Diabetic retinopathy (DR) is a prevalent complication, affecting approximately one-quarter to one-third of all diabetic patients. Notably, according to the International Diabetes Federation’s 2015 global survey, about 5% of these individuals develop diabetic macular edema (DME), a major contributor to blindness in this population (Yau et al., 2012). Currently, it is widely accepted among scholars (Wei et al., 2021; Xia et al., 2024; Feng et al., 2013) that retinal ischemia-hypoxia and the breakdown of the blood-retinal barrier serve as principal contributors to the upregulation of various factors. This upregulation subsequently leads to increased vascular permeability, thereby facilitating the development of macular edema. Accordingly, VEGF antagonist therapy has gained considerable attention as a treatment strategy for DME. The therapeutic effect of these drugs is mediated through VEGF inhibition, resulting in the preservation or enhancement of visual acuity in affected individuals (Schmidt-Erfurth et al., 2014). Ranibizumab (Lucentis) is a recombinant humanized monoclonal IgG1 antibody that targets all isoforms of VEGF-A. Numerous clinical trials have confirmed the significant efficacy of ranibizumab in treating DME (Dervenis et al., 2017; Nikhil et al., 2025).

However, the high cost of the reference ranibizumab places it beyond the financial reach of the majority of patients. This limited affordability may lead to poorer treatment adherence and, consequently, restrict its widespread clinical application. Biosimilars are defined as biological products that are highly similar to an already approved reference biologic and are marketed after the originator’s patent expires, with demonstrated equivalence in safety and efficacy (Sharma et al., 2021). Qilu Pharmaceutical’s biosimilar ranibizumab injection (Rimmyrah) received marketing approval from China’s National Medical Products Administration (NMPA) on 19 August 2024. This approval marks it as the first ranibizumab biosimilar to be authorized for use in China. The active ingredient of a biosimilar is essentially the same as that of its reference drug, although the production process may introduce minor differences (Sameera et al., 2016). To our knowledge, there are no published reports from clinical studies directly comparing the efficacy of reference ranibizumab and the biosimilar (Rimmyrah) in patients with DME.

This study aims to compare the efficacy and safety of the ranibizumab biosimilar (Rimmyrah) with the reference ranibizumab in patients with DME, thereby providing evidence to support the rational clinical use of biosimilars.

Macular edema represents a significant complication of the microvascular lesions commonly associated with diabetes mellitus. It arises from a series of pathological changes induced by impaired retinal microcirculation. Furthermore, recent studies indicate that the incidence of diabetic retinopathy has been rising annually and has emerged as a leading cause of vision impairment among diabetic patients. VEGF, a potent mitogen and permeability-enhancing cytokine, is primarily secreted by vascular endothelial cells. It functions by stimulating the proliferation, migration, and permeability of nascent endothelial cells, thereby driving pathological neovascularization. In the treatment of DME, anti-VEGF agents are administered to block this signaling pathway, which in turn reduces macular edema (Campochiaro et al., 2014; Wells et al., 2015; Massin et al., 2010). Prior to the advent of anti-VEGF therapy, macular laser photocoagulation was the standard of care for DME. While effective in reducing macular edema, this laser treatment offered limited benefits in terms of visual acuity improvement (Bressler et al., 2016).

The current anti-VEGF armamentarium for diabetic macular edema (DME) comprises conbercept, aflibercept, and ranibizumab (Lin et al., 2025; Liu and Li, 2019; Jiajia et al., 2024; Zhou et al., 2021; Liberski et al., 2022; Kun et al., 2021). The combined effect of patent expirations for originator biologics and advances in biotechnology has spurred the development of biosimilars. These products have well-established quality, safety, and efficacy profiles that are comparable to their reference products (Ashish et al., 2025). OCTA is a rapid, non-invasive imaging technology that has emerged recently. It enables the quantitative assessment of retinal capillary vessel density and foveal avascular zone area in the macular region. The effect of anti-VEGF therapy on macular perfusion remains controversial. Some studies (Campochiaro et al., 2014) suggest it improves perfusion, whereas others indicate it may exacerbate retinal ischemia (Shimura and Yasuda, 2010). Previous studies have reported that the biosimilar ranibizumab Razumab© can serve as an effective treatment option for wet age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, demonstrating short-term efficacy by reducing central foveal thickness and improving visual acuity (Gopal et al., 2020).

To our knowledge, there are no published reports from clinical studies directly comparing the efficacy of a ranibizumab biosimilar (Rimmyrah) and reference ranibizumab in patients with DME. This study aimed to evaluate the differences in therapeutic efficacy between a ranibizumab biosimilar and the reference ranibizumab in patients with DME by comparing BCVA, CRT, FAZ area, SVD and DVD in the macular region, as well as the incidence of complications before and after treatment.

The results of this study showed that both groups had significant improvements from baseline in BCVA and CRT at 3, 6, and 12 months post-treatment (P < 0.05). At the 12-month follow-up, FAZ area was significantly reduced, while both the SVD and DVD were significantly increased compared to pre-treatment values (P < 0.05). This is consistent with the results of previous studies (Campochiaro et al., 2014). However, there were no statistically significant differences in any outcome measures between the two groups at any time point. The main risks associated with intravitreal anti-VEGF therapy include infection, hemorrhage, glaucoma, cataract, and cardio-cerebrovascular accidents (Schmidt-Erfurth et al., 2014). Elevation of intraocular pressure is among the most commonly reported adverse events. Compared with baseline, neither group exhibited a statistically significant change in IOP. During the study period, no other systemic or serious ocular safety concerns were identified. Over a 12-month follow-up, this study provides evidence that the ranibizumab biosimilar (Rimmyrah) showed similar safety and efficacy profiles to its reference product in the treatment of DME. This conclusion is consistent with previous research findings on other ranibizumab biosimilars. For example, a Phase III randomized controlled trial comparing OPTIMAB® (another ranibizumab biosimilar) with the innovator product demonstrated that there were no statistically significant differences between the two in terms of visual acuity benefits, anatomical improvements, and safety in the treatment of patients with neovascular age-related macular degeneration (AMD), establishing the non-inferiority of the biosimilar (Parth et al., 2024). Extending the evaluation to the microvasculature using OCTA, we found that the two treatments yielded similar improvements in macular perfusion parameters, such as FAZ area, SVD, and DVD. These results bridge evidence from conventional efficacy measures to microvascular restoration, thereby reinforcing the biosimilar’s holistic therapeutic value in managing DME.

Although improvements in the FAZ area and vascular density were observed, caution is warranted in directly equating these OCTA findings with true microvascular reperfusion, due to known methodological constraints such as segmentation errors and projection artifacts. The OCT-A improvements noted in our study should thus be regarded as a promising anatomical correlate, providing preliminary support for similar microvascular effects between the two agents. Their definitive clinical significance, however, requires further validation alongside functional visual outcomes.

The results are consistent with the scientific basis for biosimilar approval, which requires high similarity in amino acid sequence, three-dimensional structure, target affinity, and pharmacological mechanism to the reference product. With comparable efficacy established, the principal advantage of the biosimilar lies in its substantially lower cost. Given that treatment expense significantly influences patient adherence, reducing the financial burden may improve treatment persistence and long-term outcomes. In an era increasingly oriented toward value-based healthcare, biosimilars represent a viable strategy for delivering equivalent clinical benefits at a lower cost.

While the relatively conservative “3+PRN” regimen used in this study (with fewer mean annual injections) may reduce treatment burden, it could also explain the more modest magnitude of visual improvement observed compared to some intensive treatment protocols. Nevertheless, the highly similar therapeutic responses and outcomes exhibited by both groups under this regimen precisely underscore the comparability of the biosimilar in real-world clinical practice.

This study thus offers evidence from both efficacy and economic viewpoints to inform clinical practice: choosing a biosimilar without sacrificing effectiveness can optimize healthcare resource allocation and align with public health priorities. Several limitations should be noted, however, including the modest sample size, the 12-month follow-up duration, and the absence of a formal cost-effectiveness analysis (CEA). Moreover, the limitations of this study include its retrospective design and the relatively small sample size (35 patients per group), which may have limited the statistical power and increased the risk of a Type II error, thereby reducing the ability to detect potential minor differences between the two groups. Future real-world investigations with larger cohorts and extended observation periods are warranted to confirm long-term efficacy and safety. Further health-economic studies are also needed to quantify the cost savings and health gains associated with biosimilar use in DME, thereby providing stronger evidence for policy-making.

In conclusion, the ranibizumab biosimilar represents an effective and cost-efficient treatment option for DME. We recommend that clinicians consider efficacy, safety, patient financial status, and local healthcare resource availability when selecting therapy, and regard biosimilars as a rational alternative in management plans. Ongoing surveillance of real-world performance and safety, coupled with clear patient-clinician communication regarding treatment options, will support optimized outcomes in DME care.