Instillation Of Eye Drops Research Articles

Ocular Pharmacology.

Treatment of ocular diseases presents unique challenges and opportunities for the clinician and for the clinical pharmacologist. Ophthalmic pharmaceuticals, typically given as liquids, require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Ocular tissue levels are challenging to obtain in humans, and the clinical pharmacokinetics is typically blood levels, which are primarily related to safety, rather than efficacy. The eye is a closed compartment with multiple physiological barriers with esterases and transporters, but relatively little cytochrome oxidases. Delivery routes include topical, intravitreal, and systemic. Patient dosing involves not only adherence issues common to all chronic diseases, but also performance requirements on eye drop instillation. Therapeutically, ocular diseases and their pharmacological treatments include both those analogous to systemic diseases (e.g., inflammation, infection, and neuronal degeneration) and those unique to the eye (e.g., cataract and myopia).

Safety and Tolerability of Anti–microRNA-328 Ophthalmic Solution, SHJ002, in Pediatric Subjects: First-in-Human Clinical Study

microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children. This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability. There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as "unrelated to study drug." SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials. gov identifier: NCT04928144.

The Effect of Alternating Monocular Instillation of 0.125% Atropine in Korean Children with Progressive Myopia.

Objectives: To identify the effect of alternating monocular instillation (AMI) of 0.125% atropine in Korean children with progressive myopia. Methods: This retrospective single-center study included 120 children with progressive myopia. A total of 60 children (mean age 9.2 ± 2.0 years) wearing glasses who received AMI of 0.125% atropine for one year were allocated to the treatment group. The remaining 60 children (mean age 9.2 ± 1.9 years) with the same refraction, SE, and axial length (AL) who did not receive any treatments except for wearing glasses were allocated to the control group. Ocular findings and the progression rate were compared between the groups pre- and post-treatment, and adverse events were investigated in the treatment group. Results: The mean spherical equivalent (SE) at baseline was -3.87 ± 1.55 D in the control group and -3.90 ± 1.56 D in the treatment group. Pre-treatment SE, age, and AL were similar between the groups; however, post-treatment SE and AL changes were smaller in the treatment group (-0.36 ± 0.46 D/y, 0.21 ± 0.20 mm/year in the treatment group vs. -1.02 ± 0.57 D/y, 0.51 ± 0.20 mm/year in the control group) (Ps < 0.001). The pre-treatment progression rate diminished in the treatment group compared to the control group after one year (p < 0.001), and the changes in pupil size under mesopic and photopic conditions in the treatment group increased by 0.03 ± 0.05 mm and 0.76 ± 0.90 mm, respectively. Regarding adverse events, a tingling sensation was noted in two patients (3.3%) in the treatment group. Conclusions: Alternating monocular 0.125% atropine eye drop instillation may be effective and suitable for progressive myopia in Korean children.

An Investigation Into the Orthoptist Experience of Instilling Eye Drops in Children Attending the Eye Clinic.

Eye drops instillation in children is a fundamental part of accurately examining a child's eyes. Unfortunately eye drops can be a distressing experience for children, parents/guardians and orthoptists. The purpose of this research is to focus on the experiences of orthoptists and delve deeper into their views and explore if improvements can be made. This was a Qualitative study involving semi-structured interviews with 8 registered and currently practicing orthoptists in the UK. The interviews were undertaken online via Microsoft TEAMS. Thematic analysis was carried out for the purposes of data analysis. 3 major themes were identified (1) how orthoptist frame instilling eye drops, (2) techniques to address challenges, and (3) improvements to eye drops instillation process. Orthoptists were aware that instilling eye drops in children brought specific challenges such as distress and resistance; however they saw it as an essential part of their job. Orthoptists understood their role within a wider team which delivered eye care to children effectively and that there was a division of they believed that. Orthoptists were aware that the eye drops may cause some distress, however this did not affect compliance with treatment such as wearing glasses and/or a patch. Orthoptists believed verbal and non-verbal communication with the child was essential. Help was sought from parents or colleagues for physical restraint if required. Orthoptists suggested adapting to children with additional needs and giving out eye drops to parents/carers to instill at home if dilation in the eye clinic became difficult. They suggested improvements such as assistance from play specialists, developing a pre-procedural information video, practise as a student, the study of the medical exemptions module and the potential of using eye sprays instead of eye drops. The study reiterates the importance of verbal and non-verbal communication. The results may facilitate recommendations for change such as encouraging the study of medical exemptions and help support a case for play specialist support regularly, and the encouragement to develop a pre-procedural information video to improve quality of care. This is currently inconsistent across different Trusts in the UK. The study could result in improvements to current practise and influence other fields of medicine such as blood tests and MRI scans in children. The study also recommends further studies to investigate the parental perspective of instillation of eye drops in their child's eyes when they attend the eye clinic.

A supramolecular hydrogel eye-drop alleviates inflammation via clathrin-mediated endocytosis

The modulation of inflammation is effective to treat many ocular surface diseases. Thus the low bioavailability of common anti-inflammatory eye-drops urges the development of ocular drug delivery systems to extend the ocular retention and enhance the cellular uptake for improving anti-inflammatory effect of eye-drops. Here we covalently conjugate two molecules of clinically anti-inflammatory drug (i.e., dexamethasone) with a small peptide (i.e., Tyr–Glu–Asn–Pro–Thr–Tyr) to generate an anti-inflammatory hydrogel eye-drop. With a self-assembled ability, the designed supramolecular hydrogel achieves gel–sol–gel transition by varying shearing forces which increases the pre-corneal retention of drug. The fluorescent imaging reveals the efficient cellular uptake of designed conjugate via clathrin-mediated endocytosis. A rodent model of endotoxin-induced uveitis verifies that the supramolecular hydrogel eye-drop suppresses inflammation responses without ocular irritation. As a rational approach to design anti-inflammatory drugs as eye-drops, this work overcomes the frequent instillation of clinical eye-drops and further improves the bioavailability of anti-inflammatory drugs, which may provide an effective and household way to fight ocular surface inflammation.

Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress.

Several blinding diseases affecting the retina and optic nerve are exacerbated by or caused by dysregulated inflammation and oxidative stress. These diseases include uveitis, age related macular degeneration, diabetic retinopathy and glaucoma. Consequently, despite their divergent symptoms, treatments that reduce oxidative stress and suppress inflammation may be therapeutic. The production of inflammatory cytokines and their activities are regulated by a class of proteins termed Suppressors of Cytokine Signaling (SOCS). SOCS1 and SOCS3 are known to dampen signaling via pathways employing Janus kinases and signal transducer and activator of transcription proteins (JAK/STAT), Toll-like Receptors (TLR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen activated kinase (MAPK) and NLR family pyrin domain containing 3 (NLRP3). We have developed cell-penetrating peptides from the kinase inhibitory region of the SOCS1 and SOCS3 (denoted as R9-SOCS1-KIR and R9-SOCS3-KIR) and tested them in retinal pigment epithelium (RPE) cells and in macrophage cell lines. SOCS-KIR peptides exhibited anti-inflammatory, anti-oxidant and anti-angiogenic properties. In cell culture, both Th1 and Th17 cells were suppressed together with the inhibition of other inflammatory markers. We also observed a decrease in oxidants and a simultaneous rise in neuroprotective and anti-oxidant effectors. In addition, treatment prevented the loss of gap junction proteins and the ensuing drop in transepithelial electrical resistance in RPE cells. When tested in mouse models by eye drop instillation, they showed protection against autoimmune uveitis, as a prophylactic as well as a therapeutic. Mice with endotoxin-induced uveitis were protected by eye drop administration as well. R9-SOCS3-KIR was particularly effective against the pathways acting through STAT3, e.g. IL-6 and VEGF-A mediated responses that lead to macular degeneration. Eye drop administration of R9-SOCS3-KIR stimulated production of antioxidant effectors and reduced clinical symptoms in mouse model of oxidative stress that replicates the RPE injury occurring in AMD. Because these peptides suppress multiple pathogenic stimuli and because they can be delivered topically to the cornea, they are attractive candidates for therapeutics for uveitis, macular degeneration, diabetic retinopathy and glaucoma.

Eyedrop Instillation Technique by Medical Interns: Assessment and Impact of Video-Assisted Training

Abstract Aim: To assess the eyedrop instillation technique by medical interns, and to study the effect of video-assisted training. Methods: This was a hospital based prospective study performed on interns of teaching institute. First, interns were asked to instil the eye drops on volunteers which was video recorded. Interns were then given ‘video-assisted training’ (VAT) of correct technique and again reassessment was performed immediately, after one-week and one-month interval. All the recorded videos were evaluated by a single independent blinded expert and scored according to the scoring system devised by subject experts based on the available literature. The data were entered in Microsoft Office Excel and statistical analysis was performed. Results: The study showed that before training 43.80% had good practice with mean test score of 6.32 ± 1.63. Immediately after video-assisted training, there was significant improvement in technique of instilling eye drop with mean test score of 9.01 ± 0.62 (P &lt; 0.0001), after one week, the mean test score was 9.52 ± 0.71 (P &lt; 0.0001), and after one-month, mean test score was 9.56 ± 0.75 (P &lt; 0.0001). Each step of eyedrop instillation was compared before and after the VAT and the difference was found to be statistically significant (P value &lt; 0.05). Conclusion: In our current study, initially interns had practised incorrect technique of instillation of eyedrop. But after video-assisted training there has been notable improvement in the technique of instilling eyedrop. Periodic VAT might be helpful in ensuring them to follow the correct technique regularly.

Physiologically Based Pharmacokinetic Modeling and Clinical Extrapolation for Topical Application of Pilocarpine on Eyelids: A Comprehensive Study

Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases. To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.

Self-Lubricating, Living Contact Lenses.

The increasing prevalence of dry eye syndrome in aging and digital societies compromises long-term contact lens (CL) wear and forces users to regular eye drop instillation to alleviate discomfort. Here a novel approach with the potential to improve and extend the lubrication properties of CLs is presented. This is achieved by embedding lubricant-secreting biofactories within the CL material. The self-replenishable reservoirs autonomously produce and release hyaluronic acid (HA), a natural lubrication and wetting agent, long term. The hydrogel matrix regulates the growth of the biofactories and the HA production, and allows the diffusion of nutrients and HA for at least 3 weeks. The continuous release of HA sustainably reduces the friction coefficient of the CL surface. A self-lubricating CL prototype is presented, where the functional biofactories are contained in a functional ring at the lens periphery, outside of the vision area. The device is cytocompatible and fulfils physicochemical requirements of commercial CLs. The fabrication process is compatible with current manufacturing processes of CLs for vision correction. It is envisioned that the durable-by-design approach in living CL could enable long-term wear comfort for CL users and minimize the need for lubricating eye drops.

Retinal Neurodegeneration in an Intraocular Pressure Fluctuation Rat Model.

Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis.

Safety and Tolerability of KIO-101 Eye Drops in Healthy Volunteers and Patients with Ocular Surface Disease-A Phase I Study.

Inhibitors of dihydroorotate dehydrogenase (DHODH) have been found to be potent anti-inflammatory agents. Recently, a topical formulation (KIO-101 eye drops) of a DHODH inhibitor has been developed. The aim of the present study was to evaluate the safety and tolerability of KIO-101 eye drops in Healthy Volunteers (HVs) and patients with conjunctival hyperemia. The study was carried out in a double-masked, placebo-controlled, randomized, parallel-group design with two parts. In part I, HVs received single and multiple instillations (four times daily for 12 consecutive days) of KIO-101 eye drops in ascending doses of 0.05%, 0.15%, and 0.30%, respectively. Part II was conducted in patients with conjunctival hyperemia who received 0.15% KIO-101 eye drops twice daily for 12 consecutive days. Ophthalmic and systemic safety examinations were performed on all participants. In part II, ocular hyperemia grading and an ocular surface disease index (OSDI) questionnaire were performed. 24 HVs participated in part I and 21 patients in part II. KIO-101 eye drops were well tolerated in all subjects. No serious adverse events (SAEs) occurred, and all AEs that were reported were transient and considered mild to moderate. In the highest dose cohort (0.30%), epistaxis occurred in two subjects after multiple instillations. In part II, after 12 days treatment with 0.15% KIO-101, conjunctival hyperemia decreased by -1.1 ± 0.27 points in the treatment and -0.6 ± 0.79 points in the placebo group (p = 0.0385). OSDI decreased from 47.9 ± 18.7 to 27.6 ± 19.13 points in the treatment group, while in the placebo group, a change from 41.3 ± 12.08 to 27.3 ± 18.63 points occurred. A 12-day treatment regimen with topical KIO-101 eye drops at low and mid doses was safe and well tolerated in both HVs and patients with conjunctival hyperemia. The obtained results point towards an early sign of reduction in conjunctival hyperemia.

Self-Implantable Core-Shell Microneedle Patch for Long-Acting Treatment of Keratitis via Programmed Drug Release.

Bacteria-induced keratitis is a major cause of corneal blindness in both developed and developing countries. Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., <5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self-implantable core-shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH-responsive antimicrobial nanoparticles (NPs), Ag@ZIF-8, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti-angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF-8 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core-shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti-angiogenic and anti-inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics.

Novel Drug Delivery Systems for the Management of Fungal Keratitis.

Fungal keratitis (FK) is a dangerous corneal infection that is common in tropical and subtropical areas. Its incidence is extremely high, and ocular trauma and contact lenses can lead to FK, but its common treatment such as using topical antifungal eye drop instillation is often less effective because of several drawbacks of the drugs typically used, including limited ocular penetration, high frequency of dosing, poor biocompatibility, and the potential for severe drug reactions. Therefore, the development of novel drug delivery devices for the treatment of FK is urgent. The urgent need for novel drug delivery devices to treat FK has led to the development of several techniques, including nanoparticles (NPs), in situ forming hydrogels, contact lenses, and microneedles (MNs). However, it is important to note that the main mechanisms differ between these techniques. NPs can transport large amounts of drugs and be taken up by cells owing to their large surface area and small size. In situ forming hydrogels can significantly extend the residence time of drugs because of their strong adhesive properties. Contact lenses, with their comfortable shape and drug-carrying capacity, can also act as drug delivery devices. MNs can create channels in the cornea, bypassing its barrier and enhancing drug bioavailability. This article will go over novel medication delivery techniques for treating FK and make a conclusion about their advantages and limitations in anticipation to serve the best option for the individual therapy of FK.

Myopia progression following 0.01% atropine cessation in Australian children: Findings from the Western Australia - Atropine for the Treatment of Myopia (WA-ATOM) study.

A rebound in myopia progression following cessation of atropine eyedrops has been reported, yet there is limited data on the effects of stopping 0.01% atropine compared to placebo control. This study tested the hypothesis that there is minimal rebound myopia progression after cessation of 0.01% atropine eyedrops, compared to a placebo. Children with myopia (n = 153) were randomised to receive 0.01% atropine eyedrops or a placebo (2:1 ratio) daily at bedtime during the 2-year treatment phase of the study. In the third year (wash-out phase), all participants ceased eyedrop instillation. Participants underwent an eye examination every 6 months, including measurements of spherical equivalent (SphE) after cycloplegia and axial length (AL). Changes in the SphE and AL during the wash-out phase and throughout the 3 years of the study (treatment + wash-out phase) were compared between the treatment and control groups. During the 1-year wash-out phase, SphE and AL progressed by -0.41D (95% CI = -0.33 to -0.22) and +0.20 mm (95% CI = -0.46 to -0.36) in the treatment group compared to -0.28D (95% CI = 0.11 to 0.16) and +0.13 mm (95% CI = 0.18 to 0.21) in the control group. Progression in the treatment group was significantly faster than in the control group (p = 0.016 for SphE and <0.001 for AL). Over the 3-year study period, the cumulative myopia progression was similar between the atropine and the control groups. These findings showed evidence of rapid myopia progression following cessation of 0.01% atropine. Further investigations are warranted to ascertain the long-term effects of atropine eyedrops.

The effects of self-video feedback on the eyedrop instillation techniques of glaucoma patients: a prospective randomized controlled trial

BackgroundTo evaluate the effectiveness of instillation technique education using self-video feedback in glaucoma patients.MethodsSixty-two patients who self-instilled glaucoma eyedrops were randomly assigned to the self-video feedback and control groups according to the block randomization. Each group of the patient was asked to instill eyedrops, and videos were recorded. For the control group, only an educational video was provided. In the self-video feedback group, the patients provided educational video and feedback using a recorded video of their own instillation. After 1 month of education, the patient's instillation techniques were video-recorded again. We divided the steps of instilling eyedrops into ten steps and evaluated whether each step was properly performed using the recorded images from each patient. The main outcome was the proportion of patients who properly instilled their eyedrops in each step.ResultsBefore education, there was no significant difference in the proportion of patients who were properly instilled between the two groups. In the group that received video feedback, the proportion of patients who instilled the eyedrops correctly after education in some items was significantly higher than that of the control group, and in particular, the educational effect of 'avoids touching dropper to eyelid or eyelash' was superior.ConclusionsIn patients with glaucoma, education on the method of instillation was effective in improving the techniques of instillation. In the items that required accurate actions, the video feedback that allowed the patient to observe themselves had a better improvement effect compared to the traditional education method.Trial registration numberKCT0008090 (09/01/2023, retrospectively registered).

Retinal neurodegeneration in intraocular pressure fluctuation rat model

Aims/Purpose: The role of IOP fluctuation is controversial in development and progression of glaucoma in clinical trials. We investigated effects of intraocular pressure fluctuation on retinal neurodegeneration and their mechanisms in rats.Methods: Male Sprague–Dawley rats were treated with IOP‐lowering eyedrops (brinzolamide and latanoprost) or saline for 8 weeks. IOP‐lowering eyedrops were put on Monday and Thursday for the irregular instillation group or daily for the regular instillation group, and saline was put daily for the control group. IOP was measured daily under general anaesthesia using a rebound tonometer. Oxidative stress, reaction of microgliosis and the number of retinal ganglion cells (RGCs) were measured.Results: Mean IOP was lower both in the irregular instillation group (9.6 ± 0.4 mmHg) and the regular instillation group (9.5 ± 0.4) than the control group (10.1 ± 0.4 mmHg, p &lt; 0.001). Standard deviation (SD) of IOP was higher in the irregular instillation group (0.8 ± 0.1 mmHg) than the regular instillation group (0.5 ± 0.1 mmHg) or the control group (0.6 ± 0.3 mmHg, p &lt; 0.001). Oxidative stress measured by dihydroethidium, oxidative DNA damage exhibited by 8‐hydroxy‐2′‐deoxyguanosine, and immunostaining for nitrotyrosine were upregulated (All p &lt; 0.001). Expression of glial fibrillary acidic protein in the optic nerve head was more increased in irregular instillation group than the control group, but not in the regular instillation of eyedrops (p = 0.001). Expression of anti‐ionized calcium binding adaptor molecule (Iba‐1), a marker for microglia and P2Y12 known as a chemotactic receptor for microglia did not show a significant difference between the irregular instillation group and the control group. Expression of cleaved caspase‐3 was greater in the irregular instillation group than other two groups (p &lt; 0.001). The number of RGCs stained with anti‐Brn3a antibody was lower in the irregular instillation group than other two groups (p = 0.002).Conclusions: IOP fluctuation induced by treatment of irregular instillation of IOP‐lowering eyedrops reduced the number of RGCs. Our findings indicate that IOP fluctuation induced by treatment of irregular instillation of IOP‐lowering eyedrops could lead to degeneration of RGCs probably by increasing oxidative stress and microgliosis.

Evaluation of Self-Competence in Eye-Drop Instillation in Healthy Young Adults

Aim: To evaluate the ability of self-instillation of eye drops in healthy adults. Methods: Participants who are older than 18 years old with no ocular or systemic pathologies were included in the study. All subjects underwent a complete ophthalmological evaluation including best corrected visual acuity (BCVA), intraocular pressure measurement, anterior and posterior segment examinations. Participants were given a 5 ml bottle of sodium hyaluronate 0.15% (Dryex, Abdi Ibrahim, Turkiye) and were instructed to install one drop to each eye. Dominant hands of the participants were noted and eye-drop instillation was evaluated for each eye. Success was defined as putting one drop on the ocular surface, not touching the bottle tip to surrounding tissues nor to the ocular surface, and not putting more than one drop. Results: A total of 50 participants, 27 (54%) female and 23 (46%) male were included in the study. The mean age was 28.0±8.1 (18-40) years, and the mean best corrected visual acuity (Snellen) was 1.0 (all participants had 20/20 visual acuity). The number of participants who managed to instill the eye-drop to both eyes successfully was 13 (26%). When both eyes were encountered, the rate of he successful ability to instill at least 1 drop was 62%, bottle tip touch was 39%, and more than one drop flow was 27%). Conclusion: The success rate of self-using of eye drops is lower than expected (26%) in healthy young adults, and patient education on eye-drop instillation might be a necessity for every patient.

IMPACT OF BODY POSITION AND ARM USE ON EYE DROP INSTILLATION IN OLDER ADULTS

Abstract Visual impairments in older adults are associated with declines in physical, cognitive and social functioning, often leading to a loss of independence and quality of life. Increased age is a major risk factor, with conditions such as glaucoma having a 7-fold increase in prevalence from the 50s to the 80s (Klein &amp; Klein, 2013). Treatment in the form of eye drops is commonly prescribed yet suboptimal adherence can significantly impact outcomes (Newman-Casey et al., 2015). The purpose of this preliminary study was to determine the effects of body posture and hand use on eye drop instillation success in a sample of 20 healthy, non-eye drop users (mean age: 70.0 +/- 3.7 y). Participants administered eyes drops without instruction while seated, standing and in a supine position. Video analysis was used to determine the number of attempts before successful instillation occurred (failed attempts) as well as whether participants used one or two hands. Despite published recommendations to use both hands (Davis et al, 2018), only 65% adopted a bimanual approach. The percentage of failed attempts was lowest in the supine (11.6%) compared to the seated (25.7%) or standing (21.2%) positions. Pinch strength was not correlated with successful instillation as has been previously reported (Naito et al., 2021), possibly due to participants’ overall level of physical functioning. Based on these results, a supine position is recommended for eye drop instillation where the head and neck are stabilized.

Exploring Cell-Penetrating Peptides as Penetration Enhancers in Eye Drop Formulations Using a Reconstructed Human Corneal Epithelial Model.

Ocular tissues function as biological barriers that hinder drug delivery, depending on the target tissue and route of administration, and must be overcome to achieve the desired therapeutic effect. Penetration enhancers have long been investigated to improve corneal drug penetration via eye drop instillation; however, further development is warranted owing to potential safety concerns. In the present study, we focused on cell-penetrating peptides (CPPs) as a penetration enhancer to address the requirements and explored CPP candidates suitable for corneal drug delivery. Using a reconstructed human corneal epithelial tissue model, LabCyte CORNEA-MODEL24 as an alternative to animal testing that is expected to have higher reproducibility than extracted eyeballs and octa-arginine (R8) as a representative model CPP with simple structure, we investigated the enhancement of 6-carboxyfluorescein (6-FAM) uptake by fluorescence imaging and the potential of eye irritation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Also, surface plasmon resonance (SPR) evaluated the interaction between R8 and model compounds, suggesting that the stronger interaction could facilitate the corneal uptake of compounds. A comparative screening study of corneal uptake using various CPPs showed that the CPPs other than R8 also have the potential to enhance the corneal uptake of 6-FAM. In particular, penetratin (PNT) showed stronger fluorescence intensity. Through these findings, this manuscript provides beneficial information for the development of a novel corneal penetration enhancer with CPPs. In the future, it is expected that the basic findings with R8 will be verified to be applicable to other CPPs for development as penetration enhancers for eye drop formulation.

Usability of an Eye Drop Delivery Aid for Single-Dose Instillation: Results from a Market Research Study.

One of the challenges of treating chronic ocular diseases like vernal keratoconjunctivitis (VKC), glaucoma, and ocular surface disease is patient adherence to topical medication. To support correct eye drop instillation, a variety of delivery aids have been developed for both single-dose and conventional multi-dose containers. To evaluate Dropaid™ Single-dose, an eye drop delivery aid designed for single-dose containers, a usability study was conducted on 30 parents and caregivers of patients with VKC. After assessing the ability to squeeze a single eye drop from the single-dose container onto the eye of a pediatric medical dummy, the delivery aid was evaluated using an 11-point Likert scale on a variety of characteristics: from "very difficult" (-5) to "very easy" (+5). The majority of participants rated the task of opening the single-dose units (SDUs), preparing, and positioning the Dropaid™ Single-dose device as "very easy". When providing a single eye drop from the container, 87% of participants rated the Dropaid™ Single-dose device as either "very easy" or "easy", with a median rating score of +5.0 (interquartile range [IQR], 4.0-5.0). For general ease of use, 84% considered the delivery aid as either "very easy" or "easy", with a median score of +4.0 (IQR, 3.0-5.0). Most participants (93%) rated Dropaid™ Single-dose as either "very comfortable" or "comfortable" to hold, with a median score of +5.0 (IQR, 4.0-5.0). The Dropaid™ Single-dose delivery aid demonstrated rapid learning and ease of use across all stages of application, including opening the container, eye drop administration, and handling comfort. Although designed for use with single-dose containers to help eye drop instillation in patients with VKC, Dropaid™ Single-dose may provide a wider utility across a range of other ocular diseases such as glaucoma and dry eye.