Will I Lose Vision from AMD?

Will I lose vision from AMD?
anatomy of the eye (click on image to enlarge)

What are the risk factors of losing vision?

If you have been diagnosed with AMD, you may ask, “Will I lose vision from AMD?” There are many risk factors that lead to the worsening of age-related macular degeneration (AMD).  Some are genetic (inherited) and some are environmental.  However, one the greatest risk factors is age.  This is, the older you are with AMD, the greater the risk of loss of vision.  Genetic testing can reveal high risk genes, such as CFH and ARMS2.  Therefore, a family history of vision loss from AMD increases your risk.  Other important factors that affect the risk of losing vision include tobacco use and diet.

What are the stages of AMD?

There are several stages of AMD that affect the risk of severe loss of vision: early, intermediate, and late AMD.  Early AMD presents with medium sized deposits under the retina called drusen.  These eyes usually have no symptoms and the vision is good.  Intermediate AMD have large drusen and/or brown pigmentary changes under the retina.  These changes frequently result in slow recovery from bright light (like coming in from outdoors) and the need for good lighting while reading.  Late AMD causes distortion of straight lines and blind spots in the vision from geographic atrophy (loss of retinal tissue) and/or neovascularization (new blood vessels grow under the retina that bleed and cause blind spots from scar tissue).  Geographic atrophy is also called advanced dry AMD, whereas neovascularization is called wet AMD.  

How can I determine my risk of late AMD with vision loss?

A point system has been developed to determine your risk of loss of central vision from late AMD.  Exam findings in each eye are given a point value.  Then, all the points are added together from the two eyes to arrive at risk of progression to late AMD within 5 years.  

Exam FindingPoint Value
medium drusen0.5
large drusen1
pigmentary changes1
geographic atrophy or neovascularization2
Add the points from findings in each eye
From: Ferris FL 3rd, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120(4):844-851. doi:10.1016/j.ophtha.2012.10.036

At total score of 1 yields a low risk of late AMD of under 5% in five years.  With 2 points, the risk is 12 percent.  Three points means a risk of 25% at five years.  And 4 points means there is a 50% chance of late AMD in five years.  Another way to calculate your risk of late AMD is to use an online calculator.  

How bad can the vision fall from late AMD?

Late macular degeneration may cause a large blind spot in the center of the vision in both eyes.  Although this renders an individual legally blind, it is important to remember that it is extremely rare to lose all vision from AMD.  The peripheral vision usually remains strong and this allows a person to get around a room and care for himself independently.  

Does everyone lose most of their central vision in late AMD?

No.  Many people retain useful vision.  Patients with advanced dry AMD may be treated with Syfovre or Izervay to slow the progression of geographic atrophy.  There are a host of medications that slow the loss of vision from wet AMD, including Avastin, Lucentis, Eylea, Beovu, and Vabysmo.  There is high expectation that further developments from ongoing research will offer even better odds of retaining useful vision in the future.  Those patients who do lose vision from AMD can be helped with low vision aids.  

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

Copyright  © 2023 Designs Unlimited of Florida.  All Rights Reserved.

Izervay for Dry Macular Degeneration

Izervay for dry macular degeneration
anatomy of the eye (click on image to enlarge)

What is Izervay?
The FDA approved Izervay for dry macular degeneration in August 2023. It is a new medication for the treatment of geographic atrophy caused by dry-type age related macular degeneration (AMD).  Izervay is given by injection into the eye.

What is geographic atrophy?

Geographic atrophy is a common cause of loss of central vision in AMD.  It occurs when retinal receptor cells die.  It leaves blinds spots and missing areas in the vision.  Until 2023, there was no treatment for geographic atrophy from AMD.    

What does Izervay do?

Izervay blocks complement proteins (C5) in the body.  Complement participates in the normal inflammatory response.  And the inflammatory response is important to fight infection.  However, in AMD the complement proteins contribute to the development of geographic atrophy and loss of vision.  

How well does Izervay work?

Izervay is not a cure for dry AMD.  Importantly, it does not reverse past damage by geographic atrophy.  Izervay, when given by monthly injection, reduces the rate of worsening of geographic atrophy by 28% over 18 months of treatment as compared with sham injection.  We anticipate this will delay blind spots from interfering with central vision.  

What are the adverse effects of Izervay?

As with all intraocular injections there are risks.  The risks involved with the introduction of a needle into the eye include bleedinginfection, and retinal detachment.  These complications may require surgery and risk loss of vision.  

Can Izervay cause wet macular degeneration to start?

The known risks of Izervay include the new occurrence of wet AMD with blood vessel growth threatening loss of vision.  In the phase 2/3 study, wet AMD developed in 12% of eyes treated with Izervay compared with 3% in eye with sham injection over a period of 18 months.  This represents a 400% increased risk of new-onset wet AMD.  It is important to avert the development of wet AMD because the treatment of wet AMD involves routine, long-term injections of antiVEGF medications to prevent severe loss of vision. 

What about the risk losing vision from infection?

There is a risk of infection (endophthalmitis) after any eye injection.  At this time, we do not know if Izervay may increase the risk of developing infection or worsen the final vision after infection.  The suppression of the natural defense against infection by Izervay, explains the concern over increased risk of infection with Izervay.  

Should I receive Izervay injections?

If you have dry age-related macular degeneration with geographic atrophy, Izervay appears to delay the loss of central vision over time.  However, long-term monthly injections are required.  And you must carefully consider the risks of treatment.  Your doctor will help you make this important decision.

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

Copyright 2023 Designs Unlimited of Florida. All Rights Reserved.

Diet and Age-Related Macular Degeneration

diet and age-related macular degeneration
anatomy of the eye (click on image to enlarge)

What is age-related macular degeneration?

A Mediterranean diet can protect against loss of vision from AMD.  But first, what is AMD?  Age-related macular degeneration (AMD) is the most common cause of visual loss in older Americans.  The macula is the area of the retina in the back of the eye that is responsible for seeing details in the central vision.  The retina is a thin layer of delicate nerve tissue that lines the inside wall of the eye like the film in a camera.  In the eye, light is focused through the lens onto the retina, which “takes the picture” and sends the image to the brain.  Macular degeneration is a disease that affects the central vision. It does not affect peripheral vision— the ability to see objects off to the side when looking straight ahead.  This means that macular degeneration alone does not result in total blindness.  

What lifestyle changes offer protection against macular degeneration?

Over the years, mounting evidence shows that lifestyle changes appear helpful to limit the risk of vision loss from age-related macular degeneration.  For example, tobacco exposure appears to worsen macular degeneration.  This means do not smoke tobacco and limit second-hand exposure to tobacco. Conversely, exercise appears to lessen the risk of vision loss from AMD.  Try to walk 20 minutes a day for starters.  Later, try to add some light weight-bearing exercises with dumbbells.  Finally, there is marginal evidence to recommend protecting your eyes from excessive sunlight.  Wear a hat and sunglasses if outdoors for several hours.  Diet is another way in which a patient may afford protection against AMD.  The Mediterranean diet is associated with reduced risk of cardiovascular disease and reduced risk of vision loss from AMD.

What is a Mediterranean diet?

The Mediterranean diet includes high intake of extra-virgin olive oil, vegetables (especially, leafy greens), fruits, cereals, nuts/legumes, moderate intake of fish and other meat, dairy products, and red wine, and low intake of eggs and sweets.   Red meats appear inflammatory.  Therefore, many recommend eating red meat only on rare occasions (no more than one serving per week).  Drinking one alcoholic beverage per day appears helpful; however,, avoid high intake of alcohol (greater than two alcoholic beverages per day).  Fish and seafood, on the other hand appear protective.  Try to include a serving of fatty fish like salmon at least three times a week.  If you are not a fan of seafood, consider taking coated fish oil capsules once a day.  The coated formulations help to avoid a fishy aftertaste.    

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

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Copyright  © 2023-2024 Designs Unlimited of Florida.  All Rights Reserved.

Syfovre for Dry Macular Degeneration

Syfovre for dry macular degeneration
anatomy of the eye (click on image to enlarge)

What is Syfovre?
Syfovre (pegcetacoplan) is a new medication approved by the FDA in February 2023 for the treatment of geographic atrophy caused by dry-type age related macular degeneration (AMD).  It is given by injection into the eye.

What is geographic atrophy?

Geographic atrophy (GA) is a common cause of loss of central vision in AMD.  It occurs when retinal receptor cells die.  As a result, GA leaves blinds spots and missing areas in the vision.  Until now, there was no treatment for geographic atrophy from AMD.    

How does Syfovre work?

Syforvre blocks the complement proteins in the body.  Complement proteins regulate the normal inflammatory response of the body.  The inflammatory response is important to fight infection.  However, in AMD the complement proteins appear to cause harm, as they contribute to the development of geographic atrophy and loss of vision.  

How well does Syfovre work?

Syfovre is not a cure for dry AMD.  Syfovre does not reverse the past damage by geographic atrophy and does not keep it from getting worse.  However, Syfovre, when given by monthly injection, slows the rate of worsening of geographic atrophy by 19-22% over two years as compared with sham injection. There was no measured benefit in visual acuity or visual function during the two-year study, perhaps because it would take longer for the benefits to be measured.   

What are the adverse effects of Syfovre?

As with all intraocular injections there are risks.  The risks involved with the introduction of a needle into the eye include bleeding, infection, and retinal detachment.  These complications may require surgery, and they risk loss of vision.  The known risks of Syfovre include the new development of wet AMD with blood vessel growth threatening loss of vision.  In the phase 2 study, wet AMD developed in 20.9% of eye treated with Syfovre compared with 1.2% in eye with sham injection.  This represents a 1,742% increased risk.  Post hoc analysis suggests the risk of new wet AMD from Syfovre may be reduced by avoiding treatment in high-risk eyes.  It is important to avert the development of new wet AMD because the treatment of wet AMD involves routine, long-term injection of antiVEGF medications to prevent severe loss of vision. 

There is risk of infection (endophthalmitis) after eye injections   The rate of infection with Syfovre was 1-2%…much higher than the rate of infection with other medications given by injection.  This increased risk may be explained by the suppression of the natural immune defense by Syfovre.  There is also a 1.7% risk of ischemic optic neuropathy. This is an unusual complication among the various drugs used for injection into the eye.

The decision to use Syfovre with the intent to slow the progression of dry AMD (geographic atrophy) must be weighed against the potential adverse effects in any given patient.

NOTE: As of August 19, 2023 the Syfovre phase 3 study results have not been published or available for review by prescribing physicians. These studies provided the basis on which the FDA gave approval for marketing Syfovre in the US.

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

Copyright  © 2023 Designs Unlimited of Florida

Vabysmo (faricimab) Therapy

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What is Vabysmo therapy?

            Vabysmo therapy (pronounced, “vah-BYE-smo”) is a treatment for wet-type macular degeneration and diabetic macular edema. It involves repeated injections of medication into the eye to stop abnormally leaky blood vessels. Vabysmo is the trade name of the medication and faricimab is the research/generic name. On January 28, 2022, the FDA approved Vabysmo for use in the United States based on standard phase 3 study results (Yosemite/Rhine Studies for diabetic macular edema and Tenaya/Lucerne Studies for wet macular degeneration).    

How effective is Vabysmo therapy?      

            Vabysmo may last longer than other drugs currently available to treat these conditions. However, it has been my experience that Vabysmo offers little additional benefit in diabetic macular edema. I currently prefer Lucentis in patients treated for diabetic macular edema. 

            In wet-type macular degeneration (wAMD), Vabysmo does appear to last longer than other currently approved medications in some patients. However, there appears to be an increased risk of loss of vision from RPE tear in patients with serous retinal pigment epithelial detachment in the setting of age-related macular degeneration.    

What are the risks of Vabysmo therapy? 

            Severe complications are very rare, but risks of Vabysmo injection include bleeding, infection, retinal detachment, glaucoma, cataract, and loss of vision/loss of the eye. The risk of retinal detachment is about 1 in 5,000 injections, but the visual results are poor despite surgical repair. In initial studies there appeared to be a low risk (1.8%) of stroke with this type of therapy. The risk of stroke may be related to the older age of patients in which it is used. Further investigation will provide more information. Non-infectious inflammation is less common with Vabysmo than brolucizumab (Beovu), another drug that offered drug treatment at reduced intervals. Although rare, inflammation did occur in Vabysmo (1-2% of cases) more than twice as often as it did with Eylea (1% or less). Pregnancy should be avoided while on Vabysmo therapy. 

What do I expect after a Vabysmo injection?

Be careful not to rub the eye after the injection because the eye may remain anesthetized for several hours. You may be given eye drops and instructions on how to use them. Physical activity is not limited after the injection. Tylenol or Ibuprofen may be used if there is discomfort, but severe pain should be reported to your doctor without delay. It is normal to experience a red area on the white of the eye, which disappears in one to two weeks. If you have any questions or concerns, please call the office.

UPDATE October 2022: I have been using Vabysmo in the office. I am pleased with the results in patients with wet AMD in that I can extend the treatment interval further than with older drugs. These findings are in concert with a recent two-year report of the Tanaya Study at the American Academy of Ophthalmology. However, patients with large serous pigment epithelial detachments (PED) appear to be at greater risk of vision loss from rips in the PED. In contrast to eyes with macular degeneration, I have not been impressed with superior effectiveness of Vabysmo in patients with diabetic retinopathy.

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

Copyright ©2022 Designs Unlimited of Florida.  All Rights Reserved

Lumega-Z: Worth the cost?

What is Lumega-Z?

Lumega-Z is a vitamin/mineral/antioxidant supplement that is taken by mouth and is labelled a medical food. A medical food is simply a name used to identify a product that is taken by mouth and produced by a company for the purpose of treating disease and/or improving health.  By definition, medical food must be prescribed by a physician and not sold over-the-counter.  Lumega-Z is presumed to improve retinal health and potentially prevent or treat macular degeneration.  

What does Lumega-Z do?

Lumega-Z aims to increase the amount of protective pigment in the macula with the hope that it will be helpful in the management of macular degeneration.  Guardion is the company that makes Lumega-Z.  They state in their website: “The Company’s current focus is on the Macular Protective Pigment (“MPP”), a bio-marker and major risk factor for developing Age-Related Macular Degeneration (“AMD”) and other retinal disorders.”

I take issue with this statement.  “Macular Protective Pigment” has not been shown to be a major risk factor for AMD.  Furthermore, the company cites no clinical research (even in their website for ophthalmologists) to support their claim that clinical benefit is derived from using their product.  

Perhaps, we may assume there is benefit from Lumega-Z as another nutritional supplement (PreserVision AREDS-2) has been shown to reduce the risk of progression of macular degeneration.  However, there are no current studies to compare the effectiveness of Lugema-Z with PreserVision AREDS-2.  Alas, the company itself concludes: “Guardion Health Sciences, the maker of Lumega-Z, cannot guarantee…any vision benefit with treatment.”

What about the company that makes Lumega-Z?

Gardion’s business plan is provide medical food (a label that means their product is for medical use and must be provided via prescription) to patients with ophthalmologists who partner with Guardion (and may derive financial benefit).  Gardion’s spokesman, Dr Hovenesian, is a refractive and cataract surgeon from California. His on their medical board of directors and a shareholder.  He is not a retina specialist.  

Is Lumega-Z worth the cost?

Lumega-Z costs twice as much as Preservision AREDS-2.  However, it has not been scientifically demonstrated to be twice as good as PreserVision AREDS-2.  Indeed, it has not even been shown to be equivalent to PreserVision AREDS-2.  At the time of this publication, I am of the opinion that Lumega-Z is not worth the cost.  I currently recommend PreserVision AREDS-2 to patients with AMD at risk for loss of vision as determined by examination.  

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

Pentosan (Elmiron) and Your Eyes

See Anatomy of the Eye

What side effects can pentosan polysulfate have on my eyes?

Although pentosan polysulfate (PPS) is of proven benefit for interstitial cystitis, it may cause damage to the eyes.  Early symptoms may be subtle.  Blurred vision, especially with reading, is common.  Straight lines may appear wavy or distorted.  There may be a slow adaptation from light to dark environments.  Blind spots or missing areas may occur in the central vision.  These symptoms are due to retinal damage; however, they are not specific to pentosan polysulfate damage.  The Eye MD (retina specialist) must use special tests to determine whether vision symptoms are due to pentosan polysulfate or other types of retinal conditions such as macular degeneration.    

Who is at risk of losing vision?

Ocular side effects appear to be related to a build-up of medicine in the body over years.  The longer a person has been on PPS, the greater the chances of developing retinal damage.  Although the average duration of use at the time of diagnosis is 15 years, some patients develop symptoms as early as three years after starting the medication.  With continued use of PPS, additional permanent damage occurs that may result in loss of vision.

What can I do to protect myself?

Pentosan polysulfate is an effective medication for control of pain with interstitial cystitis.  However, it is important to monitor your eyes for side effects that might indicate the need to stop the medication.  The Amsler grid chart should be checked at least once a week testing each eye separately, using glasses if needed.  Look for a missing part of the grid either above or below the central dot while looking only at the center of the grid.  Additionally, your Eye MD should examine your eyes every year with specific testing to look for early signs of retinal changes.  It may be useful to see a retinal specialist who has training in this area.

What happens if I develop retinal changes from pentosan polysulfate?

If early retinal changes are found, pentosan polysulfate may be discontinued.  By discontinuing pentosan polysulfate at an early stage, vision may be saved.  Continued examination is important to monitor the eyes for further changes.  There is no specific treatment for retinal toxicity from pentosan polysulfate. However, if blood vessels grow under the retina, treatment may be helpful as with wet macular degeneration.

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

Copyright  © 2019-2022 Designs Unlimited of Florida. All Rights Reserved.

Visudyne Photodynamic Therapy

globe anatomy
Anatomy of the Eye (click on image to enlarge)

What is photodynamic therapy?

Photodynamic therapy (PDT) is a treatment for retinal conditions in which leaky blood vessels threaten to cause permanent loss of vision. PDT involves the injection of a light-sensitive dye into the vein of the arm. The dye, called Visudyne, concentrates in the abnormal blood vessels that leak fluid and/or blood under the retina. A diode laser then activates the Visudyne, which seals the leaky blood vessels without the use of cauterizing lasers. By avoiding the use of cautery, PDT is able to treat abnormal leaking vessels with a much lower chance of causing a blind spot in the vision from the treatment. For this reason PDT is sometimes called the “cold laser.” PDT has largely replaced the cauterizing (hot) laser in the treatment of age-related macular degeneration and central serous chorioretinopathy.

What do I expect after photodynamic therapy?

For 48 hours you should avoid direct sunlight, which could activate some of the dye in your system before it is eliminated from the body. Sunlight or Halogen light may cause a severe light reaction and should be avoided during this time. For this reason it is advisable to come to the office for treatment wearing a long-sleeved shirt, gloves, long pants, socks, closed shoes, and a hat. Make arrangements for someone else to drive, so you may remain shielded from light in the back seat of the car on the way home from the office. After PDT, there are no limitations in physical activity or visual activity. Some doctors recommend against straining or heavy work for one week after the treatment to avoid putting too much pressure on the blood vessels in the eye. Although some blurring of vision is common immediately after treatment, severe changes in the vision should be reported to the doctor. It may take months for the treatment to take effect. Repeated treatments with PDT may be used as needed in difficult cases.

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

Copyright  © 2018-2022 Designs Unlimited of Florida.  All Rights Reserved.

The risk of stroke with treatment of Age-Related Macular Degeneration

The mainstay of treatment of wet-type age-related macular degeneration (AMD) requires the intraocular injection of medication (e.g. Avastin, Lucentis, Eylea, Beovu, and Vabysmo) to prevent loss of vision. Although effective, this treatment entails some degree of risk. For example, infection may occur at a rate of about one in one thousand to one in five thousand injections. Moreover, there may be a low increased risk of stroke.

Although some studies do not show increase risk (Campbell), other large studies have demonstrated an increased risk of stroke. In one study the increased risk of stroke appeared to be 1 in 127 patients within one year after starting treatment for AMD (Schlenker). These studies were unable to prove that the medication itself was responsible for the increased risk of stroke. For example, it may be that people with new-onset wet AMD are at a higher risk of stroke than others. In 2019 a population-based study demonstrated no increased risk of stroke and heart attack related to AMD treatment (see reference). Additional research in ongoing.

Given this information what are the options? Certainly, a patient may decide not to treat macular degeneration and risk loss of vision in an effort to decrease the risk of stroke. Another option may be to minimize the frequency of injections. That is, if the macular degeneration remains stable after several monthly injections, consider extending the time interval between injections. In this manner there is less exposure to the drug. Furthermore, if the wet-AMD appears to have reached end-stage with significant loss of vision, the injections might be stopped altogether. If done carefully, one may reduce the risk of a sudden recurrence of wet-AMD with further loss of vision while off treatment.

The type of medication used for injection has not been proven to make a difference in the risk of stroke. Although Martin et al found a slight increase in stroke risk with Avastin compared with Lucentis, these findings were not supported by Chakravarthy and Schlenker. More research is needed to better define risk of stroke and how we may minimize the risk. A recent meta-analysis of current data as of 2022 (Reibaldi) supports Lucentis over the other agents as being safer from a systemic risk of heart attack and stroke.  Please refer to my blog on medication choices for treating retinal problems.

By Scott E. Pautler, MD

For a telemedicine consultation with Dr Pautler, please send email request to spautler@rvaf.com. We accept Medicare and most insurances in Florida. Please include contact information (including phone number) in the email. We are unable to provide consultation for those living outside the state of Florida with the exception of limited one-time consultations with residents of the following states: Alabama, Arkansas, Connecticut, Georgia, Minnesota, and Washington.

References:

Ophthalmology 2012 119:1604-1608 Campbell

AJO 2015 160:569-580 Schlenker

Ophthalmology 2012 119:1388-1398 Martin

Ophthalmology 2012 119:1399-1411 Chakravarthy

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