Drop Instillation 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.

Evaluation of lidocaine for auriculopalpebral nerve block in dogs: Onset, duration, and effects on intraocular pressure and eye examination.

Accurate intraocular pressure (IOP) measurement is essential for managing glaucoma, requiring tonometry. Local anesthesia is typically used, but nerve blocks may be needed for blepharospasm. This study investigated the efficacy of auriculopalpebral nerve block with lidocaine in achieving eyelid akinesia and its influence on IOP in dogs. In a randomized, blinded trial, 12 healthy adult mixed-breed dogs (24 eyes) received either auriculopalpebral nerve block with 2% lidocaine (n = 12 eyes) or no block (n = 12 eyes). Tetracaine drops were used for topical anesthesia in half of blocked/non-blocked eyes, and the rest of the eyes got artificial tears as control. The impact of nerve block was evaluated through assessments of menace response, palpebral reflex, and IOP before the block, after drop instillation, and at 15-min intervals until block dissipation. Auriculopalpebral nerve block provided effective eyelid akinesia in 58.5% (7/12 eyes) at 15 min, reaching 91.7% (11/12 eyes) at 30 min, indicating peak efficacy. Subsequently, the block gradually diminished, with 66.7% (8/12 eyes) and 33.3% (4/12 eyes) maintaining akinesia at 45 and 60 min, respectively. Importantly, neither auriculopalpebral nerve block nor tetracaine administration significantly affected IOP measurements (p > .05). Auriculopalpebral nerve block using lidocaine demonstrated efficient eyelid akinesia, peaking at 30 min postinjection. This technique proved to be safe with no notable alterations in IOP, suggesting its potential utility in canine ophthalmology for procedures requiring eyelid akinesia, particularly in the management of glaucoma where maintaining accurate IOP measurements is crucial for diagnosis, treatment, and monitoring the disease.

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.

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.

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.

Netarsudil 0.02% Alters Episcleral Venous Flowrates: A Clinical Trial Using Erythrocyte-Mediated Angiography

ObjectiveTo characterize the effect of netarsudil 0.02% on episcleral blood flow in treatment naïve glaucoma suspect or ocular hypertension subjects. DesignProspective, unmasked, single-arm cohort study. ParticipantsTen treatment-naïve patients with a diagnosis of glaucoma suspect or ocular hypertension. MethodsErythrocyte mediated angiography (EMA) was used to measure episcleral erythrocyte velocity, vessel diameter, and blood flow at baseline before treatment, 1 hour after drop instillation (T1), 1 to 2 weeks after daily netarsudil 0.02% drop use (T2), and 1 hour after drop instillation at the 1-to-2-week timepoint (T3). Intraocular pressure (IOP) and blood pressure were measured at each visit. Main outcome measuresChange in episcleral venous erythrocyte velocity, diameter, and blood flow between timepoints analyzed using generalized estimating equation (GEE) models. ResultsOf the 18 eligible study eyes of 10 enrolled treatment-naïve subjects, baseline IOP was 16.8±3.6mmHg (mean±SD), which significantly decreased to 13.9±4.2mmHg at T1, 12.6±4.1mmHg at T2, and 11.8±4.7mmHg at T3 (p<0.05 at each timepoint compared to baseline). Episcleral vessels averaged 61.3±5.3μm in diameter at baseline which increased significantly at all post-treatment timepoints (78.0±6.6, 74.0±5.2, 76.9±6.9 μm, respectively; mean±SD, p<0.05 for each timepoint). Episcleral venous flowrates were 0.40±0.22 uL/min (mean±SD) at baseline, which increased significantly to 0.69±0.45 uL/min at T1 (p=0.01), did not significantly differ at T2 (0.38±0.30 uL/min), and increased significantly to 0.54±0.32 uL/min at T3 (p<0.05 compared to baseline and T2). ConclusionsNetarsudil causes episcleral venous dilation at all timepoints and resulting increases in episcleral venous flowrates one hour after drop instillation. Increased episcleral venous flow, associated with decreased episcleral venous pressure (EVP), may result in lowered IOP.

Efficacy ofhydroxypropyl-guar dropsin improving tear film index and ocular surface dynamicsusing two treatment methods under a controlled desiccating environment.

This study aimed to assess the efficacy of hp-guar eye drops on tear film index and ocular surface dynamics under desiccating conditions using protection and relief treatment modalities. The 12 normal, non-dry eye participants were subjected to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21°C. The participants were screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST), tear production using the Ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and Schirmer strips. Tear production was calculated by the Tear Function Index test (TFI). The mean tear film osmolarity decreased significantly from 296mOsm/L at 40% RH to 285mOsm/L at 5% RH (p = 0.01). Conflicting responses were seen for osmolarity in protection and relief. Mean tear osmolarity was significantly higher in the protection method in comparison to the relief method (p = 0.005). The mean TFI increased from 557 at 40% to 854 at 5% (p = 0.02). A significant increase in TFI was observed in the relief method in comparison with both 40% (p = 0.001) and 5% (p = 0.04). In the relief method, the mean TFI score went up to 1139 when hp-guar was installed. A significant improvement in ocular comfort was experienced in both the protection (p = 0.041) and relief (p = 0.010) methods at 5% RH. The instillation of hp-guar drops in the relief method resulted in a significant reduction in OST. The mean OST dropped to 33.01 ºC, significantly lower than the recorded OST for both normal (p = 0.040) and dry (p = 0.014) environmental conditions. Hp-guar drops significantly improve tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, an improvement in tear production and a decrease in ocular surface temperature were seen. Hp-guar performance could be maximized for the management of exposure to adverse environments by using a treatment protocol that targets the most affected parameters in each group of patients. Using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.

Enhancing the Technique of Eye Drop Administration through Evaluation and Education: A Quality Improvement Initiative

Purpose: To evaluate the eye-drop administration technique and see the effect of education in improving the eye drop delivery method. Study Design: Interventional case series. Place and Duration of Study: Central Park Teaching Hospital Lahore from May-2022 to September-2022 Methods: This study includes 341 patients who had been self-administering eye drops as a treatment for glaucomaor any other disorder. The patients were asked to instill the drop by using a 5ml Systane bottle, as they should do at home. Two observers assessed the technique. Patients were educated about the techniques and they were re-assessed in the form of a post-test. They were evaluated by the same observers again. Data was analyzed suing Fisher’s Exact test. Results: A significant improvement was observed in several parameters, including the mean time (in seconds) taken to instill the first drop, the number of drops squeezed, the number of drops reaching the conjunctival sac at the first attempt, hand washing, shaking the bottle before instillation, tilting the head backwards during drop instillation, and the occurrence of drops falling on the cheek (p ≤ 0.05). Conversely, statistically insignificant improvements were noted in parameters such as touching the tip of the dropper and closing the eye for a minute. Conclusion: The findings underscore the importance of enhancing patient education regarding the correct technique for drop instillation.

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.

The Short-term Effects of Artificial Tears on the Tear Film Assessed by a Novel High-Resolution Tear Film Imager: A Pilot Study.

The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device. The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant. For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA ( P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline. We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient.

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.

Antioxidant insights of wild olive (acebuche) oil ophthalmic nanoemulsions against arterial hypertension

Aims/Purpose: Many systemic and ocular disturbances are closely related to oxidative stress, including hypertensive eye diseases. In this context, the oral administration of wild olive oil, also known as acebuche (ACE) oil (Olea europaea var. sylvestris), proved to modulate local production of reactive oxygen species (ROS) by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase1. Here we aimed to develop an ophthalmic formulation based on ACE oil as a localized therapy against oxidative damage associated with arterial hypertension (AH).Methods: Nanoemulsions (NEs) of ACE oil were successfully produced, characterized, and evaluated in vivo in terms of efficacy. The antioxidant properties of these NEs were tested in mice with AH induced via administration of Nω‐nitro‐L‐arginine‐methyl‐ester (L‐NAME), which underwent intravitreal or topical ophthalmic treatment with ACE oil NEs. At the end of the treatments, a histological analysis of the cornea and retina was performed together with an evaluation of the activity/expression of NADPH oxidase in these ocular tissues.Results: Adequate ophthalmic formulations were designed to present the features for ophthalmic administration, including a nanometre size (below 200 nm), moderate negative ZP, adequate osmolality and pH, among others. Histological analysis indicated that NEs reduced hypertension‐dependent morphological alterations in the cornea and retina. Furthermore, the evaluation of the activity and expression of NADPH oxidase suggest a noticeable antioxidant effect of NEs through downregulation of NOX1, NOX2 and NOX4 isoforms and counteracting excess ROS production in the hypertensive eye.Conclusions: Topical administration, via intravitreal or drop instillation, of an ophthalmic formulation based on ACE oil NEs might show promise against ocular pathologies related to AH. Interestingly, this therapeutical approach provided better outcomes compared to long‐term dietary administration of the oil, both in terms of cumulative dose and treatment time required.

Role of corneal sensory nerves in tearing and blinking

The cornea is innervated trigeminal neurons classified in three different functional types: polymodal nociceptor, mechano‐nociceptor and cold thermoreceptor neurons. Corneal sensory nerves are responsible of the conscious sensations evoked by corneal stimulation, and are also involved in the trophic maintenance of the tissue. Besides, corneal nerve activity is also involved in the regulation of the protective functions of the ocular surface such as tearing and blinking.Regulation of reflex and basal tearing is integrated at the brainstem and, in both cases, under the influence of the sensory inflow provided by several types of corneal sensory nerves. While reflex tearing is induced selectively by the stimulation of corneal polymodal nociceptors, basal tearing rate depends on the spontaneous activity of cold thermoreceptors. Thus, when cold thermoreceptors are silenced by environmental warming, basal tearing is compromised.Voluntary, reflex and spontaneous (basal) blinking present differences in their characteristics and regulation mechanisms. Voluntary blinking depends on the direct instructions generated at the brain cortex, acting over the motor neurons located at the facial nucleus. Reflex blinking is integrated at the brainstem, being induced by the stimulation of the cornea and periocular skin, and even by loud sounds. Spontaneous blinking is claimed to be controlled by a CNS centre that established a blinking pattern. This pattern is modified under different conditions such as cognitive activity, being for example reduced during visual attentional tasks in order not to lose relevant visual information. When the activity of corneal cold thermoreceptors is abolished or reduced by ocular instillation of local anaesthetics, the frequency and characteristics of the spontaneous blinking is not modified. However, when the activity of cold thermoreceptors is increased for prolonged periods (for instance after topical instillation of F6H8 drops, which reduces the ocular surface temperature), blinking pattern become more regular and an increased number of blinks of larger the amplitude and shorter duration are induced. This increased blinking frequency produced when the activity of cold thermoreceptors is increased is sufficient to even counteract the reduction of blinking frequency induced during visual tasks performance. The increase in blink frequency driven by corneal cold thermoreceptors' activation may constitute a protective mechanism to prevent excessive desiccation of the ocular surface.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)

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.

The influence of topical anesthetic and fluorescein on non-contact tonometry measurements using ultra-high-speed dynamic Scheimpflug

This study aimed to investigate the effects of topical anesthetic and fluorescein drops on intraocular pressure (IOP), central corneal thickness (CCT) and biomechanical properties as measured by Corvis ST (CST-Oculus; Wezlar, Germany) in healthy eyes. A cross-sectional observational study was conducted on 46 healthy patients. The CST measurements were obtained before and immediately after the instillation of topical anesthetic and fluorescein drops. Pre-post instillation data were statistically analyzed. IOP measurements were compared to Goldmann's Applanation Tonometry (GAT), which was also performed after drops instillation. Biomechanical parameters analyzed included applanation 1 velocity, applanation 2 velocity, applanation 1 time, applanation 2 time, whole eye movement, deflection amplitude, and stiffness parameter at first applanation. A statistically significant difference in IOP, both for non-corrected IOP (IOPnct) and biomechanically corrected IOP (bIOP), was observed before and after the instillation of eyedrops. Despite this statistical significance, the observed difference lacked clinical relevance. The IOPnct demonstrated a significant difference pre and post-anesthetic and fluorescein instillation compared to GAT (14.99 ± 2.27 mmHg pre-instillation and 14.62 ± 2.50 mmHg post-instillation, versus 13.98 ± 2.04 mmHg, with p-values of 0.0014 and 0.0490, respectively). Comparable findings were noted when justaposing bIOP to GAT (14.53 ± 2.10 mmHg pre-instillation and 13.15 ± 2.25 mmHg post-instillation, against 13.98 ± 2.04 mmHg, with p-values of 0.0391 and 0.0022, respectively). Additionally, CCT measurements revealed a statistically significant elevation following the administration of topical anesthetic and fluorescein drops (from 544.64 ± 39.85 µm to 586.74 ± 41.71 µm, p < 0.01. None of the analyzed biomechanical parameters showed statistically significant differences after drops instillation. While the administration of topical anesthetic and fluorescein drops induced a statistically significant alteration in both IOPnct and bIOP readings, these changes were not clinically consequential. Furthermore, a notable statistical rise was observed in CCT measurements post-drops instillation, as determined by CST. Yet, corneal biomechanical parameters remained unaffected.

The effects of non-prostaglandin hypotensive drops with preservative on central retinal thickness after phacoemulsification

BACKGROUND: Primary open angle glaucoma is often associated with cataract. The correlation between the use hypotensive drops, in particular non-prostaglandin hypotensive drops with preservative, and the change in central retinal thickness after phacoemulsification with intraocular lens implantation continues to be relevant.&#x0D; AIM: To evaluate central retinal thickness and pseudophakic cystoid macular edema incidence after phacoemulsification with intraocular lens implantation in patients with primary open-angle glaucoma using non-prostaglandin hypotensive drops with preservatives.&#x0D; MATERIALS AND METHODS: 94 patients (108 eyes) with cataract were enrolled in the study, divided into 3 groups: the first group 21 patients (27 eyes), and the second group 21 patients (23 eyes) with primary open-angle glaucoma using non-prostaglandin hypotensive drops with preservative; the third (control) group included 52 patients (58 eyes) without ocular comorbidities. All patients underwent uncomplicated phacoemulsification with intraocular lens implantation. In the post-op period, patients of the first group received topical antibiotics and steroids, patients of the second and the third groups received the same treatment and non-steroidal anti-inflammatory drops as well. Central retinal thickness was measured using optical coherence tomography before surgery, 2 weeks, 2 and 6 months after surgery.&#x0D; RESULTS: The central retinal thickness increase in comparison with baseline values was more significant in the first group than in the second and the third groups, and the time of recovery to baseline values during 6 months after surgery was longer. Pseudophakic cystoid macular edema was not identified in any group.&#x0D; CONCLUSIONS: The use non-prostaglandin drops with preservative in patients with primary open-angle glaucoma does not affect pseudophakic cystoid macular edema development after uncomplicated phacoemulsification. Instillations of non-steroidal anti-inflammatory drops in the post-op period reduce the time of central retinal thickness recovery to baseline value.