New tried-and-true treatments for retinal vein occlusion

Retinal vein occlusion (RVO) is the second most common retinal vascular disease worldwide, following diabetic retinopathy. RVO frequently can result in severe visual impairment stemming from the development of macular edema and retinal ischemia.^1,2

Recently established treatments for RVO have taken a giant leap forward from laser photocoagulation since intravitreally injected anti-VEGF therapies arrived on the market. Those drugs ultimately became the standard of care.

Ranibizumab (Lucentis; Genentech) was the first anti-VEGF drug approved to treat RVO in 2010.³ The dexamethasone 0.7 mg implant (Ozurdex; Allergan), approved in 2009, is a long-acting steroid implant that continues to be used for chronic, stubborn cases of RVO, with data highlighting its role in long-term management.⁴

Newest anti-VEGF additions to the RVO armamentarium

Faricimab-svoa (Vabysmo; Genentech)

This received FDA approval to treat RVO on October 26, 2023. This approval is the third indication for the drug, which is also a treatment for neovascular age-related macular degeneration (AMD) and diabetic macular edema. The approval was based on the results of 2 phase 3 studies that showed the early and sustained visual improvements that were noninferior to aflibercept (Eylea; Regeneron).

The special characteristic of faricimab is that it is a bispecific antibody that addresses the macular edema associated with RVO by blocking VEGF-A and angiopoietin-2. It is the first and only such drug.⁵

The global phase 3 BALATON (NCT04740905) and COMINO (NCT04740931) studies found that monthly treatment with faricimab-svoa provided early and sustained improvement in vision in people with branch and central RVO, meeting the primary end point of noninferior visual acuity gains at 24 weeks compared with aflibercept.⁵ Both studies also met the secondary end point, demonstrating that faricimab-svoa achieved rapid drying of retinal fluid.⁶

At 24 weeks in BALATON (n = 553), the adjusted mean best corrected visual acuity (BCVA) change from baseline to week 24 was +16.9 letters (95% CI, 15.7-18.1) with faricimab vs +17.5 letters (95.03% CI, 16.3-18.6) with aflibercept. In COMINO (n = 729), BCVA gains were similarly robust: +16.9 letters (95% CI, 15.4-18.3) with faricimab vs +17.3 letters (95.03% CI, 15.9-18.8) with aflibercept. Anatomic improvements were also comparable, with an adjusted mean central subfield thickness reduction of of −311.4 µm vs −304.4 µm in BALATON and −461.6 µm vs −448.8 µm in COMINO (faricimab vs aflibercept, respectively).

Safety signals were comparable between arms, with similar ocular adverse event (AE) rates across trials: BALATON 16.3% (n = 45) with faricimab vs 20.4% (n = 56) with aflibercept, and COMINO 23.0% (n = 84) vs 27.7% (n = 100), respectively.

“Faricimab will enable us, as retina specialists, to lower the treatment burden for our patients,” according to Jennifer I. Lim, MD, who holds the Marion H. Schenk Esq, Chair in Ophthalmology for Research in the Aging Eye as UIC Distinguished Professor of Ophthalmology and is the Vice Chair for Diversity, Equity and Inclusion and Director of the Retina Service at University of Illinois at Chicago (UIC).⁷

Aflibercept 8 mg (Eylea HD; Regeneron)

This received FDA approval on November 19, 2025, for the treatment of macular edema associated with RVO. This higher dose of aflibercept was introduced after Eylea 2 mg was approved to treat central RVO by the FDA in September 2012 and branch RVO in October 2012.

“[RVO] is the second most common retinal vascular disease, yet the need for monthly injections has long made it difficult for many patients to stay on their treatment schedule, increasing the risk of vision loss. With the FDA’s approval of aflibercept 8 mg for RVO, we now have an option that, based on clinical data, may allow patients to receive injections far less frequently than with aflibercept 2 mg and other anti-VEGF therapies,” explained Seenu M. Hariprasad, MD, chair of the Department of Ophthalmology and Visual Science at the University of Chicago.⁸

Regeneron issued a news release on November 19, 2025, stating the following: “The FDA approval for the treatment of RVO is based on data from the phase 3 QUASAR trial (NCT05850520) that evaluated the efficacy and safety of Eylea HD compared to Eylea (aflibercept) injection 2 mg in patients with RVO. QUASAR met its primary end point at 36 weeks, with Eylea HD patients dosed every 8 weeks (after either 3 or 5 monthly doses) achieving noninferior visual acuity gains compared to those receiving Eylea dosed every 4 weeks. The Eylea HD results were consistent across patients with branch [RVOs] and those with central retinal or hemiretinal vein occlusions.”⁹

At 36 weeks in the phase 3 trial, patients receiving Eylea HD every 8 weeks—after either 3 (n=293) or 5 (n=298) initial monthly loading doses—achieved mean observed BCVA improvements of +17.0 letters and +19.1 letters, respectively, compared with +17.8 letters in the monthly aflibercept 2 mg arm (n = 301). The least squares mean differences vs aflibercept 2 mg were −0.1 letters and +0.8 letters, respectively (both P <.0001 for noninferiority, 4-letter margin). The mean observed BCVA at week 36 reached 72.8 and 74.6 letters in the 8-mg groups compared with 72.0 letters with monthly 2 mg dosing. Notably, durability outcomes were strong, with 88% to 93% of Eylea HD–treated patients maintaining 8-week dosing intervals through week 36.

Safety findings were consistent with the established profile of aflibercept. Increased intraocular pressure (5%) was the only ocular treatment-emergent AE occurring in 5% or more of patients. There was 1 reported case each of endophthalmitis and retinal vasculitis.

The Biosimilars

A number of biosimilars have been approved by the FDA in recent years to treat the macular edema that develops after RVO. These highly similar versions of existing complex biologic drugs (commonly called reference products) are held to a standard of having no clinically meaningful differences in safety, purity, or potency. Generally, they aim to offer patients lower-cost, but equally effective treatment options.

Ranibizumab Biosimilars

• Byooviz (ranibizumab-nuna, Samsung Bioepis)
  • The first ophthalmic biosimilar approved in the US on September 17, 2021, for RVO, wet AMD, myopic choroidal neovascularization, and macular edema after RVO and myopic choroidal neovascularization^10,11
• Cimerli (ranibizumab-eqrn, developed by Formycon AG and Bioeq AG; later acquired by Sandoz)
  • Approved in August 2022 as an interchangeable biosimilar, meaning it can be substituted for Lucentis at the pharmacy level without a new prescription (subject to state law)

Aflibercept Biosimilars

• Yesafili (aflibercept-jbvf, Biocon Biologics)
  • Approved in May 2024 as an interchangeable biosimilar for RVO and other retinal conditions¹¹
• Opuviz (aflibercept-yszy, Samsung Bioepis)
  • Approved in May 2024 as an interchangeable biosimilar for RVO¹¹
• Ahzantive (aflibercept-mrbb, Formycon AG/Klinge Biopharma)
  • Approved on June 28, 2024, for all Eylea indications, including RVO
• Enzeevu (aflibercept-abzv, Sandoz)
  • Approved in August 2024 as an interchangeable biosimilar
• Eydenzelt (aflibercept-boav, Celltrion)
  • Approved in October 2025 for the treatment of RVO
• Pavblu (aflibercept-ayyh, Amgen Inc)
  • Approved in late 2024/early 2025 for RVO and other retinal diseases¹¹

New pipeline therapy

New treatments are under investigation for RVO, and, according to Singer and Kabat,¹¹ one that is worthy of attention is ANXV (Annexin A5, Annexin Pharmaceuticals), an investigational new drug that contains the human protein Annexin A5, produced by recombinant techniques in Escherichia coli. ANXV can protect cells, reduce adhesive properties, and influence immune cell activity, with a mechanism of action that involves the blocking of phosphatidylserine, according to the authors.

“In patients with RVO, aberrantly externalized phosphatidylserine on erythrocytes is believed to be partly responsible for the pathogenic adherence of erythrocytes to endothelium, and this enhanced aggregation capacity likely contributes to the onset of RVO by predisposing to circulatory stasis and/or thrombus formation,” according to Singer and Kabat.

Previous RVO Therapies

Before the previously mentioned technologies were introduced, physicians relied on steroid injections. Steroids have been used for more than 25 years to manage retinal conditions that present with macular edema. The SCORE trials (NCT00105027) evaluated the safety and efficacy of intravitreal triamcinolone in eyes with macular edema due to RVO.¹¹ Grid laser photocoagulation was once considered the gold standard for this complication; it was hypothesized to increase oxygen diffusion from the choriocapillaris into the inner retina, leading to autoregulatory vasoconstriction and reduced leakage.¹¹

Other interventions have included vitrectomy, blood thinners, and management of risk factors.¹²

References

1. Romano F, Lamanna F, Gabrielle PH, et al. Update on retinal vein occlusion. Asia Pac J Ophthalmol (Phila). 2023;12(2):196-210. https://doi.org/10.1097/APO.0000000000000598

2. Jing Y, Li D. Faricimab for retinal vein occlusion: a review of current evidence and future perspectives. Front Pharmacol. 2025;16.1646806. https://doi.org/10.3389/fphar.2025.1646806

3. Fiebai B, Odogu V. Intravitreal anti vascular endothelial growth factor agents in the management of retinal diseases: an audit. Open Ophthalmol J. 2017;11:315–321. doi:10.2174/1874364101711010315

4. Waknine Y. Dexamethasone intravitreal implant approved for retinal vein occlusion. Medscape Medical News. June 24, 2009. Accessed March 23, 2026. https://www.medscape.com/viewarticle/704854?form=basic

5. FDA approves Genentech’s Vabysmo for the treatment of retinal vein occlusion (RVO). News release. Genentech. October 26, 2023. Accessed October 27, 2023. https://www.gene.com/media/press-releases/15009/2023-10-26/fda/approvesgenentechs-vabysmo-for-the-

6. FDA accepts application for Genentech’s Vabysmo for the treatment of retinal vein occlusion (RVO). News release. Genentech. May 9, 2023. Accessed October 27, 2023. https://www.businesswire.com/news/home/20230508005106/en/FDA-Accepts-Application-for-Genentechs-Vabysmo-for-the-Treatment-of-Retinal-Vein-Occlusion-RVO

7. Hutton D. Faricimab maintained vision improvements with extended treatment intervals up to 4 months for people with retinal vein occlusion in phase III studies. Ophthalmology Times. October 11, 2023. Accessed March 23, 2026. https://www.ophthalmologytimes.com/view/faricimab-maintained-vision-improvements-with-extended-treatment-intervals-up-to-4-months-for-people-with-retinal-vein-occlusion-in-phase-iii-studies

8. Eylea HD approved for RVO. Retinal Physician. November 24, 2025. Accessed March 23, 2026. https://retinalphysician.com/news/2025/eylea-hd-approved-for-rvo/

9. Eylea HD (aflibercept) injection 8 mg approved by FDA for the treatment of macular edema following retinal vein occlusion (RVO) and for monthly dosing across approved indications. News release. Regeneron. November 19, 2025. Accessed March 23, 2026. https://newsroom.regeneron.com/news-releases/news-release-details/eylea-hdr-aflibercept-injection-8-mg-approved-fda-treatment/#:~:text=The%20FDA%20approval%20for%20the,retinal%20or%20hemiretinal%20vein%20occlusionsFirst biosimilar approved for neovascular age-related macular degeneration (nAMD). MERIT. Accessed March 23, 2026. https://meritcro.com/first-biosimilar-approved-for-neovascular-age-related-macular-degeneration-namd/#:~:text=FDA%20Approval,high%2Dquality%20biological%20products.%E2%80%9D

10. Singer M, Kabat AG. Advances in the management of retinal vein occlusion. Eyes on Eyecare. January 6, 2026. Accessed March 23, 2026. https://eyesoneyecare.com/resources/advances-in-the-management-of-retinal-vein-occlusion/

11. Retinal vein occlusion (RVO). Cleveland Clinic. Updated June 19, 2023. Accessed March 23, 2026. https://my.clevelandclinic.org/health/diseases/14206-retinal-vein-occlusion-rvo