Author Archives: Scott Pautler

HTLV1-Associated Uveitis

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HTLV1-associated uveitis
Anatomy of the eye (click on image to enlarge)

What is HTLV1?

HTLV1 is a virus that causes HTLV1-associated uveitis. It is an abbreviation for human T-lymphotropic virus type 1.  First isolated in 1980, HTLV1 belongs to the retrovirus group that also includes the virus that causes HIV/AIDS.  Retroviruses are called “retro” because they use a pathway to reproduce that is the reverse of what most organisms use.  The genetic map of retroviruses is RNA, which is converted inside host cells to DNA by a special enzyme (reverse transcriptase).  The host cell is then directed to produce more virus particles.  HTLV1 is called “lymphotropic” because it tends to infect lymphocytes, which are a type of white blood cell involved with immunity (see Legrand).  

How and where do you get exposed to HTLV1?

Because most people with HTLV1 infection remain without symptoms, they carry the virus and spread it to others by sexual contact (semen), shared blood (e.g. IV drug-shared needles, organ transplantation), and by breast milk.  HTLV1 is found in most frequently in people from Brazil, Japan, sub-Saharan Africa, Honduras, Iran and the Caribbean islands.  However, due to international travel, HTLV1 may be found anywhere in the world.

What problems does HTLV1 cause?

Many people who are exposed to HTLV1 develop no symptoms. However, because HTLV1 affects white blood cells, it may cause autoimmune conditions, as well as blood cancer. For example, autoimmune conditions include seborrheic dermatitis (infective rash), paralysis (tropical spastic paresis), and uveitis (see Schierhout). Examples of blood cancer include T-cell lymphoma and leukemia.

What is Uveitis?

Uveitis (pronounced, “you-vee-EYE-tis”) is a general term used to describe inflammation inside the eye.  The uvea is the name given to the layer of tissue in the eye that has a brown color (melanin pigment) and blood vessels, which serve to provide blood supply and protect the eye from excessive light.  The uvea can be divided into separate parts, which perform different functions in the eye: the iris, the ciliary body, the pars plana, and the choroid (see anatomy of the eye).  Therefore, in any one patient uveitis is usually given a more specific name depending on where most of the inflammation is located in the eye. Sometimes, uveitis affects tissues not considered a part of the uvea.

What type of uveitis is most common with HTLV1?

Intermediate uveitis is the most common type of uveitis caused by HTLV1. In intermediate uveitis the inflammation mainly centers in the vitreous gel (the clear gel that fills the eye). This type of uvetiis is called intermediate because it affects the middle or intermediate part of the eye. That is, the vitreous gel fills the eye and is located in an intermediate position between the front and the back of the eye. Vitritis and pars planitis are other names for intermediate uveitis.    

Who is most likely to develop HTLV1-associated uveitis (HAU)?

The age group most likely to be affected by HAU is between 20-49 years; however, any age group may develop HAU (see Mochizuki).  Female are affected by HAU twice as often as males (see Takahashi).  It appears that the eye inflammation (uveitis) is caused by the effect of HTLV1 infection on the behavior of white blood cells (lymphocytes), rendering them more likely to mistakenly attack the eye (see Mochizuki).  HAU may occur with or without other ocular inflammatory conditions, such as thyroid eye disease (see Nakao). Likewise, HAU may occur with or without non-ocular HTLV1-associated conditions, such as paralysis, rash, or blood cancer. 

What are the symptoms of HTLV1-associated uveitis (HAU)?

The most common symptoms include tiny floating spots which move or “float” in the vision.  They are usually numerous and may cause a veil-like appearance in the vision.  Sometimes blind spots, blurred vision, distortion, or loss of side vision occurs. The eye may be painful, red, tearing, and light sensitive if other parts of the eye are also inflamed (5-10% of cases).  Symptoms may be mild or they may be severe and disabling.  Only one eye is affected in about half of all cases of HAU (see Takahshi).

How is HTLV1-associated uveitis (HAU) diagnosed?

Diagnosis can be difficult.  Blood tests are performed to identify HTLV1 infection in patients with findings that suggest HAU.  One FDA-approved test is produced by MP Biomedicals Diagnostics: HTLV blot 2.4 (EIA).  Sometimes, accurate diagnosis requires multiple tests.  

How is HTLV1-associated uveitis (HAU) managed?

There is no cure for HTLV1 infection.  To limit the damage from inflammation, HAU is treated with anti-inflammatory medication in the form of eye drops, injections, or pills.  When pills are used, the eye doctor may coordinate medical care with the expert assistance of a rheumatologist.  Rarely, surgery is required to treat uveitis.  Episodes of inflammation may last from weeks to many years.  HAU is a serious eye problem and may result in loss of vision (see Takahashi).  However, by seeing your eye doctor and taking the medications exactly as recommended, damage to your vision can be minimized.  Most people with HAU keep good vision (See Nakao).  In some cases, HAU may go away, but return at a future date in about 50% of cases (see Takahashi).  Therefore, if you become aware of symptoms of uveitis in the future, do not hesitate to contact your doctor. 

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.

Reduce the Risk of Wet AMD from Syfovre

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how to reduce the risk of wet AMD from Syfovre
anatomy of the eye (click on image to enlarge)

What is Syfovre?

Before talking about how to reduce the risk of wet AMD from Syfovre, we must learn about AMD and Syfovre. Syfovre is the first FDA-approved treatment to reduce the risk of losing vision from dry age-related macular degeneration (AMD) due to geographic atrophy.  In the phase 2 study, eyes treated by monthly injection of Syfovre showed a reduction in the rate of progression of 29%.  It is important to note that Syfovre does not reverse past damage from dry AMD, and it is not a cure for dry AMD.  

Does Syfovre increase the risk of wet AMD?

A major concern of treatment is the adverse effect of new wet AMD developing in eyes treated with Syfovre.  Wet AMD is another form of advanced AMD in which abnormal blood vessels start to grow under the center of the retina (the macula).  The abnormal vessels in wet AMD will cause a large central blind spot in the vision unless treated with regular injections of antiVEGF medicines.  Among eyes treated with Syfovre in the phase 2 study, 20.9% of treated eyes developed new wet AMD compared with 1.2% of eyes in the study who did not receive this treatment.  Therefore, in an effort to prevent loss of vision from dry AMD, Syfovre raises the risk of vision loss from new wet AMD. 

How can we reduce the risk of wet AMD in eyes treated with Syfovre?

There are several things to consider that may be helpful in reducing risk.  Table 1 shows the effect of avoiding the use of Syfovre in eyes whose fellow eye already has wet AMD.  This is a risk factor for developing wet AMD in the second eye.  The risk of the second eye developing wet AMD appears to be further increased with the use of Syfovre.  Among eyes undergoing monthly Syfovre injection, the risk of new wet AMD is reduced to 12% compared with 20.9% of all study eyes and 33.3% of eyes with wet AMD in the fellow eye.  Similarly, in eyes undergoing Syfovre injection every other month, the risk of new wet AMD is reduced to 3.9% compared with 8.9% of all study eyes and 17.9% of eyes with wet AMD in the fellow eye.  Therefore, patients who already have one eye with wet AMD may wish to reduce their risk of developing wet AMD in their second eye by avoiding the use of Syfovre.

Table 1: FILLY phase 2 study: New wet AMD among study eyes. Studying the effect of wet AMD in the fellow eye

ParametersSham (no drug)Monthly drug injectionEvery other Month drug injection
All study eyes1.2%20.9%8.9%
Fellow wAMD0%33.3%17.9%
No fellow wAMD1.9%12%3.9%
Eyes without wet AMD in the fellow eye had lower rates of wet AMD (wAMD) among treated eyes.

Table 2 (below) shows the difference among study eyes with and without a known risk factor for developing wet AMD…the double layer sign (DLS).  The risk of an eye with DLS in developing wet AMD appears to be further increased with the use of Syfovre.  Therefore, among eyes undergoing monthly Syfovre injection, the risk of new wet AMD is reduced to 13.3% among eyes without the DLS compared with 20.9% of all study eyes and 30% of eyes with the double layer sign.  Similarly, in eyes undergoing Syfovre injection every other month, the risk of new wet AMD is reduced to 2% among eyes without the DLS compared with 8.9% of all study eyes and 17.9% of eyes with DLS.  Therefore, patients who have the double layer sign may wish to reduce their risk of developing wet AMD by avoiding the use of Syfovre.  

Table 2: FILLY phase 2 study: New wet AMD among study eyes. Studying the effect of the double layer sign (DLS) which elevates the risk of wet AMD

ParametersSham (no drug)Monthly drug injectionEvery other Month drug injection
All study eyes1.2%20.9%8.9%
DLS present4.2%30%24%
DLS absent0%13.3%2%
Eyes without the double layer sign (DLS) had lower rates of wet AMD among treated eyes.

Comments on the use of Syfovre:

Studies show that It may take over two years of treatment in order to see a benefit in vision. Patient selection may reduce the risk of new wet AMD in treated eyes.  However, patient selection alone will not reduce the risk of other adverse effects including inflammation, infection, hemorrhage, retinal detachment, and ischemic optic neuropathy.  Further risk reduction may be possible by reducing treatment frequency from monthly to every other month, but this reduces the effectiveness of the treatment in slowing the rate of progression of GA from 29% to 20%.  Careful assessment is warranted for each patient to determine if the benefits of Syfovre outweigh the potential risks.

By Scott E. Pautler

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.

How is Color Blindness Inherited?

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how is color blindness inherited
anatomy of the eye (click on image to enlarge)

How are genes and heredity involved in color vision?

You ask, “how is color blindness inherited?” But first we must separate color blindness into two groups: acquired and congenital. Acquired color blindness starts after birth and may worsen over time. Congenital color blindness is present from birth and does not worsen with time. This blog is about congenital color blindness and it is an inherited trait.  It appears to have evolved to give a competitive advantage in the visual perception of the environment.  For example, the ability to tell the difference between red and green allows a gatherer to find the red fruit among the green leaves of a plant more easily than a competitor who cannot see the color difference.  

What are DNA, genes, and chromosomes?

Most cells in the body contain a nucleus that contain DNA, which codes for proteins.  The DNA is organized into genes, which, in turn, are organized into large units called chromosomes.  Each of us has 23 pairs of chromosomes (as in the Ancestry.com genetic test, “23 and me”).  The pair consists of one set of chromosomes from the mother and one from the father.  Collectively, they represent the genetic blueprint of the individual.  

Are there different degrees of severity?

Color perception is complex.  There are many genes that have an impact of the ability to see color.  Therefore, there is wide variation in the ability to perceive colors among individuals.  There are a few, well-recognized causes of major color deficiency in humans and the most common is red-green color deficiency.  These individuals have difficulty seeing the difference between red and green.  Despite this limitation, they function well.  They have no trouble with the blue-yellow spectrum.   

What is the most common form of color blindness?

Red-green color deficiency is the most common form of color blindness. The genes for red-green color deficiency are located on the X chromosome.  The X chromosome is one of the two sex (as in gender) genes, the other being the Y chromosome.  Females possesses two X chromosomes and males possess an X and a Y chromosome.  A child receives one sex chromosome from each parent.  Thus, females inherit one X (either of the two maternal X chromosomes) from her mother and one X (the only paternal X chromosome) from her father.  Males inherit one X (of her two X’s) from his mother and the (only) Y from his father.  I emphasize the number of chromosomal options because it has an impact on heredity of genetic traits, as we will see later.   

Is red-green color deficiency a recessive trait?

The red-green color deficiency trait is considered a recessive trait by genetic specialists.  That is, the trait is only (prominently) apparent if the affected gene is not paired with a normal gene (remember that each gene on each chromosome is one of a pair…one from each parent).  Recessive genes on the X chromosome (X-linked recessive genes) are inherited in a peculiar fashion because, in males, there is no X pair.  Instead, males have only one X chromosome.  Therefore, an X-linked recessive gene manifests itself with symptoms in males, but not in females (with a normal fellow X chromosome).  This explains the difference in the prevalence in color deficiency between males and females.  Overall, color deficiency is present in about 8% of males compared with 0.5% of females.

What does this mean for me and my family?

The practical translation from the genetic explanation is somewhat simpler.  The father with red-green color deficiency will not give any of his sons the gene for color deficiency.  This is because the gene is located on his X chromosome and he gave his sons his Y chromosome.  However, the father will pass on the X-linked recessive gene to ALL of his daughters.  Because the trait is recessive, the daughters will not be red-green deficient.  This assumes that their fellow (paired) X chromosome from their mother is normal.  The color vision deficiency, however, will appear in 50% of the daughters’ male children.  Likewise, half of their daughters will carry the trait asymptomatically.

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.

Syfovre for Dry Macular Degeneration

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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

Physician Alert: DEA Phishing Scam

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A warning to all physicians! There is a fraudulent telephone scheme in progress in which an “agent from the DEA” calls doctors at their offices claiming that the doctor’s medical license is at risk of being frozen due to drug trafficking performed with the doctor’s medical credentials. They provide and verify your medical license number and NPI (easily obtainable information). After describing the drug trafficking incident, you are asked to cooperate to “clear your name” and bring the criminals to justice. Legal statutes are repeatedly referenced to enforce “confidentiality.” The scammers do not want you to consult with anyone. Of course, in order to avoid having your personal bank accounts frozen, they want to collect information. The Drug Enforcement Administration has issued a warning regarding scammers impersonating DEA agents. The person who called my office was “Agent Michael A. Davis” (the name was verified by my administrator as an employee of DEA) calling from 571-454-9198. When I refused to give my banking information, veiled threats were made. No information was disclosed.

I called the real Drug Enforcement Administration at 202-307-1000 to confirm the fraudulent nature of the call. Please beware of this elaborate scheme and save yourself time and potential financial loss.

This scam capitalizes on the integrity of the doctor, the respect for the DEA, and the fear of interruption of patient care. The scammer presents an elaborate background story to gain credibility. References are given to governmental agencies such as the FBI and FTC. Governmental statutes are cited to support the investigation and need for confidentiality (“you may tell no one about this investigation”). No probing for banking information occurs until very late in the conversation…about 45 minutes into the interrogation.

The DEA will never contact a physician by telephone and request personal or sensitive information. They present information about legal actions or legitimate investigations in person and/or by mail on official letterhead.

Sunken Eyes from Glaucoma Drops

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sunken eyes from glaucoma drops
anatomy of the eye (click on image to enlarge)

How is glaucoma related to sunken eyes?

Sunken eyes from glaucoma drops is not an uncommon problem. Glaucoma is an eye condition that usually requires treatment with drops to lower the pressure in the eye.  Some of the drops are known to cause the eyes to appear sunken in the socket.  An early symptom is superior sulcus recession, which is a loss of fullness of the upper lid.  Later, the eye may appear deeper or lower in the socket.  

sunken eye
Sunken left eye due to artificial eye implant. Note the upper lid appears less full. Also the artificial eye is sunken deeper in the socket and is positioned slightly lower compared with the right eye. This appearance is similar to what may occur with the use of prostaglandin eye drops for glaucoma. Image courtesy of the American Academy of Ophthalmology.

Do all glaucoma drops cause sunken eyes?

No. There are many classes of drugs used as eye drops to lower intraocular pressure.  Among the many classes of drops available to treat glaucoma, only prostaglandin analogues are known to cause sunken eyes.  Examples of glaucoma drops in this class include Xalatan (Xelpros, latanoprost), Travatan (travoprost), Lumigan (Durysta, bitamoprost), Zioptan (Tafluprost), and Vyzulta.  This class of eye drops also may cause the color of the iris to turn brown, and the lashes may grow darker and longer.  Rarely, macular edema may cause blurred vision. 

What can be done to treat or prevent sunken eyes?

There is no treatment for sunken eyes once they occur from prostaglandin analogues.  Therefore, if sunken eyes are to be avoided, prevention is the key.  Although prostaglandin analogues are among the most effective drops to lower the intraocular pressure, there are other classes of drops to choose from.  They include the following:

  • Beta blockers effectively lower the pressure by 25-30%, but they may aggravate asthma.  
  • Alpha agonists also lower the pressure, but may cause low-grade inflammation in the eye.  
  • Cholinergics may be effective, but make the pupils small, which may affect night vision.  
  • Carbonic anhydrase inhibitors are effective, but may worsen pre-existing corneal edema.  
  • Rho-kinase inhibitors lower pressure, but often cause redness of the eyes.  It may also cause tearing due to reversible blockage of the tear duct in the eye lids.

Finally, if the prostaglandin class of eye drops is felt to be the best choice, Omlonti is a new drug (approved by the FDA in 2021) in this class that is less likely to cause sunken eyes.  However, among eyes with lens implants there may be a 5-15% chance of blurred vision from macular edema when using Omlonti.  Your glaucoma specialist will work to help choose the best medicine for you and will help to determine if laser or incisional eye surgery would be a preferred option to lower the eye pressure.

By Scott E. Pautler, MD

Copyright  © 2023 Designs Unlimited of Florida

Genetic Testing and Eye Disease

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Anatomy of the eye. Image courtesy of Caitlin Albritton.

Why consider genetic testing?

Genetic testing is used to identify gene variants known to cause certain eye problems.  Testing may be helpful to confirm a diagnosis suspected on clinical findings.  Knowing the causative gene may also be helpful to better understand the inheritance pattern in order to inform other family members and to assist with family planning.  Finally, much research and progress have been made in the treatment of inherited eye disease. 

What tests are available?

There are a number of options when it comes to genetic testing.  In general, it is better to order specific test panels rather than testing all of the genes (whole-exome sequencing).  For example, there are tests geared to identify specific inherited retinal diseases (IRD) with a high degree of accuracy.

Who pays for genetic testing?

Insurance companies generally do not cover the cost of genetic testing.  The cost of testing is variable depending on the lab and the scope of the tests.  For example, Molecular Vision Lab charges $650 for a test panel of 1024 genes looking for inherited retinal disease. 

How can I get genetic testing?

If your ophthalmologist suspects an inherited retinal disease, he/she may order testing.  The type of test will depend on the diagnosis under consideration.  If you are a resident of the United States and have not had prior testing, you may be eligible for testing at no charge.  However, you may be asked to participate in a program in which you may be contacted by researchers.  Certainly, you may choose to keep your personal information private.  

Over time, I anticipate genetic testing will become more readily available and the cost will be covered by insurance.  The treatment and cure of some inherited retinal diseases is now a reality, and the future holds the promise of further progress with continued research. 

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

Why you look up when walking in the dark?

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Have you wondered why you look up when walking in the dark?  There is an anatomic explanation for this behavior.  To understand this issue better we will give a brief anatomy lesson.  

Anatomy of the eye. Image courtesy of Caitlin Albritton.

How is the eye is like a camera?

The eye is like a spherical camera.  The image above is an artistic version of an eye with the top half removed to reveal the inside anatomy.  The eye works by allowing light to enter the eye through the clear cornea.  The light then passes through the pupil, the circular opening in the iris.  The rays of light are focused by the lens, which lies behind the iris.  Light then travels through the clear vitreous gel that fills the eye.  The focused beam of light finally strikes the retina, which is like the film, or CCD array, in the back of a camera.  The retina contains receptors (photoreceptors) that detect light and then send a tiny electrical signal to the brain for interpretation.  

What is the difference between the rod and cone receptors?

There are two main types of retinal photoreceptors used for vision: cones and rods.  The cones work best in bright illumination and detect color.  The rods work best in dim illumination and do not detect color.  The rods are the photoreceptors used to navigate at night in dim light.  As it turns out, the retinal photoreceptors are not distributed across the retina evenly.  Most of the cones are located in the macula…the center of the retina.  This is the area of the retina that humans use to see sharp details with good color perception during the daytime.  When you look directly at an object, light reflected from its surface is directed onto the macula.  

Where in the retina are the rods and cones located?

The rods are located in the retina around, but not in the macula (the center of the retina).  Therefore, your best night vision is not provided by the central retina.  Indeed, many notice they see stars in the night sky the best if they look slightly off center from the area of interest.  Furthermore, the concentration of rods in the retina is greater above the macula than below the macula (Curcio, 1990).  Consequently, the best vision for walking at night is when the eyes look slightly up.  In this position, dim light from the path ahead falls onto the retina above the macula, where the rods are able to process the image much better than the cone-rich macula.  

Why did the human eye evolve this way?

Presumably, evolutionary pressure helped create this anatomical situation.  Even during the daytime, the amount of light entering the eye varies with gaze direction.  When looking straight ahead on a sunny day, more light enters the eye from above than from below the midline.  Light reflected from the ground is dimmer than light entering the eye from the sun above.  So even in the daytime, vision is aided by having more rod photoreceptors in the top half of the retina than from the bottom half.  Remember, light from below the eye, strikes the top part of the retina and light from above the eye strikes the bottom part of the retina.  Thus, due to the optical qualities of light and the anatomy of the eye, you may find yourself looking upward when walking around in the dark.  

By Scott E. Pautler, MD

Copyright  © 2022-2023 Designs Unlimited of Florida.  All Rights Reserved.

Computer Glasses

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Having trouble seeing the computer screen?

Do you have difficulty seeing the computer with your glasses?  Do you have difficulty keeping your head positioned to focus the progressive lenses on details at near?  Do your eyes feel fatigued after working on the computer?  You are not alone and there is a solution to your problem.  The problem frequently lies with the limitations of progressive lenses used to treat presbyopia.

What is presbyopia?

Presbyopia means “old eyes.”  It is the name given to the inability to focus at near that comes on with age.  Early in life, the eye has the ability to focus at distance and near with ease.  This property is called accommodation.  That is, the lens of the eye can change shape to alter the focus of the eye to adjust to different distances.  Therefore, presbyopia is the loss of accommodation due to the inability of the lens to change shape with age.  

Typically, when people reach the age of forty or fifty, if the eyes are focused at distance (either naturally or with glasses/contact lenses), the vision at near becomes difficult.  At that point, you need longer arms or “reading glasses” (also called, “cheaters”).      

What are readers, bifocals, trifocals, and progressive lenses?

There are a variety of lenses designed to treat presbyopia.  If a person has “normal” eyes focused at distance without glasses, standard over-the-counter reading glasses are used to treat presbyopia.  If a person needs glasses for distance vision, bifocal lenses are sometimes used. Bifocal lenses are designed with two lens segments.  The top segment is focused at distance and the bottom lens segment is focused at near.  There is usually a visible line on the lens that separates the top section from the bottom section.  The bifocal lens is helpful, but is limited by an inability to focus at an intermediate distance.  That is, the top section of the lens focuses well at 20 feet and beyond.  And the bottom section focuses well at near.  But the intermediate distance between distance and near is blurred for presbyopic eyes.  

So, trifocal lenses were developed.  Trifocals use a third lens segment.  The segment is located just below the distance segment and above the near segment to provide help with focusing at the intermediate distance.  Trifocals can be difficult to use.  It takes time to learn which lens to use for which distance (by tilting the head back the right amount).  And the intermediate lens power is less than ideal for focusing within the intermediate distance of three to twenty feet.  

Then came progressive lenses.  Progressive lenses are the most expensive lenses.  They are made to provide a top section of the lens for distance vision and this works well.  However, there is a compromise made in the lens in order to improve the focus in the intermediate and near range.  Specifically, the lens is molded to provide a narrow section of the lens leading from the top (distance) and bottom (near) sections of the lens.  This allows for accurate focusing at any point in the intermediate range (3-20 feet) as the head is tilted back slowly to find the appropriate section of the progressive lens to focus at any distance needed.  It takes time to learn how to hold the head in proper position to focus at intermediate and near distances in part because the zone of clear vision through the molded lens is very narrow.  Herein lies the difficulty with using progressive lenses for computer work.

How are my progressive lenses giving me trouble at the computer?

Viewing the computer screen presents unique challenges.  First, the screen is situation two to three feet from the eyes.  Second, the screen is broad and requires some degree of scanning across the screen.  The progressive lens is not designed well to solve these challenges.  While the progressive lenses work well for routine use of the eyes, the narrow zone of focus of the lens at intermediate and near distances requires constant fine movement of the head to keep the image in focus across the breadth of the computer screen.  This effort causes fatigue and frustration.

What is the solution?

While some people can tolerate the limitations of progressive lenses while working on the computer, others require a different type of lens.  Computer glasses may be prescribed that employ the less expensive bifocal lens style.  The top part of the bifocal is focused on the computer screen (rather than for distance) and the bottom part of the bifocal is focused for deskwork.  This lens avoids the narrow bridge of focus that limits the progressive lens.  That is, the entire top lens is focused for scanning the computer screen.  Similarly, the entire bottom portion of the computer glasses (bifocal) is available to scan papers on the desk. 

To facilitate the process of obtaining computer glasses, I recommend an individual use a tape measure to record the number of inches from your forehead to the computer screen.  Similarly, measure the distance to the desk for near work.  With these measurements in hand, the optometrist or ophthalmologist can prescribe precise bifocal glasses for computer and near work.  These computer glasses will not work for distance vision, but will likely relieve the frustration and fatigue when working at the computer for an extended period of time.

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.

Who Owns your Eye Doctor?

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In the old days, the doctor owned his own medical practice, but he was dependent on the confidence of his patients for success.  He was motivated to please his patients because they could choose any doctor they wanted.  In this regard, the patients owned their doctor.  The hospital was motivated to provide equipment the doctor needed for his patients because he could choose to bring his patients to any of the area hospitals.  The hospitals competed for the best doctors to bring their patients in for care.  

Then came government intervention.

In the name of cutting the cost of medical care, the government passed laws that pushed the balance of medicine in favor of insurance companies and hospitals.  For the first time, insurance companies began dictating treatment choices to the doctor and patient.  Hospitals took control of physician’s medical practices and turned their attention away from the doctor and his patients.  Consequently, the value of the doctor’s medical practice was eroded.  In addition to losing the decision-making privileges, physicians were burdened with regulations and requirements from the government that reduced the time available to care for their patients.     

Then came private equity (PE).

As doctors found the practice of medicine more complicated, frustrating, and less rewarding, businessmen (private equity) decided they could run the medical office more profitably than the doctor.  They began to purchase medical practices with the intent of increasing the value (profits) in order to sell the practice later at a higher price to another group of businessmen.  And so on, and so forth.  The businessmen have no interest in medical care for the patient.  Rather, they care about the profit derived from running the office. 

So, who owns your doctor? 

Is your doctor working for you, or is he working for a businessman?  You need to know.  And It is not always easy to tell.  For example, when private equity buys physicians’ practices, they usually do not change the name of the office.  And, initially, they may keep the same staff.  But the message within the office is clear.  The primary goal is efficiency and cost-cutting for the purpose of making greater profit.  The steps to achieve this goal may include reducing the quality of the health care givers.  It may include ordering more tests and procedures than what was done in the past.  The emphasis is not typically to provide the highest quality of care for the patient.

What can a patient do?

Ask around about your doctor.  Your doctor may or may not be at liberty to discuss this issue with you.  However, other doctors outside the practice may know.  It is essential to know if you “own” your doctor or if someone else does.  This is a critical question as the doctor answers to the boss.  And your health (and life) may depend on the answer.  In the Tampa Bay area, I am aware of several ophthalmology offices that have been purchased by private equity.

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.

Methotrexate for Uveitis

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

Why is methotrexate used to treat uveitis?

Uveitis is a general term used to describe inflammation inside the eye.  There are different types of uveitis described by the location most affected in the eye.  Uveitis is also separated by cause: infection or no infection.  If an infection is found, antibiotics are prescribed.  However, if there is no infection and the inflammation (uveitis) threatens loss of vision, medications are used to reduce the inflammation to protect the eye.  Steroid medications are the first line of defense.  Steroids work quickly and effectively in the short term.  However, if the inflammation lingers, steroids may have unacceptable side effects to use long term.  This is when medications like methotrexate are often used to quell inflammation and protect the vision with fewer side effects in the long term.  Methotrexate is well-studied, safe, effective, and inexpensive.  It is often the first drug used to minimize the need for steroids in treating uveitis.  It is as effective as a more expensive drug in the same class called mycophenolate mofetil (FAST Trial).

How does methotrexate work?

Methotrexate works to suppress the immune system.  The immune system includes white blood cells that are helpful to attack infections.  However, sometimes the immune system attacks your own body and causes damage.  Examples of this include rheumatoid arthritis, psoriasis, and uveitis.  In these conditions it may be necessary to suppress the immune system enough to prevent damage to healthy tissues in the body.  There are many different types of immunosuppressants; methotrexate is classified as an antimetabolite (like azathioprine and mycophenolate mofetil).  Antimetabolites interfere with the production of DNA in rapidly dividing cells.  However, this mechanism may not be the primary way methotrexate works to treat uveitis.  It also suppresses the immune system by impairing lymphocyte (white blood cells) function. Although antimetabolites are effective in treating uveitis, there are not effective in treating joint disease in HLA B27.

How is methotrexate taken?

Methotrexate is taken weekly (on the same day of each week) by pill or subcutaneous injection.  It is usually recommended by an ophthalmologist and prescribed by a rheumatologist.  The role of the ophthalmologist is to help determine the optimal dose required to treat uveitis in a given patient.  The rheumatologist monitors for side effects by examination and blood tests.  Methotrexate may take up to six months to show its optimal benefits.  During this time, other medications, like steroids, may be used to keep the uveitis under control.  

What are the side effects of methotrexate?

Many side effects are possible, but they are generally reversible if detected early.  Allergic reactions are rare, but should be reported to your doctor without delay.  Common side effects include loss of appetite, upset stomach, tiredness, drowsiness, headache, diarrhea, and hair loss.   Serious side effects may involve the liver (jaundice), lung (cough, shortness of breath), kidney (fluid retention, swelling), and the blood (bleeding).   There are fewer sided affects with methotrexate compared with another commonly used antimetabolite, azathioprine (Galor 2008).  At one time, there was concern that methotrexate might cause cancer.  However, the SITE extension study (reported at AAO October 2022) showed that methotrexate actually reduces the risk of cancer among patients treated for uveitis. 

What should a patient do while on methotrexate?

While on methotrexate do not become pregnant.  Avoid alcohol as it may increase the risk of liver damage.  Avoid live-virus vaccines (usually given in childhood).  Report signs of infection to your doctor.  Report side effect from methotrexate listed above.  Take folic acid (also known as vitamin B9, Leucovorin) to reduce the side effects of methotrexate.  Some recommend avoiding folic acid on the day of the week you take the methotrexate.  

Your doctor has selected methotrexate to protect your vision.  The benefits of treatment are felt to outweigh the potential risks.  Do your part to make sure to take the medication exactly as prescribed and report problems without delay. 

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  © 2022-2023 Designs Unlimited of Florida. All rights reserved.

Is a Drug Study for Me?

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What is a drug study?

In the United States, new drugs designed to treat disease must be approved by the Food and Drug Administration (FDA).  Drug companies must design and pay for studies that demonstrate reasonable safety and efficacy to gain FDA approval, after which they may market their drugs to doctors and patients for a profit.  Because pharmaceutical sales are so profitable, drug companies are highly motivated to develop new drugs.  This effort helps patients who need better drugs to treat disease.  

What are the phases of drug study?

Initially, drugs are developed by basic scientists who have reason to believe a new drug may be useful based on its chemical interaction with the body.  Initial studies are performed in the laboratory and often involve animal studies.  If basic safety criteria are met in the lab, the drugs may be brought to Phase 1 study in which some human subjects (usually, a dozen or two) are given the drug to look for a beneficial effect and lack of adverse effects.  If a drug passes Phase 1, a Phase 2 study is designed to help determine the best dose of drug.  More patients are recruited for these studies, but often number fewer than one hundred.  If successful, a Phase 3 study is planned to gain approval by the FDA.  These studies randomly assign drug treatment to patients in a manner that neither the treating doctor nor the patient knows what drug they are using.  It is hoped that this method will avoid bias and offer a true assessment of the drug effect.  The schedule of administration is completely designed by the drug company, but must be approved by the FDA.  Unfortunately, this oversight may lack rigor.  Phase 3 studies often include several hundred patients.  Key endpoints of treatment are diligently recorded and adverse drug effects are monitored carefully.  Finally, after FDA approval, drugs may be studied in a Phase 4 study looking further for adverse effects and/or new uses for other diseases.  It is obvious that more is known about the effectiveness and safety of a drug the further along the study sequence it passes.  Nonetheless, some adverse effects are not discovered until years after a drug has been approved for use by the FDA.   

What are the benefits of participating in a drug study?

Apart from feeling good about being a part of drug development, patients may benefit from participating in drug studies.  For example, the patient may gain access to a helpful drug that would not have been available otherwise.  In addition, the drug company usually offers to pay for the medication and treatment visits during the course of the study.  They often offer to pay cash to the patient in the form of a stipend for transportation to study visits.

What are the risks of being in a drug study?

Not surprisingly, with potential benefits come potential risks.  For example, most drugs that enter the process of study, do not meet with success.  That is, they are found to be inferior to existing medications or they are found to have unacceptable adverse effects.  This is one risk a patient must accept.  Secondly, the decision to treat and method of treatment is guided by strict protocols aimed to favor the study drug; not necessarily in the best interest of the patient.  The doctor is given limited independent authority to alter treatment within the study.  However, the patient may always exit the study at any time should he or his doctor decide.  It is critical to remember that exposure to an unproven drug carries with it the risk of unknown risk of adverse effects.  Complicating matters more, the doctor is highly compensated by drug companies to recruit patients for drug studies.  During these times of decreasing physician compensation by Medicare and insurance companies, doctors may be under financial duress to cover the high cost of office overhead. There is a risk that the doctor may be motivated more by financial compensation than the best interest of the patient.  Hopefully, this risk is not significant.  The risk of adverse effects is highest in the early stages of study when less is known about the drug.  Therefore, caution must be exercised with phase 1 and phase 2 studies.  Phase 3 studies are safer, but still not without risk.  Phase 4 studies are the safest because the drug has already been approved for use by the FDA; however, sometimes the full extent of adverse effects is still not known.  Therefore, when considering study participation, at a minimum a patient should ask what phase study is being offered them.

So, should I participate in a drug study?

In the end, drug studies are an essential part of discovering new medicines to treat disease.  If you feel you may benefit from a study drug and/or currently-approved drugs are not satisfactory to you, a drug study may be worth considering. However, you must accept the risks of being treated by a drug that has not been studied extensively for safety and efficacy in the past and is being used under a protocol designed by a drug company whose primary interest is gaining drug approval by the FDA.  If in doubt, it may be best to seek a second opinion from a doctor outside of the drug study.  

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  © 2022-2023 Designs Unlimited of Florida.  All Rights Reserved

Fluorescein Angiography Without Injection

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globe anatomy
anatomy of the eye (click on image to enlarge)

What is oral fluorescein angiography?

Fluorescein angiography (FA) is a useful method of photographing the eye.  Although it is usually used to study the blood flow to the retina, it is also used to study the iris and other eye structures.  FA is usually performed by injecting fluorescein dye into a vein of the arm, after which special photographs are taken of the eye.  However, when a vein is not easily accessible, the dye may be administered by mouth in the form of a drink.  

When to consider oral fluorescein angiography?

Oral fluorescein angiography may be considered whenever access to a vein presents a challenge.  Sometimes, this situation is encountered with children or adults who are strongly averse to pain, as the dye injection may be uncomfortable.  In other cases, the veins are simply too small or are otherwise difficult to inject.  In these instances, oral fluorescein angiography may be considered as an alternative to intravenous FA.  

What is the disadvantage of oral fluorescein angiography?

The main disadvantage of oral FA is a potential decrease in the quality of the images of the retina.  However, there are several steps that may be taken to optimize the image quality.  Another disadvantage of oral FA is that the dye tastes bitter.  The may be overcome, in part, by mixing the fluorescein dye with apple juice or with water sweetened by sugar or a non-nutritive sweetener.    

How is the procedure performed?

For adults, two 5ml vials containing fluorescein 10% solution are mixed in a cup with 1-4 ounces of apple juice, orange juice, or sweetened water.  The best images are achieved if the drink is consumed in one gulp.  It is fine to “wash down” the bitter taste with additional beverage of choice.  Using an SLO fundus camera programmed for FA, take one photo per minute for each eye (set timer) until the retinal vessels start to fill.  This is usually about 4-5 minutes from start time.  Once all the vessels fill well, peripheral views may be captured.  Afterwards, one image is captured every 5 minutes until ending the photos 20-30 minutes from the start time.  If the images are not satisfactory, the test may be repeated after an overnight fasting without food.       

How is the fluorescein dosage adjusted by patient weight?

The amount of 10% fluorescein dye may be adjusted downward for patients weighing less than 90 pounds.  This adjustment is especially important for children.  The recommended dosage is 25mg/kg.  As fluorescein dye is supplied in 5ml vials of 10% solution for injection, the table below may be used for dosing by weight in pounds:

Patient Weight (lbs)Fluorescein 10% Dose
404.5cc
505.5cc
606.5cc
708.0cc
809.0cc
9010cc
>9010cc

By Scott E. Pautler, MD

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

The Far-Sighted Eye

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globe anatomy
anatomy of the eye (click on image to enlarge)

What is hypermetropia?

A hypermetropic eye is a far-sighted eye.  Without glasses the vision may be good at distance or blurred, but the vision is usually blurred or strained at near without glasses.  Hypermetropia is different from presbyopia (aging eyes).  Hypermetropia affects many people and is treated with glasses, contact lenses, and, rarely, laser surgery.  It is a common underlying reason for the need to wear optical correction (glasses).  

What causes hypermetropia?

Hypermetropia is an inherited condition that usually develops in childhood or early adulthood.  The eye develops with either a flat cornea or a short eyeball length, or both.  As a result, the image entering the eye is focused behind the plane of the retina.  In this case, the eye tries to focus the lens to make the image projection sharp.  Sometimes, the natural lens in the eye can compensate for the focusing of images, but often eyeglasses or contact lenses are needed.  The outer appearance of the eye is not usually changed.  It is not obvious that an eye is hypermetropic by inspecting the outside of the eye.       

Why is it important to know about hypermetropia?

Although most people with hypermetropia do not develop complications, some far-sighted people are at increased risk of losing vision from narrow-angle glaucoma, central serous choroidopathy (also known as central serous retinopathy), and choroidal effusion.  

Angle-Closure Glaucoma is a condition in which the pressure inside the eye damages nerve tissue that helps you see.  High pressure is the result of closure of the internal drain in the eye.  The pump inside the eye does not sense the closure of the drain; it continues to pump fluid into the eye.  The drain cannot keep up with the pump, so the pressure inside the eye rises.  This pressure may or may not cause pain or discomfort.  Over time, the pressure slowly takes away the side vision.  If undetected and untreated, it may cause total, irreversible blindness.  The best way to diagnose glaucoma is to have regular eye exams each year with pressure measurements and gonioscopy.  Treatment is effective in preventing vision loss.  Laser is often used to open the drain.  Sometimes operative surgery is required with or without removal of the lens in the eye (to make more room for the drain to stay open).  Often, eye drops are needed long-term to keep the pressure under control.

Central Serous Chorioretinopathy is an uncommon cause of vision loss from hyperopia.  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 onto the retina, which “takes the picture” and sends the image to the brain.  In hypermetropic eyes, the layer under the retina called the choroid becomes crowded and thickened.  The outer coat of the eye known as the sclera may be thickened as well.  As a result of thickened choroid and sclera, the flow of fluid inside the eye that normally drains out through these structures, is restricted.  This fluid may then collect under the retina and cause the central vision to become blurred or distorted even with proper glasses.  Distortion is when straight lines look wavy or crooked.  Blood vessels under the macula may bleed causing sudden blurring, blind spot, or distortion.  Any of these symptoms should be reported to the eye doctor without delay, as early treatment with laser may prevent further loss of vision.

Choroidal Effusion is a separation of the choroid from the sclera, the wall of the eye. This is different from retinal detachment.  When the choroid detaches, it is no longer in proper position inside the eye.  As a result, symptoms of a dark curtain or shadow slowly starts off to the side and takes away the vision as the choroid detaches.  Pain is not common.  The diagnosis is made by a retinal specialist; it is critical to identify and differentiate choroidal detachment from retinal detachment and tumors.  Treatment of choroidal effusion is typically started with medications.  Sometimes, however, surgery is needed.  

Will refractive surgery help prevent these complications of hypermetropia?

Although refractive surgery (laser correction) is effective at changing the shape of the cornea to help eliminate the need for corrective lenses (glasses and contacts lenses), it does not restore the natural shape of the eye.  Therefore, it is still necessary to be aware of the warning signs of possible complications from hypermetropia.

What should a hypermetropic patient do?

Using your eyes to read or work at a computer will not weaken them.  Remember to have your eyes examined once a year with special attention to the opening of the drainage apparatus (the corneoscleral angle).  Not all eye doctors are proficient with determining the risk of angle-closure glaucoma; therefore, consider seeing a fellowship-trained glaucoma specialist if needed.  In Tampa there are several choices including doctors Levitt, Gamell, Richards, King, and Fridman.  Apart from an annual exam, report the following symptoms to your eye doctor without delay:

Sudden-onset pain in the eye (sometimes, associated with nausea)

Sudden-onset redness (especially, if associated with pain and blurred vision)

Loss of side-vision (possibly, a very late sign of glaucoma)

By Scott E. Pautler, MD

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

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.

 

Visual Snow Syndrome

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globe anatomy
anatomy of the eye (click on image to enlarge)

What is visual snow?

Visual snow is the name for a visual symptom that looks like static on a television not tuned to a station.  It has also been likened to pixelation on a computer screen.  Many tiny flickering lights are usually seen in both eyes at the same time and encompasses the entire visual field.  In some instances, it is worse in bright illumination like a bright sunny day.      

What is the difference between primary and secondary visual snow syndrome?

Visual snow may be seen in patients without an underlying disease.  In these cases it appears to be caused by hyperexcitability of the visual cortex of the brain.  This is often called primary visual snow syndrome (VSS).  Primary VSS is a diagnosis of exclusion.  That is, other diagnoses must be excluded before the diagnosis of primary VSS is made.  Primary VSS is related to migraine; indeed, many people who report visual snow also have migraine visual symptoms with or without headache.  Other related symptoms include palinopsia (visual persistence of an image after the eyes are closed or look away), floaters and spots (entopsia), difficulty seeing in dim light (nyctalopia), difficulty seeing in bright light (hemeralopia), and flashes of light (photopsia).   Other associated symptoms include ringing in the ears (tinnitus) and dizziness that varies with head position (postural vertigo).     

Visual snow may be a symptom of an underlying disease (secondary visual snow syndrome).  In this situation, it is critical to identify the underlying cause and offer treatment where possible.  Secondary visual snow may originate from the retina or the brain.  A well-described retinal cause of visual snow is due to digoxin toxicity.  It usually occurs in elderly people who take digoxin for heart problems.  It indicates the need to stop taking digoxin or lower the dose.  Failure to reduce the dose may result in severe complications, including death.  Other rare causes of visual snow include eye disease, immune disease, infectious disease, psychiatric disease, prescription drugs, past use of hallucinogens, head trauma, brain tumor, seizure disorder, and brain degenerative disease.

What causes the primary visual snow syndrome?

The cause of primary VSS is not known.  It is felt to be due to an error in central processing in the back of the brain (occipital lobe).  Special brain scans show hypermetabolism in the lingual gyrus of the occipital lobe in the back of the brain.  

How is primary visual snow syndrome diagnosed?

The diagnosis is made on the basis of typical symptoms after testing has ruled out an underlying disease of the eye or brain.  MRI brain scan is often used to rule out tumor, multiple sclerosis, degeneration, and stroke.  EEG may be used to rule out seizure disorder.  A spinal tap may be needed to rule out idiopathic intracranial hypertension.  Pattern reversal VEP usually demonstrates loss of habituation of the occipital lobe in the brain (indicative of hyperexcitability). A neurologist usually arranges for testing as needed. An ophthalmologist may be helpful in ruling out eye disease.

What can be done about these symptoms?

It is difficult to treat primary VSS.  Medications such as lamotrigine and topirimate may be helpful in some patients.  Tinted glasses or clip-on lenses may also be helpful to minimize the symptoms of visual snow.  Placing a yellow or orange tinted cellophane sheet on top of reading material helps some. Riboflavin and magnesium supplements may be of benefit for migraine and visual snow, as well. For many patients it is helpful to know that primary VSS is a benign condition that does not progress to blindness.

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.

Note: This blog is supported by its readers via small commissions that may be earned through hyperlinks.  The commissions do not increase the price you pay and do not affect the content of this article.  Thank you for your support.  

Copyright 2022-2023 Designs Unlimited of Florida. All Rights Reserved.

Black Spots After Eye Injection

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globe anatomy
anatomy of the eye (click on image to enlarge)

What are these circular spots in my vision after an eye injection?

Sometimes after an eye injection, a patient may see one or more black circular spots that move in the vision with head movement.  They are usually in the lower part of the visual field, though they move up toward the center of the visual field if you position your head face down.

What causes these symptoms?

These black spots are due to air bubbles in the medicine that is injected into the eye.  They appear immediately after injection.  They are harmless and take 1-2 days to dissolve and disappear.  Less commonly, small black circular spots may float in the vision after injection due to small silicone bubbles that are used to lubricate the syringe.  These silicone bubbles do not dissolve, but they may float away from the retina and become less noticeable over time.

What should be done about these symptoms?

If the spots are due to air bubbles, these symptoms fade without treatment.  If the spots are due to silicone bubbles, they may come and go over time.  It is best not to track them with your eyes as they may become more bothersome.  Try to look past these floaters and ignore them if possible.  If they persistently interfere with the vision, vitrectomy surgery may be considered to remove them.  This is rarely necessary.

What other symptoms can mimic this problem?

These black spots are considered a type of “floater.”  Floaters are any visual spot in the vision that “floats” or moves somewhat independent of eye movement.  Sometimes floaters may come on suddenly and appear like dots and fibers.  This is typical for bleeding inside the eye.  If dots and fiber-like floaters come on more slowly (hours to days), they may be a sign of infection or inflammation.  Rarely, cancer may present as many tiny floating spots in the vision.   

Floaters are distinct from blind spots (scotoma) that are fixed in the visual field and move only when the eye moves.  You cannot “catch up” or move away from a blind spot by moving the eye.  Blind spots are usually due to problems with the retina or optic nerve.  A progressive blind spot that begins in the peripheral vision and enlarges over hours to days may be due to a retinal detachment and requires a prompt examination.  Retinal detachment is often described as a curtain or shadow covering the vision.

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

Byooviz Therapy

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anatomy of the eye (click on image to enlarge)

What is Byooviz?

            Byooviz is a drug used to treat wet-type macular degeneration, wet-type myopic macular degeneration, and macular edema due to retinal vein occlusion.  It involves repeated injections of medication into the eye to stop abnormal, leaky blood vessels.  Byooviz is an FDA-approved biosimilar drug similar to Lucentis.  Consequently, it costs less than Lucentis (About $1100 per injection of Byooviz compared with $1800 per injection with Lucentis).  Unlike Lucentis, Byooviz is not approved for diabetic retinopathy. 

What is the difference between biosimilar drugs and generic drugs?

While generic drugs are chemically identical with trade-name drugs, biosimilars are not identical to their reference drugs which they attempt to duplicate.  Because biosimilar drugs are different chemically, they may behave differently in terms of effectiveness and side effects.  They may not be as effective as their reference drug and they may have more side effects.  For this reason, biosimilar drugs need to be monitored closely prior to approval by the FDA, as well as after approval by health care providers.  Some adverse effects are not recognized until a drug has been used in thousands (if not more) of patients.  

How effective is Byooviz therapy?      

             Byooviz was shown to be very effective and similar to Lucentis when given every 4wks up to 48 weeks for wet-type macular degeneration.  Currently, therapy often starts with monthly injections until maximal vision is restored. Afterwards, the injections may be given less frequently to maintain stable vision.  It is not known how Byooviz will perform in this setting.

What are the risks of Byooviz therapy? 

            Severe complications are very rare, but risks of Byooviz injection (like Lucentis) include bleeding, infection, retinal detachment, glaucoma, cataract, and loss of vision/loss of the eye. There appears to be a small increased risk (1%) of stroke with these types of medications. The risk of stroke may be related to the older age of patients in which it is used. Pregnancy should be avoided while on Byooviz therapy.              

What do I expect after a Byooviz 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.

What does Dr Pautler think about Byooviz?

It is the opinion of the author that there are several concerns about Byooviz. First, the safety and effectiveness of Byooviz need to be determined on a large scale with many more patients than studied for FDA approval. This may take several years of use. Until then, I prefer Lucentis as it has a proven track record. Secondly, the cost of Byooviz appears too high. The cost of Byooviz is less than Lucentis, but not by much. A lower cost is more appropriate given the unknown risks and long-term effectiveness of Byooviz. If I have a patient whose insurance covers Lucentis, that is my choice over Byooviz at this time. If a patient has a Medicare Advantage insurance plan, I may be forced to use Byooviz.

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

What is the Best Drug for Eye Injections?

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Two common retinal causes of vision loss are wet age-related macular degeneration (wAMD) and diabetic macular edema (DME).  In both of these conditions a signaling protein (called VEGF) is released that promotes blood vessel leakage with loss of vision.  A major advance in treatment came about with the development of drugs that block the effect of VEGF.  These drugs (called antiVEGF) reduce the risk of vision loss and offer some improvement in vision in patients with wAMD and DME.  Unfortunately, these drugs need to be administered as an injection into the eye.  Consequently, drug manufacturers work to design drugs offering the best vision with the longest interval between injections (fewer injections).  

What drugs are available and how effective are they?

The first drug to reduce the rate of loss of vision in wAMD was Macugen (pegaptanib).  It is no longer used because newer drugs are more effective in offering improvement in vision.  While Lucentis (ranibizumab) was under development, its parent drug Avastin (bevacizumab) was found to be effective for wAMD.  Both Avastin and Lucentis appear more effective than Macugen.  Eylea (aflibercept) was developed to block the effect of VEGF and another factor (placental growth factor) involved in blood vessel leakage; consequently, there is moderate evidence that it is more effective than Avastin and Lucentis in DME and offers a longer treatment interval in wAMD.  Newer drugs include Beovu (brolucizumab) and Vabysmo (faricimab).  There is little evidence to know if they are more effective than Eylea. Finally, Eylea is now formulated in a higher concentration (Eylea HD).  

What is the cost of these drugs?

All of the drugs used to treat wAMD and DME are expensive with the exception of Avastin.  Avastin was manufactured and priced to treat colon cancer.  After it was released, doctors at the Bascom Palmer Eye institute discovered it was effective in treating wAMD.  Thus, the small dose needed to inject into the eye costs about $50.  This is in contrast to the other drugs on the market, which cost around $2000 per injection.   

What are the adverse effects of these drugs in the eye?

Problems may occur from the injection of medications into the eye.  The injection itself has risks apart from the drug that is injected; we will not discuss those risks here, but they include pain, elevated eye pressure, hemorrhage, infection, retinal detachment, and loss of vision.  The drugs themselves may cause inflammation in the eye.  Usually, inflammation causes pain, redness, light sensitivity, floaters, and decreased vision.  Typically, it can be treated with drops and it resolves without permanent damage.  However, sometimes the inflammation can be severe with permanent loss of vision.  Inflammation induced by drugs is very rare with Avastin and Lucentis.  It occurs in about 1% of Eylea injections, 2% of Vabysmo injections, and 4-5% of Beovu injections.  The inflammation with Beovu may be especially severe with permanent loss of vision. The risk of infection appears less in drugs that are pre-packaged in a syringe for injection (Lucentis and Eylea), and greater in drugs that must be prepared for injection (Avastin, Vabysmo, Eylea HD, and Beovu).

What are the adverse effects of these drugs outside the eye?

There is concern about effects of these drug outside the eye.  All of these drugs leave the eye, enter the blood vessels and are removed from the body through the urine.  On their way out of the body, there is concern that they may increase the risk of heart attack and/or stroke.  There is considerable debate as to whether there is a measurable effect or not.  Some have estimated that the systemic risk may be about 1%.  However, patients with known risk factors (hardening of the arteries, tobacco use, high blood pressure, high cholesterol, overweight, and diabetes) may be more likely to suffer a heart attack or stroke with the use of antiVEGF drugs.  In one study, patients with diabetic macular edema were at 17% (range: 2-33%) higher risk of death when undergoing frequent injections up to 2 years.  Another study, demonstrated increased risk of stroke or heart attack in diabetic patients with a history of past stroke or heart attacks. Therefore, this group of patients may benefit from careful drug selection.  Of all the drugs, Lucentis is cleared the most rapidly from the body and has the least systemic effects.  

Want a summary of the cost, effectiveness, and safety?  

Summary:

AntiVEGF drugCostEffectivenessSafety
AvastinCheap: ~$50GoodRepackaging*
LucentisExpensive: ~$2,000Goodsafest systemically**
EyleaExpensive: ~$2,000Better1% inflammation
Eylea HDExpensive: ~$2000?Better1% inflammation or greater?
VabysmoExpensive: ~$2,000?Better 2% inflammation
BeovuExpensive: ~$2,000?Better4-5% inflammation
A list of drugs available in the US approved for injection into the eye

* Repackaging increases risk of infection, floaters, and discomfort for dull needles

** Especially relevant when repeated injections are required in diabetic patients

What is my professional preference?

I have employed all of these drugs for my patients.  When cost is an issue, an insurance company may insist on the use of Avastin.  I generally prefer Lucentis in my diabetic patients for its superior systemic safety.  Eylea can be helpful to extend treatment intervals (longer time between injections) in wet macular degeneration.  Eylea may also be safer in patients who also have glaucoma, or at risk of developing glaucoma. I have been favorably impressed with Vabysmo in extending treatment intervals even further in wAMD, but I am less impressed with any advantage in my patients with DME (diabetic macular edema).  I am currently exploring the role of Eylea HD, especially to extend the treatment interval in patients with wet AMD. Due to the risk of inflammation with loss of vision from Beovu, it is not my preferred agent. Lucentis biosimilars (Cimerli and Byooviz) are not my preferred agents at this time…I am awaiting further evidence on their safety and effectiveness.  

Are doctors paid by drug companies to use their drugs?

There are varying amounts of profit margins and rebates given to doctors by drug companies in an effort to promote the use of their drugs. Usually, the newer the drug, the greater the inducement. To determine if your doctor is receiving large payments by drug companies, visit the CMS website and enter your doctor’s name in the search box.

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 © 2022-2024 Designs Unlimited of Florida.  All Rights Reserved.

Medicare Advantage: a Medical Disadvantage

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What is Medicare Advantage?

Medicare Advantage is an insurance plan available through Medicare Part B.  Medicare Part B is the insurance that covers the cost of physician services.  The traditional Medicare Part B insurance covers 80% of the physician’s fee after an annual deductible has been met.  Medicare Advantage is a program designed to cut costs of medical care.  It covers a greater part of the physician’s fee and also covers some accessory services such as eye glasses.  However, it restricts access to some services compared with the traditional Medicare Part B insurance.      

Why might someone choose Medicare Advantage?      

The main reason for choosing Medicare Advantage is to reduce the out-of-pocket costs of health care.  The benefits are obvious.  However, the costs in terms of limited access to treatment must be carefully considered.    

What are the limitations of Medicare Advantage? 

Medicare Advantage attempts to reduce the cost of medical care.  They do this by limiting access to expensive treatments.  For example, they require that physicians use the least expensive drug (called Avastin) for retinal disorders such as diabetic retinopathy, macular degeneration and retinal vein occlusion.  Avastin must be compounded by a pharmacy after it has been manufactured because it is not FDA-approved for use in the eye.  Therefore, there are increased risks including infection and floaters from silicone oil droplets.  Other, more expensive drugs (called Lucentis) reduce the risk of stroke and heart attack after injection into the eye, especially in people who require repeated injections (such as in diabetic retinopathy).

 Patients who are on the traditional Medicare Part B plan currently have access to the newest drug for macular degeneration and diabetic retinopathy, called Vabysmo.  As of the time of this article, Medicare Advantage plans do not allow doctors to use this drug even though it offers the potential for fewer injections compared with other drugs such as Avastin.  As with most things in life, you get what you pay for.  If you opt to save money by signing up for Medicare Advantage, you can expect less in terms of medical care.  Medicare Advantage plans may turn out to put you at a disadvantage.

By Scott E. Pautler, MD

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

Portable Low-Vision Magnifiers

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There are various eye conditions that may result in loss of vision with limited potential for recovery with treatment.  In these situations, good lighting and magnifiers are essential for making best use of low vision.  Magnifying glasses and large closed-circuit TV magnifiers are large and heavy.  They are most useful for home use.  However, away from home, these devices may be too cumbersome.  An ideal solution to the problem, is the portable digital magnifier.  The small magnifiers are lighter than an old-fashioned magnifying glass and are easily transportable.  And, certainly, they may be used around the home, as well.

A number of my patients endorse the portable low-vision magnifiers listed below.  They come in various sizes depending on your needs and the size of your carrying bag.  They also vary in the amount of magnification provided.  They are particularly helpful when shopping for brands and prices in the grocery store.  Reading a menu at a restaurant is made much easier with these devices.  The added independence gained with a proper magnifier makes my patients less dependent on others for help and adds to their quality of life.    

Please refer to the links below for pricing on Amazon:

Small Portable Magnifier with 3.5″ screen with up to 25x zoom magnification

Large Portable Magnifier with 5″ screen with up to 32x magnification

Large Portable Magnifier with 5″ screen with up to 48x magnification and voice prompt function.

By Scott E. Pautler, MD

Note: This blog is supported by its readers via small commissions that may be earned through these links.  The commissions do not increase the price you pay and do not affect the content of this article.  Thank you for your support.  

Susvimo: Lucentis Port Delivery

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globe anatomy
anatomy of the eye (click on image to enlarge)

What is Lucentis therapy?

            Lucentis therapy is a treatment for wet-type macular degeneration.  It usually involves repeated injections of medication into the eye to stop abnormal, leaky blood vessels. It is now also available through port delivery (called Susvimo).  After a tiny reservoir is implanted in the eye at surgery, a painless injection to fill the port is performed every 6 months.     

How effective is Lucentis therapy?      

             Lucentis was proven in extensive studies to be very effective. In wet-type macular degeneration, a large study showed that monthly injections of Lucentis over a two-year period offered a 90% chance of stable or improved vision. Similar benefits are seen in other retinal conditions as well. Traditionally, therapy often starts with monthly injections until maximal vision is restored. Afterwards, the injections may be given less frequently to maintain stable vision. The Lucentis port delivery appears to be as effective as Lucentis monthly injections, but with fewer injections.    

What are the risks of Lucentis therapy? 

            Severe complications are very rare, but risks of Lucentis injection include bleeding, infection, retinal detachment, glaucoma, cataract, and loss of vision. There appears to be a small increased risk (1%) of stroke with Lucentis. The risk of stroke may be related to the older age of patients in which it is used. Pregnancy should be avoided while on Lucentis therapy. 

            The port delivery method (Susvimo) is associated with more adverse events (19%) compared with monthly Lucentis injections (6%). Among eyes with the implanted port, 5-10% had bleeding inside the eye causing floaters and blurred vision. The blood cleared over several weeks to months. In 5.4% of eyes with the implanted port, the conjunctiva (skin-like layer that covers the eye) does not remain intact overlying the implant and additional surgery is often needed.  In 1-2% of eyes with an implanted port, infection may occur.  This is a very serious event that requires surgery and may result in permanent loss of vision/loss of the eye. In 1-3% of eyes with an implanted port, a retinal detachment required additional surgery and sometimes resulted in loss of vision.  Non-infectious inflammation occurs in about 20% of implanted eyes; it usually responds to eye drops. The benefits of fewer injections with the port delivery method must be weighed against the risks involved with the port. It is the opinion of the author that the risks of the Susvimo port delivery may outweigh the benefits at this time for most patients. Newer medications (Vabysmo) are available that appear to last longer than other treatments such as Lucentis injections. Therefore, Susvimo port delivery may be unnecessary.

What do I expect after a Lucentis 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. 

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.

Vabysmo better than Eylea?

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Yosemite/Rhine Studies: a critical analysis

The Yosemite and Rhine Studies were twin randomized, double-masked, multicenter non-inferiority trials comparing the efficacy of faricimab (Vabysmo) vs aflibercept (Eylea) in the treatment of diabetic macular edema.

The study abstract begins with the statement, “To reduce treatment burden and optimize patient outcomes in diabetic macular oedema, we present the 1-year results from two phase 3 trials of faricimab, a novel angiopoeitin-2 and vascular endothelial growth factor-A bispecific antibody.”  However, analysis of the data reveals the study report did NOT demonstrate reduced treatment burden at one year.  It did demonstrate potential non-inferiority of faricimab compared with aflibercept with an increased treatment burden in the faricimab arms of the studies. 

Treatment burden was greater in both faricimab treatment arms of both studies compared with aflibercept. Table 1 reveals 25% greater injections in the faricimab q8 week group compared with aflibercept.  The faricimab group received 10 injections at 52 weeks compared with aflibercept at 9 injections.  The faricimab group did not experienced a reduced treatment burden compared with aflibercept.  Moreover, the faricimab group sustained a more intense treatment burden to meet the “non-inferiority” assessment compared with aflibercept.  

Table 1. Injection schedule for faricimab (Fq8) and aflibercept (Aq8) q8 week study arms.

wk#1481216202428323640444852total
Fq81111110101010110
Aq8111110101010109

There was only one subgroup of eyes that received one less injection of faricimab at one year compared with aflibercept.  There were 63 eyes of 286 (22%) in Yosemite and 66 eyes of 308 (21%) in Rhine who underwent 7 faricimab injections within the group randomized to “personalized treatment interval” (PTI) compared with 8 injections in the aflibercept group.  Unfortunately, the visual and anatomic outcomes of this subgroup of faricimab eyes were reported a part of the entire PTI group, which overall had more injections than the aflibercept group. 

The primary outcome of the study was the number of letters of improvement on the standard ETDRS chart. However, because of the uneven staggered injection schedule between the q8 week treatments groups, the method to calculate the visual improvement outcome favored faricimab over aflibercept.  The study design called for averaging the measurements of visual improvement over a three-month time frame (i.e. at week 48, 52, and 56).  As a result, the three averaged measurements for faricimab (Fq8) was 4 weeks, 8 weeks, and 4 weeks post-injection (average 5.3 weeks), while the three measurements for aflibercept (Aq8) were 8, 4, and 8 weeks post injection (average 6.6 weeks).  Thus, the unevenly staggered injection schedule resulted in a final visual endpoint measurement inappropriately in favor of faricimab.  

Even in the subgroup of faricimab (Fpti) that touted one 16week treatment interval, the visual acuity measurements were taken at 16weeks, 4weeks, and 8 weeks post-injection.  This represents an average of 9.3 weeks post-injection; this is nowhere near the measurement taken at 16 weeks.  In addition, the acuity outcomes in the Fpti group were reported as a group without reporting the acuity gains made specifically by the subgroup of eyes extended to a 16-week interval.  Therefore, the reported acuity gains do not apply to this subgroup with extended treatment.       

A secondary outcome of the study was the central subfield macular thickness (CST).  This measurement shows the anatomic improvement in macular edema.  The slope of the thickness curve trended toward a more rapid decrease in both arms of faricimab compared with aflibercept during the monthly injection stage (initial loading stage).  Analysis of the results after the loading stage (monthly injections), both faricimab and aflibercept showed a similar jagged curve demonstrating a drop-off of treatment effect during the no-treatment month.  A similar jagged response is not seen in the Fpti group as the treatment intervals varied within that group.  The rebound in edema seen in both faricimab and aflibercept suggests the durability of the treatment effect may be similar.  These studies did not perform a direct comparison of faricimab and aflibercept on the same personalized treatment interval protocol.

Remarkably, these limitations of the study were not discussed in the published article and the FDA granted approval of faricimab for use in the United States based on these data drawn from an imperfect study design that favored faricimab.  More research is needed in order to determine if faricimab is truly non-inferior to aflibercept and whether faricimab may offer a reduced treatment burden.  

UPDATE Oct 2022: I have been using Vabysmo in the office. I am please with the results in patients with wet AMD in that I can extend the treatment interval further than with older drugs. However, patients with large serous pigment epithelial detachments (PED) appear to be at greater risk of vision loss from rips in the PED. 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

Yosemite and Rhine Studies: an editorial

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Faricimab was recently approved by the FDA for the treatment of diabetic macular edema (DME). It is the first drug which simultaneously blocks vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang 2). The anti-VEGF-A action is shared with bevacizumab, ranibizumab, and aflibercept; and stabilizes microvascular permeability and inhibits neovascularization. The Ang 2 inhibition works via the angiopoietin and Tie signaling pathway to reduce microvascular permeability by a pathway independent of VEGF-A blockade. Preclinical studies suggested that faricimab might be more effective than simple anti-VEGF inhibition in treating diabetic macular edema. In particular, there were expectations for improvement over the status quo in duration of action. If similar efficacy with lesser treatment burden were possible, this would help overtaxed clinicians and patients and begin to close the real-world versus randomized trial performance gap.1

The results of two identical, phase 3 randomized clinical trials, YOSEMITE and RHINE, were recently published, allowing clinicians the opportunity to assess how the efficacy of faricimab matches the promise of the preclinical studies.2 There were 3 groups in the randomization: faricimab 6 mg q 8 weeks (F8), faricimab 6 mg with a personalized treatment interval (FPTI), and aflibercept 2 mg q 8 weeks (A8). The study authors reported the following in their paper:

  1. With A8 as the comparator, both F8 and FPTI were noninferior (4 letter margin) based on a primary outcome of mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56.
  2. There were no differences in safety events among the 3 groups.
  3. In the FPTI group, more than 70% of patients achieved every-12-week dosing or longer at 1 year.
  4. Reductions in CST and proportions of eyes without center-involved DME (CI-DME) over 1 year consistently favored faricimab over aflibercept.
  5. Faricimab demonstrated a potential for extended durability in treating CI-DME.

Based on the evidence in the paper, are the claims substantiated? 

With respect to noninferiority of mean change in best corrected visual acuity, the answer is qualified by the authors’ method of measurement. Because the three groups got last injections at different times, there was no single visit for which assessment of final visual acuity was intuitive. Therefore, the authors averaged the visual acuities measured at 48, 52, and 56 weeks. For the F8 group, the 3 components of the average were 4 weeks post-injection (the measurements taken at 48 weeks), 8 weeks post-injection (the measurements taken at 52 weeks), and 4 weeks post-injection (the measurements taken at 56 weeks), implying that the average last visual acuity was at 5.33 weeks post-injection ([4+8+4]/3=5.33). For the A8 group, the 3 components of the average were 8 weeks post-injection (the measurements taken at 48 weeks), 4 weeks post-injection (the measurements taken at 52 weeks), and 8 weeks post-injection (the measurements taken at 56 weeks), implying that the average last visual acuity was at 6.66 weeks post-injection ([8+4+8]/3=6.66). That is, the A8 group was disadvantaged relative to the F8 group by virtue of the F8 group having more injections in the first year, and an injection nearer to the outcome measurement times. This issue might have been averted had the F8 group received the same 5 initial monthly injections as the A8 group.    

It is difficult to provide an analogous comparative calculation for the FPTI group. The relevant information is depicted in figure 3B, but the scale of the figure is microscopic, and only estimates can be made. For example, the YOSEMITE panel of figure 3B, the red-boxed subgroup, appears to comprise 63 patients. For these patients, the 3 components of the average were 16 weeks post-injection (the measurements taken at 48 weeks), 4 weeks post-injection (the measurements taken at 52 weeks), and 8 weeks post-injection (the measurements taken at 56 weeks), implying that the average last visual acuity was at 9.3 weeks post-injection ([16+4+8]/3=9.3). Likewise, for the RHINE panel of figure 3B, the red-boxed subgroup, appears to comprise 67 patients with the average last visual acuity at 9.3 weeks.  At the other extreme of the figure (the bottom) sits the group of eyes that could never be extended beyond 4 weeks.  For YOSEMITE and RHINE this group appears to comprise 19 and 23 patients, respectively. The average last visual acuity for these eyes would be 4 weeks. In between these extremes of the figure, one would need to do an analogous calculation for every row in the figure, pooling all the results for an overall average. This is clearly more than a reader can be asked to do. The authors should have done it and reported the result in the paper, to allow the reader to see if the outcome time for the FPTI group is comparable to the A8 group. The suspicion is that they are not comparable.

Regarding the claim that the safety results of the three groups were equivalent, we agree with the authors’ interpretation. There is no evidence that faricimab is less safe to use over the 52 weeks of follow-up reported.

The authors claim that over 70% of the FPTI group were able to enter the q 12 week dosing interval. The specific term they chose was “achieved” to signal this distinction. However, entering 12 week dosing is different from demonstrating that faricimab can sustain such intervals. The primary outcome at 52 weeks did not give enough time to determine if those eyes entering 12 week or longer durations could sustain that performance, or whether they would regress to require shorter interval injections. In YOSEMITE, 169 eyes (59%) and in RHINE, 172 eyes (56%) completed one 12wk interval to be assessed for successful completion. The reader has no idea if this proportion will be sustained in the second year of the trial, and it would be an unfounded assumption to expect the entrance to q12 week intervals to be maintained. This outcome will be of great interest when the 2-year results are reported. Only 22%/21% (Yosemite/Rhine) actually completed a 16-week interval and none were treated long enough to determine sustainability of this interval.

Another problem with the authors’ claim on duration of effect has to do with a form of spin, specifically type 3 spin, in the classification of Demla and colleagues.3 A reader might think that this achievement by faricimab distinguishes it from aflibercept, but that inference would not be warranted because of the study design. There was no aflibercept personalized treatment interval arm of the randomization, which would be required to make a claim that increased duration between injections was an advantage of faricimab. While true that a drug company investing in faricimab has no obligation to provide an opportunity for the competitor’s comparator drug to perform as well, the authors cannot claim that the feature displayed by faricimab is a differentiator worthy of a clinician’s choice as a deciding factor in the question of which drug to use. It is also true that the authors don’t make this claim differentiating the drugs, but in presenting asymmetric evidence as they do, an erroneous inference is easy to make, which we seek to avert.

The authors’ claim of superior drying effectiveness for faricimab is supported by the presented data, but unremarked by the authors was evidence of similar durations of drying action of faricimab and aflibercept. To see this, examine figure 3C. The slope of the thickness curve trended toward a more rapid decrease in both arms of faricimab compared with aflibercept during the monthly injection stage (initial loading stage).  In an analysis of the graphs after the loading stage (monthly injections), both faricimab and aflibercept showed a similar jagged curve demonstrating a drop-off of treatment effect during the no-treatment month. A jagged response is not seen in the FPTI group because the treatment intervals varied within that group.  The zig-zag rebound of edema seen in both faricimab (F8) and aflibercept (A8) groups suggests the durability of the treatment effect may be similar between the two drugs.  These studies did not perform a direct comparison of faricimab and aflibercept on the same personalized treatment interval protocol.

The authors’ contention that faricimab rendered a higher proportion of eyes free of CI-DME is warranted by the data they present.

Finally, the authors emphasize the potential of faricimab for lesser burden of treatment because of potential longer durability. This emphasis is unsupported by the evidence presented. The F8 group received 10 injections. The A8 group received 9 injections – hence no decreased burden favoring faricimab over aflibercept in this comparison. It is more complicated to analyze in the FPTI group because the needed information is not reported, but we can make some inferences. There were 63 eyes of 286 (22%) in Yosemite and 66 eyes of 308 (21%) in Rhine that achieved the opportunity to extend treatment; these eyes underwent a total of 8 faricimab injections at week 52.  This number represents the least number of scheduled injections and only one less than the aflibercept group. The remainder of eyes were scheduled to have more than 8 injections, but the pooled average is difficult to parse from figure 3B.  We can easily note that from the figure that the greatest number of injections at week 52 in this arm of the study was 14 injections in eyes that required monthly treatment (19 eyes (7%) in Yosemite, and 22 eyes (7%) in Rhine).  This is far more than the 9 injections of A8, and does not demonstrate a reduced treatment burden among eyes in the faricimab group compared with aflibercept. When the remainder of eyes between the extremes of figure 3B are added in to the calculation of average treatment burden, which we encourage the authors to report, we suspect that it was greater for the FPTI arm of the study than for A8, not less.  

In summary, YOSEMITE and RHINE provide data that faricimab as administered in the studies was equivalent to aflibercept in the primary visual outcome, and superior to aflibercept as given in the study in drying the macula. No data were presented supporting a claim that treatment burden is less with faricimab than aflibercept. The published data show that a proportion of eyes can be managed with a reduced injection burden with faricimab, but provide no evidence that this would differentiate faricimab from aflibercept were aflibercept plugged into the same personal treatment interval algorithm. There was no arm of the study that would allow such a comparison to be made. The published data substantiate that faricimab has a greater macular drying effect than aflibercept, but the see-saw central subfield thickness curve in the non-loading phase of the first year suggests that the duration of drying by faricimab is no greater than with aflibercept.

The FDA has approved faricimab for the treatment of CI-DME based on YOSEMITE and RHINE. Retinal specialists will be making choices of which drug to use. An economic perspective will enter into the decision. The clinical decision will not be based exclusively on efficacy. The offered average costs for aflibercept and faricimab to the editorialists are $1747 and $2168, respectively. Is the $441 differential cost a reasonable price to pay for the documented differences in drug performance? Our opinion is no. There is no published difference in visual outcomes, nor any published difference in durability, because it wasn’t checked. There is a difference in macular drying, analogous to the superior drying effect of aflibercept over bevacizumab in the better-vision group of protocol T (eyes with CI-DME)or in the aflibercept versus bevacizumab group in SCORE-2 (eyes with central retinal vein occlusion with macular edema).4,5 We, and many others, did not think that differences warranted the use of aflibercept over the less expensive bevacizumab in cases similar to those in the better seeing group of protocol T or eyes like those studied in SCORE-2, nor do we think that drying difference seen in YOSEMITE and RHINE between faricimab and aflibercept is reason to choose the more expensive drug. We congratulate the authors of these studies for providing ophthalmologists with new options for treating diabetic macular edema, but nothing they have published suggests that this option marks a milestone in reducing treatment burden in DME. The 2-year results will be more informative for decision-making than the 1-year results, and we encourage the authors to remedy the flaws in their year -1 results data presentation so that the 2-year data are more useful.

By David J. Browning, MD, PhD and Scott E. Pautler, MD

References

   1.   Kiss S, Liu Y, Brown J, et al. Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema. Clin Ophthalmol 2014;8:1611-1621.

   2.   Wykoff CC, Abreu F, Adamis AP, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 2022;DOI:https://doi.org/10.1016/S0140-6736(22)00018-6.

   3.   Demla S, Shinn E, Ottwell R, Arthur W, Khattab M, Hartwell M, Wright DN, Vassar M. Evaluaton of “spin” in the abstracts of systematic reviews and meta-analyses focused on cataract therapies. Am J Ophthalmol 2021;228:47-57.

   4.   Diabetic Retinopathy Clinical Research Network, Welss JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush AN, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FJ, Friedman SJ, Melia M, Pieramici D, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 2015;372:1193-1203.

   5.   Scott IU, VanVeldhuisen PC, Ip MS, et al, SCORE2 Investigator group. Effect of bevacizumab vs aflibercept on visual acuity among patients with macular edema due to central retinal vein occlusion: the SCORE2 randomized clinical trial. JAMA 2017;317:2072-2087.

Diamox and Neptazane for the Eye

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What are carbonic anhydrase inhibitors (CAI)?

            CAI medicines are sometimes prescribed to lower the pressure in the eye either to control pain or to decrease the chances of damage to the eye from high pressure (as in glaucoma). They may also be used to decrease abnormal fluid leakage from blood vessels in the retina (e.g. retinitis pigmentosa). These pills are very effective and may be used along with eye drops to lower the eye pressure. The two most common pills used are Diamox (acetazolamide) and Neptazane (methazolamide).

What side effects might be encountered?

            While you are taking these medicines, you may notice a tingling sensation in the fingers, toes, or lips; an altered sense of taste; a loss of appetite; drowsiness; a “washed out” feeling; or an increase in urination. These are not allergic reactions, but should be reported to the doctor if they become bothersome.

            It may be helpful to take potassium supplements (e.g. banana) while on CAI to prevent low potassium levels in the blood. Low serum potassium may cause muscle cramps and weakess, abdominal cramps, palpitations, faintness from low blood pressure, and depression. 

            The dosage of CAI may be reduced in patients with reduced kidney function (see table below). CAI may not be used in advanced cases of liver cirrhosis.

            Only rarely do severe reactions occur. Be sure to report hives, skin rashes, gout, allergy to sulfa antibiotics, kidney stones, kidney failure, mental depression, liver failure, blood in stool or mouth, easy bruising, or anemia.

What other medicines might interact with CAI?

            Other drugs rarely interact with CAI and an adjustment in dosage is sometimes needed. CAI may increase the effect of diuretics (HCTZ, lasix, bumex, etc.), high-dose aspirin, and quinidine. CAI may increase the effect of digoxin (lanoxin), phenytoin (Dilantin), carbamazepine, primidone, and lithium. Caution should be used when taking metformin for diabetes; CAI may increase the risk of lactic acidosis. Be sure to notify your doctor if you are taking any of these medicines.

How to adjust the dosage in kidney failure?

            The table below shows how to adjust dosage of acetazolamide (Diamox) in the setting of kidney disease.

Glomerular Filtration Rate (GFR) in mL/minDosage
20-50 250 mg up to 4 times a day
10-20250 mg up to 2 times a day
<10 or on dialysis250 mg daily or 3 times a week

reference: https://kidneydiseaseclinic.net/renaldrugs/Acetazolamide.php

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.

Lattice Degeneration

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globe anatomy
anatomy of the eye (click on image to enlarge)

What is lattice degeneration?

Lattice degeneration is a condition in which the retina develops areas of abnormal thinning.  The thinning occurs as the retina stretches during growth of the eye.  The retina is a “tissue-paper” thin layer of nerve tissue, which lines the inside of the eye like the film in a camera.  In the eye, light is focused onto the retina, which “takes the picture” and sends the image to the brain.  Lattice degeneration is most common in near-sighted people and affects about 7% of the general population.          

What causes lattice degeneration?

Lattice degeneration appears to be an inherited condition that usually develops in childhood or early adulthood.  The eye, which is round like a ball at birth, becomes oval like an egg.  The elongation of the eye causes the retina to stretch.  As a result, thin areas develop in the retina similar to “stretch marks” that occur in the skin with growth or weight gain.    

Why is it important to know about lattice degeneration?

            Lattice degeneration in itself causes no symptoms or loss of vision.  It is important because lattice degeneration predisposes eyes to retinal detachment, which can cause permanent blindness without treatment.  With age, trauma, or inflammation, the vitreous gel that fills the eye begins to condense and pull away from the retina.  If the retina has become weakened by lattice degeneration, it is more likely to tear when pulled upon.  A tear in the retina allows fluid from the vitreous gel to seep under the retina as the retina detaches.  Fortunately, only one in 200 eyes with lattice degeneration ever develop retinal detachment.  Usually no treatment of lattice degeneration is needed, but symptoms of new floating spots or fibers should be reported to the doctor promptly. An examination may disclose breaks in the retina, which may be treated in the office with laser.  The appearance of a dark curtain or shadow from the side-vision like an eclipse of the moon is an even more serious symptom that may indicate retinal detachment and require major eye surgery to repair. 

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.