Real-world experience with intravitreal dexamethasone for DME

Patients who are non-responders to anti-vascular endothelial growth factor (VEGF) therapy may benefit from intravitreal dexamethasone. (Image Credit: Adobe Stock/R. Gino Santa Maria)

Reviewed by Anat Loewenstein, MD

Intravitreal dexamethasone (Ozurdex, Allergan) has a role in the treatment of patients with diabetic macular edema (DME). Patients who are non-responders to anti-vascular endothelial growth factor (VEGF) therapy may benefit from intravitreal dexamethasone, according to Anat Loewenstein, MD, Professor & Director, Dept Ophthalmology, Tel Aviv Medical Center; President, Israeli Ophthalmological Society; and The Sidney A. Fox Chair in Ophthalmology, Faculty of Medicine, Tel Aviv University, Israel.

Loewenstein described her findings at the Clinical Trials at the Summit 2023, Park City, UT.

Significant percentages of patients have been reported to be non-responders to the first-linetherapy for DME.

A step forward is that recent studies have begun to identify optical coherence tomography (OCT) biomarkers that identify patients who may and may not respond to anti-VEGF therapy. For example, the biomarkers predictive of a response include the presence of subretinal fluid, an intact inner segment and outer segment junction, and no hyperreflective foci.

Biomarkers that are predictive of an insufficient responseare the absence of subretinal fluid, a damaged inner segment and outer segment junction, and the presence of hyperreflective foci.

Additional biomarkers include that the absence of disorganization of retinal inner layers bodes well for patients. The dexamethasone implant has the ability to ameliorate that disorganization. “Disorganization of the retinal inner layers may serve as a biomarker in DME treated using the dexamethasone implant,” Loewenstein said.

In real-world practice settings, treatment-naïve eyes were more likely to gain 10 letter of visual acuity or better, a difference that reached significance (P<0.01).¹

Along with that vision improvement, the central subfield thickness decreased significantly (P<0.001) compared with baseline in treatment-naïve eyes by 304 microns compared with a decrease of 252 microns in eyes refractory to treatment. The decrease did not differ significantly at the end of the study.

A representative case was that of a 63-year-old women with type 2 diabetes for 20 years. She was treated with 4 bevacizumab injections (Avastin, Genentech Inc.), 3 injections of ranibizumab (Lucentis, Genentech Inc., 3 injections of aflibercept (Eylea, Regeneron); despite this the visual acuities remained 6/60 and the central macular thicknesses wee, respectively,582, 526, and 586 microns. Treatment with Ozurdex resulted in a visual acuity of 6/20 and a central macular thickness of 280 microns.

To switch or not to switch

A comparison² of treat-naïve eyes with previously treated eyes showed that treatment-naïve eyes had over a 35% more moderate visual gain (≥10 letters) (46.1% vs 33.9% p=0.001), and treatment-naïve eyes had a 45% more significant visual gain (≥ 15 letters) (28.8% vs 19.8% p=0.06), Loewenstein described.

The duration of the DME seems to be a relevant factor in that study in that eyes with early DME, defined as less than 6n months, had a 40% more moderate visual gain (≥ 10 letters), and (47.4% vs 33.9% p=0.001) and 40% less moderate visual loss (≥ 10 letters) in early DME eyes (8.2% vs 13.5% p=0.029).

The MEAD study³ demonstrated that changes in the central macular thickness and the BCVA over 3 years showed cycles of 3 to 4 months are clearly visible in the 2 parameters. The similarity of the real-life results to the MEAD trial validate the data,” Loewenstein said.

The PRECISION trial, a prospective multicenter randomized comparative trial evaluating the treatment response to intravitreal aflibercept versus intravitreal dexamethasone with allowance for the combination aflibercept in eyes with DME, is currently underway. It is expected to provide an understanding of imaging biomarkers in DME. The results are expected in 2024.

She concluded that Ozurdex has a role in the management of our patients with good results in any DME and should be considered as a treatment in non-responders, patients who had a major cardiovascular event, and patients who are unwilling to undergo frequent treatments.

References

1. Iglicki M, Busch C, Zur D, et al. Dexamethasone implant for diabetic macular edema in naive compared with refractory eyes: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.Retina 2019:39:44-51.

2. Rajesh B, Zarranz-Ventura J, Fung AT, et al. Safety of 6000 intravitreal dexamethasone implants. Br J Ophthalmol2020;104:39-46.

3. Boyer DS, Belfort R, Bandello F, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 2014;121:1904-14.