Treating diabetic macular edema (DME) has evolved from the ETDRS-style focal/grid laser being the standard of care since 1985 to the modern era of pharmacotherapy-with anti-vascular endothelial growth factor (VEGF) injections now taking center stage as primary treatment for most patients.
By Kamal Kishore, MD; Special to Ophthalmology Times
Dr. KishoreTreating diabetic macular edema (DME) has evolved from the ETDRS-style focal/grid laser being the standard of care since 1985 to the modern era of pharmacotherapy-with anti-vascular endothelial growth factor (VEGF) injections now taking center stage as primary treatment for most patients.
Studies show DME may be driven by both VEGF and inflammatory cytokines, with cytokines playing a larger role in more severe cases.
Corticosteroids are frequently used in the subset of patients that do not respond sufficiently to anti-VEGF injections and have even been used as a first-line therapy in some studies. With that in mind, manufacturers have made available long-term implants to reduce the treatment burden for DME patients.
Most retina specialists are familiar with the 0.7 mg sustained-release dexamethasone intravitreal implant (Ozurdex, Allergan), approved by the FDA in June 2009. The implant has an approximate duration of 3 to 6 months.
In September 2014, the FDA approved a fluocinolone acetonide (FAc) intravitreal implant 0.19 mg (Iluvien, Alimera Sciences) for the treatment of DME in patients previously treated with corticosteroids without an adverse effect. Its duration is about 36 months.
The FAc implant is made of a non-biodegradable polyimide tube measuring 3.5 mm in length and 0.37 mm in diameter. It contains a permeable membrane of polyvinyl alcohol at one end, which initially releases 0.25 mcg/day of FAc in the vitreous. The implant is supplied in a sterile, single-use, preloaded applicator with a hollowed out 7.5-mm long, 25-gauge needle. It is covered with a protective cap and packaged in a sealed sterile tray that can be stored at room temperature.
All intravitreal injection procedures should include adequate anesthesia and should be carried out under aseptic conditions with generous application of 5% aqueous povidone iodine (Betadine) drops to the ocular surface.
It is also advisable to clean the lid margins, eyelashes, and periocular skin with a commercially available cotton-tipped swab soaked in 10% povidone iodine solution. A sterile speculum keeps the eye open and frees the other hand that holds a sterile cotton tipped applicator.
My assistant and I wear facemasks to prevent contamination of the operative field by oral flora. The injection is performed in the office by reclining the examination chair to a near-horizontal position under the illumination provided by a binocular indirect ophthalmoscope (BIO) and magnification provided by +2 D lenses contained in the eyepieces of the BIO and my presbyopic glasses. I no longer prescribe pre- or post-injection antibiotic drops.
My preference for anesthesia is subconjunctival infiltration of the quadrant of intravitreal injection with 0.2 to 0.3 mL 1 to 2% lidocaine without epinephrine using a sterile 30-gauge needle. A drop of proparacaine instilled 5 minutes prior to subconjunctival injection of lidocaine provides surface anesthesia. The subconjunctival injection is performed several millimeters from the limbus, where tissues are less sensitive to pain.
The patient must be warned that the lidocaine injection due to its acidic pH is often associated with temporary stinging that lasts a few seconds. I allow 5 to 10 minutes for anesthetic to take full effect.
After verifying presence of the implant through the window of the applicator, push in the center of the button to visibly depress it, and then advance it by continuous and steady forward pressure to the curved black line on the device.
Release the button and visually ensure that it rises up. If the button does not rise up, the device cannot be used and must be discarded.
I advise holding the button with the finger and thumb of the supporting hand and nudge it to ensure it has risen completely. Keep the device level or the needle end pointing slightly up during this step to maintain correct implant positioning. Once the button is in up position at the curved black line, the device is ready.
Removing the cap
Removing the cap
Compared with Ozurdex, the cap covering the Iluvien needle is smaller, smooth, lacks a collar, and can be hard to grip. In about 20% of cases, the cap is difficult to remove, perhaps due to excessive amount of adhesive used to secure the cap to the applicator.
Rather than trying to pull it straight out, I now twist it clockwise and counter clockwise until the seal breaks.
The process of hollowing out the 25-gauge needle slightly blunts it and makes it more delicate. Therefore, straight or near-straight entry is preferable to markedly angled entry as commonly used for Ozurdex. Due to smaller gauge of the Iluvien needle compared with that of Ozurdex, there is less likelihood of wound leak and therefore less need for an angled approach.
The FAc implant is released into the vitreous cavity by advancing the button all the way. After the needle has been inserted and its position verified, press at the back end of the actuator button with your index finger and steadily advance it in its guide rail as far as it goes to release the implant. Usually an audible click is heard as the back of the actuator button is depressed. After the button has been advanced all the way, rotate the device slightly clockwise and counterclockwise to let the implant disengage from the needle. Unlike Ozurdex’s spring-loaded mechanism to shoot the implant into the vitreous cavity, the FAc implant may “hang” at the needle tip and must be allowed to release before the needle is withdrawn.
The needle is withdrawn and its track covered by the sterile cotton-tipped applicator to prevent wound leak. A drop of Betadine is instilled and the lid speculum is removed. Check to ensure the patient has formed vision.
Kamal Kishore, MD
Dr. Kishore is president of Illinois Retina and Eye Associates, Peoria. He has no financial interest in any products mentioned.