Branch Retinal Vein Occlusion: Current Insights into Diagnosis and Treatment Advances

Branch retinal vein occlusion (BRVO) remains one of the most common retinal vascular disorders, and its impact is far from benign. Affecting more than 16 million people globally, BRVO accounts for nearly four times as many cases as central retinal vein occlusion (CRVO). Its prevalence is especially high among middle-aged and elderly populations and, if left untreated or poorly managed, can lead to irreversible vision loss. Yet despite the breadth of research and rapid advances in imaging and pharmacotherapy, BRVO still presents critical challenges in both diagnosis and treatment.

At its core, BRVO is a consequence of venous obstruction—most often at an arteriovenous crossing in the retina—where a stiff, atherosclerotic artery compresses the underlying vein. This compression leads to turbulent flow, endothelial damage, and thrombosis. While that mechanical process is central, the downstream effects—namely retinal ischemia, inflammation, and elevated vascular endothelial growth factor (VEGF) levels—are what drive the clinical picture: macular edema, hemorrhage, and, in some cases, neovascularization.

The natural course of BRVO is unpredictable. Some patients recover visual acuity without intervention, particularly those with limited ischemia or nasal occlusions. But in others, especially when the macula is involved, persistent edema and ischemic damage can cause permanent vision loss. The development of collateral circulation offers a potential route to spontaneous improvement, but this process is neither guaranteed nor sufficient in most cases.

Advancements in diagnostic imaging have transformed how BRVO is understood and managed. Optical coherence tomography (OCT) has become indispensable, not only in identifying macular edema but in tracking treatment response and prognosticating outcomes. Features such as central macular thickness, integrity of the ellipsoid zone, and presence of hyperreflective foci provide important visual cues on disease severity. Optical coherence tomography angiography (OCTA), a newer modality, allows clinicians to non-invasively evaluate microvascular changes, such as capillary nonperfusion or early neovascularization, that are pivotal in guiding therapy.

On the treatment front, intravitreal anti-VEGF injections have become the cornerstone of BRVO management, particularly for macular edema. Agents such as ranibizumab, aflibercept, and off-label bevacizumab consistently outperform older therapies like laser photocoagulation. Newer anti-VEGF drugs like brolucizumab offer the promise of extended dosing intervals but bring concerns around ocular inflammation and safety that remain under investigation. Despite their efficacy, these biologics require frequent injections and monitoring, and treatment burden remains a key concern for patients and providers alike.

Corticosteroids provide an alternative or adjunctive therapy, particularly for patients who are unresponsive to or unable to tolerate anti-VEGF agents. Intravitreal dexamethasone implants and off-label fluocinolone acetonide offer longer-acting options, but their benefits are tempered by risks of intraocular pressure elevation and cataract formation. As a result, careful patient selection and follow-up are paramount.

While monotherapy remains the standard for most patients, combined regimens are gaining attention. Pairing anti-VEGF therapy with corticosteroids, NSAIDs, or subthreshold laser treatment may enhance outcomes, reduce injection frequency, and provide more durable control of edema. However, robust comparative trials are lacking, and much of the data comes from small or heterogeneous studies.

Surgical interventions, including arteriovenous sheathotomy and vitrectomy, are typically reserved for severe or refractory cases. Though conceptually appealing, particularly in relieving mechanical vein compression, their clinical benefit is still under debate. Vitrectomy may play a more established role in managing complications like vitreous hemorrhage or tractional retinal detachment.

As current therapies mature, emerging treatments are pushing the boundaries of what’s possible. Gene therapy, for example, is being explored to achieve sustained suppression of VEGF or to correct molecular abnormalities underlying vascular dysfunction. Peptide-based agents and small-molecule inhibitors are also under investigation, aiming to selectively target inflammatory or angiogenic pathways without the drawbacks of large-molecule biologics. Early-phase trials show promise, but hurdles remain in drug delivery, immunogenicity, and long-term safety.

The management of BRVO is increasingly moving toward individualized, biomarker-driven care. Parameters such as baseline macular thickness, cytokine profiles, and the presence of specific OCT features may help predict treatment response and guide therapy selection. The integration of advanced imaging, functional testing like microperimetry, and even metabolomic analysis may further refine this precision approach.

Yet despite these advances, unmet needs persist. Recurrence of macular edema is common, often requiring long-term treatment. Resistance to anti-VEGF therapy, whether due to pharmacokinetics or underlying pathophysiology, continues to affect a subset of patients. Systemic factors—such as hypertension, hyperlipidemia, and diabetes—also remain central to both risk and recurrence, emphasizing the need for interdisciplinary management.

Ultimately, the future of BRVO care lies in a multifaceted strategy: one that combines early detection, precision diagnostics, targeted therapy, and long-term monitoring. As newer modalities move from bench to bedside, the focus must remain not just on anatomical outcomes but on preserving functional vision and improving quality of life for patients. With continued research and collaborative care, the burden of BRVO may finally begin to lift.