Anti-VEGF therapies changed the game, but the game’s moving on. As new contenders—from eye drops to gene editing—step onto the field, diabetic eye disease treatment is evolving fast. Here’s what’s next in the race to outsmart retinal damage.
When you think of turning back the clock on vision loss in people with diabetes, the spotlight usually falls on the heavyweights: vascular endothelial growth factor (VEGF) inhibitors. They’ve long dominated the fight against retinal diseases such as diabetic retinopathy (DR) and diabetic macular edema (DME). But the story doesn’t end there.
A new generation of treatments—from simple eye drops to gene therapies—is stepping up to the plate. Let’s see what’s making headlines in the evolving world of diabetic eye care.
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VEGF was just the beginning
The arrival of VEGF inhibitors like aflibercept, ranibizumab and bevacizumab in the early 2000s marked a seismic shift in retinal disease management.
The Phase IIb CLARITY trial, led by Prof. Sobha Sivaprasad (UK) and published in 2017, demonstrated that anti-VEGF therapy could outperform pan-retinal photocoagulation in proliferative diabetic retinopathy.1
But here’s the catch: anti-VEGF therapy itself isn’t cutting it for everyone. Data shows that nearly half of patients with DME fail to achieve optimal results with VEGF inhibition alone.
In fact, patients treated with aflibercept, bevacizumab or ranibizumab still had persistent DME in 44% to 68% of cases at two years.2
“Anti-VEGF alone is insufficient for nearly 50% of people with diabetic macular edema, so non-VEGF pathways need to be evaluated,” said Prof. Sivaprasad. The conclusion? It is high time to look beyond VEGF inhibition.
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Exploring new pathways
Dexamethasone eye drops. Meet OCS-01, a high-concentration (15 mg/ml) dexamethasone eye drop from Oculis (Zug, Switzerland). It could become the first non-invasive treatment for DME, offering convenient early-stage management and compatibility with other therapies in later stages.3
Stage 1 of the Phase III DIAMOND trial, involving 148 patients, has been completed. The company reported a “significant increase in visual acuity…and a reduction of macular edema, all with robust statistical significance,” compared to Phase II data. Topline results are expected in Q2 2026.3
Angiopoietin-2 (Ang-2). A key player in DME pathophysiology, Ang-2 influences vascular stability and inflammation. Six Phase III trials comparing faricimab (6 mg)—a dual Ang-2/VEGF-A bispecific antibody—with aflibercept suggest that dual-pathway inhibition offers superior disease control, managing both neovascularization and vascular leakage.4
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“Based on the evidence…earlier treatment with a dual pathway inhibitor has the potential to improve long-term patient outcomes,” noted Chaudhary et al. in a 2024 paper.4
The long game
Imagine fewer injections, fewer visits and a steadier course of treatment.
Earlier in 2025, Roche’s (Basel, Switzerland) Susvimo (ranibizumab implant, 100 mg/mL) became the first FDA-approved continuous delivery treatment for DME, offering a much-needed reprieve from monthly appointments.5
The approval was based on the Phase III PAGODA study, where patients refilled every six months achieved non-inferior visual gains (9.6 eye chart letters) compared with monthly ranibizumab injections (9.4 letters).5
Meanwhile, gene therapy is carving out its place in the retina realm.
“Advances in nucleic acid therapeutics like siRNA, miRNA and CRISPR/Cas9 have shown efficacy in preclinical models, reducing VEGF levels and neovascularization,” wrote Mengistie Diress et al. in a 2025 paper.6
AAV-based vectors such as RGX-314 (Regenxbio; Maryland, USA) and ADVM-022 (Adverum Biotechnologies; California, USA) promise long-term anti-VEGF expression, while newer non-viral lipid-polymer systems improve stability and targeting. However, safety, complexity and vector limitations remain key challenges.
The race is on to refine these technologies into durable, safe solutions that match the intricate dynamics of DR.
Real-world vs trial reality
When all is said and done, what works in a clinical trial can often hit snags in daily practice.
Patient visits get delayed, comorbidities interfere and some hard-hit populations may not be captured at all.
“Less treatment burden is key to successful treatment,” Prof. Sivaprasad noted. “If drugs can be delivered every six months, it would be a great relief to patients, caregivers and the health system as a whole.”
These factors are central in why the next wave of therapies is so important. They must reduce burden, increase durability and fit real-world patient lives, not just ideal trial conditions.
Cost, limited availability, uncertain long-term safety, and the need for robust head-to-head evidence against current first-line therapies all pose barriers to widespread adoption, said Prof. Sivaprasad.
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The future could be hybrid
Given that VEGF inhibition alone fails to deliver ideal outcomes for many, combination strategies are increasingly compelling.
If you ask what moves the needle most? Prof. Sivaprasad did not hesitate, saying, “Trials on combination therapies that test vision outcomes and durability.”
Simply put, the next big leap will not come from yet another individual drug. It will come from smart combinations, longer-lasting therapies, fewer clinic visits and wider reach.
The next play
The question has shifted from “what blocks VEGF best?” to “what else can we do?”
The next revolution in diabetic eye care won’t hinge on a single drug, but on how cleverly these therapies are combined, delivered and adapted to real-world needs. Because in the world of vision care, teamwork—molecular or otherwise—just might make the dream work.
Editor’s Note: This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore. A version of this article was first published in PIE Issue 37.
References
- Sivaprasad S, Prevost AT, Vasconcelos JC, et al; CLARITY Study Group. Clinical efficacy of intravitreal aflibercept vs panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): A multicentre, single-blinded, randomised, controlled, Phase 2b, noninferiority trial. Lancet. 2017;389(10085):2193–2203.
- Bressler NM, Beaulieu WT, Glassman AR, et al. Persistent macular thickening following intravitreous aflibercept, bevacizumab, or ranibizumab for central-involved diabetic macular edema with vision impairment: A secondary analysis of a randomized clinical trial. JAMA Ophthalmol. 2018;136:257–269.
- Diabetic Macular Edema (DME). Oculis. 2025. Available at: https://oculis.com/our-areas-of-focus/diabetic-macular-edema/. Accessed on October 24, 2025.
- Chaudhary V, Mar F, Amador MJ, et al. Emerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases. Graefes Arch Clin Exp Ophthalmol. 2025;263:1239–1247.
- FDA approves Roche’s Susvimo as the first and only continuous delivery treatment for the leading cause of diabetes-related blindness. Roche. February 4, 2025. Available at: https://www.roche.com/media/releases/med-cor-2025-02-04. Accessed on October 24, 2025.
- Diress M, Ionescu CM, Foster T, et al. Toward a new frontier in diabetic retinopathy treatment: A synergistic approach using gene therapy and nanotechnology. Journal of Drug Delivery Science and Technology. 2025;111:107172.
