11/18/21, 1:25 PM
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`Macular Degeneration: Timeline of Vision Loss Progression
`
`=
`
`verywellheatth
`
`Q
`
`EYE HEALTH
`
`MACULAR DEGENERATION
`
`Macular Degeneration: Timeline of Vision
`Loss Progression
`
`By SherryChristiansen Updated on March 21, 2021
`
`@W Medically reviewed by JohnstoneM.Kim,MD
`
`Table of Contents
`
`PathologyofAMD
`
`Early-StageAMD
`
`Intermediate-StageAMD
`
`Late-StageAMD
`
`Macular degeneration, also known as age-relatedmaculardegeneration
`(AMD), is the namefor a condition involving a group of long-term
`(chronic), degenerative eye diseases. AMD is the leading causeof legal
`blindnessin the U.S. and in many other countries aroundthe globe. "!
`
`The condition involves several stages, from the early stage, to the
`intermediate, andfinally, to the late-stage (which often involves vision
`loss). But not everyone with AMDgoesthroughall of the stages, and many
`people do notlose their vision; those whodo reachthe late-stage of the
`disorderare often able to maintain normalvision for mostof theirlifetime.
`
`Advertisement
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
`
`
`
`Mylan v. Regeneron,
`IPR2021-00881
`
`U.S. Pat. 9,254,338,
`Exhibit 2264
`
`1/23
`
`Exhibit 2264
`Page 01 of 23
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`11/18/21, 1:25 PM
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`Macular Degeneration: Timeline of Vision Loss Progression
`
`So, what is the mac
`
`»SS progression?
`
`Whatdoesclinical r
`
`https:/Awww.verywellhealth.com/macular-degeneration-timeline-5069947
`
`Exhibit 2264
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`Page 02 of 23
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`Exhibit 2264
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`Macular Degeneration: Timeline of Vision Loss Progression
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`The Pathology of AMD
`
`AMDimpactspartof the retina called the macula, causing irreversible
`deterioration, which can result in visual distortions and may eventually
`cause vision loss. The macula is an oval yellowish area near the center of the
`retina in the eye;it’s the region responsible for clear, straight forward
`vision.
`
`Theretina is a layer of cells that are light sensitive. Thesecells trigger nerve
`impulses that pass through theoptic nerveto the brain, wherevisual
`images are formed.
`
`Macular degeneration is diagnosed by a comprehensive eye exam and other
`tests such as scansofthe retina. Small yellow deposits—called drusen—are
`often detected. They are a normalpartof aging.
`
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`
`But when drusenbegin to grow larger in size and number,they can lend
`themselves to the deterioration of the macula andput a personatrisk for
`macular degeneration. '?! Once a certain numberandsize of drusen are
`detectable by the ophthalmologist, the macular degeneration timeline of
`vision loss progression may begin.
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
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`3/23
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`Macular Degeneration: Timeline of Vision Loss Progression
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`Advertisement
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`
`Two Forms of AMD
`
`There are two formsof age-related macular degeneration (AMD)including
`the wet form and the dry form. DryAMD involves the presence of drusen, as
`well as pigment changesthat can impact a person’s vision over time;
`usually, dry AMDprogressesvery slowly.
`
`WetAMD involves the abnormal growthofblood vessels underthe retina
`
`that leak or burst, causing visual distortion, blank spots, and rapid decline
`in vision. Some people experiencesevere visual impairment within days or
`weeksof the onset of wet AMD.!?!
`
`Advertisement
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
`
`4/23
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`Exhibit 2264
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`Page 04 of 23
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`Exhibit 2264
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`11/18/21, 1:25 PM
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`Macular Degeneration: Timeline of Vision Loss Progression
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`
`
`Related:WetandDryFormsofMacularDegeneration
`
`Vision Loss Timeline
`
`You may find conflicting resources regarding the average timeline involved
`from initial diagnosis of AMDto the pointof vision loss. But, according to
`ophthalmologist Joshua Dunaief, MD, “Fortunately, most patients with
`AMDcan keep goodvision for their entire lives, and even those who lose
`their central vision almost always maintain their side, or peripheral
`vision." 4!
`
`There are three stages/phases of macular degeneration that are generally
`recognized—early, intermediate, andlate.'5!
`
`Early-Stage AMD
`
`Early-stage AMD involves medium-sized drusen deposits seen upon eye
`examination. No pigment changesare present, and there is usually no
`vision loss at this stage of the disease. '°! Early-stage AMDis usually
`detected upon a routine eye examination by an opthalmologist (eye medical
`professional) or other healthcare provider.
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
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`§/23
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`Macular Degeneration: Timeline of Vision Loss Progression
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`Duringthis initial stage, an ophthalmologist can detect drusen, long before
`symptomsoccur. The healthcare provider may advise you to have frequent
`eye exams to monitor for new signs or symptomsthat could indicate
`progression of macular degeneration.
`
`Even if you have no symptoms, it’s very important to follow the healthcare
`provider’s advice on the regularity of eye exams oncethe early stage of AMD
`has beenidentified.
`
`Action Steps During the Early Stage
`
`There are several things you can do,in an effort to help stave off the
`progression of AMD once youareinitially diagnosed with stage-one
`macular degeneration, these include:
`
`If you smoke, quitsmoking. Several large studies have indicated that
`smoking more than doubles a person’s risk of AMD. [5!
`Eat a balanced diet, rich in dark green leafy vegetables (such as romaine
`lettuce, kale, and spinach), yellow and orangefruits and vegetables (such as
`cantaloupe, apricots, orange and yellow peppers, sweet potatoes and
`squash) and omega6fatty acids (found in wild-caught, cold-waterfish,
`like salmon).
`Visit your ophthalmologist regularly. Follow your healthcare provider’s
`advice on howoften to get eye exams.
`Start doing self-screenings to check for progression of AMD. The Amsler
`chart, with horizontal and vertical lines, is the most common home
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
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`6/23
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`Exhibit 2264
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`Macular Degeneration: Timeline of Vision Loss Progression
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`recommend howoften to perform the exam. Some experts advise a weekly
`screening.'7!
`Get your blood pressure checked regularly, have routine physical exams,
`and maintain a heart-healthy lifestyle when it comesto diet, exercise, and
`managingstress. According to the American Macular Degeneration
`Foundation (AMDF)risk factors for AMD include being overweightor
`having uncheckedheart disease or high blood pressure.'®!
`Avoid long-term exposureto bright sunlight withouteye protection.[®!
`
`
`
`Related: 7WaystoPreventMacularDegeneration
`
`Timeline of Progression From Early Stage
`
`Age-related macular degeneration usually begins at age 55 or older. Thereis
`a very low risk of progression from theearly stage to the late stage of AMD
`(which involvesvision loss) within five years after diagnosis.
`
`In fact, one study discovered that only 15%of those with small drusen at
`diagnosis, continued on to develop large drusen. (which are often noticeable
`during the intermediate or late-stages of AMD). '9!
`
`Intermediate-Stage AMD
`
`Intermediate-stage AMD involves large drusen, or multiple medium-sized
`drusen and/or pigment changesare presentin oneor both eyes, upon
`examination by the ophthalmologist. Pigment changes,also called retinal
`pigmentepithelium (RPE) disturbances, can leadto visionloss.
`
`The RPE is the pigmentedlayer of the cells (located between the retina and
`the layer of blood vessels, called the choroidlayer). Studies suggest that the
`RPE is where macular degenerationstarts to occur.''°! The function of the
`RPEis to absorb light and transport nutrientsto theretinalcells. "°!
`
`Symptomsthat commonly occur during the intermediate stage could
`include subtle changesin vision, but for many people, there are no
`symptomsyet. Some people begin to see black or gray spots in the center of
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
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`7/23
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`Macular Degeneration: Timeline of Vision Loss Progression
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`Action Steps During the Intermediate Stage
`
`There are a couple of things you can doatthis stage:
`
`Special vitamins calledAREDS2vitamins may beprescribed to help slow
`
`downthe progression of AMD during the intermediate stage, if your
`ophthalmologist has not already doneso.
`Follow your ophthalmologist’s recommendations about eye exams and
`self/home screenings. Those with intermediate AMDare at a much higher
`risk of developing late-stage AMD (with visionloss). (11)
`
`Timeline From Intermediate to the Late Stage
`
`If a person in the intermediate-stage of AMD haslarge drusenin oneeye,
`there is a 6.3% chance of developing late-stage AMD (with vision loss)
`within five years of diagnosis. But if the large drusenis present in both
`eyes, the likeliness of developing late-stage AMDincreases to 26%.
`
`In a study, approximately 37%of those in the intermediate-stage of AMD
`with medium drusenin one eye, went on to develop large drusen and 71%of
`those who had medium drusenatbaseline, developed large drusen at the
`10-year follow-up. 2!
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
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`8/23
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`Exhibit 2264
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`Page 08 of 23
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`Exhibit 2264
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`Macular Degeneration: Timeline of Vision Loss Progression
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`Late-stage AMDinvolves either the wet form of AMD or dry AMD;in the
`late-stage either form of AMD causesdistortion of vision and/orvisionloss.
`The wet form of AMD progresses much faster than the dry form, and wet
`AMDis much morelikely to causevision loss.
`
`Whencentral vision loss begins, objects may appeardistorted or blurry at
`first, but in the late-stage of the disease, objects in the middle of yourline
`of vision cannotbeseenatall, although in the peripheral field (side vision)
`objects are usually still visible, but it may be difficult to decipher what they
`are, !61
`
`In the late-stage of the disease, a person may nolongerbe able to recognize
`faces and although they maystill have peripheral (side) vision, they may be
`consideredlegallyblind.'!
`
`Action Steps for Late-Stage AMD
`
`There are several treatmentoptions for late-stage AMD(including
`treatment for wet or dry AMD). Important steps to take after a diagnosis of
`late-stage AMDinclude:
`
`Talk to your ophthalmologist about treatment options, there are many
`options, and new treatmentis always on thehorizon.
`Discuss with your healthcare provider the option of surgery to implant a
`lens that can magnify your view of images and enable the functional
`portions of your eye take over from the damaged parts. The surgery doesn’t
`workfor everyone, butit’s a viable option for some people with late-stage
`AMD.
`If surgery isn't an option for you, discuss options for working with an
`occupational therapist. A therapist can help people with low vision learn
`how to use many types of adaptiveequipment (such as audible clocks and
`computer programsthat read webpagesout loud) to help you function
`better.
`If you've been diagnosed with wet AMD,talk to your ophthalmologist about
`treatment options, the launch of new treatment such as anti-VEGFtherapy
`is touted to have revolutionized the treatment of wet AMD."3!
`Discuss any symptomsof anxiety or depression with your healthcare
`provider and be opento various types of available treatment (such as
`
`https:/Avww.verywellhealth.com/macular-degeneration-timeline-5069947
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`9/23
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`Macular Degeneration: Timeline of Vision Loss Progression
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`to the manylosses and challenges involved in havinglowvision. "4!
`
`Timeline for Late-Stage AMD
`
`There are several factors which influence how long it takes for AMD to reach
`the late-stage, wherevision loss occurs.
`
`Accordingto a study published by the National Center for Biotechnological
`Information, approximately 1 to 3 people out of 100 with small drusen have
`vision loss within thefirst five years of diagnosis and 50%of those with
`larger drusen experience late-stage vision loss withinfive years. '°!
`
`It’s important to note that in a small percentage of cases, dry AMD can
`progress to wet AMD.In fact, according to the American Macular
`Degeneration Foundation, about 10%ofall cases of age-related macular
`degeneration become wet AMD(typically a person has dry AMDfirst and
`progresses toward wet). '"5!
`
`Wet AMDusually progresses quickly and vision loss can occur within daysif
`left untreated. That is the reason it’s so important to have your eyes
`checked frequently and to perform home-screenings (such as the Amsler
`Chart) as instructed by your ophthalmologist.
`
`Wasthis page helpful?
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`10/23
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`Macular Degeneration: Timeline of Vision Loss Progression
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`TCSaSStVaySveTTTwasewintyemp©TeveieVeetSee
`
`Fact checked by Angela Underwood
`
`
`
`EYE HEALTH
`
`Types of Macular Degeneration: Wet, Dry, and Stargardt
`Disease
`
`Medically reviewed by Bryan M. Wolynski, OD
`
`
`
`
`EYE HEALTH
`How Is Dry Age-Related Macular Degeneration Treated?
`
`Medically reviewed by Johnstone M. Kim, MD
`
`https:/Awww.verywellhealth.com/macular-degeneration-timeline-5069947
`
`11/23
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`Exhibit 2264
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`Page 11 of 23
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`Exhibit 2264
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`11/18/21, 1:25 PM
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`Macular Degeneration: Timeline of Vision Loss Progression
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`
`
`WhatIs Dry Age-Related Macular Degeneration (AMD)?
`Medically reviewed by Johnstone M. Kim, MD
`
`EYE HEALTH
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`How Are Macular Degeneration and GlaucomaDifferent?
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`
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`
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`
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`
`By Troy Bedinghaus, OD
`
`https:/Awww.verywellhealth.com/macular-degeneration-timeline-5069947
`
`12/23
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`Exhibit 2264
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`Macular Degeneration: Timeline of Vision Loss Progression
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`
`
`Vitamins and Supplements for Macular Degeneration
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`
`
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`
`Medically reviewed by Johnstone M. Kim, MD
`
`https:/Awww.verywellhealth.com/macular-degeneration-timeline-5069947
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`13/23
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`Macular Degeneration: Timeline of Vision Loss Progression
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`EYE HEALTH
`
`Do You Have Symptomsof Macular Degeneration?
`Medically reviewed by Ami A. Shah, MD
`
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`
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`
`https:/Awww.verywellhealth.com/macular-degeneration-timeline-5069947
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`14/23
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`Exhibit 2264
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`Macular Degeneration: Timeline of Vision Loss Progression
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`EYE HEALTH
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`
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`
`https:/Awww.verywellhealth.com/macular-degeneration-timeline-5069947
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`15/23
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`Macular Degeneration: Timeline of Vision Loss Progression
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`Medically reviewed by Johnstone M. Kim, MD
`
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`Macular Degeneration: Timeline of Vision Loss Progression
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`Exhibit 2264
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