Defining AMD Treatment Protocol

Intravitreal injections are the gold standard for the treatment of exudative macular disorders such as neovascular AMD, DME, and RVO, granting a high intraocular concentration with a low systemic exposure. However, according to Luis Arias Barquet MD, PhD, some key questions still need to be answered: “What is the best drug to treat our patients? Which is the best treatment protocol? Do we need to apply the same treatment for all patients? What will future treatments be?”

To identify the best drugs available for the patient, Dr Arias explained it is important to observe the many different pathways that can be targeted by a drug for treating retinal disorders, adding the anti-VEGF blockade remains the most effective pathway for treating these conditions.

The first generation of anti-VEGF agents, such as ranibizumab and aflibercept 2 mg—while effective—needed a high frequency of injections to obtain good visual and anatomical results. The need for multiple monitoring follow-ups and treatments contributed to a huge socio-economic burden for the patient and the healthcare system and risked compromising treatment efficacy due to a lack of compliance.

The latest generation of anti-VEGF agents moved efforts a step further: Faricimab is the first bispecific antibody designed to target both VEGF and angiopoietin-2, used in a 6 mg clinical dose. Aflibercept 8 mg is the same fusion protein of the previous generation but with a modified molar concentration to enhance clinical effectiveness. Brolucizumab is a small antibody fragment with a very low molecular weight in a 6 mg dose.

Dr Arias observed these drugs have very similar visual results compared to the previous generation but with better anatomical results, resulting in longer durability that translates into fewer injections and longer treatment intervals—a breakthrough for the management of these conditions.

The high potency of brolucizumab, for example, keeps the macula dry for up to 6 months, Dr Arias said. Even so, the drug has had some safety issues regarding intraocular inflammation in 4% of cases, sometimes severe, requiring a balance of the risks and benefits.

Given this need for balance, no one treatment stands out as the best treatment protocol. Every treatment protocol can be helpful if done correctly, he explained, showing the results of a multicentre study he conducted that compared reactive (fixed, PRN) and proactive treat-and-extend (T&E) regimens.¹ There are no clinical differences, he stated.

However, while the T&E approach was more popular with drugs such as aflibercept 2 mg, the tendency with the new drugs is a move towards a fixed regimen with longer intervals of up to 16 weeks. Besides anti-VEGF, the efficacy of treatments such as Ozurdex (INN-dexamethasone) and Iluvien (fluocinolone acetonide) is indisputable, he added.

Regarding new incoming treatments, Dr Arias highlighted the potential of port delivery systems that can be surgically implanted once and eventually refilled directly in the office. He said gene therapy is also extremely promising, explaining that the rationale is “to teach retinal cells to produce their own anti-VEGF molecules, a very promising alternative to intravitreal injections.”

Dr Arias spoke at the 2024 ESCRS Congress in Barcelona.

Luis Arias Barquet MD, PhD is Head of the Retina Department of Ophthalmology at Bellvitge University Hospital in Barcelona, Spain. luisariasbarquet@gmail.com

1. López-Gávez MI, Arias-Barquet L, Figueora MS, García-Layana A, Ruiz-Moreno JM, In-Eye Study Group. “Bimonthly, treat-and-extend and as-needed ranibizumab in naïve neovascular age-related macular degeneration patients: 12-month outcomes of a randomized study,” Acta Ophthalmol, 2020; 98(7): e820–e829.