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Should an early switch to intravitreal steroids be considered in DME patients with a suboptimal response to anti-VEGF therapy?
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A proactive approach
There are now sufficient data to show that switching early makes sense if a patient does not respond adequately to anti-VEGF therapy. My recommendation is to switch between three and five injections and not wait longer if the signs of inadequate response are there. In addition to central retinal thickness, there are several other parameters to evaluate that are specific for DME because they are related to inflammation. OCT technology is now able to look at the retina in great detail and to detect signs of persistent DME that does not respond to therapy.
One of the signs is persistent DRIL, disorganization of the inner retinal layers, which has been shown in several studies to correlate with poor visual acuity outcomes. Another parameter is disruption or loss of the photoreceptor inner and outer segment junction and external limiting membrane. OCT can show presence of subretinal fluid, intraretinal cystoid fluid, hard exudates and other parameters, well described in the Euretina recommendations for the evaluation of DME.
We also consider visual acuity. If there is no significant effect on visual acuity from the therapy, because we have an alternative, it is good to switch. I am not so concerned about the side effects of steroids. First of all we have cataract, which occurs earlier in eyes treated with steroids. However, we also know that diabetes is a cataractogenic disease, and these patients develop cataract earlier than others. I do not see cataract as a major issue if the retina is safe. Second is IOP, but we know from many observational trials that IOP in more than 90% of the cases is easily controlled with topical treatment. We must of course monitor IOP on a regular basis, but there is no doubt that preserving the retina is priority.
We recently did a cluster analysis of a small population of 50 eyes, and using a specific algorithm, we were able to show that it makes sense to switch the patient between three and five injections.
Albert J. Augustin, MD, is professor and chairman, Department of Ophthalmology, Klinikum Karlsruhe, Germany. Disclosure: Augustin reports he receives speakers honoraria from Alimera and Allergan.
A more cautious approach
There are three populations of DME patients in whom I consider using intravitreal steroids for the management of DME. The first are patients who are incompletely responsive to repeated anti-VEGF injections. In these patients, I consider adding a steroid agent, but how I define “incompletely responsive” is individualized. In the presence of a modest response, if the patient is happy and seeing improvement with anti-VEGF dosing, I often continue with the same course until I maximize the improvement. I judge improvement over time primarily by anatomy. In my experience, Snellen vision can be variable, but the anatomy based on OCT is reliable and consistent. So, if I am not seeing a consistent drying effect with anti-VEGF dosing, I will consider switching to or adding a steroid agent. My threshold for switching is on average somewhere between three and six anti-VEGF injections.
There are two issues that I discuss with my patients when I consider incorporating an intravitreal steroid into their management, the well-known risk factors associated with steroids: increased IOP and cataract acceleration. In my opinion, when I administer intravitreal steroids, I permanently change the trajectory of cataract progression, even with one injection, so I am often hesitant to incorporate a steroid in patients with relatively clear lenses. I definitely have a higher threshold for steroid initiation in that population. Second, if there is any history of glaucoma or other concern about IOP elevation, I avoid intravitreal steroids if possible. The other population of DME patients in whom I consider using intravitreal steroids are those with an adequate response to anti-VEGF dosing but who require frequent, repeated injections. In those patients, intravitreal steroids may be valuable to decrease the treatment burden because they can impart a more durable pharmacologic effect.
Finally, in post-vitrectomy eyes with DME, intravitreal steroids can be valuable. These patients, who are often pseudophakic, often have an earlier point of transition from anti-VEGF to intravitreal steroids in my clinic. I do think there is a role for steroids in treating DME. In some patients I use steroids early. In others, I wait longer. Individualized decisions are based on the patient and the response to anti-VEGF injections.
Charles C. Wykoff, MD, PhD, is from Retina Consultants of Houston. Disclosure: Wykoff reports he is a consultant for Genentech, Regeneron, Allergan and Alimera.