Anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed the management of retinal diseases worldwide. In daily clinical practice, conditions such as neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) are no longer diseases in which our only objective is to slow visual decline. Across many regions, we now expect to preserve vision and, in a substantial proportion of patients, to improve it.¹

This success, however, has come with important challenges. Retinal diseases treated with anti-VEGF agents are typically chronic and require repeated intravitreal injections over many years. As retina specialists, regardless of geography, we see firsthand the cumulative burden these injections place on patients, caregivers, clinics, and health care systems. Even in well-resourced environments, long-term sustainability has become a concern. In low-income and middle-income countries, cost remains a major barrier to access, continuity of care, and adherence.

It is in this global context that biosimilar anti-VEGF agents have emerged. Over the past decade, I have been closely involved in the scientific evaluation, regulatory understanding, and real-world use of biosimilars across multiple regions. For most retina specialists today, the question is no longer whether biosimilars work, but how they can be integrated responsibly into everyday clinical practice.^2,3

Why Biosimilars are Fundamentally Different From Generics

One of the most persistent misconceptions surrounding biosimilars is the assumption that they are simply generic versions of biologic drugs. This misunderstanding exists among both patients and clinicians. Biologics are large, structurally complex proteins produced in living systems, and even originator biologics demonstrate inherent variability between manufacturing batches. Exact replication is therefore not possible.

Biosimilars are developed through a rigorous, stepwise process designed to demonstrate high similarity to the reference biologic in structure, function, efficacy, safety, and immunogenicity. Extensive analytical characterization forms the foundation of development, followed by functional assays assessing VEGF binding and biologic activity. Only after this similarity is convincingly demonstrated do developers proceed to clinical trials designed to confirm equivalence rather than independently establish efficacy.

From my perspective, understanding this scientific and regulatory framework is essential. Regulatory agencies across the world have adopted a “totality of evidence” approach that is intentionally demanding. Biosimilars are not shortcuts; they are carefully evaluated alternatives built on robust comparative science.¹

The Global Regulatory Landscape

One important aspect often overlooked in clinical discussions is the degree of global regulatory convergence around biosimilars. Although approval pathways differ in structure between regions such as the United States, Europe, and Asia, the scientific principles underlying biosimilar approval are remarkably aligned.

Most major regulatory agencies require a stepwise demonstration of similarity, emphasize analytical and functional comparability, and allow extrapolation of indications when scientifically justified. This harmonization has enabled biosimilars developed in 1 region to gain acceptance across multiple markets, contributing to broader global confidence.

At the same time, regional differences in post-marketing surveillance, pharmacovigilance infrastructure, and health care delivery mean that continued real-world monitoring remains essential. From a clinician’s perspective, this reinforces the importance of evaluating biosimilars not only at the time of approval, but also as experience accumulates.²

Why Biosimilars Matter on a Global Scale

Anti-VEGF therapy is resource- intensive. Even modest differences in per-injection cost can have substantial implications when multiplied over years of treatment and across millions of patients worldwide. As populations age and the prevalence of diabetes continues to rise globally, demand for retinal services is increasing at a pace that challenges many health care systems.

In several regions, biosimilars have already had a meaningful impact on access to care. Lower drug costs have allowed more patients to be treated, follow-up intervals to be maintained, and undertreatment to be reduced. In other regions, biosimilars are only beginning to enter routine practice, often driven by payer policies or national health care priorities.

Importantly, biosimilars are not intended to replace innovation. Rather, they help create space for innovation by alleviating cost pressures associated with long-term use of established biologics.

Ranibizumab Biosimilars: Global Maturity and Breadth

Ranibizumab biosimilars represent the most mature and widely adopted class of anti-VEGF biosimilars. As summarized in Table 1, multiple ranibizumab biosimilars are approved across North America, Europe, Asia, and other regions, reflecting broad regulatory confidence.

In my own clinical experience and collaborative work, ranibizumab biosimilars have shown predictable efficacy and safety across diverse patient populations and indications.^4-9 Long-term use and switching from originator ranibizumab have not revealed unexpected concerns when appropriate manufacturing oversight and pharmacovigilance are maintained.¹⁰ As a result, ranibizumab biosimilars are no longer considered novel in many parts of the world, but rather a routine component of retinal care.

Aflibercept Biosimilars: Rapid Expansion and Growing Confidence

Aflibercept biosimilars represent the next major phase in biosimilar anti-VEGF therapy. As outlined in Table 2, several aflibercept biosimilars have now achieved regulatory approval across multiple regions, with additional agents in late-stage development.

Table 2. Manufacturers and brands of biosimilar aflibercept 2 mg

Phase 3 trials of aflibercept biosimilars have demonstrated equivalence to reference aflibercept in both nAMD and DME, with comparable gains in best-corrected visual acuity and reductions in retinal thickness. Safety profiles and immunogenicity rates have also been similar, without new safety signals.

Although real-world experience with aflibercept biosimilars is more recent than with ranibizumab biosimilars, early data from multiple countries are reassuring. Initial real-world studies suggest that aflibercept biosimilars perform as expected in routine practice, including in patients switched from the reference product.¹¹ As familiarity grows, aflibercept biosimilars are likely to play a significant role in expanding access and choice globally.

Safety and Immunogenicity: Lessons From Trials and Practice

Safety is understandably the most sensitive issue when introducing any intravitreal therapy. Based on both clinical trial data and real-world experience, the safety profile of anti-VEGF biosimilars has been reassuring.

Early post-marketing experiences—referring to safety data collected after regulatory approval through routine clinical use, pharmacovigilance reporting systems, and real-world observational studies—highlighted the importance of manufacturing consistency and active surveillance. These experiences did not undermine the biosimilar concept but instead demonstrated that surveillance systems function as intended. Manufacturing processes were refined, quality controls were strengthened, and safety outcomes improved accordingly.

Through my involvement as chair of the International Retina Biosimilar Study Group (Inter BIOS Group), I have had the opportunity to evaluate real-world data from multiple countries. Across these data sets, biosimilars have consistently demonstrated safety profiles comparable to their reference products, without unexpected adverse events.

The Role of Real-World Evidence

While Although randomized clinical trials are essential for regulatory approval, real-world evidence is often what ultimately shapes clinician confidence. Real-world data reflect routine practice, diverse patient populations, variable adherence patterns, and differing healthcare infrastructures.

Our The collaborative international work (of Inter BIOS Group) has shown that biosimilars deliver expected visual and anatomic outcomes in everyday care, including in patients who have been switched from originator biologics.^4-9,11 These findings have been consistent across geographic regions, reinforcing the generalizability of biosimilar performance.

Switching Patients: A Universal Challenge

Switching stable patients from an originator biologic to a biosimilar is often the most sensitive aspect of adoption. Scientifically, switching studies have not demonstrated meaningful differences in outcomes.¹⁰ Clinically, however, success depends heavily on communication and trust.

In my practice, I emphasize transparency, clear explanation, and reassurance regarding ongoing monitoring. Avoiding language that suggests compromise is critical, as biosimilars should be positioned as equivalent therapeutic options rather than inferior alternatives.

Economic and System-Level Considerations

Economic considerations vary widely depending on healthcare systems, reimbursement structures, and patient out-of-pocket costs. In some regions, biosimilars are essential to making anti-VEGF therapy feasible at all. In others, they offer incremental savings that support long-term sustainability.

Regardless of setting, cost considerations should inform—but never replace—clinical judgment. The ultimate goal should always remain high-quality, patient-centered care.

Final Thoughts

Biosimilars will become an increasingly routine part of retina care worldwide. As experience grows and real-world data continue to accumulate, comfort levels among retina specialists will rise. At the same time, innovation in retinal therapeutics will continue to expand our treatment options. Rather than competing with innovation, biosimilars may help ensure that innovation remains accessible by reducing financial barriers and supporting sustainable care models.

From a global perspective, biosimilar anti-VEGF agents represent an important evolution in retinal care. Based on the available evidence and my own experience across regions, they can be integrated safely and effectively when used thoughtfully.

For retina specialists worldwide, the challenge is not indiscriminate adoption, but informed, patient-centered implementation. When solid science, real-world evidence, and clear communication come together, biosimilars can play a meaningful role in improving access to care while maintaining the standards our patients expect. OM

Ashish Sharma, MD, is a retina specialist at Lotus Eye Hospital and Institute in Coimbatore, Tamil Nadu, India, and chair of the International Retina Biosimilar Study Group. He is a consultant to Ajanta Pharma, Allergan, Bayer Pharma, Cadila Pharma, Intas Pharma, Lupin Pharma, Novartis, Oculis, Sun Pharma, and Zydus Lifesciences, and a paid speaker for Abdi Ibrahim Pharma, MS Pharma, Nitto Medic, Roche, and Samil Pharma. Reach him at drashish79@gmail.com.

References

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2. Sharma A, Kumar N, Kuppermann BD, Bandello F, Loewenstein A. Understanding biosimilars and its regulatory aspects across the globe: an ophthalmology perspective. Br J Ophthalmol. 2020 Jan;104(1):2-7. doi: 10.1136/bjophthalmol-2019-314443. 

3. Sharma A, Kumar N, Parachuri N, Bandello F, Kuppermann BD, Loewenstein A. Biosimilars for rRetinal dDiseases: aAn uUpdate. Am J Ophthalmol. 2021 Apr;224:36-42. doi: 10.1016/j.ajo.2020.11.017.

4. Sharma, A., Nicholson, L., Vazquez-Alfageme, C. et al. FYB-201 bBiosimilar ranibizumab (Ongavia/Ranivisio/Cimerli) eEfficacy and sSafety in cClinical sSettings – FORCE study. Eye (2025).https://doi.org/10.1038/s41433-025-04030-7

5. Ueda-Consolvo T, Ishida M, Nakamura T, Yanagisawa S, Tsuboi K, Wakabayashi T, Hayashi A, Sharma Aet al; International Retina Biosimilar Study Group (Inter BIOS Group). Biosimilar ranibizumab (BS1) - early experience from Japan (BRIJ study). Eye (Lond). 2024 Jul 23. doi: 10.1038/s41433-024-03220-z. 

6. Sharma A, Arunaprakash J, Das A, Nayaka A, Kumar N, Parachuri N, Kuppermann BDet al. Ranizurel safety evaluation in real-world -(RaSER) study. Am J Ophthalmol Case Rep. 2022 Feb 2;25:101358.

7. Song JR, Park UC, Lee CS, Cho JJ, Kim JY, Baek SC, Jeong A, Sharma A, Kim JH, Sagong M, Woo SJet al; International Retina Biosimilar Study Group (Inter BIOS Group). Real-world outcomes of ranibizumab biosimilars in various retinal diseases: a Korean multi-center experience-ROSE Korea Study. Sci Rep. 2026 Jan 9. doi: 10.1038/s41598-025-34325-4.

8. Sharma A, Sheth J, Mishra C, Chakraborty D, Meshram B, Purohit Set al; International Retina Biosimilar Study Group (Inter BIOS Group). Ranibizumab biosimilar (Oceva) - real-world experience from India (RORE study). Expert Opin Biol Ther. 2025 Dec;25(12):1353-1358. doi: 10.1080/14712598.2025.2606897. 

9. Sharma A, Holz FG, Kumar N, Sarraf D, Ayachit S, Mishra C, Tufail A, Chakraborty D, Rachitskaya A, Eichenbaum D, Banker A, Parachuri N, Kumar A, Loewenstein A, Bandello F, Wakabayashi T, Woo SJ, Kuppermann BDet al. Biosimilar rRanibizumab (Ranieyes) safety and efficacy in the real world: BRESER sStudy. J Vitreoretin Dis. 2025 Feb 27;9(3):24741264251322213. doi: 10.1177/24741264251322213. 

10. Sharma A, Loewenstein A, Parachuri N, Kumar N, Kuppermann BD. Biosimilar to bBiosimilar aAnti-VEGF switching for retinal diseases. J Vitreoretin Dis. 2023 Sep 29;7(6):474-476. doi: 10.1177/24741264231202080. 

11. Avadzadeh S, Sharma A, Parvaresh MM, Ghasemi Falavarjani K; International Retina Biosimilar Study Group (Inter BIOS Group). Aflibercept 2 mg biosimilar (Tyalia)-real-world experience from IRAN (ATRIA study). Eye (Lond). 2025 Aug;39(11):2159-2163. doi: 10.1038/s41433-025-03813-2.