Tag Archives: Eylea

Lucentis Biosimilars: Byooviz and Cimerli

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Lucentis Biosimilars

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

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

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

Is Eylea HD for Me?

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Is Eylea HD for me?
anatomy of the eye (click on image to enlarge)

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

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

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

Vabysmo better than Eylea?

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Yosemite/Rhine Studies: a critical analysis

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

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

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

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

wk#1481216202428323640444852total
Fq81111110101010110
Aq8111110101010109

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

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

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

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

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

UPDATE Oct 2022: I have been using Vabysmo in the office. I am please with the results in patients with wet AMD in that I can extend the treatment interval further than with older drugs. However, patients with large serous pigment epithelial detachments (PED) appear to be at greater risk of vision loss from rips in the PED. I have not been impressed with superior effectiveness of Vabysmo in patients with diabetic retinopathy.

By Scott E. Pautler, MD

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

Copyright  © 2022 Designs Unlimited of Florida

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

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

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

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

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

By Scott E. Pautler, MD

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

References:

Ophthalmology 2012 119:1604-1608 Campbell

AJO 2015 160:569-580 Schlenker

Ophthalmology 2012 119:1388-1398 Martin

Ophthalmology 2012 119:1399-1411 Chakravarthy

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Retinal Vein Occlusion

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What is a retinal vein occlusion (RVO)?

Retinal vein occlusion means blockage of a vein in the retina.  The retina in your eye is like the film inside a camera.  The retina “takes the picture” of objects you look at and sends the message to the brain.  The retina is a living tissue, which requires blood supplied by tiny vessels.  Retinal veins are blood vessels that drain blood out of the retina. An abnormal blood clot in a retinal vein causes a blockage (occlusion) of the blood flowing out of the retina.  Depending on the location of the occlusion, vein occlusions are divided into branch retinal vein occlusion and central retinal vein occlusion.

retinal vein occlusion
anatomy of the eye (click on image to enlarge)

Who is at risk for a retinal vein occlusion?

Retinal vein occlusions occur in 1-2% of people over 40 years of age. Retinal vein occlusions are more common in people who are overweight, use tobacco or estrogen, or have hardening of the arteries, diabetes, high blood pressure, sleep apnea, glaucoma, or blood disorders.

What are the symptoms of a retinal vein occlusion?

Blurring of vision may occur if excess fluid (edema) leaks from the veins into the center of the retina.  Floaters can look like tiny dots or cobwebs moving about in your vision.  They may be due to bleeding from the retina into the central gel of the eye.  Pain is rare and may be due to high pressure in the eye (neovascular glaucoma).

What treatment is available?

There is no cure, but treatment may improve vision or keep the vision from worsening.  Your doctor may allow time for the vein to heal.  Sometimes eye drops or pills may be prescribed.  Medicine injections (Avastin, Lucentis, Eylea, steroids) may help recover vision and may be applied without pain in most cases. Injections may be required for the long-term; about half of eyes with central retinal vein occlusion require injections for at least three years. Injections for retinal vein occlusion are safe in regard to risks of problems outside the eye. However, there appears to be a low risk of stroke (intracranial hemorrhage) of <4/1000 every year of treatment.

Laser may stabilize or improve the vision.  The vision may not return to normal following treatment as there may be some permanent damage to the retina from the occlusion.  In some cases when treatment cannot improve the vision, laser is used to prevent severe pain and complete blindness.

Your doctor is going to order appropriate tests and recommend the best course of action to take at this time.  The retinal vein occlusion will not be worsened by your daily activities or by using your eyes. You may monitor the vision with the Amsler grid test.  It is important to be seen by your primary care doctor to treat risk factors of hardening of the arteries to prevent stroke and heart attack.

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.

recent BRVO
blood spots and white exudates in retina from recent brach retinal vein occlusion (click on image to enlarge)
healing BRVO
Fewer blood spots as vein occlusion heals with Avastin (click on image to enlarge)
CRVO
Recent-onset central retinal vein occlusion of left eye

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Painless eye injections

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painless eye injections
Eye anatomy

Why are eye injections given?

Increasingly, medicines are injected into the eye to treat a variety of conditions including macular degeneration, diabetic retinopathy, and retinal vein occlusion. Many different medications are injected including Lucentis, Avastin, Eylea, Beovu, Vabysmo, Syfovre, Izervay, and steroids. Especially, because these medicines may require repeated injections over time, it is essential these injections cause no pain. Therefore, we go out of our way to provide painless eye injections.

What choices of anesthesia is available?

There are currently many different ways to anesthetize the eye before an injection. Most doctors use an anesthetic eye drop. Additional local anesthesia is usually given with either a pledget, a gel, or a painless injection. A pledget is a small piece of cotton or other absorbent material that is soaked in anesthetic and placed inside the lower lid to numb the eye in preparation of an injection. Rarely, an anesthetic injection is needed. While an anesthetic injection sounds worse, it causes no pain (due to the anesthetic drops) and works better in some patients to avoid pain with the intraocular injection of medicine.

What needles are used for injecting medicine?

Fine needles are used for injection to minimize discomfort. The standard needle size for injections into the eye is 30 gauge. However, most medications may be injected with much finer 33 gauge needles. There are some medications, such as Syfovre, that require larger bore needles due to viscosity.

What are other causes of pain with eye injection?

In rare instances pain may occur due to an increase in the eye pressure. When medicine is injected into the eye it takes up space. Because the eyeball does not enlarge like a balloon, the pressure inside the eye increases. Usually, this increase in pressure is well tolerated. However, in some patients the increase in pressure may cause pain. In this situation the doctor may elect to remove a small amount of fluid from the eye before injecting the medicine in order to avoid the pressure increase and the associated pain.

Measures can be taken to avoid pain with most eye injections. Another issue is pain after an eye injection. Please see link for more information.

By Scott E. Pautler, MD

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

Copyright  © 2001-2023 Designs Unlimited of Florida.  All Rights Reserved.

Eylea (aflibercept) Therapy

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Eylea vial image


What is Eylea® therapy?

Eylea therapy is a treatment for diabetic retinopathy, retinal vein occlusion and wet-type macular degeneration.  It involves repeated painless injections of medication into the eye to prevent blindness by stopping abnormally leaky blood vessels that occur in the eye conditions listed above.  Other similar medications that are also used in these conditions include Avastin, Lucentis, Vabysmo, and Beovu.

How effective is Eylea therapy?

Eylea was proven in FDA-approved studies to be effective. In wet-type macular degeneration, monthly or bimonthly injections of Eylea over a one-year period offered a 95% chance of losing less than three lines on a standard eye chart. Eylea was also shown to be effective in the treatment of diabetic retinopathy and retinal vein occlusion to improve vision and prevent severe complications. The results with Eylea are similar to treatment with Lucentis, Avastin, and Beovu. Eylea therapy often starts with injections every 4-6 weeks. Afterwards, the injections may be given less frequently.  In some cases the injections may be stopped, but continued monitoring is necessary. There are several medication options apart from Eylea. The best choice of medication may depend on the underlying diagnosis. For example, patient who have glaucoma may have better pressure control while under treatment with Eylea compared with other drugs.

What are the risks of Eylea therapy?

Severe complications are very rare, but risks of Eylea injection include bleeding, inflammation, infection, retinal detachment, cataract, glaucoma, and loss of vision/loss of the eye. The risk of retinal detachment is about 1 in 5,000 injections, but the results of surgical repair are poor.  There may be an increased risk of difficultly with future cataract surgery estimated to be about 1% of cases. In these cases the fibers (zonules) that hold the cataract in place may become weaken from Eylea injection. When this occurs, special techniques are required to remove the cataract and place a lens implant. Rarely, two procedures are required to accomplish the task.  Studies are ongoing to determine if there may be an increased risk of stroke with Eylea therapy. The possible risk of stroke may be related to the older age of patients with AMD. Further investigation will provide more information. Pregnancy should be avoided while on Eylea therapy.

intra-ocular injection
Intra-vitreal injection

What do I expect after an Eylea 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 after the injection, 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 doctor’s office.

By Scott E. Pautler, MD

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

Copyright  © 2001-2022 Designs Unlimited of Florida.  All Rights Reserved.