Role of corticosteroids uncertain in AMD management

Reviewed by Marc D. de Smet, MD, PhD

There is no doubt that inflammation is a component of age-related macular degeneration (AMD), and yet the role of corticosteroid treatment in the management of eyes with AMD remains uncertain, said Marc de Smet, MD, PhD.

“Intravitreal corticosteroid treatment may be useful in eyes that have frequent recurrences while receiving anti-VEGF injections or that seem to have an insufficient response,” said Dr. de Smet, director, MIOS (Microinvasive Ocular Surgery), Lausanne, Switzerland. “In these cases, the corticosteroid can provide benefit by reducing the level of immune activation and reduce tachyphylaxis for example by the generation of neutralizing antibodies.”

Dr. de Smet said that in these cases, it is better to use a sustained-release product rather than a soluble formulation. “It may be also better to combine the corticosteroid with other modalities, such as verteporfin (Visudyne, Bausch + Lomb) photodynamic therapy (PDT),” he added. “In addition, corticosteroids may be more useful for reducing vascular leakage rather than for treating active neovascularization.”

A compilation of optical coherence tomography images outlines the outcome of a 66-year-old woman who had received 25 anti-VEGF injections before being treated with the dexamethasone implant combined with half fluence PDT performed after one week. She showed benefit for a period of about five months before developing recurrence of intraretinal fluid and decreased vision. Over the next three to four years, she was successfully maintained on treatment with the dexamethasone implant, (Image courtesy of Marc D. de Smet, MD, PhD)

Dr. de Smet’s comments about corticosteroids in the management of AMD were based on a review of the literature. He cited a study published in 2013 that randomized 37 patients to treatment with intravitreal (soluble) dexamethasone phosphate, combined with ranibizumab (Lucentis, Genentech) or the anti-VEGF agent alone [Ranchod TM, et al. Retina.2013;33(8):1600-1604].

All patients received 4 monthly injections and then as needed according to findings during follow-up. At 1 year, there was no difference between study groups in either visual acuity or central macular thickness outcomes.  

Dexamethasone study

Another study [Chaudhary V, et al. Can J Ophthalmol. 2016;51(4):302-305]

evaluated the dexamethasone implant (Ozurdex, Allergan) in a small study that included 10 patients treated with anti-VEGF injections alone or combined with the sustained-release corticosteroid.

“Dexamethasone phosphate may have a very limited effect because it is present in the eye for only 4 to 5 days,” Dr. de Smet said. “Even so, in this study using the implant that has a longer duration of action, there was still no difference in functional or anatomic outcomes at 1 year.”

Dr. de Smet pointed out that the authors, however, reported the corticosteroid may have provided a benefit considering that the patients receiving the dexamethasone implant were on average 10 years older than the anti-VEGF group.

Another study [Forte R, et al Ophthalmic Res. 2011;45(3):129-134] looked at triple therapy combining anti-VEGF injection with full fluence PDT and dexamethasone compared with anti-VEGF monotherapy. Patients included in this retrospective investigation were treatment-naïve and after an initial treatment with the monotherapy or triple therapy were followed every 1 to 2 months for signs of disease activity to guide retreatment.

Both groups had improvement in foveal thickness and visual acuity during an average follow-up of 14 and 16 months, respectively. Although there was no real difference between groups with regards to those outcomes, time to first retreatment was longer in the triple therapy group than in the eyes receiving anti-VEGF therapy alone (5.4 vs. 3.6 months).

Calvo and colleagues [Calvo P, et al. Br J Ophthalmol. 2015;96(6):723-726] investigated the dexamethasone implant in patients whose neovascular AMD responded incompletely to ranibizumab. The 7 patients included in this series had been treated for at least 24 months with ranibizumab and initially responded well, but then developed persistent intra/subretinal fluid.

The analyses of their outcomes showed stabilization of vision along with decrease in the intra/subretinal fluid and reduced central retinal thickness. “Other case control studies show similar results,” Dr. de Smet added. 

Targeting vascular leakage

Dr. de Smet discussed two cases to highlight a potential role of the sustained-release corticosteroid for managing patients with decreased vision associated with the presence of intraretinal fluid in the absence of any neovascular membrane in the subretinal space.

One patient was a 72-year-old male who had received 17 injections of an anti-VEGF agent. He was next treated with half fluence PDT, but had persistent intraretinal fluid after two sessions given at an interval of four months.

The edema resolved over time and was accompanied by improvement in vision following intravitreal placement of the dexamethasone implant. The benefit persisted for seven months, and the patient responded to retreatment with the dexamethasone implant.

The second patient, a 66-year-old woman, had received 25 anti-VEGF injections before being treated with the dexamethasone implant combined with half fluence PDT performed after one week. She showed benefit for a period of about five months before developing recurrence of intraretinal fluid and decreased vision.

Dr. de Smet reported that over the next three to four years, she was successfully maintained on treatment with the dexamethasone implant, administered about every six to eight months. The treatment was well-tolerated. The patient developed a cataract and underwent successful cataract surgery.

Marc D. de Smet, MD, PhD

E:  mddesmet1@mac.com

This article is based on a presentation given by Dr. de Smet at the 2017 Retina World Congress. Dr. de Smet is a consultant to Alcon Laboratories, Allergan, Sanofi, and Santen. He also receives lecture fees from Santen, Sanofi, and Allergan.