Corneal Infections and Dry Eye: Validating a Potential Treatment

Although the incidence of keratitis remains variable across populations, a recent review suggests an expected increase of up to 18.5% over coming decades.¹ Conversely, dry eye is highly prevalent across society, significantly impacting patient quality of life.^2,3 Topical administration remains the initial, and most common treatment method for both eye infections and dry eye.

In severe cases of keratitis, patients may need to apply eye drops every hour, often accompanied by oral medication for systemic treatment. The recovery period varies depending on the type of infection: bacterial keratitis typically lasts two to three weeks, fungal keratitis can extend to four to six weeks, while Acanthamoeba keratitis may persist for up to six months. Some infections, like viral keratitis, can frequently reoccur. In some cases of neutrophilic keratitis and fungal keratitis, therapeutic bandage contact lenses, are used.

Dry eye is often challenging to treat due to its complexity and associated co-morbidities. As Professor Colin Chan, a surgeon at Vision Eye Institute, has stated, “There is no straightforward algorithm for treating dry eye. You have to try one approach, see if it works, and then try another.”

Most dry eye treatment remains supportive or palliative in nature, however, topical treatments like corticosteroid drops or therapies such as LipiFlow and intense pulsed light (IPL) are increasingly used.4,5 Although variable in impact, these therapies have shown to be beneficial for many patients.^5,6 Ongoing treatment is expensive for most patients. Furthermore, to optimise outcomes, patients often require combining these treatments with non-preserved tears and oral omega 3 supplements. In some cases of dry eye, bandage lenses may also be indicated.

The emergence of treatments that target additional aspects of these conditions, including novel inflammatory pathways, abnormalities of the eyelid margin, and neuronal function, suggest the potential for improved and more customised treatment plans.⁷ The corresponding use of increasing contact lens technology further offers great potential in optimising patient care for these conditions.

The focus of potential treatments has been corneal infection and dry eye

New Opportunities

Due to the limitations of current treatments, both healthcare professionals and patients continue to seek additional innovative solutions. The ideal ocular surface treatment likely represents better topical drug bioavailability, sustained drug release, and reduced side effects as a more effective and long-lasting alternative to traditional eye drops.^8,9

Recently, researchers at University of Sydney (USyd) have developed a novel application which has shown significant promise. Dr Jingjing You and her team are developing a drug delivery system for the eye surface, focussing on a contact lens-based approach using collagen and plasma techniques, which has demonstrated slow drug release.

The focus of potential treatments has been corneal infection and dry eye. A contact lens-based drug delivery system could provide significant benefits for both regular contact lens users and those who wear bandage lenses. For example, with the slow release of wetting agents using this system, regular contact lens wearers might find increased comfort. Post-surgery patients, who require bandage lenses in conjunction with eye drops, could benefit from the integrated drug delivery and reduced burden of topical medication. Additional applications, such as patients with other ocular conditions who need frequent eye drop instillation, for example glaucoma, could benefit from a more convenient and effective treatment option, which this system may provide.

Patient and Industry Consultation

At the beginning of 2024, Dr You and I were awarded a place in the USyd’s PERIscope Commercialisation Award program. This program, part of a pilot, is a unique funding scheme designed to help researchers move beyond the lab and engage directly with stakeholders, validating the market potential of their research products.

During the program, as the entrepreneur lead, I interviewed 100 stakeholders, including patients, healthcare professionals, researchers, and representatives from pharmaceutical companies and medical affairs. These interactions have provided invaluable insights and feedback, helping to shape and enhance the commercial potential of our innovative research.

Most contact lens wearers were excited about the prospect of using lenses as a platform for drug delivery.

Patients’ Pain Point

To understand the patient perspective and willingness to explore novel treatments, we interviewed two main groups of patients: those with eye infections and those with dry eyes, including both contact lens wearers and non-wearers.

As expected, the most common treatments described by patients for both conditions was topical. Compliance with eye drops was often low, with patients describing the main barriers to continued treatment being prolonged treatment duration, frequent application of eye drops, discomfort or pain during use, and the need to rely on others for administration.

The impact was highlighted by patients with a history of non-severe infections, such as keratitis and conjunctivitis, who on average, reported using eye drops at least four to six times per day. Notably, many patients were more concerned with the inconvenience of treatment than the cost, reflecting a frustration with the intensity, duration, and to a lesser extent, lack of long-term success of treatments. Accordingly, patients expressed a desire for preventative methods to reduce the risk of seasonal or recurrent eye infections.

Dry eye patients, in particular, voiced frustration over the lack of effective solutions, also describing cosmetic concerns, such as red eyes, making them appear angry or causing them to constantly frown and squint due to irritation and discomfort. Reflecting published literature, more than 60% of contact lens wearers had experienced symptoms of moderate dry eye and discomfort and requested more comfortable contact lenses.

With respect to the newly developed contact lens system for drug delivery in treating both infectious diseases and dry eye, patient feedback varied significantly based on their prior experience with contact lenses. Most contact lens wearers were excited about the prospect of using lenses as a platform for drug delivery. In contrast, those without experience were more hesitant, expressing concerns about the unfamiliarity of wearing lenses.

Professional Discussion

A range of industry stakeholders were interviewed including ophthalmologists, optometrists, and allied health clinicians. Interviewees shared concerns about using contact lenses in cases of infections and dry eye, due to the possible exacerbation of these conditions through wear. However, recognising the limitations of current treatments, healthcare professionals remained highly supportive in seeking innovative solutions, particularly for the promise of sustained drug release as a more effective and long-lasting alternative to traditional eye drops.

Market Validation

Early validation of this technology has shown significant promise in developing a versatile drug delivery platform for a range of medications, providing an expanded range of potential treatment options and meeting both patient and clinician expectations. Securing regulatory approval for a combined product like this – an ophthalmic medical device with integrated drug delivery – typically involves a more complex and rigorous process however the current PERIscope Commercialisation Award program has provided an excellent opportunity for the team to identify key stakeholders, understand their pain points and needs, and integrate these insights at an earlier stage in research and development.

Ms Yuan Fang is a PhD candidate at the University of Sydney, supervised by Dr Jingjing You. Her research explores the intersection of biomaterials engineering, eye care, and drug delivery systems.

Ms Fang’s academic journey began with a Bachelor’s degree in Anatomy and Histology, combined with Software Development, followed by an Honours degree in Cell and Biological Development. She was awarded the University of Sydney International Scholarship for her PhD, as well as the 2023 ARVO (Association for Research in Vision and Ophthalmology) Annual Meeting International Travel Grant and the PERIscope Commercialisation Award, furthering the impact of her research.

References

1. Aiello F, Afflitto GG, Nucci C, et al. Perspectives on the incidence of Acanthamoeba keratitis: A systematic review and meta-analysis. Ophthalmology. 2024 Aug 8:S0161-6420(24)00462-7. doi: 10.1016/j.ophtha.2024.08.003.
2. Stapleton F, Velez FG, Lau C, Wolffsohn JS. Dry eye disease in the young: A narrative review. Ocul Surf. 2024 Jan;31:11-20. doi: 10.1016/j.jtos.2023.12.001.
3. Lin CW, Lin MY, Lin IC, et al. Impact of dry eye disease treatment on patient quality of life. Front Med (Lausanne). 2024 Feb 28;11:1305579. doi: 10.3389/fmed.2024.1305579.
4. Bhujel B, Oh SH, Kim JY, et al. Current advances in regenerative strategies for dry eye diseases: A comprehensive review. Bioengineering (Basel). 2023 Dec 29;11(1):39. doi: 10.3390/bioengineering11010039.
5. Pucker AD, Yim TW, Conto JE, et al. LipiFlow for the treatment of dry eye disease. Cochrane Database Syst Rev. 2024 Feb 5;2(2):CD015448. doi: 10.1002/14651858.CD015448.pub2.
6. Roucaute E, Huertas-Bello M, Sabater AL. Novel treatments for dry eye syndrome. Curr Opin Pharmacol. 2024 Apr;75:102431. doi: 10.1016/j.coph.2024.102431.
7. Valdés-Arias D, Locatelli EVT, Galor A, et al. Recent United States developments in the pharmacological treatment of dry eye disease. Drugs. 2024 May;84(5):549-563. doi: 10.1007/s40265-024-02031-6.
8. Coco G, Buffon G, Taloni A, Giannaccare G. Recent advances in nanotechnology for the treatment of dry eye disease. Nanomaterials (Basel). 2024 Apr 12;14(8):669. doi: 10.3390/nano14080669.
9. Wu KY, Dave A, Carbonneau M, Tran SD. Smart contact lenses in ophthalmology: innovations, applications, and future prospects. Micromachines (Basel). 2024 Jun 30;15(7):856. doi: 10.3390/mi15070856.