Introduction • AMD is the leading cause of vision loss in Americans over the age of 60 • Advanced AMD is the leading cause of vision loss and irreversible blindness worldwide in those over the age of 50 • As many as 11 million Americans have some level of AMD UPDATE ON AMD 2021 – Expected to increase to nearly 22 million by 2050 • More than glaucoma (2.2 million) and DR (7.7 million) Steven Ferrucci, OD, FAAO COMBINED Chief, Optometry Sepulveda VA Professor, SCCO/MBKU 1 2 Introduction Dry AMD • Exciting time to be interested in AMD • Currently mainstay treatment for Dry AMD revolves around prevention of progression through vitamins, nutrition and lifestyle • Many new treatments now available for AMD changes – Years ago, we had nothing at all to offer patients with AMD – Rheophoresis, Laser, Anecortave Acetate did not prove effective – Smoking #1 modifiable risk factor for getting AMD as well as its • Current Treatments progression! • Potential Treatments • One study showed 90% of pts with AMD were not advised to quit smoking • Early detection of conversion from dry to wet may result in better • New Diagnostic Equipment treatment for patients 3 4 AREDS AREDS 2 • First large scale study looking at nutrition and ocular health • AREDS 2: Enrollment ended June 2008 with ≈4200 patients followed • 3640 pts followed on average for 6.3 years for six years – Effect of lutein, zeaxanthin and omega 3 on AMD – Results released October 2001 – Effect of eliminating beta carotene on AMD • Results showed that 25% risk reduction to developing advanced – Effect of reducing zinc on AMD AMD in pts with intermediate (stage 3) AMD or worse – Effect of supplements on cataracts 500 mg vitamin C 400 IU vitamin E – Validate the AMD scale from original AREDS 15 mg vitamin A (25,000 IU beta carotene) 80 mg zinc • Results released May 5, 2013 2 mg copper 5 6 1 “Wet” AMD AREDS2 Formulation • Neovascular “wet” AMD • Vitamin C (500 mg) – Mainstay of treatment consists of serial intravitreal injection of anti-VEGF agents Anti-VEGF Pegaptanib Ranibizumab Aflibercept Brolucizumab Bevacizumab • Vitamin E (400 IU) Agents (Macugen®) (Lucentis® ) (Eylea® ) (Beovu® ) (Avastin® ) FDA approval 2004 2006 2011 2019 Not approved • Beta Carotene (15 mg) ANCHOR VIEW HAWK Pivotal studies VISION MARINA CATT 1 and 2 HARRIER • Lutein (10 mg)/Zeaxanthin (2 mg) IVAN – VEGF inhibitors have demonstrated improved visual and anatomic outcomes • Zinc (80 mg zinc oxide) compared with other therapies VEGF = vascular endothelial growth factor. • Copper (2 mg cupric oxide) AAO. AMD preferred practice guidelines, 2019 (www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp). Kulkarni K, Prenner JL. Rev Ophthalmol. 1/13/2006. (www.reviewofophthalmology.com/article/an-update-on-macugen-trials). URLs accessed 5/30/2020. • Omega-3 fatty acids (DHA/EPA) 7 8 Anti-VEGF Agents Anti-VEGF Agents: Delivery and Dosage • VEGF is a primary driver of blood vessel growth and leakage in AMD • Delivered intravitreally • Anti-VEGF agents block and neutralize VEGF – Results in decreased intra- and sub-retinal fluid • Dosing schedule and agent used varies – May also decrease risk of scar tissue formation • In general • Serious adverse effects (endophthalmitis) rare – Loading dose with 1 injection per month for 3 months, then inject based on FA, OCT, or other clinical findings • Less serious events (subconjunctival hemorrhage, vitreous hemorrhage, – Reduces patient burden while still delivering good results floaters) are also uncommon , et al. Br J Ophthalmol. 2016;100:1623-1628. Kress B. Review of Optometry. 2019 (https://www.reviewofoptometry.com/article/antivegf-where-are-we-now). Accessed June 10, 2020. Treating Wet AMD with Anti-VEGF drugs. 2016 (https://www.reviewofophthalmology.com/article/treating-wet-amd-with-antivegf- drugs). Accessed June 10, 2020 Pongsachareonnont P, et al. Clin Ophthalmol. 2018;12:1877-1885. Yeo NJY, et al. Front Pharmacol. 2019;10:1363. HolZ FG, et al. Br J Ophthalmol. 2016;100:1623-1628. American Society of Retina Specialists (ASRS). Intravitreal injections. (www.asrs.org/content/documents/fact-sheet-30-intravitreal-injections.pdf). Sukgen EA, et al. Int Ophthalmol. 2017;37:215-219. Living well with low vision. (https://lowvision.preventblindness.org/2013/06/25/betadine-and-eye-pain/). URLs accessed 5/30/2020. 9 10 Anti-VEGF Agents: Outcomes Other Treatment Options Lucentis1 Eylea2,3 Beovu4 Possible Not advised • Photodynamic therapy • Intravitreal steroids • • • ~30% gained at least 15 94% stable vision at 2 95% of patients (PDT) with verteporfin as monotherapy years treated maintained letters by year 1 • Intravitreal steroids in • Radiation therapy acuity • Less fluid and greater • 34–41% gained 15 combination with PDT or • Electrical stimulation reduction in CST vs letters or more • 7.9–10.9 letters mean anti-VEGF agents • Macular aflibercept improvement of • • Average gain of 11.3 Laser photocoagulation translocation vision • At 1 year, half of subjects • letters at 1 year and Observation/suspension of therapy on 3-month dosing 10.7 letters at 2 years treatment CST = central subfield thickness. AAO. AMD preferred practice guidelines, 2019 (www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp). 1. Brown DM, et al. Ophthalmology. 2009;116:57-65.e5. 2.Nguyen QD, et al. Invest Ophthalmol Vis Sci. 2011;52: abstract 3073. 3. Accessed 5/30/2020. Wong DT, et al. Retina. 2020;40:1010-1020. Giancipoli E, et al. J Ophthalmol. 2018:5612342. Veritti D, et al. Schmidt-Erfurth U, et al. Invest Ophthalmol Vis Sci. 2011;52:E-Abstract 1650. 4.Dugel PU, et al. Ophthalmology. 2020;127:72-84. Expert Rev Ophthalmol. 2010;5(5):681-688. 11 12 2 Beovu update Is AMD Under diagnosed? • In Feb, 2020, American Society of Retinal Specialists (ASRS) issued a • 25% of eyes deemed normal on DFE by eye care provider (both ODS warning reporting 14 cases of retinal vasculitis following injection of Beovu and MDs) had macular characteristics that indicated AMD – 11/14 were occlusive and resulted in vision loss – Of those, 30 % had level that would have been treatable with • In March, Novartis concluded that retinal vasculitis, retinal artery nutritional supplements – Eye care providers knew pts were being specifically screened for occlusion, or severe vision loss occurred in 8.75-10.08 out of 10,000 AMD injection • Another study showed that 79% pts with AMD were first diagnosed • Added to warning label with avg acuity of 20/50 from AMD! – Intraocular inflammation in 4% of pts – Artery occlusion in 1% • Advised to avoid if pts had h/o inflammation to any other anti-Vegf agent – BOTTOM LINE: WE ARE NOT DOING ENOUGH TO DETECT AMD!!! Prevalence of undiagnosed Age-Related Macular Degeneration in Primary Eye Care Neely DC et al. JAMA ophthalmol 2017: 135(6): 57--575 13 14 Standard of Care Comparison: Two Multifactorial Diseases MacuLogix’s AdaptDx GLAUCOMA AMD • Dark adaptation is a sensitive marker for early AMD • The AdaptDx measures dark adaptation • Cup-to-Disc Ratio Drusen A rapid test of dark adaptation using the AdaptDx has been found to have a 90% sensitivity Structure for detecting dark adaptation impairment associated with AMD • Decreased dark adaptation may precede clinical findings of AMD by as much as 3 years • Dark adaptation is more sensitive than other tests such as Snellen acuity, contrast sensitivity, or visual fields which are about 25% sensitive. Function Visual Field Dark Adaptation Macular Pigment Optical Density (MPOD) Intraocular Pressure (IOP) Contrast Sensitivity Risk Corneal Thickness Genetic Testing Demographics and Family History Demographics, Family History, Lifestyle 15 15 16 Impaired Dark Adaptation is Earliest Biomarker of AMD AdaptDx Validated in Multi-Site Study sources: Owsley, C et al. Ophthalmology. 2016;123(2):344-351. sources: Jackson GR, et al. Invest Ophthalmol Vis Sci. 2014;55(3):1427-1431. High Sensitivity Correctly identified 90.6% RESEARCH SHOWS: of confirmed AMD cases Impaired dark adaptation Ouridentifies callsubclinical AMD High Specificity at least three ALSTAR Study Correctly identified to action 90.5% years before of confirmed normal cases it can be seen with imaging, Prospective Study of Subclinical AMD OCT or clinical exam. • Sample consisted of 325 adult's w/o clinically detectable AMD High Accuracy • At baseline, 24% of the subjects exhibited impaired dark adaptation 90.6% • AMD status determined at 3-year follow-up visit overall 17 18 17 18 3 AdaptDx Advantages SuccessfuL Precedent Glaucoma AMD • No preadaptation required • Protocols as rapid as 5 minutes • Low patient burden Humphrey Perimeter MacuLogix • Easy to operate •Psychophysical test •Psychophysical test • CPT 92284 ($64 avg.) •5 minute duration •5 minute duration •$65 reimbursement (CPT 92083) •$65 reimbursement (CPT 92284) • FDA 510K cleared •Current eye care profit center •New, potentially larger eye care (K100954) profit center 19 20 Foresee Home At-risk Patients May Convert to Wet AMD at Any Point Between Follow-up Visits Visit Visit 1 2 Converts Converts Converts after office between before office visit office visits visit More likely Less likely to to lose vision lose vision Reference: Rauch R, et al. Retina. 2012;32(7):1260-1264. 22 21 22 ForeseeHome® product overview AREDS2-HOME Study Uses Preferential Intent to Treat (ITT) Hyperacuity ForeseeHome population results plus standard care arm Standard care arm Perimetry (PHP) 6,000+ actively 1520 testing patients 763 participants 757 participants participants Medicare covered 51 CNV Mean follow