From 'Artificial Tears' to 'Natural Tear Restoration': A Paradigm Shift in Dry Eye Therapy

Many people are deeply impressed by the mute girl’s “single tear” in the movie Kung Fu Hustle; however, in real life, countless patients with dry eye disease suffer from the distress of being unable to produce tears.

Dry Eye Disease: No Longer Just “Dry Eyes”It is a multifactorial disease of the ocular surface, characterized by loss of tear film homeostasis accompanied by symptoms of ocular discomfort. Key elements in its pathophysiological progression include tear film instability, hyperosmolarity of the tear film, inflammation and damage to the ocular surface.

Under normal conditions, the lipids, proteins, water, electrolytes, and cytokines in tears are relatively balanced, maintaining the tear film in a stable state to prevent desiccation of the ocular surface epithelium. Any qualitative or quantitative changes in these components can alter tear film stability, thereby leading to the onset and progression of dry eye disease.

In China, the spread of this disease is far outpacing public expectations. According to disclosed data, more than 300 million people in China are suffering from dry eye disease. Behind this figure lies an emerging “national health crisis.”

For a long time, “hydration” has been the logical approach to managing dry eye disease. However, the medical community is undergoing a paradigm shift, moving from external “hydration” to internal “water generation.”

At the “Caring for Dry Eye Patients, Ushering in the Era of Natural Tears—2025 Conference on New Advances in Dry Eye Diagnosis and Treatment and the Construction of an Ocular Surface Health Ecosystem,” He Yong, founder of the Zhongguancun Precision Medicine Foundation, revealed a startling statistic: “Over 300 million people in China are affected by dry eye disease.” This figure clearly demonstrates that dry eye is no longer a niche concern but a common and highly prevalent condition affecting the general population.

Dry eye disease affects a remarkably broad population. Actress Huang Shengyi, sharing her personal experience, noted that she developed symptoms such as dry eyes and visual fatigue due to prolonged reading of electronic materials while pursuing her degree; meanwhile, her young child was diagnosed with early-stage dry eye disease after frequently rubbing their eyes.

This reflects that dry eye is no longer the “exclusive domain” of middle-aged and older adults or specific professions, but rather a widespread health issue transcending age, occupation, and lifestyle. With the combined effects of factors such as the proliferation of electronic devices, increased use of contact lenses, and worsening environmental pollution, the incidence of dry eye continues to rise. This further confirms the trend of dry eye disease spreading across all age groups, indicating that anyone can inadvertently become a patient.

Studies on risk factors for dry eye disease in children have identified excessive use of video display terminals, contact lens wear, insufficient sleep, and poor dietary habits as established causative factors.

So, which groups need to be particularly vigilant? Professor Zhang Mingchang from Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, clearly identified two high-risk groups characterized by “long-term” behaviors: first, individuals who wear contact lenses for extended periods, as chronic irritation from the lenses and care solutions can easily lead to dry eye; second, those who rely heavily on eye drops for prolonged periods. Furthermore, Professor Liu Zuguo, Director of the Eye Institute at Xiamen University, emphasized that poor lifestyle habits are strongly associated with the incidence of dry eye disease, most notably among individuals who use mobile phones and computers extensively over long periods. The common feature among these groups is that the ocular surface microenvironment remains in a state of chronic stress or disruption, leading to compromised tear film stability.

Despite the large patient population, there is a significant gap in public awareness, with most people still stuck at the stage of “just using eye drops for dry eyes.”

According to reports, the traditional "exogenous hydration" strategy, which involves the frequent use of artificial tears, may temporarily alleviate dryness. However, its single-component formulation fails to mimic natural tears, which contain a variety of proteins and growth factors. Furthermore, there is a volume mismatch: a single drop of eye drops often exceeds the eye's fluid capacity by two to three times. Excessive instillation can wash away native tears, and the retention time of eye drops on the ocular surface is extremely short; within 15 minutes after administration, the drug concentration may drop to just 0.1% of the initial level. Long-term use can lead to dependency and may suppress the lacrimal glands' intrinsic secretory function, resulting in glandular hypofunction, dormancy of native tear production, and exacerbated imbalance in tear film homeostasis.

Zhang Mingchang warns that long-term reliance on certain eye drops, particularly the “viral” brands containing preservatives, may trap the eyes in a vicious cycle of increasing dryness with continued use. Merely providing external “hydration” addresses only the symptoms and fails to resolve the underlying issues of insufficient tear secretion or an unstable tear film.

This approach, which addresses symptoms rather than the root cause, fails to resolve the underlying issues of insufficient tear secretion or tear film instability and may even exacerbate the condition.

Confronted with the challenges in dry eye treatment, the medical community is undergoing a paradigm shift from “external hydration” to “endogenous tear production.”

According to DIResearch statistics, the global dry eye disease market has shown a steady expansion trend. The global market size for dry eye disease reached RMB 46.088 billion in 2025 and is projected to reach RMB 64.288 billion by 2032, with a compound annual growth rate (CAGR) of 4.87% from 2025 to 2032. This data reflects the significant market potential and development space in the field of dry eye treatment.

In the future, dry eye treatment will place greater emphasis on addressing root causes and systemic regulation, trending toward personalization, precision, and comprehensive management.

Experts present emphasized that the core of this shift lies in the fact that the optimal tear film is the body’s own “native tears,” which are rich in nutrients, immune factors, and reparative components that no artificial tear solution can fully replicate. The therapeutic goal is no longer simple supplementation, but rather the restoration and activation of the body’s endogenous tear secretion function.

As with Grand Pharma’s varenicline tartrate nasal spray, the world’s first neuromodulatory nasal spray for dry eye disease, Liu Zuguo pointed out that its innovation lies in a dual breakthrough in both therapeutic pathway and mechanism—shifting from the eyes to the nasal cavity, thereby establishing a novel paradigm of “treating ocular diseases via the nose.”

The mechanism of action of this drug ingeniously leverages human physiological reflexes. Professor Jie Ying from Beijing Tongren Hospital, Capital Medical University, elaborates that varenicline stimulates the trigeminal nerve within the nasal cavity, thereby activating the “nasolacrimal reflex arc.” This signal is transmitted via neural pathways, ultimately reaching and activating the lacrimal glands, accessory lacrimal glands, as well as the meibomian glands and goblet cells. Its distinct advantage lies in its ability to promote not only aqueous layer secretion but also the secretion of mucins and lipids, thereby maximizing the simulation of the natural tear film’s three-layer structure and achieving full-layer replenishment—an outcome unattainable with single-component artificial tears.

Clinical study data further support its efficacy. Professor Jin Xiuming of the Second Affiliated Hospital of Zhejiang University School of Medicine noted that global clinical studies involving more than 1,300 cases have demonstrated that this drug can significantly improve tear secretion and subjective symptoms in patients with dry eye disease. It rapidly alleviates dry eye symptoms within five minutes after administration, increasing baseline tear secretion by more than 10 mm.

Professor Wan Pengxia from the First Affiliated Hospital of Sun Yat-sen University shared two classic cases: a 32-year-old designer showed significant repair of corneal epithelial damage after use; an elderly patient with Sjögren's syndrome also experienced marked improvement in ocular surface damage after adding varenicline to the combination therapy.

Perhaps this will usher in the “Era of Native Tears.” In the future, dry eye treatment is evolving from a singular “hydration” model to a multidimensional therapeutic system encompassing “tear production, repair, and regulation.”

Beyond varenicline, new technologies are continually emerging in the global field of dry eye treatment. For instance, artificial intelligence-based ocular surface image analysis systems enable precise classification of dry eye subtypes; genetic testing holds promise for identifying individuals susceptible to dry eye, thereby facilitating early intervention; and combination pharmacotherapy along with comprehensive therapeutic approaches will become mainstream.