Covered topics include:

  • Profiles of the Experienced Injector
  • Preparing the Patient for the Injection
  • Injection Procedure
  • Postinjection Protocol
  • Pearls for Injecting the Dexamethasone Intravitreal Implant

The US Food and Drug Administration (FDA) approval of the dexamethasone intravitreal implant (OZURDEX®, Allergan, Inc.) was the first time that any medical therapy was indicated for macular edema secondary to branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). Previously, laser was the only approved treatment option for BRVO patients, while the standard of care for CRVO was observation. Thus, this indication opened the door for clinicians to be able to treat these patients and help improve their visual acuity on label.

Additionally, the subsequent approval of the dexamethasone intravitreal implant for the indication of noninfectious posterior segment uveitis also widened the field of treatment options for this devastating disease.

The dexamethasone intravitreal implant is delivered via injection using a 22-gauge needle in an office-based procedure. With any intravitreal injection procedure, however, it is important to follow protocols that ensure safety and help increase patient comfort. Retina Today recently had the opportunity to speak with several clinicians who have varying experience with injecting the dexamethasone intravitreal implant for the indications of BRVO, CRVO, and, to a lesser extent, noninfectious posterior segment uveitis. According to all of the doctors with whom we spoke, their learning curve for the injection procedure was shallow. In this insert to Retina Today, sponsored by Allergan, Inc., physicians provide their own experiences with injecting the dexamethasone intravitreal implant and offer pearls on different steps in the procedure and tips on how they advise patients along the way.

Profile of the Experienced Injector

Michael A. Singer, MD: I have performed approximately 200 injections with the dexamethasone intravitreal implant—approximately 95% for retinal vein occlusion (RVO) and 5% for noninfectious posterior segment uveitis. In my experience, it took me three to five injections to become completely comfortable with the procedure. I am constantly modifying my technique, and I have found that over time, I inject with a more fluid motion than in the past. In the past I injected at a 15º-30º angle, but I have gone from this more parallel angle to one that is more perpendicular—60º-75º—almost a semicircular way of entering the sclera.

Julia A. Haller, MD: I have not found the injection technique for the dexamethasone intravitreal implant to be particularly difficult. Retina surgeons are accustomed to inserting cannulas in eyes that are approximately the same gauge as the injector needle, which is 22 gauge, and the injection itself takes a few seconds. It is, however, a little more involved than performing the intravitreal injections to which we are accustomed.

Gaurav Shah, MD: I have injected the dexamethasone intravitreal implant in approximately 45 to 50 patients, mostly for RVO, but I have also injected the implant for some noninfectious posterior segment uveitis patients since the FDA approval. In my opinion, it takes one or two injections to become fully comfortable with the procedure; in general, it is not a complicated process, particularly for retina surgeons who are accustomed to inserting trocars for surgery. The actual injection takes approximately 30 to 45 seconds.

Pravin U. Dugel, MD: I have been using the dexamethasone intravitreal implant since early in its development. Thus far, I have injected the implant in approximately 50 patients, primarily for RVO. Although it is hard for me to say how difficult the injection procedure is to learn because I have been performing this for so long, I do believe that the learning curve is small for the implant, provided the clinician understands that it requires more effort than a typical intravitreal injection to push the larger gauge needle into the eye. This means that patients feel more pressure during the injection. It is also important that doctors counsel their patients about what to expect. For instance, when the medicine is going in, patients will hear a click. Some patients may find this to be disconcerting, so it is wise to inform them ahead of time.

David S. Boyer, MD: I have implanted approximately 50 dexamethasone intravitreal implants, mostly for RVO but a few for noninfectious posterior segment uveitis since its approval for that indication.

Jeffrey S. Heier, MD: I have performed approximately 20 injections of the dexamethasone intravitreal implant thus far for a variety of situations in patients with macular edema due to RVO or in noninfectious posterior segment uveitis. In general, I do not counsel patients any differently for the implant injection than I do for any intravitreal injection.

David Callanan, MD: I have performed over 100 injections with the dexamethasone intravitreal implant, mostly for patients with RVO, but a few for patients with noninfectious posterior segment uveitis. I have found that the difficulty of the injection varies depending on the thickness of the sclera. In patients who have a really thick sclera, it takes longer and requires more pressure to get through it. I have injected the implant in patients with a normal to less thick sclera, and the 22-gauge needle goes through easily.

Preparing the Patient for the Injection

Dr. Singer: Before administering the injection of the implant, I tell my patients to expect a feeling of pressure. I advise them to be still and that the procedure is very quick—I have found that if I divert a patient's attention, he or she does not even realize that they are receiving an injection until it is over. The injection itself takes me approximately 5 seconds.

My protocol for anesthesia includes instilling povidone- iodine and then using two cotton-tip applicators that are soaked in proparacaine to rub the conjunctiva for approximately 30 seconds. I then use a subconjunctival lidocaine 2% and epinephrine injection because I have found that it helps to decrease the incidence of subconjunctival hemorrhage. After I give the anesthetic, I will see two or three patients (5-10 minutes) and then return to administer the injection of the dexamethasone intravitreal implant.

I employ calipers, both to mark the spot where I will inject, but also to test the eye for sensation. I then apply povidone-iodine again, wait 20 to 30 seconds to allow for bacterial eradication, and then I prepare the injection. When I take the applicator from the carton and the foil, I carefully pull off the cap of the needle and then pull out the safety to ensure that the implant is still in the applicator.

Dr. Haller: Prior to the injection, I numb the eye further with a subconjunctival injection of lidocaine and wait for it to take effect for approximately 1 to 2 minutes. I use povidone-iodine prior to the injection to disinfect the ocular surface.

Dr. Shah: When I see a patient and I decide that he or she fits the criteria for the dexamethasone implant, I instill a drop of a fourth-generation fluoroquinolone and then one drop of tetracaine hydrochloride 0.5%. The patient then fills out the appropriate paperwork (consent, insurance forms), allowing the drop to penetrate for approximately 10 to 15 minutes. At the time of prep, I will instill another drop of tetracaine and have that sit for approximately another 5 minutes. I find that the tetracaine helps to minimize postinjection subconjunctival hemorrhage. The 22-gauge needle for the implant is larger than the needles I use for other intravitreal injections, so I want to do as much as I can to prevent blood being drawn into the eye during the procedure.

I use a speculum along with a cotton-tip applicator to stabilize the eye for injection. I tell patients to expect a sensation of pressure on their eye as I make the injection and that they will hear an audible click as the medicine is released.

Dr. Dugel: My preinjection anesthesia protocol is no different than it is for any other intravitreal injection I perform. After we know a patient is going to have an injection, one of the technicians will dip one or two cotton-tip applicators in 4% lidocaine and place it inferotemporally to numb that part of the eye. I then inject subconjunctival lidocaine in the area where I will do the injection and step out of the room to see another patient. During that time, the technician instills povidone-iodine to clean the eye, lids, and lashes, after which another drop of lidocaine is applied. This routine has been effective and my patients have not reported any pain during the injection.

I would not recommend using topical drops or gels because this procedure requires a larger needle and increased pressure for injection. Patients do feel the injection pressure required for this injection, and if it hurts, it is never a good experience.

Dr. Boyer: When a patient comes in to have the implant injected, I tell them that they will feel a good amount of pressure. If he or she has had a previous intravitreal injection, I explain that the sensation of pressure will be greater with the dexamethasone intravitreal implant. I advise patients of the side effect of IOP elevation, which is usually controlled well with glaucoma drops.

Prior to the injection, all patients receive a topical drop of tetracaine and then I give a subconjunctival injection of lidocaine, ballooning the area, which not only anesthetizes, but also offers space to reduce the risk of vitreous prolapse. I then let the patient sit for approximately 10 to 12 minutes. After that time, I flush the eye with povidone-iodine, place the lid speculum, and proceed with the injection.

Dr. Heier, MD: Prior to the injection, I administer povidone-iodine and a subconjunctival injection of lidocaine and wait 5 minutes for the anesthetic to take effect. When taking the tip off the injector to expose the needle, it is important not to have the needle touch the tip as the needle can be blunted, making entry more difficult.

Dr. Callanan: Before I inject the implant, I soak a cotton- tip applicator in proparacaine and hold it to the site. I put a drop of povidone-iodine in the cul-de-sac and administer a subconjunctival lidocaine 2% and epinephrine injection. I wait approximately 5-10 minutes, during which time I will see one or two patients. By that time, the povidone-iodine is dry and I put the lid speculum in, after which I take another cotton-tip applicator that has been soaked in povidone-iodine and I roll it over the quadrant where I will inject. I do not use preinjection antibiotics.

Injection Procedure

Dr. Singer: For the actual injection, I have the patient lie back in the chair and, stabilizing the eye with a cotton cotton- tip applicator to prevent rotation, I upwardly displace the conjunctiva and inject, needle bevel-up, at approximately a 60º angle. If the needle enters the sclera at too shallow an angle, it is not going to have enough torque to reach far enough posteriorly. When I come across this problem, I pull back, lift my hand up, and increase the angle by about 15º. The maximum angle that I will employ is 75º, keeping the needle bevel-up.

Once the safety stop touches the sclera, I rotate to a perpendicular 90º and, aiming toward the posterior pole, push down the actuator button on the handpiece slowly until I hear the click. I wait 5 seconds to ensure that there is no recoil of medicine and then I take a cotton-tip applicator, roll it back over the insertion point, rotate my hand down, and pull the needle out.

Dr. Haller: I perform the injection inferotemporally and so I ask the patient to look up, which also helps to stabilize the eye. I use an oblique angle, approximately 30º-45º, which is similar to my incision for vitrectomy. I will occasionally use a cotton-tip applicator to displace the conjunctiva and to stabilize the eye.

When making the injection, I use the same amount of pressure that I would when inserting cannulas. If I encounter a sclera that is particularly tough, I will apply slightly more pressure.

When injecting the dexamethasone intravitreal implant in vitrectomized eyes or eyes with filtering blebs, I do not necessarily change my technique—I might push a bit harder, but I am prepared for that. I use a cotton-tip applicator as I withdraw the injector and rub it over the incision to ensure that it is sealed.

Dr. Shah: I make my incision at a 30º angle and, as the safety stop meets the eye, I rotate the injector to a 90º angle and slowly depress the actuator button to release the implant. If I encounter a tough sclera, I will make the injection more slowly—I try to twist the handpiece as I inject so that it slides in without more pressure.

Although I do inject the dexamethasone intravitreal implant in vitrectomized eyes, I would be more hesitant for someone to start his or her first injection on such a patient. This particular type of patient may be more likely to have some hypotony after the injection, so one needs to be more vigilant in terms of proper technique. The only thing that I change about my injection technique is to increase the bevel in my incision, entering at a flatter angle so that I achieve a wound that seals well. I would also be cautious with patients who have deep-set orbits, because these eyes tend to be pushed back into the globe, making the injection difficult.

I always check the placement of the implant postinjection. It can be hard to see because it may be anterior in the vitreous space, but 90% of the time, I can actually see the implant as it goes in.

Dr. Dugel: I perform the injection inferotemporally because this location ensures that the implant will not be sitting in the line of patients' vision. I angle the incision as much as possible—20º—without having it flat. I do not change my approach for a tough sclera.

When I have completed the injection and am taking the needle out of the eye, I angle the incision back to 20º, just as I would for trocar removal in surgery, and remove the needle with my right hand, using my left hand to slide a cotton-tip applicator over the incision to provide counter pressure and minimize vitreous incarceration.

In regard to vitrectomized eyes, I do not change any aspect of my injection technique. If, however, a patient has undergone multiple surgeries with large incisions and there are areas of scleral thinning, I would avoid such areas.

Dr. Boyer: Displacing the conjunctiva with a cotton- tip applicator, I enter the sclera at a fairly straight 10º-20º angle. Once I feel that the needle is in, I turn it to approximately 90º and aim posteriorly, and I push it in very quickly. If you push the needle slowly, it will not go into the eye. An analogy would be trying to push a straw into an orange. If the straw is pushed hard with a quick motion, it might get into the orange, but if pushed slowly, the straw will bend. The needle should not be advanced past the Teflon safety sleeve. I then press the actuator button very slowly to release the implant.

After the implant is in the eye, I withdraw the needle exactly as I insert it—I turn the handpiece from 90º to an almost flat, 10º angle and pull the needle out of the wound. I use a cotton-tip applicator to go over the wound to ensure that there is no leaking vitreous or any other sign of fluid, and then I check the wound internally to ensure that there is no bleeding and the entire implant is in the proper place.

Dr. Heier: I enter the sclera at a 30º transverse angle. Once the needle has entered the eye, I turn the handpiece perpendicularly and aim toward the posterior segment. I find that a more transverse entry makes it easier. If I find that the sclera is tough, I will often twist the injector as I am moving in at the perpendicular angle.

I use counter-pressure with a cotton-tip applicator on the equator of the globe to stabilize the eye if I have to press and twist the injector fairly hard.

For vitrectomized eyes, I am concerned about wound leaks, so when I am withdrawing the injector from the eye, I use a cotton-tip applicator and massage the area lightly for approximately 30 seconds and then have the patient stay in the office for a bit longer so I can assess for any leakage.

Dr. Callanan: I inject at a 20º-30º angle. For a tough sclera, I rotate the handpiece slightly while advancing the needle. It is helpful to use nontooth forceps or a cotton-tip applicator to apply counter pressure and stabilize the globe during the injection. I also roll a cottontip applicator over the injection site immediately after withdrawing the needle.

Postinjection Protocol

Dr. Singer: After the injection, I always double-check that the implant is where I want it in the eye—sometimes it is easy to see, and other times it is not, but usually when I have the patient look in the direction that I have injected, inevitably I'll see the implant somewhere near the vitreous base. When injecting in patients who have had vitrectomies, wound leaks are of greater concern. For these patients, I carefully check the incision postinjection to ensure that I have made a good biplanar incision.

I send the patient home with a topical antibiotic and instructions to use it every 2 hours on the first day and then four times a day for 2 days following. We tell patients that if they notice any changes, such as acute pain, they should call.

I see patients back in 4 to 6 weeks, and it is at that time that we check IOP. Almost all IOP rises with the dexamethasone intravitreal implant can be addressed with glaucoma drops. For vitrectomized eyes, I make a more biplanar incision and take great care to check for wound leaks. Before I send these patients home, I check to ensure that the IOP is at a normal level.

Dr. Haller: After the injection, I instill povidoneiodine because it has a detergent effect on the cilia. I instill an antibiotic ointment to protect against punctate keratitis and irritation.

I counsel all of my patients who receive an intravitreal injection that the most significant risk is endophthalmitis. I instruct patients to call the office immediately if they notice an increase in floaters, pain, or increased redness. Unless there is a problem, I typically see patients back at approximately 60 days postinjection.

Dr. Shah: After the injection I instill a drop of fourthgeneration fluoroquinolone. If there is none on hand, I will give the patient a bottle of Polytrim to instill for a few days after the injection. I typically see patients for follow- up 3-4 weeks after the injection, telling them to call the office if they experience any increased redness or pain that seems to worsen over time. If a patient has had a subconjunctival hemorrhage, however, there will be more redness, so I am careful to explain this to him or her.

Dr. Dugel: I will usually see patients 1 month after the injection, but will have them come into the office 1 to 2 weeks after the injection for an interim pressure check. In my experience, any subsequent rises in IOP can usually be managed with topical glaucoma drops.

Our patient counseling prior to discharge is the same as with any intravitreal injection: We instruct patients to call the office if they notice any loss of vision or discomfort. Although the eye will be red after an injection, we tell patients to maintain a low threshold for any other structural or functional changes. We send patients home with antibiotic drops that they take for 3 days postinjection.

Dr. Boyer: Although I am not convinced postinjection antibiotics are necessary, I do use them. If no vitreous is leaking and everything appears normal, I do not check IOP postinjection. I see patients 4 weeks later.

I send patients home with instructions to call if they have any difficulties with their vision such as haze, or if they have any pain. The eye will certainly be red after an injection, but if there is unusual discomfort or any discharge, the patient must be examined.

For most of my patients, the greatest amount of discomfort comes from the povidone-iodine, so I apply ointment and use a patch for all of my patients at the end of the procedure.

I do not change my technique for vitrectomized eyes; however, I do maintain a higher level of concern regarding hemorrhages due to neovascularization, particularly in patients with diabetes. If I observe any leakage due to a soft globe, I will patch the patient as usual and see him or her back the next day. This has not, however, been a problem in my practice.

Dr. Heier: After a routine dexamethasone implant injection, I see patients back in 1 month. If I have any concerns about a wound leak, I may see a patient back the next day, although this scenario is highly unusual. With the dexamethasone implant, IOP is usually not an issue. I do have patients' IOPs checked before they leave the office postinjection, but it is rarely an issue, partly because of the force that is used to inject the implant. Before patients leave the office, we instruct them to call us if they notice significant pain or decrease of vision that is different from what they experienced immediately after the injection of the implant.

Dr. Callanan: After the injection, I instill a single drop of a fourth-generation fluoroquinolone in all eyes postinjection. Patients with thin sclerae or with a history of diabetes or vitrectomy receive a bottle of antibiotics with instructions to use them for 2-3 days afterward.

Michael A. Singer, MD, is the Managing Partner and Director of Clinical Trials at Medical Center Ophthalmology Associates, in San Antonio, TX. He is also Assistant Clinical Professor at the University of Texas Health Science Center of San Antonio. He can be reached at msinger@mcoaeyecare.com.

Julia A. Haller, MD, is Professor and Chair of Ophthalmology at Thomas Jefferson University and Thomas Jefferson University Hospital in Philadelphia. She is Ophthalmologist in Chief at Wills Eye Institute in Philadelphia. Dr. Haller can be reached at +1 215 928 3000.

Gaurav Shah, MD, is the Co-director of the Retina Fellowship and is a Professor of Clinical Ophthalmology at Washington University and a Partner at Barnes Retina Institute in St. Louis, MO. He can be reached at +1 314 367 1181 or at gkshah1@gmail.com.

Pravin U. Dugel, MD, is Managing Partner of Retinal Consultants of Arizona in Phoenix; Clinical Associate Professor of Ophthalmology, Doheny Eye Institute, Keck School of Medicine at the University of Southern California, Los Angeles; and Founding Member of the Spectra Eye Institute in Sun City, AZ. He can be reached at pdugel@gmail.com.

David S. Boyer, MD, is a Clinical Professor of Ophthalmology at the University of Southern California Keck School of Medicine, Department of Ophthalmology, in Los Angeles. Dr. Boyer may be reached at vitdoc@aol.com.

Jeffrey S. Heier, MD, is a Clinical Ophthalmologist specializing in diseases of the retina and vitreous at Ophthalmic Consultants of Boston. He can be reached at jsheier@eyeboston.com.

David Callanan, MD, is a vitreoretinal specialist at Texas Retina Associates in Dallas and an Associate Clinical Professor at the University of Texas-Southwestern Medical Center. He can be reached at dcallanan@texasretina.com.