Dexamethasone implant rivals anti-VEGF in real-life DMO studies

A dexamethasone implant improves visual acuity more than anti-vascular endothelial growth factor (VEGF) injections do in real-life studies in patients with diabetic macular oedema (DMO), researchers say.

"All these data argue in favor of the earlier use of [dexamethasone], either as a first-line therapy in naive patients or more quickly as a second-line therapy," wrote Laurent Kodjikian at the University of Lyon in France and colleagues in BioMed Research International.

The apparent superiority of the dexamethasone implant is not due to differences in the baseline visual acuity of patients in these trials, but could be attributed to the lower number of treatments required or superiority of the dexamethasone molecule, the researchers speculate.
In recent years, photocoagulation has given way to intravitreal injections for treatment of DMO because photocoagulation often leaves scars that impair vision.

The agents currently used in intravitreal injections are 3 anti-VEGF treatments, bevacizumab (Avastin, Genentech), ranibizumab (Lucentis, Novartis) and aflibercept (Eylea, Regeneron); and 1 slow-release corticosteroid implant of dexamethasone (Ozurdex, Allergan).

All 4 of these treatments have significantly improved patients' visual acuity in clinical trials. But these trials necessarily limit the kinds of patients included, for example by excluding patients with very high or very low visual acuity, patients with certain comorbities, and patients who have already received other treatments. Patients in these trials may also be more adherent to treatments than the average patient in clinical practice.

For this reason, investigators have also followed patient populations in routine practice. But since these real-life observational studies lack control groups and are more likely to lose patients to follow-up, Kodjikian and colleagues argue, it is useful to review a large number of such studies.

They undertook such a review using the PubMed database on February 1, 2018. They identified 189 studies, 129 of anti-VEGF treatments and 60 of the dexamethasone implant. Excluding interventional studies and those with either a follow-up of less than 6 months or a cohort of less than 11 patients, they narrowed these down to 32 anti-VEGF with a total of 6,842 eyes and 31 dexamethasone implant studies with a total of 1,703 eyes.

The patients in the anti-VEGF studies had a mean baseline visual acuity of 57.3 letters. The follow up was a mean of 15.6 months. During follow-up, these patients received a mean of 5.8 injections and gained a mean of 4.7 letters.

The patients in the dexamethasone implant studies had a mean baseline visual acuity of 51.5 letters. The mean follow up was 10.3 months. During follow-up, these patients received a mean of 1.6 injections and gained a mean of 9.6 letters.

The drawback of dexamethasone implants is a higher risk of adverse effects. The pivotal trial showed cataract related events in 67.9% and intraocular pressure (IOP) increase over 25 mm Hg in 32.0% of phakic eyes treated with the 0.7 mg implant, compared to a 20.4% incidence of cataract and 4.3% incidence of IOP increase in the sham group.

By comparison, DCR-net reported a cumulative probability of sustained IOP elevation of initiation of IOP-lowering therapy of 9.5% with ranibizumab and 3.4% for the sham group.

In these real-life studies, the incidence of cataract formation was between 0% and 15.5% in the anti-VEGF studies. None of them reported a statistically significant increase in IOP. In the dexamethasone implant studies, the incidence of cataract formation was between 0% and 50%, depending on the number of injections. IOP elevation was found in between 0% and 29.5% of studies.

One explanation for the lower baseline visual acuity in the dexamethasone implant studies could be that this treatment is mostly used as a second-line treatment in routine practice, so the patients in these studies have a longer duration of DMO and therefore a lower visual acuity, the researchers note.

But the dexamethasone implant appears particularly effective in patients with high baseline visual acuity. Segmenting the patients into groups by baseline visual acuity, the researchers found that those starting with less than 50 letters gained 10.5 letters with the dexamethasone implant but only 4.3 with anti-VEGF injections. Those with more than 60 letters of baseline visual acuity gained 8.8 letters with the dexamethasone implant and only 3.1 letters with anti-VEGF injections.

This shows that the difference in the treatment effect is not only due to baseline visual acuity, the researchers argue.

The real-life results with the dexamethasone implant appear better than the results in clinical trials, the researchers noted. This may be because the dexamethasone implant may be given at earlier stages of the disease in the real-life studies than in the clinical trials, the researchers pointed out. The reverse is true with anti-VEGF injections, probably because patients receive fewer injections in real life than in the clinical trials, they said.