Response to the Letter to the Editor by Michael Colucciello,MD,FASRS,Entitled “Steroid/Anti-VEGF Combination Therapy for Neovascular AMD”

Dear Editor:

We would like to thank Michael Colucciello for his critical reading of our recently published article. ¹ In his thoughtful letter to the editor, ² he referred to his personal experience, which was published in 2008. ³ In this article, the author described the outcomes of combining triamcinolone (TA) and an antivascular endothelial growth factor agent (anti-VEGF) for the treatment of neovascular age-related macular degeneration (nAMD). Previously, he noted the pathophysiology, which involves both angiogenic and inflammatory factors. These factors induce macrophage activation, which may contribute to a fibrovascular switch^4–6 and the development and progression of nAMD and geographic atrophy (GA). ⁷ Since then, this has never been confirmed on clinical grounds, as he noted in his letter.

Until a decade ago, the combination of anti-VEGF agents and corticosteroid drugs such as TA was broadly used in many European centers, including ours, in patients with an unsatisfying response to treatment and/or a high treatment demand with the aim of improving functional outcomes and reducing the burden of treatment for both patients and caregivers.^8,9 Since then, more potent drugs have been approved for the treatment of nAMD, and considering corticosteroids for anti-VEGF therapy has become rare.

Patients receiving combined anti-VEGF and TA treatment frequently experience not only a rise in intraocular pressure and progression of cataracts but also visual disturbance for several days until weeks induced by the crystalline material in the optic axis. The problem of visual disturbances has been overcome by the broad availability of the dexamethasone (Dex) implant, which was approved for the treatment of diabetic maculopathy, retinal vein occlusion, and inflammatory macular edema but not for nAMD; thus, Dex is an off-label treatment for nAMD.

However, compared with TA, Dex is a safer treatment, but significantly adds to treatment costs and has barely received cost coverage from the national health systems. Therefore, its application has been restricted to a few of the most frustrating cases of advanced nAMD, as in our series. Based on the low number of cases and relevant case selection bias, we are not in a position to assess the potential beneficial influence of these procedures on the development and progression of diffuse and geographic macular atrophy.

Corticosteroids have been used more restrictively since then, not only because of the availability of more potent drugs but also because of their side effects, namely, a not excluded risk of macular atrophy and tachyphylaxis in response to TA.^10,11 It is conceivable that newer drugs with anti-VEGF and anti-inflammatory potential, such as faricimab, which blocks proinflammatory and macrophage-activating angiopoietin-2, might affect the development and progression of GA without causing steroid-related side effects. ¹²

Although the pathogenesis of AMD is only partially understood, highly variable and driven by multiple genetic and environmental inflammatory factors, we fully support Dr. Colucciello's postulate to assess the impact of combined anti-inflammatory and anti-VEGF therapy for nAMD on the development and progression of macular atrophy based on data from recent randomized clinical phase 3 studies.