Time for a paradigm shift in the treatment of DME

October 21, 2016

Well tolerated and effective, anti-VEGF therapy is the current gold standard to treat DME. However, one treatment simply does not fit all and VEGF may just be one piece of a much larger puzzle. The fact that some DME patients have a limited response to anti-VEGF therapy is representative of this concept; we are discovering that there are additional inflammatory mediators that may be crucial components to the DME picture.

Editor’s Note: Welcome to “Eye Catching: Let's Chat,” a blog series featuring contributions from members of the ophthalmic community. These blogs are an opportunity for ophthalmic bloggers to engage with readers with about a topic that is top of mind, whether it is practice management, experiences with patients, the industry, medicine in general, or healthcare reform. The series continues with this blog by Joshua Mali, MD, a vitreoretinal surgeon at The Eye Associates, a private multispecialty ophthalmology practice in Sarasota, FL. The views expressed in these blogs are those of their respective contributors and do not represent the views of Ophthalmology Times or UBM Medica.

The opportunity to improve a patient’s quality of life makes my job very rewarding. As a retinal specialist, I see patients every day who face the debilitating realities associated with retinal conditions such as macular degeneration and diabetic macular edema (DME). My goal is to calm their fears and ease anxiety by offering them the best possible treatment protocols available. 

In recent years, we have experienced tremendous advances in medical technology and pharmacology specific to treating patients who suffer from retinal disease. I continuously seek out and study these new modalities so that I have all the tools currently available to provide my patients with the highest standard of care.

DME therapy: It’s not one size fits all

Well tolerated and effective, anti-VEGF therapy is the current gold standard to treat DME. However, one treatment simply does not fit all and VEGF may just be one piece of a much larger puzzle. The fact that some DME patients have a limited response to anti-VEGF therapy is representative of this concept; we are discovering that there are additional inflammatory mediators that may be crucial components to the DME picture.

Therefore, steroids are an intriguing treatment modality as they are known to affect multiple points along the inflammatory cascade. In addition, patients that have been on monthly anti-VEGF therapy may experience a negative psychological response to the prospect of a monthly needle in their eye, or in younger patients, frequent and repeated downtime from work is not an ideal option. Often, the frequency and expense of the treatment becomes burdensome on the patients, their families, the healthcare system, and on providers. Rather than risk leaving vision on the table for these patients, we must consider alternative therapies such as long-acting steroids and laser photocoagulation, or a combination of these treatment modalities.

Patient selection

 

Patient selection

As I discussed in my previous article, patient selection is critical. When contemplating steroidal treatments, selecting the right patients reduces the likelihood of exacerbating cataract development or increasing IOP, which are both commonly associated with corticosteroid therapies. Generally, pseudophakic patients make the best candidates; however, I must consider the risks and benefits with phakic patients and determine whether an advancing cataract is more important than the damage caused by DME. Patients with a cup to disk ratio > 0.8 are contraindicated for steroids, and I also rule out patients who have experienced a clinically significant increase in IOP in response to a topical or intravitreal steroid. Finally, I exclude patients with a compromised lens capsule or zonular dehiscence to avoid the possibility of implant migration to the anterior chamber, in addition to patients sensitive to floaters.

 

What’s the alternative?

For patients meeting the treatment criteria, I offer a long-term steroidal therapy (Iluvien, Alimera Sciences). The nonbioerodable implant is designed to deliver a continuous microdose of fluocinolone acetonide (FAc) to treat DME. Designed specifically for intraocular use, the tiny implant (3.5 mm x 0.37 mm) can have clinical efficacy for up to 36 months and may possibly eliminate, or at least significantly reduce, the need for and frequency of anti-VEGF or repeated steroid injections.

Surgical technique: The Mali Maneuver

I perform the implantation in the office following my typical sterile preparation protocol for an intravitreal injection, including using a lid speculum and betadine solution to sterilize the eye. Anesthesia protocol includes a subconjunctival injection of lidocaine in the region of the injection site.

To prepare the injector, I remove it from the sterile packaging and look through the “window” to confirm that the implant is inside the injector. The little yellow implant is about 1/25th the size of a grain of rice, but it is easy to see through the clear window. The injector also has a safety feature to prevent the implant from coming out should the device be turned upside down. Next, I push the back end of the applicator button up to the black indicator mark. This removes air from the system and pushes the implant to the “ready” position.

Implantation is a two-step process and is quite easy with the specially designed applicator. I prefer a two-handed technique to help with stabilization and control (“The Mali Maneuver”); otherwise, I perform the injection just as I do for any intravitreal injection: straight insertion (no bevel) 4 mm posterior to the inferotemporal limbus in the pars plana. Once inserted into the vitreous up to the marked point on the needle, I use my other hand to push the applicator button in a down-forward motion to release the implant into the vitreous.

An empty applicator is my assurance of transference to the vitreous. However, I like to directly visualize the implant to confirm correct placement. To get a good view of the inferior retina, I have the patient lay back and look down in the chin up position.

Case study

 

Happy patients = happy doctor

The implant has proven its efficacy and safety both clinically and personally to me based on my patient outcomes. When anti-VEGF therapy has limited efficacy, we now have an excellent long-term treatment option that may lift the burden of frequent office visits and costly anti-VEGF injection treatments. Patients whom I have treated with the long-term therapy enjoy comparable or better visual outcomes than those treated with anti-VEGF. In follow up visits, these patients continue to do well and are happy. When my patients are happy, I am happy.

 

Case study

This is one of my recent patients who nicely demonstrates not only the excellent clinical efficacy but also the ability of a treatment to improve a patient’s lifestyle and allow them to live life to the fullest.

A 65-year old pseudophakic patient presented to me with a history of battling DME for five years in the right eye. The patient had received multiple treatments in the past including intravitreal Triesence (Alcon) and Ozurdex (Allergan, Inc.) with no rise in IOP, focal laser, and monthly Aflibercept (Eylea), Ranibizumab (Lucentis), and Bevacizumab (Avastin) intravitreal injections.     

The patient reported that the monthly injection regiment was detrimental to his lifestyle and he felt that he is burdening his family with the need for frequent transportation. He inquired about longer lasting treatments, thus I provided him with the option of the long-term implant.

Clinical course

 

Clinical course

Before treatment:

•                VA:  20/60- OD

•                IOP: 18 mm Hg

•                OCT demonstrated chronic persistent cystoid macular edema (CME) – See Figure 1

Courtesy of Joshua Mali, MD

 

Post treatment 90 days with the implant:

•                VA: 20/20 OD (patient stated that he now has the best vision he has ever had!)

•                IOP: 21 mm Hg

•                The implant was in an ideal location in the vitreous  

•                No adverse reactions noted on clinical exam or subjectively by the patient.

•                OCT demonstrated a sustained resolution of DME – See Figure 2

Courtesy of Joshua Mali, MD

 

Joshua Mali, MD, is a vitreoretinal surgeon at The Eye Associates, a private multispecialty ophthalmology practice in Sarasota, Florida. He can be reached at 941-792-2020. He is currently a consultant and shareholder at Alimera Sciences and a consultant at Allergan, where he also conducts research and receives clinical study funding.