The shadow of eye disease looms large over patients across the globe. Known as a 'blindness-causing killer' of the fundus, Diabetic Macular Edema impacts more than 30 million individuals worldwide. Meanwhile, Allergic Conjunctivitis plagues 20%-30% of the population, significantly eroding visual clarity and overall well-being.

Source: Internet

Yet, traditional treatments are fraught with unspeakable pain points. For those with fundus diseases, monthly intravitreal injections bring not just physical stinging, but deep psychological dread. For patients with surface conditions, standard eye drops struggle to breach the corneal barrier, often 'flowing away' immediately after instillation, leading to minimal therapeutic effect. It is these unmet clinical demands that are fueling the revolutionary evolution of ophthalmic delivery systems.

Source: Int J Mol Sci

Macular Degeneration Pathological Schematic

I. The Unfortunate Compromise: From Topical Application to Invasive Injection

From the 19th century to the early 21st century, ophthalmic drug delivery evolved from topical application to invasive injection. Early treatments, such as atropine ointment and sulfonamide eye drops, yielded minimal efficacy. Post-20th century, intravitreal injections of penicillin and anti-VEGF agents improved therapeutic outcomes but introduced risks like high infection rates and injection phobia, causing 40% of elderly patients to delay follow-up visits due to fear.

This era of exploration laid the foundation for pharmaceutical innovation. Companies like Novartis and Santen optimized ocular surface formulations, while Roche and Bayer specialized in anti-VEGF injections. Their early strategic layouts were heavily reliant on safety and efficacy data derived from fundamental animal models.

II. Dual-Line Breakthrough: Non-Invasive Delivery and Precision Injection

Advancements in materials science and molecular biology have propelled ophthalmic delivery into a "Non-Invasive Revolution." Non-invasive eye drops and precise minimally invasive injections have become the core focus, with customized animal models serving as the critical bridge connecting laboratory research to clinical application.

1. Eye Drops: Penetrating the Corneal Barrier for Non-Invasive Targeting

Traditional eye drops struggle to penetrate the corneal barrier. Today, leveraging technologies such as penetration enhancers and nanocarriers allows drugs to reach deep lesions directly, transforming the treatment paradigm for posterior segment diseases.

OCS-01 by Oculis (Switzerland), utilizing OPTIREACH® technology, penetrates the cornea to reach the macula. Phase III clinical trials for Diabetic Macular Edema (DME) demonstrated efficacy comparable to anti-VEGF injections, while simplifying administration to three daily drops and eliminating injection risks. Oculis is simultaneously advancing new drugs like OCS-02 to continuously upgrade non-invasive technologies.

Source: Internet

In the field of ocular surface diseases, Japan’s Santen and China’s Hengrui Medicine have optimized the molecular weight of sodium hyaluronate, launching long-acting bioadhesive eye drops. With a moisture-retention duration of over 4 hours, these drops effectively ease dry eye symptoms and repair the corneal epithelium.

Domestically, Runer Ophthalmology’s Emedastine Difumarate Eye Drops offer quick relief from allergic conjunctivitis. Approved for marketing in March 2025, it became the first domestic product in this category. It also obtained Priority Review from the CDE and was deemed to have passed the consistency evaluation.

2. Injection Upgrade: Precision Minimally Invasive + Domestic New Drugs Optimize Invasive Treatment Experience

For diseases requiring injection therapy, such as intraocular tumors, innovations in equipment and formulations have made invasive procedures safer and less painful, with animal models providing guarantees for protocol optimization.

On November 26, 2025, Boyaojing (Aflibercept Biosimilar) from Shandong Boan Biotech was officially approved for marketing by the NMPA. Indicated for the treatment of adult neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME), it becomes the second domestically approved aflibercept biosimilar, following Qilu Pharmaceutical’s Zhuochuming® (approved in December 2023).

The originator drug, Eylea®, co-developed by Regeneron and Bayer, is a humanized fusion protein. It binds to VEGF-A, VEGF-B, and Placental Growth Factor (PlGF) simultaneously. Compared to anti-VEGF monoclonal antibodies, it offers a broader range of targets and durable VEGF inhibition, effectively improving visual acuity with a favorable safety and tolerability profile.

Phase III clinical data demonstrated no significant differences in visual improvement or safety between Boyaojing and the originator drug. The launch of this domestic biosimilar not only improves drug accessibility but also further drives the optimization of injection administration protocols.

The core of the evolution in ophthalmic drug delivery technology is "patient-centricity," and animal models serve as the critical bridge connecting basic research to clinical application. Every technological breakthrough during this transformative period relies on the support of customized animal models.

Reference：

Qu S, Lin H, Pfeiffer N, Grus FH. Age-Related Macular Degeneration and Mitochondria-Associated Autoantibodies: A Review of the Specific Pathogenesis and Therapeutic Strategies. Int J Mol Sci. 2024;25(3):1624. Published 2024 Jan 28. doi:10.3390/ijms25031624

Rat Retinal Macular Degeneration Model

Introduction:

Age-related macular degeneration (AMD) is categorized into dry and wet forms. Dry AMD involves choroidal atrophy, drusen, and retinal pigment epithelium (RPE) loss, driven largely by oxidative stress. Sodium iodate, an antimetabolite, selectively damages the RPE, making it an ideal agent to induce AMD-like pathology in animal models.

Modeling Protocol:

BN Rats: 5-week-old rats were injected via tail vein with 1% sodium iodate on Day 1 and Day 16. Validated via fundus photography on Day 46.

SD Rats: 8–10-week-old rats received 1% sodium iodate via tail vein on Day 0 and Day 15. Validated on Day 28.