete picture of the presenter’s intended message. The slides are intended to be used in conjunction with the content of Ms. Larose’s verbal lecture to understand the complete intended message. Therefore, please do not copy or reproduce these slides without permission from the author. Learning Objectives Describe pathophysiology, etiology, epidemiology, classification and diagnosis of Age-Related Macular Degeneration (AMD) Identify risk factors for AMD diagnosis and progression considering specific patient factors List patient specific goals of therapy for AMD Explain AMD to a patient and discuss common supplements used in treatment and prognosis. Recommend micronutrient supplementation to a specific patient considering available evidence for effectiveness and potential for adverse effects Describe the role of VEGF inhibitors and their place in therapy for AMD Patient Case: Meet Tom Provo 70-year-old male patient Ethnicity: Black Nova Scotian Past medical history: Hypertension, Dyslipidemia Medications: HCTZ 25mg daily, rosuvastatin 10mg daily Social History: Smoker Family history: POAG (mother), MI & AMD (father)  What is the Pharmacist’s role? How will this condition affect Potential Actions for Pharmacists: my vision now and in the Prescribe What is my future? diagnosis and Order how do you spell Is there anything I can do? Administer the name of the condition? Should I make lifestyle changes? Educate Recommend Dispense What symptoms should I watch for Can my AMD Change be treated? Refer Epidemiology Estimated global prevalence of AMD is ~ 8.7% In 2020 ~190 million persons worldwide have AMD In 2040 an estimated 288 million persons will be affected Estimated global cost of visual impairment (AMD) > $300 billion, More than $250 billion in direct health care costs More prevalent: Risk Factors: European or North American ancestry - Increased age Similar between men and women - Smoking Increasing age (typically 55+) - Uncontrolled hypertension - BMI > 25 kg/m2 - Genetic factors / family history New England Journal of Medicine. Age-Related Macular Degeneration, 2021 Pathophysiology & Etiology 2 key parts of the retina: Macula & Peripheral Retina Macula gives us our central vision, most of our color vision and allows us to see fine details clearly. It has the highest concentration of photoreceptor cells AMD occurs when there is a breakdown of the macula https://youtu.be/uUXKNwr0qqU Hansen, John T., and Netter, Frank H. Netter's Clinical Anatomy. Third ed. Philadelphia: Saunders, 2014. Chapter 8: Head and Neck.  Advanced = Late Depending on the Reference Pathophysiology & Etiology AMD is classified by stages: Early AMD: diagnosed by the presence of drusen Intermediate AMD: has larger drusen and/or pigment changes in the retina Advanced AMD: may be classified as either wet or dry Neovascular or Exudative Nonexudative aka. WET aka. DRY LESS common – MORE serious – Lose vision FASTER MOST common (80% of cases) Abnormal blood vessels grow under the retina Macula thins (w/ age) + tiny clumps of protein → leak blood & fluid → scarring of the macula (drusen) grow → slow loss of central vision American Academy of Ophthalmology: AMD Clinical Presentation & Diagnosis Early or intermediate AMD are often asymptomatic. Otherwise, symptoms often include: Blurred or decreased vision in one or both eyes Distortion Blind spots (scotomas) in or around their central vision Difficulty with visual function and daily activities: Such as reading and driving, especially in poorly lit settings Diagnosis involves a detailed clinical history and comprehensive eye tests which include: Visual acuity (eye chart that measures how well you see at distances) Amsler grid testing (changes in central vision may cause the lines to appear differently) Dilated eye exam with slit lamp (visualize the retina and optic nerve) CPS: AMD Chapter New England Journal of Medicine. Age-Related Macular Degeneration, 2021 Goals of Therapy Minimize / Slow the progression of vision loss Improve vision* Minimize enlargement of central scotomas (central blur in centre of visual field) Resolve leakage of blood vessels in the macula and hemorrhage associated with neovascular AMD Optimize function and quality of life Ex: drive car, favorite activities, mobility, etc. CPS: AMD Chapter New England Journal of Medicine. Age-Related Macular Degeneration, 2021 Nonpharmacologic / Lifestyle Options QUIT SMOKING (or don’t start) Regular physical activity These reflect the Risk Factors of Maintain normal blood pressure and cholesterol levels AMD Eat a healthy diet, rich in green, leafy vegetables and fish Consult an OT or low vision clinic for setting up home to cope with low vision National Institute for Health (NIH): Age-Related Macular Degeneration Treatment Algorithm Micronutrient Supplementation Vascular Endothelial Growth Factor Inhibitors Photodynamic Therapy CPS: AMD Chapter  Micronutrient Supplementation Diagnosis of AMD Treatment Algorithm Vascular Endothelial Growth Factor Inhibitors Specialist Referral Photodynamic Therapy Intermediate Advanced Advanced Early Stage Stage Stage (dry) Stage (wet) Risk factor Subfoveal Extrafoveal Juxtafoveal Observation Observation modification CNV CNV CNV Antioxidant/ Risk factor Risk Factor Intravitreal VEGF Intravitreal VEGF Intravitreal VEGF mineral modification Modification inhibitor inhibitor inhibitor supplementation Consider OR photodynamic OR Thermal laser antioxidant/mineral Risk factor modification therapy using verteporfin photocoagulation supplementation Consider antioxidant/ Risk factor modification Risk factor modification mineral supplementation CNV: choroidal neovascularization VEGF: Vascular endothelial growth factor Consider antioxidant/ Consider antioxidant/ mineral supplementation mineral supplementation BMJ Best Practice: AMD Micronutrient (Antioxidant and Mineral) Supplementation  (Patients who DO NOT have AMD) What is the aim of this review? The aim of this Cochrane Review was to find out whether taking antioxidant vitamin and mineral supplements prevents the development of AMD. Cochrane researchers collected and analysed all relevant studies to answer this question and found five studies. Fewer cases of AMD? Study Population: Intervention: Healthy People Specific Micronutrient (do NOT have AMD) Supplementation  (Patients who DO NOT have AMD) What are the main results of this review? ∙ Taking vitamin E supplements made little or no difference to the chances of developing AMD or late AMD ∙ Taking beta-carotene made little or no difference to the chances of developing any AMD or late AMD ∙ Taking vitamin C made little or no difference to the chances of developing any AMD or late AMD ∙ Adverse effects were not consistently reported in these eye studies, but there is evidence from other large studies that beta-carotene increases the risk of lung cancer in people who smoke, or who have been exposed to asbestos. Fewer cases of AMD? Study Population: Intervention: Healthy People Specific Micronutrient (do NOT have AMD) Supplementation  (Patients who HAVE AMD) What is the aim of this review? The aim of this Cochrane Review was to find out whether taking antioxidant vitamin and mineral supplements slows down the progression of AMD and prevents visual loss. Cochrane researchers collected and analysed all relevant studies to answer this question and found 19 studies. Slower progression of AMD? Prevent visual loss? Study Population: Intervention: Patients with Early or Specific Micronutrient Intermediate AMD Supplementation  (Patients who HAVE AMD) What are the main results of this review? Taking antioxidant vitamins plus zinc probably slows down the progression to late AMD and vision loss. This may result in a small improvement in quality of life. Taking lutein alone (or with zeaxanthin) may have little or no effect on progression to late AMD and vision loss. Taking vitamin E alone may have little or no effect on the progression to late AMD and vision loss. Slower progression of AMD? Prevent visual loss? Study Population: Intervention: Patients with Early or Specific Micronutrient Intermediate AMD Supplementation Age-Related Eye Disease Study (2001) AREDS Formula Nutrient Amount Antioxidant Vitamin C 500 mg Formula AREDS Design Vitamin E 400 IU Results are based on 3,640 participants who had early (or worse) AMD. Beta-Carotene 15 mg Participants were randomized to 1 of 4 groups and followed over 5 years Copper 2 mg 56% were female, median age of 69 years of age (range of 55-80) Zinc 80 mg  Asked the question: Does the addition of L + Z ± Omega 3 AREDS 2 (2013) reduce the risk of progressing to advanced AMD (in patients with intermediate or advanced AMD) Included 2 randomizations: Chosen because observational studies showed potential benefit Primary Lutein 10mg + Zeaxanthin Placebo Omega 3 (EPA + DHA) L + Z + Omega 3 2mg Secondary (optional) AREDS 2 Formulations Vitamin C Vitamin E Beta Carotene Zinc Oxide Cupric Oxide Studied (mg) (IU) (mg) (mg) (mg) 1 500 400 15 80 2 2 500 400 0 80 2 3 500 400 15 25 2 4 500 400 0 25 2 AREDS (original) 500 400 15 80 2 Tweaked the formula due to: 1Beta Carotene was shown to cause lung cancer in current/previous smokers, 2TUL of Zinc is 40mg/day Would these changes result in a safer but just as effective product? Ophthalmology. 2012 November ; 119(11): 2282–2289  Reminder: Original AREDS formula included beta-carotene AREDS 2 Summary of Results Former (or current) smokers who took AREDS with beta-carotene had a higher incidence of lung cancer. When COMBINED with and then COMPARED to the original AREDS formulation: Omega-3s had no effect (↓ or ↑ ) on risk of progression to advanced AMD Lutein + zeaxanthin had no effect (↓ or ↑) on risk of progression to advanced AMD For participants with very low levels of lutein and zeaxanthin in their diet, adding these supplements to the original AREDS formulation helped lower their risk of advanced AMD. Participants who took AREDS2 containing lutein + zeaxanthin and no beta-carotene had a reduction in risk of advanced AMD, compared with those who took AREDS with beta- carotene. Removing beta-carotene or reducing the dose of zinc did not lead to any significant changes in effectiveness Micronutrient Supplementation: A Summary AREDS or AREDS2 supplements do NOT prevent AMD onset AREDS or AREDS2 supplements do NOT influence cataracts (positive or negative) AREDS or AREDS2 supplements REDUCE the risk of progression from intermediate to advanced AMD AREDS2 is SIMILAR or BETTER* than AREDS (with beta-carotene) for reducing the risk of progression of AMD Omega-3s do NOT have an effect on AMD onset or progression (positive or negative) Current or former smokers should take AREDS2 and AVOID the AREDS formula with beta-carotene Patients with intermediate/advanced AMD already taking a regular multivitamin should ALSO take AREDS2 supplements Patients with advanced AMD in one eye should consider micronutrient supplementation to reduce risk of 2nd eye involvement Patient Case: Tom What will we recommend? Pharmacologic Options: VEGF Inhibitors (Vascular Endothelial Growth Factor) How they work: ↓ VEGF levels = inhibit growth + regress new blood vessels in choroidal neovascular (CNV) membranes How they are dosed: intravitreal injection q 4 weeks initially (then q 8-16 weeks) by a trained HCP Common ADR: mild eye pain, subconjunctival hemorrhage, endophthalmitis, retinal detachment Efficacy: shown to improve visual acuity (compared to standard care) Agents available in Canada: bevacizumab (2005), ranibizumab (2007), aflibercept (2013), brolucizumab (2020) and faricimab (2022) EXPENSIVE – up to 1500$/injection & NOT covered by provincial drug plan Dynamed: AMD CPS: AMD Chapter Select References CPS, Therapeutic Choices Chapter: Age-Related Macular Degeneration Dynamed: Age-Related Macular Degeneration Apte RS. Age-Related Macular Degeneration. N Engl J Med. 2021 Aug 5;385(6):539-547. PMID: 34347954; Mahmood S, Fekrat S. Age-related macular degeneration. BMJ Best Practice. May 2024. https://bestpractice.bmj.com/topics/en-gb/554 National Institutes of Health (NIH) National Eye Institute resources: https://www.nei.nih.gov/research/clinical-trials/age-related-eye-disease-studies- aredsareds2