Lecture 7 - AMD Flashcards
what are the hallmark findings of dry AMD?
drusen, RPE hyperpigmentation and RPE atrophy
what are the hallmark findings of wet AMD?
choroidal neovascularization, sub-retinal/sub-RPE fluid, and sub-retinal/sub-RPE blood
what is the risk of conversion from dry to wet AMD?
1-5% chance after 1 year and 13-18% chance after 3 years
who typically gets AMD?
12-30% over age 80, 89% white and 65% female
what is the biggest risk factor for AMD?
age = risk advances with increased age (2nd is race = caucasian because RPE pigmentation is protective)
what are other risk factors for AMD besides age and race?
family history (Tyr402His and Ala69Ser - part of complement factor H gene), smoking, UV exposure, systemic diseases (cardiovascular disease, obesity, HTN, high cholesterol)
how do you calculate the risk based on smoking?
pack years = if they smoked 1 pack a day for 1 year they have a 1 pack year smoking history (if they smoke 1/2 pack a day for 50 years they have a 25 year pack history)
what are the 5 layers of bruch’s membrane?
basement membrane of RPE, inner collagenous zone, elastic fiber layer, outer collagenous zone, basement membrane of the choriocapillaris
what happens to bruch’s with aging, what increases and what decreases?
increases = type 1 collagenm debris, filamentous material, glycosaminoglycans decreases = laminin, fibronectin and type 4 collagen
what is the pathophysiology of dry AMD?
problem with RPE, bruch’s or choriocapillaris = ultimately affects the photoreceptor function as a result of oxidative stress and inflammation
what happens during oxidative stress?
radiation (UV) and oxygen side effects (pro-oxidants) produce free radicals - damaged photoreceptors are taken in by RPE cells - RPE cells cannot handle amount and results in RPE damage
what happens during inflammation?
inflammation induces complement system - forms the membrane attack complex (MAC) - MAC injures RPE cells and endothelial cells of choriocapillaris
how does RPE damage occur?
damage to matrix metalloproteins (cannot get rid of byproducts like normal) - backed up byproducts get deposited between basal lamina of RPE and bruch’s = Drusen and RPE cells disorganize = atrophy and hypertrophy
what is the composition of drusen?
basal laminar deposits = lipid and collagen
basal linear deposits = phospholipid vesicles and granules
what are the sizes of drusen?
small less than 63um, intermediate between 64-124um, and large larger than 125um
what is the histology of drusen?
hyaline material accumulations and lipid rich
what is the result of hydrophobic and hydrophilic drusen?
hydrophobic = predispose RPE detachments hydrophilic = predispose formation of CNVM
what causes RPE atrophy?
photoreceptor death, large drusen push pigment away, perfusion abnormalities and decreased vascular density, flattening of RPE detachments and regression of confluent drusen
what is geographic atrophy?
may be the end stage of Dry AMD - will never develop wet (neo) the RPE is dead
what is the pathophysiology of wet AMD?
damage to RPE stimulates neo from choroid - new vessels contain fibroblasts (aka network or membrane) = VEGF and CNVM occur
what are the symptoms of dry AMD?
may be asymptomatic, gradual vision loss, central scotomas, and amsler grid defects
what are the signs of dry AMD?
hard/soft/confluent/calcified drusen - RPE hyperpigmentation - RPE hypopigmentation - RPE atrophy - geographic atrophy
what do hard drusen look like?
small (less than 64 microns), discrete and well demarcated
what do soft drusen look like?
larger than 64 microns, poorly defined borders, yellow-white
what do confluent drusen look like?
soft drusen that have coalesced - can cause focal RPE detachment
what do calcified drusen look like?
calcification of soft drusen - more white and refractile than soft
what is RPE hyperpigmentation?
migration of RPE cells and the photoreceptor layer
what is RPE hypopigmentation?
areas where RPE cells are absent of not-pigmented, usually counter to RPE hyperpigmentation or indicates a larger area of RPE atrophy, geographic atrophy
what is RPE atrophy?
results from = large are of hypopigmentation, previous drusen, RPE detachment, choroidal neo - the choroid is visible and photoreceptors are absent (VA loss)
what is geographic atrophy?
end of cycle = large areas of contiguous RPE atrophy - causes the most visual dysfunction of dry AMD (12-20% legal blindness)
what are RPE atrophy symptoms?
decreased vision/central scotoma, missing areas on amsler grid, and may have metamorphopsia
what are the symptoms of wet AMD?
vision loss is more sudden (over 1 weeks time), metamorphopsia, and central scotoma
what are the clinical findings of wet AMD?
CNVM/gray-green CNV lesion, sub-RPE or sub-retinal (fluid, blood, lipid), sub-retinal pigment ring, irregular elevation of RPE, and pigment epithelial detachment (PED)
what are the types of PED?
serous (coalesced drusen - fluid accumulates from choroid) and vascular (CNVM pushes RPE from bruchs)
what are the 2 types of CNVM?
classic = uniform lesion with typical IVFA pattern, easier to treat
occult = irregular lesion with typical IVFA pattern
most are a combination of both
what is a disciform scar in wet AMD?
also called fibrovascular scar or net = end stage of CNVM (fibrous tissue proliferation - hemorrhage or hyperplasia of RPE)
what are normal aging changes?
only druplets (small drusen
what is early AMD?
medium drusen (greater than 63um and less than 125um) and no AMD pigmentary abnormalities
what is intermediate AMD?
large drusen ( greater than 125um) and/or any AMD pigmentary abnormalities
what is late AMD?
neovascular AMD and/or any geogrphic atrophy
what are the different tests used in AMD?
amsler grid, macula OCT, IVFA, ICG
what does drusen look like in an OCT?
within the RPE layer - local elevations/irregularities
what does RPE atrophy look like in an OCT?
missing areas of RPE layer, window defect - choroid is directly visible (more hyper-reflectivity)
what does a PED look like on an OCT?
serous PED = elevated dome shape, sharply demarcated edges, black or optically empty - fluid
fibrovascular PED = irregular borders, not black but shadowed, no dome shape pattern
what does a CNVM look like on an OCT?
looks like a fibrovascular PED, no typical dome shape, irregular borders and interior is filled with material
what does a disciform scar look like on an OCT?
intraretinal cyst - large area of scar tissue, elevated in OCT scan
what does dry AMD look like on FA?
all components will hyperflouresce except pigment with hypofluoresce (drusen hard/soft will stain directly) and the RPE hypertrophy will block NaFl
what does geographic atrophy look like on FA?
early hyperfluorescent and late scleral staining
what does a classic CNVM look like on FA?
well-demarcated lacy pattern
early phase = bright uniform hyperfluorescence
transit phase = progressively intensifies
late phase = dye leakage outside the borders
what does an occult CNVM look like on FA?
early phase = elevation of RPE, granular irregular
late phase = progressive leakage, still granular and not as diffuse/uniform as classic
when is ICG used in AMD?
most advantageous in occult CNVM in determining exact location
what is the follow up for dry AMD?
6-12 months (depends on appearance) early hard drusen = 12 months some soft drusen = 9 months extensive soft drusen = 6 months geographic atrophy = 6-12 months
what is the follow up for wet AMD?
any new area of CNVM, bleeding, fluid = refer to OMD for treatment and will follow up every 1-3 months until CNVM resolves
what is the follow up for a disciform scar?
if scarring is extensive = new treatment will not be affective, monitor every 12 months
what can patients do to self-monitor?
amsler grid 1x per week = look for metamorphopsia and missing lines, decreased vision, and central scotoma
what are some lifestyle changes for AMD?
stop smoking, sun protection, manage chronic conditions, diet
what tests do you perform if you suspect a CNVM?
OCT, FA, and preferential hyperacuity perimeter (highly sensitive to changes in photoreceptors)
what groups are AREDS 1 most effective for?
intermediate AMD and advanced AMD in 1 eye (no benefit for early AMD, geographic atrophy, CNVM or disciform scar)
what is in the AREDS 1 formula?
500mg Vitamin C, 400 IU Vitamin E, 15mg Beta Carotene, 80mg Zinc oxide, 2mg cupric oxide (copper)
what were the issues with AREDS 1?
beta-carotene is a concern with smokers (lung cancer), high levels of zinc may cause a copper deficiency, and new studies showed lutein/zeathanthin/omega 3 fatty acids may help
what did the AREDS 2 study conclude?
overall no benefit for = lutein/zeathanthin, lowering zinc dose, removing beta-carotene and adding omega 3 (only benefited smokers and those with little lutein/zeathanthin in diet)
what is the AREDS 2 formula?
500mg Vitamin C, 400 IU Vitamin E, 80mg Zinc oxide, 2mg cupric oxide (copper), 10mg Lutein, 2mg Zeathanthin
what are the vitamin recommendations?
multivitamin, AREDs 2 formula for moderate dry AMD and advanced dry/wet AMD in 1 eye
what are the treatments for CNVM?
anti-VEGF = lucentis, avastin, macugen, eylea (upon sign of CNVM inject every 3-6 months as needed)
what are other treatments for wet AMD besides anti-VEGF?
laser (at leaking vessels - rarely used), PDT (rarely used) and low vision aids
