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At the 131st Congress of the French Society of Ophthalmology in Paris, France, the role of second-generation intravitreal anti-VEGF injections compared to corticosteroid injections in treating diabetic macularedema (DME) was discussed. Both treatments are recommended as first-line options, but when both are available, Audrey Giocanti-Aurégan, MD, PhD, from Avicenne Hospital, AP-HP, Bobigny, France, advised that biomarkers identified through optical coherence tomography (OCT) should guide treatment decisions.

“Imaging provides insights into the potentially inflammatory nature of the edema,” she explained, noting that in such cases, corticosteroid treatment may be more appropriate.

Several structural biomarkers of the retina have been identified to predict the response to anti-VEGF or corticosteroids in DME. The ophthalmologist noted that his department now uses Mr-Doc software, powered by artificial intelligence, to analyze retinal structures from OCT images and assist in guiding therapeutic decisions.

DME occurs when small blood vessels supplying the macula — the central part of the retina — leak fluid due to diabetes-induced damage. This leakage causes macular swelling, leading to progressive vision loss. Diabetes remains the leading cause of acquired blindness in adults.

Current treatment options for DME include intravitreal injections of anti-VEGF or corticosteroids, such as high-dose dexamethasone or fluocinolone acetonide, a long-acting anti-inflammatory. Laser treatments like photocoagulation of capillary telangiectasias are typically used as second- or third-line therapies.

Inflammatory Biomarkers

Among the key biomarkers for DME, serous retinal detachments indicate an inflammatory type of edema. “DME with serous retinal detachment is associated with higher interleukin levels,” Giocanti-Aurégan noted. Dexamethasone shows “better anatomical response but no superiority in visual acuity” than anti-VEGF therapies.

The presence of hyper-reflective spots in retinal imaging also points to inflammatory activity caused by the activation of microglial cells. While corticosteroids reduce inflammation, they do not improve visual acuity compared to anti-VEGF treatments.

Another emerging biomarker is disorganization of retinal inner layers (DRIL), which involves poorly defined boundaries between retinal layers. “DRIL could indicate the activation of Müller glial cells, which play a crucial role in retinal homeostasis. In pathological conditions, these cells fail to perform their role,” Giocanti-Aurégan explained.

A recent study found that patients with DME and DRIL have elevated levels of glial fibrillary acidic protein, a protein produced exclusively by Müller cells. “In these patients, corticosteroids could protect Müller cells by promoting the restoration of sodium and potassium channels in these cells,” she said.

Anti-VEGF for Severe DME

“The choice between corticosteroids and anti-VEGF depends on the patient’s condition,” Giocanti-Aurégan explained, highlighting the numerous contraindications for corticosteroids. These include cases of aphakia (absence of the natural lens) or ocular infection, where anti-VEGF should be the first-line treatment.

Anti-VEGF agents are also preferred in advanced glaucoma or when the lens remains clear. They are prioritized for severe diabetic retinopathy. However, they are not recommended for patients who have recently experienced a cardiovascular event, such as a heart attack or stroke; in such cases, a dexamethasone implant is the preferred option.

Recently, second-generation anti-VEGF agents, including brolucizumab, faricimab, and 8 mg aflibercept, have become available for treating DME and age-related macular degeneration (AMD) via intravitreal injection. These newer treatments allow for longer intervals between injections, but they carry a higher risk for inflammation, warranting caution.

Second-generation anti-VEGF agents, like the first-generation drugs ranibizumab and aflibercept 2 mg, are still recommended as first-line treatments. “As a precaution, I tend to favor first-generation agents, unless the patient is unable to attend frequent visits,” said Giocanti-Aurégan.

Aflibercept 8 mg Preferred in Second Line

First-generation anti-VEGF agents are particularly recommended for first-line treatment in cases of previous uveitis, monocular patients, or bilateral DME. “We prefer to use safe molecules with minimal side effects,” added Giocanti-Aurégan.

However, recommendations for second-generation anti-VEGF agents may evolve as biomarkers are identified that show more favorable outcomes with these newer treatments. For example, a recent study found better results with faricimab compared with 2 mg aflibercept in cases with numerous exudates visible on imaging.

Switching to a second-generation anti-VEGF agent or corticosteroids should be considered if there is an unsatisfactory response to first-generation anti-VEGF. “If DME is not adequately ‘dried’ after five monthly anti-VEGF injections, I’ll switch quickly, especially if the patient has poor initial visual acuity,” she said.

If switching to a second-generation anti-VEGF, 8 mg aflibercept remains the preferred choice, especially given recent real-world data showing a higher risk for inflammation with brolucizumab, cautioned Benedicte Dupas, MD, ophthalmologist at the Sorbonne-Saint Michel Ophthalmological Center in Paris, during a discussion at the end of the presentation.

Combining Anti-VEGF and Corticosteroids?

Dupas reported that a recent study found a similar risk for retinal vasculitis in both DME and AMD patients treated with brolucizumab. “However, brolucizumab remains an excellent molecule and shouldn’t be ruled out,” she said, suggesting it could be considered for second- or third-line therapy, especially when reducing injection frequency is necessary.

To mitigate the inflammation risk associated with brolucizumab, Dupas and her team are investigating a combination treatment: brolucizumab injections with a dexamethasone implant. “So far, we’ve seen promising results and a favorable tolerance profile,” she added.

This combination of anti-VEGF and anti-inflammatory treatment is viewed as a potential breakthrough. While combination therapy has shown limited benefits in DME, “with second-generation anti-VEGF agents, we could see very interesting results,” said Pierre-Henry Gabrielle, MD, PhD, professor of ophthalmology at Dijon University Hospital, Dijon, France.

Giocanti-Aurégan disclosed relationships with AvvVie, Alco, Bayer, Horus, Novartis, Roche, and Thea. Dupas reported having no relevant financial conflicts of interest. 

This story was translated from .