The global ophthalmic eyedropper market is expected to grow due to the increasing prevalence of eye diseases like glaucoma, dry eye disease, and age-related macular degeneration. The aging population is a key factor driving this growth, as older individuals are more likely to experience these eye conditions (1).
Glaucoma, especially open-angle glaucoma, is the leading cause of irreversible blindness (2) and often requires eye drops to manage intraocular pressure.
With the elderly being six times more likely to develop glaucoma after age 60 (3), the demand for glaucoma eye drops is likely to rise. The dry eye category had the highest revenue in 2023, influenced by the frequent use of digital screens (4) and other factors like aging and pollution. Artificial tears are the main treatment for dry eye symptoms. As the market expands, manufacturers must focus on understanding and addressing patient challenges related to administering eye drops and improving home eye care management.
Historically, ointments were preferred, being easier to manufacture and less contaminable. The main problem for manufacturers was the production of solutions capable of remaining sterile over lengthy periods of time up to the opening of the container.
Up to the 1950s, this objective was attained using glass blown bottles mainly handcrafted, and the use of wood or carton for the packaging to protect the eye drop flasks was developed in parallel.
Then the quality of glass was improved, and its manufacture was automated. A new kind of glass blown bottle was developed, sealed by a rubber stopper. During use, the stopper was replaced by a plastic dropper. This type of packaging is still used.
However, given the persistent problem of the fragility of glass and its weight, manufacturers favored plastic bottles, with specific disadvantages such as the need to sterilize the bottle prior to filling (by ethylene oxide, a dangerous product to handle and costly installations), the plastic – eyedrops interaction, the permeability, etc …
Though these successive technological advances resolved the production and packaging problems of a sterile product, the problem of contamination after opening of the bottle persisted. Laboratoires Chibret, established by Jean Chibret, the father of Théa’s founder, had first the idea of systematically adding a preservative into the eye drops to fight against proliferation of micro-organisms. This practice was rapidly adopted by all manufacturers. The French and European Pharmacopeia made the addition of preservatives compulsory for multidose eye drop bottles.
Mercurial derivates were preferred but were later found to be highly allergenic. Then preference was given to the quaternary ammoniums, such as benzalkonium chloride (BAK). However, after some years of use, studies have demonstrated its harmful effects on the ocular surface (5, 6).
Moreover, the presence of preservative has eventually proven not to guarantee the non-contamination of the content of the bottle as shown in numerous studies (7, 8).
The emergence of the undesirable effects of these preservatives led manufacturers to show a preference for single-dose containers during the 1960s. These single-doses are mainly manufactured according to the blow-fill-seal principle. Their main disadvantage being the high cost of manufacture, the quantity of plastic used, and their difficult handling by elderly or by those with handling difficulties.
It wasn’t until the late 80s that Henri Chibret, a French entrepreneur and son of Jean Chibret, developed a passion for the subject. He challenged his R&D team to come up with a multidose bottle capable of delivering several hundreds of unpreserved eye drops without any risk of microbial contamination of the container after opening. Mission accomplished in 1995 for Henri Chibret’s teams who successfully brought to market the 1st preservative-free alternative to the single-doses. This technological revolution guarantees the sterility of the solution in the eye drop without the addition of a preservative. Other Preservative Free Multi-Dose bottles have been developed afterwards.
Some guidelines in regulatory frameworks were not (and sometimes still are not today) adapted to the assessment of this type of technology. Thus, the approval and marketing of products packaged in preservative-free multidose vials has been delayed in the past. However, today, all the renowned regulatory agencies in the world (FDA, EMA, MHRA, ANVISA, etc.) have already approved this type of product, based on robust supporting data, for expiry times after opening of up to 6 months. If one aspect of ophthalmic products is essential, and even more so for a non-preserved product, it is the guarantee of sterility. This is highlighted by the revision of EU GMP Annex 1: Manufacture of Sterile Medicinal Products.
The new version of Annex 1 has been expanded considerably and now contains a stronger focus on risk management and the implementation of a contamination control strategy.
Added to this are cases of contamination of ophthalmic products on the market (9), thus we can anticipate a tightening of audits and evaluations of registration files on this aspect of the guarantee of maintaining the sterile state.
Despite those challenges, we currently foresee a double opportunity to INNOVATE: the first one related to the eco-design, the second one related to the digital.
The eco-design is the systematic integration of environmental aspects from the design and development stages of products (figure 1), with the goal of reducing negative environmental impacts throughout their entire life cycle, meaning before – during – after the use of the product. This approach aims to find the best balance between environmental, social, technical and economic requirements in the design and development of products.
In our field of Ophthalmic Drug Delivery systems, the Eco-design & Eco-responsibility challenges (figure 2) can be tackled by:
• Reducing plastic consumption, as the extraction of the raw material and the end-of-life of such materials can have significant impacts on the environment.
• Reducing the drop size of products. Water is a limited resource that must be taken into account in the eco-design of products composed mostly of water, and using significant quantities of water in the processes of manufacturing.
• Increasing adherence, as treatments are efficient only when taken properly, especially in chronic diseases like glaucoma, offering more chances of positive outcomes for the patient.
Thus, the future in sight is the development of Ophthalmic Drug Delivery systems optimizing all three pillars that are ecology, economy and ergonomic.
The digital revolution is the second opportunity to innovate. Considering that electronic technologies are 2 times cheaper and 2 times more powerful every 2 years (10), this rapid advancement significantly influences various fields, including computing power, sensor technology, networking, robotics, nanotechnology, extended reality, artificial intelligence, and biosciences.
We can already see the emergence of MEMS (Micro Electro Mechanical Systems), which are sensors that combine mechanics and electronics in order to connect the physical world to the digital. Sight is not overlooked, and the development of MEMS to other physical senses could be inspiring for the ophthalmic world.
With benefits for both the patient and the healthcare professionals, this type of digital technology can enhance tracking and provide greater serenity to the patient while allowing healthcare professionals to refocus on their primary mission (figure 3).
Artificial intelligence (AI) tools and smart dispensers are increasingly used in healthcare to help patients follow their medication plans. These tools can evaluate and improve how well patients stick to their medications. Current AI technologies include mobile apps, reminder systems, and patient empowerment tools. AI is important for understanding the complex reasons behind medication non-adherence. Interventions using AI can improve communication between patients and doctors, track medication use, and empower patients, potentially leading to better health outcomes and quality of life.
However, challenges exist, like how user characteristics affect the AI tool’s effectiveness as well as the demonstration of medical efficacy for chronic diseases without immediate consequences for non-compliance, such as glaucoma. Research is needed to evaluate AI’s effectiveness in different patient groups and address challenges to wider use.
Moreover, telemedicine can improve patient outcomes, access, and satisfaction for chronic disease management. It can overcome geographical barriers and boosts patient engagement, changing global healthcare delivery. Applying these insights can improve ophthalmic care worldwide, ensuring fair and patient-centered solutions.
And finally, if eco-design or digital are not sufficient to break down barriers of patient adherence and compliance, one future challenge could be to consider alternative delivery routes like intravitreal injections and novel drug delivery systems providing controlled release. Such delivery systems imply invasive interventions, that is why efficacy must be guaranteed for several months to space out the interventions over time, as much as possible. Consequently, these drug delivery systems providing controlled release require extreme reliability. In the future, more innovations are predicated in the ocular drug delivery systems to enhance and preserve eye health, to improve patient compliance, to optimize the drug efficacy, and the management of ocular diseases.
Figure 1. Life cycle of a product.
Figure 2. Eco-design & Eco-responsibility challenges.
Figure 3. Benefits for the patient and healthcare professional
References and notes
- “Ophthalmic Eye Droppers: Market Analysis Segment Forecast From 2018 To 2023.” Grand View Research, accessed Feb 2024.
- “Glaucoma: Competitive Landscape to 2026”. GlobalData, accessed Feb 2024.
- Allison K, Patel D, Alabi O, “Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future”. Cureus, 2020, Vol 12(11), article: e11686.
- Al-Mohtaseb Z et al, “The Relationship Between Dry Eye Disease and Digital Screen Use.” Clin Ophthalmol, 2021, Vol 15, pp 3811–3820.
- Champeau EJ, Edelhauser HF. Effect of ophthalmic preservatives on the ocular surface : conjunctival and corneal uptake and distribution of benzalkonium chloride and chlorhexidine digluconate. In : Holly FJ, Lambert DW, MacKeen DL, Esquivel ED. The preocular tear film in health, disease and contact lens wear. Dry Eye Institute Lubbok, Texas 1986; 292-302
- Baudouin C. Detrimental effects of preservatives in eye drops: implications for the treatment of glaucoma. Acta Ophthalmol. 2008; 86 (7): 716-26
- Taşli H, Coşar G. Microbial contamination of eye drops. Central European journal of public health. 2001 Aug; 9(3):162-4
- Aslund B, Oslon OT, Sandell E. Studies on in-use microbial contamination of eye drops. 1978; 15(5):389–394
- https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-certain-eye-drops-several-major-brands-due-risk-eye
- Gordon E. Moore, Electronics, Volume 38, Number 8, April 19, 1965.
