In the field of ophthalmology, precision and accuracy are of paramount importance when it comes to delivering medication to the delicate tissues of the eye. Traditional eye drop delivery methods have their limitations, often leading to inconsistent dosages and wastage. Piezoelectric eye drop delivery systems could theoretically offer precise, controlled, and touchless administration of medication. Piezoelectric materials have a unique property where they generate an electric charge when subjected to mechanical stress or pressure.

Advantages:

1. Precise and controlled dosage administration
2. Minimize contamination and wastage
3. Improved patient experience and compliance to eyedrops

One of the potential main advantages of piezoelectric eye drop delivery systems is their ability to provide precise and controlled dosage administration. The mechanical pressure applied to the piezoelectric material causes it to generate an electric charge, triggering the release of eye drops. This mechanism allows for accurate and consistent dosage delivery, reducing the risk of over or under medication. With traditional eye drop methods, variations in hand pressure or technique often lead to imprecise dosage, compromising the effectiveness of treatment. Overflow of the eyedrops to the surrounding structures (e.g. eyelids, eyelashes) can cause local irritation and discomfort for patients. There is also greater risk of the medication unevenly distributing to the nasolacrimal duct, which facilitates the draining of the ocular surface into the nasal passage, potentially leading to systemic absorption of the compounds inside the eyedrops, which may lead to more side-effects.

Another significant advantage of piezoelectric eye drop delivery systems is their potential to minimize contamination and wastage. Conventional eye drop bottles are prone to contamination as they come into contact with the eye’s surface, skin, and eyelashes. Additionally, the imprecise squeeze and dropper mechanisms of traditional methods often result in excessive drops being dispensed, leading to wastage. A major portion of each conventional eyedrop administered is blinked out and drained into the nasolacrimal duct system (a small drainage system connects the eye to the nose). Piezoelectric systems address these issues by offering a touchless delivery method that eliminates contamination risk and ensures efficient drug utilization. This not only enhances patient safety but also reduces overall healthcare costs.

Piezoelectric eye drop delivery systems also offer an improved patient experience compared to traditional methods. When using conventional eye drops, the patient has to incline the face almost 90° to ensure that the eye drops are administered into the eyes under gravity – this is very physically difficult for some people, especially the elderly, and especially when multiple drops are needed per day. Piezoelectric systems allow the patient to be upright during eyedrop administration. Further, the touchless and precise nature of the technology eliminates the need for direct contact with the eye, making it more comfortable for patients, especially those with sensitive or compromised ocular tissues. Moreover, the controlled release mechanism reduces the sensation of an excessive liquid flow, making the process less intrusive and more pleasant.

In summary, piezoelectric eye drop delivery systems have the potential to optimise corneal care in several ways:

1. Treatment of Ophthalmic Diseases: Conditions such as dry eye syndrome, corneal infections, and glaucoma often require frequent and precise administration of medications. Piezoelectric devices can enhance the efficacy of these treatments by ensuring consistent and accurate dosing, leading to improved outcomes for patients.
2. Post-Surgical Recovery: Following corneal surgeries, patients often need to self-administer eye drops for an extended period. Piezoelectric delivery systems can simplify this process, reducing the likelihood of mistakes and enhancing the overall recovery experience.
3. Research and Development: The ability to precisely control the dosage and delivery of medications opens up new possibilities for researchers studying corneal diseases. Piezoelectric systems can facilitate the development of innovative therapies, targeted drug delivery strategies, and improved understanding of drug interactions with the cornea.

Figure 1: An example of a piezo-electric eyedrop delivery device, discussed in further depth by Pasquale et. al (1). Reproduced via Open Access.

Sounds great. What’s the catch? More research is needed … it will take a while until these device systems become mainstream.

References:

1. Pasquale LR, Lin S, Weinreb RN, et al. Latanoprost with high precision, piezo-print microdose delivery for IOP lowering: clinical results of the PG21 study of 0.4 µg daily microdose. Clin Ophthalmol 2018;12:2451-7.
2. Yao G, Mo X, Liu S, et al. Snowflake-inspired and blink-driven flexible piezoelectric contact lenses for effective corneal injury repair. Nature Communications 2023;14:3604.
3. Shaukat H, Ali A, Bibi S, et al. A Review of the Recent Advances in Piezoelectric Materials, Energy Harvester Structures, and Their Applications in Analytical Chemistry. Applied Sciences 2023;13:1300.

Acanthamoeba Keratitis

Acanthamoeba is a genus of single-celled amoeba commonly found in water and soil environments. Some species of Acanthamoeba are also capable of causing infections in animals. Some species of Acanthamoeba are also capable of causing serious infections in humans, including brain infections, skin infections, and acanthamoeba keratitis (an eye infection that targets the cornea). Acanthamoeba keratitis affects the cornea and can cause significant pain, redness, blurred vision, sensitivity to light, and the sensation of something in the eye. It is most common in people who wear contact lenses, but anyone can get the infection. It is so painful because the outermost surface of the cornea is exquisitely sensitive – it has a nerve density that is 300–600 times that of the skin! (1). To prevent this relatively rare infection, it is so important to practice good hygiene, especially when handling contact lenses. Never use tap water on your contact lenses, because acanthamoeba can be found in tap water. Acanthamoeba can also survive in chlorinated swimming pools (2) so protecting your contact lenses with goggles if you cannot take them off completely is a good idea. If left untreated, acanthamoeba keratitis it can lead to corneal ulcers, serious vision loss and even blindness. Treatment involves the use of anti-amoebic medications and may also include surgical removal of infected tissue. Early diagnosis and prompt treatment are crucial for the best outcome – seek eye care urgently.

Bottom Image: Corneal melting and new inflammatory growth of blood vessels in a patient with Acanthamoeba keratitis. They lost vision in this eye. Reproduced via open access (3)

References

1. Zander E, Weddell G. Observations on the innervation of the cornea. J Anat. 1951;85(1):68-99.
2. Kaji Y, Hu B, Kawana K, Oshika T. Swimming with soft contact lenses: danger of acanthamoeba keratitis. The Lancet Infectious Diseases. 2005;5(6):392.
3. Lorenzo-Morales J, Khan NA & Walochnik J: An update on Acanthamoebakeratitis: diagnosis, pathogenesis and treatment. Parasite, 2015, 22, 10.

Gene therapy describes the introduction of normal genes into cells in place of missing or defective ones in order to correct genetic disorders. Gene therapy in ophthalmology has made significant advances in recent years, with numerous clinical trials showing promising results. The eye is considered a good candidate for gene therapy; it is small and compartmentalised, requires relatively small numbers of vectors/gene copies, and has special immune response features that can be favourable for gene therapy (1). Some of the key advancements in this field include:

1. Treatment for corneal dystrophies: Corneal dystrophies are a group of inherited disorders that cause progressive clouding of the cornea, leading to vision loss. Gene therapy approaches aim to replace or repair the defective gene responsible for the disease. 
2. Treatment for Retinal Diseases: Gene therapy has shown promising results in the treatment of retinal diseases such as age-related macular degeneration, retinitis pigmentosa, and Leber congenital amaurosis. Gene therapy has shown to restore vision and improve visual acuity in patients with these conditions.
3. CRISPR-Cas9 Technology: CRISPR-Cas9 technology has allowed for precise and efficient editing of specific genes, making it a powerful tool for gene therapy in ophthalmology. This technology has been used to correct mutations that cause retinal diseases, leading to improved visual function.
4. Viral Vectors: Lentiviral and adeno-associated virus (AAV) vectors have also become a popular tool in gene therapy for ocular diseases due to their ability to efficiently deliver therapeutic genes to the retina. AAV vectors in particular have been used to deliver genes to treat conditions such as retinitis pigmentosa, choroideremia, and Stargardt disease.
5. Improved Delivery Methods: Advances in delivery methods, such as the use of subretinal injections and intravitreal injections, have improved the delivery of therapeutic genes to the retina, resulting in more effective treatment of retinal diseases.

One type of gene therapy for ophthalmology has already been approved by the United States Food and Drug Administration (FDA) to treat paediatric patients with a retinal condition called Leber congenital amaurosis who have a deficiency in the RPE65 gene (2). The RPE65 gene provides instructions for making a protein called RPE65, which is involved in the production of a molecule called 11-cis-retinal, an essential component of the visual cycle that allows people to process light.

References:

1. Bennett J. Immune response following intraocular delivery of recombinant viral vectors. Gene Ther. 2003;10(11):977-82.
2. Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390(10097):849-60.