Scott E. Pautler, M.D. Tampa

Treatment of diseases of the retina and vitreous

Which is better: Syfovre or Izervay?

Posted on December 17, 2023 by Scott Pautler

What are Syfovre and Izervay?
Syfovre and Izervay are medications used to treat geographic atrophy (GA) caused by dry-type age related macular degeneration (AMD). It is given by injection into the eye.

What is geographic atrophy (GA)?

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

How do Syfovre and Izervay work?

Syfovre and Izervay block the complement proteins in the body. Complement is involved in the normal inflammatory response of the body. The inflammatory response is important to fight infection. However, in AMD the complement proteins appear to be involved in the development on geographic atrophy and loss of vision.

How well do Syfovre and Izervay work?

Syfovre and Izervay are not cures for dry AMD. They do not reverse the past damage by geographic atrophy. Syfovre and Izervay, when given by monthly injection, was shown to reduce the rate of worsening of geographic atrophy by a small amount in a two-year study.

What are the adverse effects of Syfovre and Izervay?

As with all intraocular injections there are risks. The risks involved with the introduction of a needle into the eye include bleeding, inflammation, infection, and retinal detachment. These problems may require surgery and risk loss of vision. The known risks of Syfovre and Izervay include the new start of wet AMD threatening loss of vision. This appears to occur in 10-20% of eyes. This risk of new wet AMD 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 another medication to prevent severe loss of vision.

There is a risk of infection (endophthalmitis) after any eye injection. There is some concern that Syfovre and Izervay may increase the risk of developing infection or worsen the final vision after infection. The suppression of the natural defense against infection by both of these drugs, explains the concern over increased risk of infection. Not surprisingly, similar drugs given systemically have been shown to increase the risk of infection outside the eye.

Which is better: Syfovre or Izervay?

There have been no studies to date directly comparing Syfovre and Izervay. However, Syfovre has rarely been associated with loss of vision from ischemic optic neuropathy (1-2%) and ischemic retinal vasculitis (~1 in 10,000). To date it is not known if Izervay also shares this adverse effect. Regardless, some doctors prefer Izervay because the injection may be given with a finer needle (i.e. it is less viscous), making the injection more comfortable compared with Syfovre.

The decision to use Syfovre or Izervay with the intent to slow the progression of dry AMD (geographic atrophy) must be weighed against the potential adverse effects in any given patient. Your doctor will help you decide. Also, remember that adhering to a Mediterranean diet is also associated with slower enlargement of geographic atrophy in AMD.

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.

Lucentis Biosimilars: Byooviz and Cimerli

Posted on December 16, 2023 by Scott Pautler

What is a Lucentis biosimilar?

Lucentis is a medication used in the treatment of a variety of conditions including wet-type macular degeneration, diabetic retinopathy, and retinal vein occlusion. Lucentis biosimilars are less-expensive medications manufactured to work in a fashion similar to Lucentis. It is important to remember that Lucentis biosimilars are not identical medications to Lucentis. In the US, Lucentis biosimilars include Byooviz and Cimerli.

How effective are Lucentis biosimilars?

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. The biosimilars were approved for use by the FDA as they appear to be non-inferior. Further research will reveal more details.

What are the risks of Lucentis biosimilars?

Severe complications are very rare, but risks of Lucentis injection include bleeding, infection, inflammation, retinal detachment, glaucoma, cataract, and loss of vision. There may be a small increased risk (1%) of stroke or heart attack with Lucentis. The risk of stroke may be related to concurrent illness and the older age of patients in which these medications are used. Pregnancy should be avoided while on Lucentis therapy. All of these risks apply to biosimilars, as well. Furthermore, the question of whether biosimilars pose additional (or less) risk will be determined over time.

Why change from Lucentis to a biosimilar medication?

Usually an insurance company prompts the need to change from Lucentis to a biosimilar medication to lower their costs. This may be a disadvantage to signing up for a Medicare Advantage insurance plan. When a doctor must change from Lucentis to a biosimilar, he may need to take precautions in order to reduce the risk of problems. For example, he may initially inject Byooviz or Cimerli at 4-week intervals before attempting to extend the treatment interval in order to assure effectiveness. He may monitor the patient more closely to identify inflammation or high eye pressure. After injection, patients should report any new symptoms without delay.

Are doctors given financial incentives to prescribe Cimerli and Byooviz?

Manufacturers of new medications often provide incentives in the form of rebates to doctors. To determine if your doctor receives large payments from drug companies, visit the CMS website and enter your doctor’s name in the search box. I take great pride in advocating for my patients in the selection of medications, rather than pander to the drug companies.

By Scott E Pautler, MD

What is the Difference Between Dry and Wet AMD?

Posted on October 29, 2023 by Scott Pautler

Age-Related Macular Degeneration: Dry or Wet?

What is the difference between dry and wet age-related macular degeneration?

Age-related macular degeneration (AMD) is the most common cause of visual loss in older Americans. Doctors often talk about dry and wet types of AMD. But what is the difference? Simply put, dry AMD means there are no abnormal, leaky blood vessels. Whereas, in wet AMD there are abnormal blood vessels that grow and leak under the macula. However, this system of naming wet and dry AMD can be confusing. Therefore, newer names for the stages of AMD have been proposed.

Why is it important to distinguish between wet and dry AMD?

Dry and wet AMD cause different symptoms and are treated differently. Early and intermediate stages of AMD are often called dry AMD. These stages usually cause few symptoms, which include the need for good lighting. The treatment involves AREDS2 vitamins and a Mediterranean diet. Advanced stages of AMD are called geographic atrophy (advanced dry AMD) and neovascular AMD (wet AMD). Both types of advanced AMD are usually associated with decline in central vision, frequently affecting the ability to read, see the computer, and drive a car. Geographic atrophy (advanced dry AMD) progresses slowly with blind spots that interfere with the ability to see. Neovascular AMD (wet AMD) may advance more rapidly with distortion, blurred areas of vision, and blind spots. It is possible to have both forms of advanced AMD…geographic atrophy (advanced dry AMD) and neovascular AMD (wet AMD).

What is the treatment of advanced AMD?

The treatment of the two forms of advanced AMD is different. Furthermore, the treatment of one type of advanced AMD may aggravate the other form of AMD. However, both forms of advanced AMD benefit from the use of magnifiers and other low vision aids.

What is the treatment of geographic atrophy (advanced dry AMD)?

The Meditteranean diet is protective against advanced AMD and appears to slow the enlargement of geographic atrophy. Additionally, Geographic atrophy (GA) is currently treated with medications that inhibit the complement systems of proteins in the body that normally cause inflammation to fight infection. The two FDA-approved medications are Syfovre and Izervay. They are both given as an injection into the eye. They do not reverse the damage from GA and do not prevent GA from getting worse. They do slow down the rate of worsening of GA. There is no good evidence to show that one medication is better than the other. Long-term injections are needed over the years. And, unfortunately, both medications may cause wet AMD (neovascular AMD) to start.

What is the treatment of wet AMD (neovascular AMD)?

Wet AMD is treated with injections to stop the leaking blood vessels under the macula. These medications (Avastin, Lucentis, Eylea, Beovu, and Vabysmo) prevent further worsening of vision from wet AMD in about 90% of cases over several years. In about 40% of cases, the vision may improve. Long-term injections are usually needed over the years. There is limited evidence to suggest benefits of some medications over others. There is also some concern that the treatment of wet AMD may aggravate geographic atrophy (advanced dry AMD).

What do you do when an eye has both forms of advanced AMD?

The presence of both neovascular AMD (wet AMD) and geographic atrophy (advanced dry AMD) poses a serious problem. Both forms of advanced AMD may result in legal blindness (the loss of central vision). However, advanced AMD almost never results in complete blindness. Treatment is usually aimed at the greatest threat to vision. Specific treatment plans are made on a case by case basis. In some situations, injections are given on an alternating schedule for GA and neovascular AMD. In end-stage situations in which the chance of further loss of vision is low, all injections may be stopped. Low vision aids and assistance (family and social services) often results in high-level functioning and independence.

By Scott E. Pautler, MD

Save on AREDS Eye Vitamins

Posted on September 11, 2023 by Scott Pautler

What is age-related macular degeneration?

Age-related macular degeneration (AMD) is the most common cause of visual loss in older Americans. It comes on with age and affects the central vision. However, AREDS-2 vitamins lower the risk of vision loss.

What are AREDS-2 vitamins?

The AREDS-2 formula consists of carefully dosed vitamins, minerals and antioxidants aimed at protecting a patient against loss of vision from AMD. It consists of vitamin C, vitamin E, Zinc, Copper, lutein, and zeaxanthin.

Are there other vitamins in the market for AMD?

There are many vitamins and nutritional supplements marketed for AMD. However, the AREDS-2 formula has undergone the most testing to date. It offers the most assurance for protection against loss of vision. Other supplements have been studied much less extensively and the safety is less certain. For example, beta-carotene was used in AMD vitamins in the past, but it increases the risk of lung cancer in current and former smokers.

What are the popular brands of AREDS-2 vitamins?

There are many brands of vitamins that contain the AREDS-2 formula. PreserVision AREDS-2 and Ocuvite AREDS-2 are two popular brands. They offer good quality; however, they are expensive.

What is the least expensive brand of AREDS-2 vitamin?

There is now a high-quality alternative to the popular brands and it is much less expensive. The name is Equate Advanced Eye Health Complex by Walmart. In Tampa on September 9, 2023 the price for a box of 140 softgels (two-month’s supply) was $19.96. This compares favorably with the price of PreserVision AREDS-2 of identical quantity selling for $34.47.

By Scott E. Pautler, MD

Note: Dr Pautler has no financial interest in any of the vitamin supplements.

Izervay for Dry Macular Degeneration

Posted on August 27, 2023 by Scott Pautler

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

What is geographic atrophy?

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

What does Izervay do?

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

How well does Izervay work?

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

What are the adverse effects of Izervay?

Can Izervay cause wet macular degeneration to start?

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

What about the risk losing vision from infection?

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

Should I receive Izervay injections?

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

By Scott E. Pautler, MD

Is Eylea HD for Me?

Posted on August 23, 2023 by Scott Pautler

What is Eylea HD?

You may ask yourself, “Is Eylea HD for me?” Eylea HD is an FDA-approved medication for the treatment of wet AMD and diabetic retinopathy. It is a more concentrated form of Eylea, a medication that has been approved for use and effectively used for many years. Eyela contains 2mg of medication per injection, whereas Eylea HD has 8mg of medication per injection.

When is it helpful to use Eylea HD over Eylea?

There are several reasons Eylea HD may be better than Eylea. For example, in some eyes with severe macular degeneration or diabetic damage, current medications may not appear to be strong enough to help. Eylea HD may offer the strength needed to help prevent loss of vision in these cases. In addition, if Eylea does not last as long as needed, injections may need to be given frequently. Eylea HD offers a longer duration of action. Therefore, it may allow more time between injections.

What are the side effects?

The same side effects of Eylea remain for Eylea HD. That is, they are both given by injection into the eye. Therefore, risks include infection, inflammation, bleeding, and retinal detachment, among others. Over time, these risks are less with Eylea HD if injections can be given less often; the fewer the number of injections, the lower the risk of complications from the injection procedure. However, because Eylea HD is more concentrated, there may be increased risk of complications outside the eye. As Eylea leaves the eye and enters the blood stream, it may cause increased risk of hypertension, stroke, heart attack, and kidney disease. There is much debate about whether this risk is significant or not, but evidence suggests the risk may be higher in diabetic patients.

How can I decide if Eylea HD is right for me?

Your doctor will help you to decide. If you do not have diabetes, or past history of stroke or heart attack, the decision may be easy. However, if you have diabetes or are at high risk of stroke and heart attack, you may wish to hold off using Eylea HD until doctors have had more experience with the medication, which was newly approved for use in August 2023.

By Scott E. Pautler, MD

Diet and Age-Related Macular Degeneration

Posted on August 12, 2023 by Scott Pautler

What is age-related macular degeneration?

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

What lifestyle changes offer protection against macular degeneration?

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

What is a Mediterranean diet?

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

By Scott E. Pautler, MD

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Stop Injections for Wet AMD

Posted on August 4, 2023 by Scott Pautler

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

Can I stop injections for wet AMD?

May I stop injections for wet AMD? This is a common question. Injections are the mainstay of treatment for wet AMD. They reduce the risk of vision loss. However, they are inconvenient, uncomfortable, and costly. At first, Injections are given every month. Over time, they may be given every few months. Unfortunately, long term injections are usually needed to prevent loss of vision. However, there are situations in which injections may be stopped.

In what circumstance may injections be stopped temporarily?

In certain situations, the doctor may recommend a period of observation without injection in wet AMD. For example, a patient may have been unable to return in a timely fashion for injection. Upon delayed examination, the retinal specialist may find the wet AMD to be inactive. Moving forward, injections may be held in this case. Continued close observation is needed to detect recurrent active leakage of abnormal blood vessels in wet AMD.

Rarely, injections may result in inflammation inside the eye. Medication is prescribed to quell the inflammatory reaction to protect against permanent damage. The wet AMD may become inactive in this situation and it may be observed for reactivation.

When might the injections be stopped for the long term?

After months to years of treatment, the vision may decline despite injection therapy. This may happen due to atrophy (loss of tissue) or scarring (fibrosis). If the vision is very poor, injections may be stopped if it is clear that continued treatment will not improve the vision and further treatment is not necessary to prevent worsening of vision. Furthermore, there is limited evidence that suggests injections for wet AMD may worsen dry AMD.

What are the risks of stopping injections?

The main risk of stopping injections for wet AMD is that leaking and bleeding from abnormal blood vessels may cause further loss of vision. This may result in a larger and/or darker central blind spot. However, rarely it may result in total loss of vision in that eye.

The chances of further loss of vision off injections largely depends on whether the macula has active leakage at the time injections are stopped. In a study of 821 eyes observed for one year after stopping injection, Cornish and others found that 8% of all eyes had serious loss of vision. However, 15% of eyes with leakage at the time injections were stopped experienced severe further loss of vision. Therefore, if you have usable vision and wish to avoid further loss of vision, continued injections are preferable. However, if you do not have functional vision and there is no active leakage of the macular degeneration, the risk of further profound loss of vision is low.

By Scott E. Pautler, MD

The Use of Steroids in Endophthalmitis

Posted on May 6, 2023 by Scott Pautler

Why use steroids in endophthalmitis?

Ophthalmologists often consider the use of steroids in endophthalmitis treatment. Steroids reduce inflammation in endophthalmitis. The decrease in inflammation helps improve comfort and potentially reduces inflammatory tissue damage, such as scarring. Although it is key to treat with appropriate antibiotics for infectious endophthalmitis, topical steroids (steroid eye drops) are included in the therapeutic regimen. The physician orders the steroid eye drops frequently at the onset and monitors inflammation and eye pressure to determine the best treatment schedule.

What is the role of intravitreal steroid injections?

The role of intravitreal steroids (dexamethasone) is controversial. In a recent review and meta-analysis of endophthalmitis, there was no added benefit with the use of intravitreal dexamethasone. The reason for lack of benefit may include the short half-life of intravitreal dexamethasone (<3 hours). Nonetheless, there may be benefit derived from the use of intravitreal dexamethasone in severe bacterial infections such as those caused by Bacillus species.

What about other ways to give steroids?

In select cases there may also be a role for periocular or systemic steroids for a more prolonged steroid effect. Periocular steroids require an injection next to the eye. My preferred technique is a subtenant’s injection as described by Nozik because it is fairly pain-free. Systemic steroids are given as a pill. There are potential side-effects to the use of steroids. With steroid injections come the risk of elevation of eye pressure, which may cause glaucoma. Many side effects may occur with steroid pills including depression, high blood sugar, weight gain, brittle bones, acne, stomach ulcers, and others. Usually side-effects are preventable or treatable. The final decision of how and when to use steroids lies with the treating physician based on the circumstances of the case.

By Scott E. Pautler, MD

Laser for Central Serous Retinopathy

Posted on May 3, 2023 by Scott Pautler

What is central serous retinopathy?

Before we discuss laser for central serous retinopathy, we must ask what is central sero retinopathy. Central serous retinopathy (CSR) is an eye condition associated with loss of vision from water (serous) leakage from the choroid beneath the macula (central retina). Although it may be seen at any age, it is most common among young adult males. The leakage may be initiated by emotional stress and aggravating factors include stimulants (caffeine, cocaine, amphetamines), steroids (cortisone, prednisone, testosterone and other androgens), lack of sleep (sleep apnea), over-the-counter dietary supplements (niacin, body-builders), prescription medications (possibly Viagra and related meds), and medical conditions (Cushing’s syndrome, pheochromocytoma).

What treatment is available?

The first line of treatment is identification and elimination of any factors that are suspected to aggravate CSR. However, if leakage persists, there are a number of treatments that may be helpful. These include a special class of oral diuretics, antiVEGF injections, and lasers. Although thermal lasers may be used in selected cases, often cold lasers are preferred.

How do cold lasers (PDT) work?

Verteporfin photodynamic therapy (PDT) is the cold laser used in ophthalmology for the treatment of retinal problems. It is called “cold” because it does not use heat to cauterize tissue. Verteporfin dye is injected into the vein of the arm after which a laser is aimed into the eye to activate the dye. The activated dye releases highly reactive oxygen radicals, which chemically seal the leaking blood vessels under the retina. PDT is very effective in treating CSR. It is expensive and sometimes not covered by private insurance. PDT rarely causes a blind spot in the vision and this risk is minimized by using a low dose of Verteporfin or low power laser (reduced fluence). After PDT treatment has been completed, it is important to avoid direct sunlight (or exposure to halogen light) for 48 hours to allow time for the Verteporfin to leave the body.

Below are the photos of a 49-year-old man who had blurred vision and some distortion in his left eye for a year. His condition did not improve after a trial off caffeine. He had no medical problems and no other inciting factors were identified.

Color photos revealed some white changes in the retina (arrow) due to permanent degeneration of the retina near center of vision (fovea) due to longstanding leakage. Fundus autofluorescence photos are even more sensitive in showing this damage.

OCT (above) shows fluid under the retina (between the retina and the retinal pigment epithelium).

FA/ICGA photos (above) show the site of active leakage under the retina. Because of the lack of improvement with medical therapy and the threat of permanent loss of central vision due to long-standing leakage, this patient underwent reduce-fluence PDT. He experienced no adverse effects of laser and his vision returned to 20/20 over several months’ time.

The OCT above shows resolved subretinal fluid one month after PDT.

By Scott E. Pautler, MD

Reduce the Risk of Wet AMD from Syfovre

Posted on February 18, 2023 by Scott Pautler

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

Parameters	Sham (no drug)	Monthly drug injection	Every other Month drug injection
All study eyes	1.2%	20.9%	8.9%
Fellow wAMD	0%	33.3%	17.9%
No fellow wAMD	1.9%	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

Parameters	Sham (no drug)	Monthly drug injection	Every other Month drug injection
All study eyes	1.2%	20.9%	8.9%
DLS present	4.2%	30%	24%
DLS absent	0%	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

Syfovre for Dry Macular Degeneration

Posted on February 2, 2023 by Scott Pautler

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

Sunken Eyes from Glaucoma Drops

Posted on January 7, 2023 by Scott Pautler

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.

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

Computer Glasses

Posted on November 11, 2022 by Scott Pautler

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

Methotrexate for Uveitis

Posted on October 29, 2022 by Scott Pautler

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

Byooviz Therapy

Posted on July 30, 2022 by Scott Pautler

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

What is the Best Drug for Eye Injections?

Posted on July 10, 2022 by Scott Pautler

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 drug	Cost	Effectiveness	Safety
Avastin	Cheap: ~$50	Good	Repackaging*
Lucentis	Expensive: ~$2,000	Good	safest systemically**
Eylea	Expensive: ~$2,000	Better	1% inflammation
Eylea HD	Expensive: ~$2000	?Better	1% inflammation or greater?
Vabysmo	Expensive: ~$2,000	?Better	2% inflammation
Beovu	Expensive: ~$2,000	?Better	4-5% 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

Portable Low-Vision Magnifiers

Posted on May 22, 2022 by Scott Pautler

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

Posted on April 15, 2022 by Scott Pautler

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?

By Scott E. Pautler, MD

Vabysmo better than Eylea?

Posted on March 20, 2022 by Scott Pautler

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#	1	4	8	12	16	20	24	28	32	36	40	44	48	52	total
Fq8	1	1	1	1	1	1	0	1	0	1	0	1	0	1	10
Aq8	1	1	1	1	1	0	1	0	1	0	1	0	1	0	9

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

Yosemite and Rhine Studies: an editorial

Posted on March 20, 2022 by Scott Pautler

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:

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.
There were no differences in safety events among the 3 groups.
In the FPTI group, more than 70% of patients achieved every-12-week dosing or longer at 1 year.
Reductions in CST and proportions of eyes without center-involved DME (CI-DME) over 1 year consistently favored faricimab over aflibercept.
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

Posted on March 12, 2022 by Scott Pautler

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/min	Dosage
20-50	250 mg up to 4 times a day
10-20	250 mg up to 2 times a day
<10 or on dialysis	250 mg daily or 3 times a week

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

By Scott E. Pautler, MD

Vabysmo (faricimab) Therapy

Posted on January 29, 2022 by Scott Pautler

What is Vabysmo therapy?

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

How effective is Vabysmo therapy?

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

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

What are the risks of Vabysmo therapy?

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

What do I expect after a Vabysmo injection?

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

By Scott E. Pautler, MD

Blindness from Tattoo

Posted on April 30, 2021 by Scott Pautler

How can a tattoo cause blindness?

There are several ways in which a tattoo may threaten loss of vision. The most obvious situation is a scleral tattoo. This is a tattoo applied to the outer eye wall, the white sclera. The tattoo ink may have direct toxic effects on the eye and there is a risk of serious infection. However, even a skin tattoo applied far from the eyes may risk loss of vision. This is due to an autoimmune condition called tattoo granuloma with uveitis (TAGU). Autoimmune conditions occur when your own immune system attacks your body.

What are the symptoms of TAGU?

Various symptoms may be experienced depending on where the eye is most inflamed. Symptoms may be mild or they may be severe and disabling. The eye may be painful, red, tearing, and light sensitive. Tiny floating spots which move or “float” may be seen. Sometimes blind spots, blurred vision, distortion, or loss of side vision occurs. The visual symptoms are frequently associated with inflammation of the tattoo (elevation, redness, warmth, itching, tenderness and/or swollen lymph nodes).

Who is at greatest risk of TAGU?

Fortunately, TAGU appears to be a rare condition. However, risk factors that may increase the chance of TAGU include the size of the tattoo. The larger the tattoo, the greater the risk of TAGU. Also, a personal history or family history of other autoimmune conditions may increase the risk of TAGU. Other autoimmune conditions include sarcoidosis, rheumatoid arthritis, lupus, and Harada’s disease.

How is TAGU diagnosed?

The diagnosis of TAGU is first considered in anyone with inflammation of the eye (uveitis) in a person who has had a tattoo. A skin biopsy may be needed to demonstrate a typical form of inflammation of the tattoo. In addition, other tests may be needed to be sure the uveitis is not due to a problem unrelated to the tattoo (see uveitis questionnaire).

Take some time to carefully review and report to your doctor any unusual or unexplained symptoms such as rashes, back and joint problems. Tell your doctor if you travel abroad, spend time in rural settings, or may be exposed to animals or infections. Heredity may also play a role. Also, review and report your ancestry (for example, Asian, Mediterranean, or American Indian ancestry). When the doctor diagnoses uveitis, laboratory tests may be ordered to help determine its cause.

How is TAGU managed?

To limit the damage from inflammation, TAGU is treated with anti-inflammatory medication in the form of eye drops, injections (next to the eye or into the eye), or pills. When pills are used, the eye doctor frequently coordinates medical care with the expert assistance of a rheumatologist. Rarely, surgery is required to treat TAGU. In some cases, uveitis may be long-lasting. In these cases, years of therapy are needed to preserve vision. TAGU is a serious eye problem and may result in loss of vision or blindness. However, by seeing your eye doctor and taking the medications exactly as recommended, damage to your vision can be minimized.

In some cases, TAGU can resolve with treatment, but return at a future date. Therefore, if you become aware of symptoms of uveitis in the future, do not hesitate to contact your doctor.

What are other risks of tattoos?

Apart from eye inflammation, there are a host of health risks associated with tattoo. They include infection of the skin or blood (sepsis), hepatitis, HIV/AIDS, heart valve infection (endocarditis), scleroderma, scarring (keloid formation), and hypersensitivity reactions. Remember that the FDA does not regulate the contents of the ink that is injected into the skin. Also, government regulation is variable as it relates to training, sanitation, and infection control. Current regulations may not be adequate to protect you against harm.

By Scott E. Pautler, MD

Lumega-Z: Worth the cost?

Posted on April 11, 2020 by Scott Pautler

What is Lumega-Z?

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

What does Lumega-Z do?

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

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

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

What about the company that makes Lumega-Z?

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

Is Lumega-Z worth the cost?

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

By Scott E. Pautler, MD

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