Long-term Management of AMD. Motasem Al-latayfeh, MD Assistant Prof. Ophthalmology Hashemite University Jordan

Long-term Management of AMD Motasem Al-latayfeh, MD Assistant Prof. Ophthalmology Hashemite University Jordan

DEFINITION 1 Age-related macular degeneration (AMD) is a disorder of the macula characterized by one of the following: Presence of at least intermediate-size drusen ( 63 μm in diameter) Retinal pigment epithelium (RPE) abnormalities (hypo/hyperpigmentation) Reticular pseudodrusen Presence of any of the following features: Geographic atrophy (GA) of the RPE Choroidal neovascularization (CNV) (exudative, wet) Polypoidal choroidal vasculopathy (PCV) Retinal Angiomatous Proliferation (RAP) 1. Ferris FL III, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration. Ophthalmology 2013

DEFINITION 1 Age-related macular degeneration (AMD) is a disorder of the macula characterized by one of the following: Presence of at least intermediate-size drusen ( 63 μm in diameter) Retinal pigment epithelium (RPE) abnormalities (hypo/hyperpigmentation) Reticular pseudodrusen Presence of any of the following features: Geographic atrophy (GA) of the RPE Choroidal neovascularization (CNV) (exudative, wet) Polypoidal choroidal vasculopathy (PCV) Retinal Angiomatous Proliferation (RAP) Courtesy of Isabelle Aknin 1. Ferris FL III, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration. Ophthalmology 2013

DEFINITION 1 Age-related macular degeneration (AMD) is a disorder of the macula characterized by one of the following: Presence of at least intermediate-size drusen ( 63 μm in diameter) Retinal pigment epithelium (RPE) abnormalities (hypo/hyperpigmentation) Reticular pseudodrusen Presence of any of the following features: Geographic atrophy (GA) of the RPE Choroidal neovascularization (CNV) (exudative, wet) Polypoidal choroidal vasculopathy (PCV) Retinal Angiomatous Proliferation (RAP) Courtesy of M. Mauget-Faÿsse 1. Ferris FL III, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration. Ophthalmology 2013

Guidelines For The Management of AMD PREVALENCE

Prevalence 2 Leading cause of severe, irreversible vision impairment in developed countries: o USA in 2004: 1.75 M 40 yo neovascular AMD/geographic atrophy in at least 1 eye 7.3 M have high risk features (large drusen 125 μm) o USA in 2020: 3 M 40 yo neovascular AMD/geographic atrophy in at least 1 eye Antioxidants vitamins (e.g. vitamin C, vitamin E), lutein, zeaxanthin, and zinc progression AMD by approximately 25% at 5 years 2. Congdon N, O Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the united states. Arch Ophthl

Prevalence 3 3. Klein R, Klein BE, Tomany SC, et al. Ten-year incidence and progression of age-related maculopathy: The Beaver Dam Eye Study. Ophth

AMD is responsible for an estimated 46% of cases of severe visual loss (VA 20/200) o Although 80% of AMD patients have the nonneovascular (atrophic) form o The neovascular form is responsible for 90% of the severe VA loss

Guidelines For The Management of AMD RISK FACTORS

Risk Factors 4 Age ( 75 yo) Race (caucasians) Smoking o Dose response relationship o R AMD in subjects who did not smoke 20y = R AMD in nonsmokers o Smoking cessation is strongly recommended o Hypertension & other cardiovascular diseases are not risk factors 4. Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, SanGiovanni JP, Ferris FL, et al. Lutein/Zeaxanthin for the treatment of age-related cataract: AREDS 2 randomized trial report number 4. JAMA Ophthalmol 2013;131:843-50

Levels of antioxidants o Inconsistent data in identifying low levels of plasma levels o Antioxidants vitamins (Vit C, Vit A, beta-carotene) + zinc progression AMD by 25% at 5 years o Replacement of beta-carotene with lutein/zeaxanthin in the new AREDS2 formulation o competitive absorption of lutein/zeaxanthin o incidence lung cancer in smokers

Diet o incidence dietary intake of foods rich in omega-3 longchain polyunsaturated fatty acids (fish) o Not necessarily in the form of supplement o incidence with higher intake of saturated fat o incidence BMI

Risk Factors 5 Aspirin o Meta-analysis did not show a risk of AMD Genetic factors (Evidence I ++, I + & I - ) o Complement Factor H (CFH) Y401H polymorphism on chromosome 1( 7.4x) o ARMS2/HtrA1 gene o Hepatic Lipase (LIPC) gene o Rs3775291 variant in the toll-like receptor 3 (TLR3) gene 5. Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 2005;308:421-4

Risk Factors 5 Other risk factors o Waist/hip ratio for men o Hormonal status o Sunlight exposure o Markers of inflammation: C-reactive protein, erythrocyte sedimentation rate o Alcohol use o Vitamins B & D status, Calcium? 5. Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science

Guidelines For The Management of AMD DIAGNOSIS

DIAGNOSIS History Symptoms o Metamorphopsia o Decreased vision o Photopsia o Difficulties in dark adaptation Medication and nutrition supplement use Ocular history Medical history (including hypersensitivity reactions) Family history (AMD) Social history (Smoking) Physical examination Comprehensive eye examination Stereoscopic biomicroscopic examination of the macula

DIAGNOSIS Diagnostic tests Spectral Domain Optical Coherence Tomography o OCT-Angiography (quiescent vs. active lesions?) Fundus Fluorescein Angiography Fundus Photography Indocyanine Green Angiography o PED, Occult CNV, PCV, RAP Other tests Fundus Autofluorescence o Geographic atrophy/lipofuscin Microperimetry Adaptative Optics

Guidelines For The Management of AMD CLASSIFICATION

CLASSIFICATION 6 No AMD Early AMD Intermediate AMD Advanced AMD (AREDS category 1) (AREDS category 2) (AREDS category 3) (AREDS category 4) Control group No or few small drusen (< 63μm) Multiple small drusen Few intermediate drusen (63-124 μm) Mild RPE abnormalities Numerous intermediate drusen At lease one large druse ( 125 μm) Geographic atrophy of the RPE (Not involving the center of the fovea) Geographic atrophy of the RPE involving the center of the fovea Neovascular maculopathy: CNV (pathologic angiogenesis from the choroidal vasculature extending the a defect in Bruch s membrane Serous/hemorrhagic detachement of NSR/RPE Retinal hard exudates Subretinal/sub-RPE fibrovascular proliferation Disciform scar 6. Age-related Eye Disease Study Research Group. A randomized, 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: AREDS report number 8. Arch Ophthalmol 2001;119:1417-36

Guidelines For The Management of AMD NATURAL HISTORY

NATURAL HISTORY 7 No AMD Early AMD Intermediate AMD Advanced AMD (AREDS category 1) (AREDS category 2) (AREDS category 3) (AREDS category 4) 15% large drusen @ 10 y 15% large drusen @ 10 y When medium drusen are present in 1 eye: 37% large drusen @ 10 y Beaver Dam Eye Study 22% neovascular/geographic atrophy in the fellow eye involving the fovea @ 5 y When medium drusen are present in 2 eyes: 71% large drusen @ 10 y AREDS 35%-50% neovascular/geographic atrophy in the fellow eye involving the fovea @ 5 y 7. Chew EY, Clemons TE, Agron E, et al. Age-related Eye Disease Study Research Group. Ten-year follow-up of age-related macular degeneration in the age-related eye disease study: AREDS report number 36. JAMA Ophthalmol 2014;132:272-7

NATURAL HISTORY 8 Simplified severity scale 8. Ferris FL, Davis MD, Seddon JM, et al. Age-Related Eye Disease Study (AREDS) Research Group. A simplified severity scale for agerelated macular degeneration: AREDS report number 18. Arch Ophthalmol 2005;123:1570-4

NATURAL HISTORY 8 Simplified severity scale This simplified severity scale enables the clinician to communicate with the patient about his/her approximate risk for developing advanced AMD 8. Ferris FL, Davis MD, Seddon JM, et al. Age-Related Eye Disease Study (AREDS) Research Group. A simplified severity scale for agerelated macular degeneration: AREDS report number 18. Arch Ophthalmol 2005;123:1570-4

Guidelines For The Management of AMD RATIONALE FOR TREATMENT

Guidelines For The Management of AMD RATIONALE FOR TREATMENT Prospective randomized controlled clinical trials support the use of antioxidant vitamins and minerals for: slowing the progression to later stages of AMD Decreasing the load of other modalities of treatment In 2017, there is no proven therapy to prevent or treat geographic atrophy

Guidelines For The Management of AMD TREATMENT MODALITIES

Visual Rehabilitation

Life Style Modification

ANTI-OXIDENTS Vitamins and Minerals Lutein/Zeaxanthin Omega -3 Fatty Acids

TREATMENT MODALITIES 9 No AMD Early AMD Intermediate AMD Advanced AMD (AREDS category 1) (AREDS category 2) (AREDS category 3) (AREDS category 4) No evidence to support the use of supplements No evidence to support the use of supplements Only 1.3% Advanced AMD The rate of development of advanced AMD @ 5 y was 25% The risk of losing vision 3 lines (doubling of the visual angle) was 19 % 9. Davis MD, Gangnon RE, Lee LY, et al. Age-Related Eye Disease Study Group. The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS report number 17. Arch Ophthalmol 2005;123:1484-98

TREATMENT MODALITIES 9 No AMD Early AMD Intermediate AMD Advanced AMD (AREDS category 1) (AREDS category 2) (AREDS category 3) (AREDS category 4) No evidence to support the use of supplements No evidence to support the use of supplements Only 1.3% Advanced AMD The rate of development of advanced AMD @ 5 y was 25% The risk of losing vision 3 lines (doubling of the visual angle) was 19 % Only these two groups benefit from antioxidant vitamin and mineral supplementation 9. Davis MD, Gangnon RE, Lee LY, et al. Age-Related Eye Disease Study Group. The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS report number 17. Arch Ophthalmol 2005;123:1484-98

TREATMENT MODALITIES Anti-VEGF (Aflibercept, Ranibizumab, Bevacizumab) are currently the preferred therapy to treat neovascular AMD over PDT and laser photocoagulation 10 This applies for subfoveal, juxtafoveal and extrafoveal lesions 10 10. Heier JS et al. VIEW 1 and VIEW 2 Study group. Intravitreal aflibercept in wet age-related macular degeneration. Ophthalmology 2012;119:2537-48 11. Schmidt-Erfurth U et al. Perspectives on verteporfin therapy combined with intravitreal corticosteroids. Arch Ophthalmol 2006;124:561-3 12. Kasier et al. DENALI Study Group. Verteporfin plus ranibizumab for choroidal neovascularization in AMD: 12 months results. Ophthalmology 2012;119:1001-10 13. Larsen M et al. MONT BLANC Study Group. Verteporfin plus ranibizumab for choroidal neovascularization in AMD: 12 months results. Ophthalmology 2012;119:992-1000 14. Koh et al. EVEREST Study: Efficacy and safety of verteporfin PDT in combination with ranibizumab or alone versus ranibizumab monotherapy in patints with symptomatic macular polypoidal choroidal vasculopathy. Retina 2012;32:1453-64

Novel Treatments

Guidelines For The Management of AMD MANAGEMENT

MANAGEMENT 15 IN 2017 Patients who are currently smoking should be advised to stop Patients should be encouraged to assess their own visual acuity using monocular vision testing (i.e., Amsler grid) Education about methods of detecting new symptoms is crucial Need for promptly reporting new symptoms to an ophthalmologist Education about preventive regimens and the use of nutritional supplements (AREDS2) Electronic devices are now available to aid in the detection of neovascularization at early stage: Preferential Hyperacuity Perimetry 15. AREDS2-HOME Study Research Group, Chew EY, Clemons TE, Bressler, et al. Randomized trial of a home monitoring system for early detection of choroidal neovascularization Home Monitoring of the eye (HOME) Study. Ophthalmology 2014;121:535-44

ForeseeHome Device Hyperacuity Visual Field Test Hyperacuity signals are briefly presented within the central visual field Patient s response to perceived distortion recorded using computer mouse Data is analysed in comparison to normative database and new visual field defects are identified.

MANAGEMENT 16 IN 2017 No AMD (AREDS category 1) Early AMD (AREDS category 2) RECOMMENDED TREATMENT Observation with no medical or surgical therapies Intermediate AMD (AREDS category 3) Advanced AMD (AREDS category 4) FOLLOW UP RECOMMENDATIONS Control group No or few small drusen (< 63μm) Multiple small drusen Few intermediate drusen (63-124 μm) Mild RPE abnormalities Advanced AMD with bilateral subfoveal geographic atrophy or disciform scars Numerous intermediate drusen At lease one large druse ( 125 μm) Geographic atrophy of the RPE (Not involving the center of the fovea) Geographic atrophy of the RPE involving the center of the fovea Neovascular maculopathy: Return exam @ 6-24 mo if asymptomatic, or prompt exam for new symptoms suggestive of CNV CNV (pathologic angiogenesis from the choroidal vasculature extending the a defect in Bruch s membrane Serous/hemorrhagic detachement of NSR/RPE Retinal hard exudates Subretinal/sub-RPE fibrovascular proliferation Disciform scar OCT, FFA, Fundus Photos as appropriate 16. American Academy of Ophthalmology. Preferred Practice Pattern. Age-Related Macular Degeneration. 2015 last update.

MANAGEMENT 16 IN 2017 RECOMMENDED No AMD TREATMENT Early AMD (AREDS Antioxidant category 1) vitamin and mineral supplements as recommended in the original AREDS/AREDS2 reports Control group No or few small drusen (< 63μm) (AREDS category 2) Multiple small drusen FOLLOW UP RECOMMENDATIONS Few intermediate drusen (63-124 μm) Monitoring of monocular Mild RPE near abnormalities vision (reading/amsler grid) Return exam @ 6-24 mo if asymptomatic, or prompt exam for new symptoms suggestive of CNV Intermediate AMD (AREDS category 3) Numerous intermediate drusen At lease one large druse ( 125 μm) Geographic atrophy of the RPE (Not involving the center of the fovea) Advanced AMD (AREDS category 4) in one eye Geographic atrophy of the RPE involving the center of the fovea Neovascular maculopathy: CNV (pathologic angiogenesis from the choroidal vasculature extending the a defect in Bruch s membrane Serous/hemorrhagic detachement of NSR/RPE Retinal hard exudates Subretinal/sub-RPE fibrovascular proliferation Disciform scar 16. American Academy of Ophthalmology. Preferred Practice Pattern. Age-Related Macular Degeneration. 2015 last update.

Guidelines For The Management of AMD CONCLUSION

Conclusion AMD is the leading cause of irreversible visual impairment in the developed countries Early detection and treatment are crucial to help preserve patients quality of live Smoking cessation is strongly recommended The use of nutritional supplements (AREDS2), when indicated, rate of development of advanced AMD by 25% in 5 years All patients should be educated about the prognosis of the disease and the potential value of treatment as appropriate for their visual and functional status Patients can be educated that while central visual loss is common, total visual loss is extremely rare hence the role of low vision aid