5 observations about corticosteroids for DME treatment

Reviewed by Rishi P. Singh, MD

Findings from studies investigating intravitreal corticosteroids for treatment of diabetic macular edema (DME) provide information about their efficacy and safety, including some understanding of how they compare with anti-VEGF therapy.

However, forthcoming results from the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol U are anticipated to help retina specialists better define how to incorporate corticosteroids into the treatment algorithm for DME, said Rishi P. Singh, MD. Protocol U is a short-term study that randomized eyes with central-involved DME persisting after anti-VEGF therapy to continue anti-VEGF therapy alone or with an intravitreal corticosteroid implant,

“With anti-VEGF therapy, we have excellent treatment options for DME,” said Dr. Singh, associate professor of ophthalmology, Case Western Reserve University, Cleveland, and president, Retina World Congress. “We know, however, from clinical trials of anti-VEGF therapy that persistent DME is a common finding. Furthermore, anti-VEGF therapy is being dosed less frequently in clinical practice compared with clinical trials, and the difference in treatment limits visual outcomes.”

Based on available evidence for corticosteroid clinical trials, Dr. Singh made five observations about their efficacy and safety for treatment of DME:

• Corticosteroids, unlike anti-VEGF therapy, address the inflammatory component of DME pathophysiology;

• Corticosteroid treatment can provide similar cumulative improvement in visual acuity but with a lower injection burden compared with anti-VEGF therapy;

• Corticosteroids can prevent progression to proliferative diabetic retinopathy (PDR);

• Conversion to corticosteroid treatment has resulted in good outcomes in patients with DME recalcitrant to anti-VEGF therapy;

• The IOP responses associated with corticosteroid treatment are predictable and manageable.  

Anti-inflammatory activity

Findings from many studies show that the pathophysiology of diabetic retinopathy and DME is multifactorial and involves an inflammatory response in addition to VEGF activity.

“Therefore, controlling the inflammatory component of DME can potentially augment the treatment approach for patients,” Dr. Singh said.

Evidence of the benefit of intravitreal corticosteroid treatment for decreasing inflammatory factors in eyes with DME is available from a study by Sohn et al. [Am J Ophthalmol. 2011;152(4):686-694] in which patients had fellow eyes randomized to intravitreal treatment with triamcinolone acetonide or bevacizumab (Avastin, Genentech). Bevacizumab was associated with a significant reduction in VEGF levels only whereas VEGF levels and inflammatory cytokines were significantly reduced in the triamcinolone-treated eyes.

Visual acuity improvement

Dr. Singh discussed the functional benefit of corticosteroid treatment for DME based on visual acuity area under the curve (AUC) data. He explained that this parameter, which captures medication benefit over an entire observation period, has greater relevance than single visual acuity measurements considering the prolonged duration of treatment for DME.

Citing data from the pivotal studies (FAME) evaluating the fluocinolone acetonide implant 0.19 mg (Iluvien, Alimera Sciences) and for patients who received ranibizumab (Lucentis, Genentech) plus deferred laser in DRCR.net Protocol I, Dr. Singh showed that the visual acuity AUCs over the 2-year period post randomization were comparable for the corticosteroid and anti-VEGF therapy groups.

“The lack of difference between groups was particularly apparent when looking at the population of pseudophakic eyes not susceptible to corticosteroid-induced cataract,” Dr. Singh said.  

Disease modification, other benefits

Evidence that corticosteroid treatment can prevent progression to proliferative diabetic retinopathy (PDR) comes from the fluocinolone acetonide implant pivotal studies in which time-to-first progression to PDR was significantly reduced in eyes implanted with the fluocinolone implant compared with the sham-treated controls.

“In addition, time-to-first progression was also significantly reduced in the subset of patients with significant capillary loss, who are at the highest risk of developing proliferative disease over time,” Dr. Singh said.

A benefit of corticosteroid therapy for reducing DME and improving best-corrected visual acuity (BCVA) in patients who failed anti-VEGF therapy was reported in some small studies, but also shown in a recently published meta-analysis by Khan et al. that included 3,859 patients with recalcitrant DME treated with intravitreal sustained-release dexamethasone (Ozurdex, Allergan) [Ophthalmic Surg Lasers Imaging Retina. 2017;48(2):160-166.].

IOP response

Although intravitreal corticosteroid treatment is associated with elevation in intraocular pressure (IOP), clinical trial results provide an understanding of the response and risk factors, Dr. Singh said.

Data from studies investigating the dexamethasone implant show that IOP increases most often after the first injection, but a corticosteroid IOP response is less likely to occur with repeat injections. Elevated IOP returns towards baseline by 6 months when the implant has released its medication load.

Also, noteworthy are data from the fluocinolone acetonide implant pivotal studies that showed patients with prior intravitreal exposure to corticosteroids were less likely than their counterparts without such a history to need surgical intervention for glaucoma after implantation of the fluocinolone acetonide implant.

Information about the incidence and risk factors for ocular hypertension in eyes treated with the dexamethasone implant is available from the SAFODEX study that showed eyes with pre-existing glaucoma receiving dual or triple therapy had a higher rate of elevated IOP [Retina. 2016 Oct 20. Epub ahead of print].

Rishi P. Singh, MD

E: drrishisingh@gmail.com

This article is based on a presentation given by Dr. Singh at the 2017 Retina World Congress. He receives grant support and is a consultant to Genentech and Regeneron.