Instillation Of Eye Drops Research Articles

Rapid and selective removal of preservative from ophthalmic formulations during eyedrops instillation

About 70% of eyedrops contain benzalkonium chloride (BAK) as a preservative to prevent the growth of microorganisms. While preservatives are mandated to maintain sterility, many patients exhibit irritation and toxicity to such compounds. We propose to mitigate the ocular toxicity in the ocular formulations without compromising sterility by designing a device that can be incorporated into an eyedrops bottle to selectively remove the preservatives during the process of drop instillation. Here, we specifically focus on macroporous poly(2-hydroxyethyl methacrylate) (pHEMA) gel due to its excellent biocompatibility and high partition coefficient for BAK. In addition to specific selectivity for BAK, the device also requires high hydraulic permeability to allow drop dispensing without excessive pressure drop. The pHEMA monolith can remove nearly 100% of contained BAK from a 25ml, 0.012% BAK solution with negligible uptake of the hydrophilic drugs such as timolol and dorzolamide. The filter, however, had to be pre-equilibrated with hydrophobic drugs to reach a high separation of BAK without reducing the concentration of the active drug. The average hydraulic permeability of the filter was 0.025 Darcy, which is about 5-fold lower than the ideal value. Incorporation of a pHEMA macroporous gel into an eyedrops bottle can virtually eliminate the exposure of the eyes to the preservatives without compromising the sterility. Our novel design can eliminate the preservative induced toxicity from eyedrops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases such as glaucoma and dry eyes.

Prominent Decrease of Tear Meniscus Height With Contact Lens Wear and Efficacy of Eye Drop Instillation.

To investigate the change in tear meniscus height (TMH) before and after wearing soft contact lenses (CLs) of different water contents (WCs) and the influence of eye drop instillation on TMH during CL wear. Tear meniscus heights were measured using anterior segment optical coherence tomography in 20 normal subjects wearing a high-WC CL (WC, 69%) in 1 eye and a low-WC CL (WC, 24%) in the other. Tear meniscus height change after eye drop instillation with 3% diquafosol ophthalmic solution or saline with CL wear was evaluated at 5, 15, 30, and 60 min after instillation. A significant decrease in TMH was observed after lens insertions of both CLs. Tear meniscus height was significantly decreased with high-WC CL wear compared with that with low-WC CL wear. With high-WC CL wear, TMH increased significantly (P<0.001) at 5 min after the instillation of 3% diquafosol ophthalmic solution compared with the baseline values and then returned to the pre-instillation level. No significant TMH changes were found with the instillation of either eye drop (diquafosol or saline) with low-WC CL wear. Tear meniscus height decreased with CL wear, especially with high-WC CL wear. Significant increases in TMH were observed at 5 min after the instillation of diquafosol ophthalmic solution with high-WC CL wear. The increases in TMH after diquafosol instillation tended to be greater than those after saline instillation at least for 30 min with both high-WC and low-WC CLs.

How 'Drug Aware' are our Glaucoma Patients?

ABSTRACTBackground: Poor knowledge, attitude and self-care practices (KAP) as regards medication compliance is a major concern in the management of glaucoma. This study aims to evaluate the knowledge, attitude regarding eyedrop instillation and self-care practices pertaining to eyedrops in diagnosed glaucoma patients.Methods: In this cross-sectional, open-ended questionnaire-based study, 101 consecutive glaucoma patients on medication were recruited from an urban tertiary care hospital of North India. A self-designed 10-point KAP questionnaire that addressed patient-, medication-, environment- and physicians related factors was used.For each desirable answer, the participant gives a score of 1 was given and for each undesirable answer a score of ‘0’ was given for each question. The total scores for each domain were calculated separately along with the total score. The association between the individual domain scores, the total score and various sociodemographic parameters were compared using unpaired t-test. Analysis of variance (ANOVA) test was used to compare the means, where the exposure variable had more than two categories.Results: Out of 101 participants, 98% knew the reason why they were instilling the medicine. Only 61.4% subjects knew that the eyedrops should be stored in cool and dry place. Nearly 30% participants believed that two eyedrops could be instilled back to back. Half of the participants (55.4%) did not consider missing a dose of medicine to be significant. Majority (89.1%) of the participants asked the doctor about the drug dosage and timings and 71.3% of them did not use the eyedrops beyond 40 days after opening the vial. 37.6% participants believed that the medicine could be discontinued without asking the doctor, once the symptoms are relieved. Eighty percent patients checked the vial for correct drug name and expiry date before buying. 57.4% of the participants washed their hands before instilling the eyedrops. Only 23.8% patients asked their doctor for alternate medication name, in case they do not get the primary medication.There were no statistically significant differences in the mean domain and total scores between males and females and between urban and rural patients.There were no statistically significant differences in knowledge (p = 0.059) and attitude (p = 0.809) scores in people with different educational qualification. But education had a statistically significant relation with the practice scores (p = 0.004) and total scores (p = 0.047).Conclusion(s): There exists marked variation in the reported practices, even in the very basic prerequisites of instilling eye-drops like washing of hands, checking the expiry date before the usage of eyedrops.The findings in our study suggest a need to better educate our patients by providing them detailed information about eyedrop and its administration. This would help to reduce patients’ frustration, improve compliance and increase the efficacy of anti-glaucoma therapy.How to cite this article: Mohindroo C, Ichhpujani P, Kumar S. How ‘Drug Aware’ are our Glaucoma Patients? J Curr Glaucoma Pract 2015;9(2):33-37.

Effects of osmoprotective eye drops on tear osmolarity in contact lens wearers

ObjectiveTo evaluate the impact of osmoprotective eye drops on tear osmolarity and patient comfort, and to compare its efficacy with a commercially available lubricant in contact lens (CL) wearers. DesignProspective, cross-sectional study. ParticipantsForty eyes of 20 first-time CL wearers were included. MethodsTear osmolarity measurements using TearLab osmolarity system were performed in each eye of subjects at 8 am, and 2, 4, and 8 h after that on the first and second days, and at 12:00 on the third day and eighth days. On the second day and afterward, all eyes were fitted Purevision 2 (Bausch & Lomb) soft CLs. Subjects instilled Optive (Allergan) osmoprotective eye drops into their 1 eye (group 1) and Refresh tears (Allergan) eye drops into their other eyes (group 2) after 2 hours of CL wear on the third day and afterward. Ocular comfort with eye drops was also assessed. ResultsThere were no significant differences between the tear osmolarity measurements of the groups on the first day. On the second day, osmolarity significantly increased from baseline after 4 h of CL wear (p < 0.05) but returned to baseline after 8 h of CL wear (p > 0.05) in both groups. Tear osmolarity measurements of group 1 were significantly lower than those of group 2 on the third and eighth days (both p < 0.05). The mean comfort scores were significantly higher in group 1. ConclusionsTear osmolarity increases within the first hours of CL wear, and instillation of osmoprotective eye drops prevents this increment in patients wearing CLs.

Videographic Assessment of Glaucoma Drop Instillation.

ABSTRACTPurpose: To assess the effect of patient education on videotaped topical instillation of artificial tear drops on subsequent topical instillation.Materials and methods: Forty-five patients, who had been using glaucoma drops for at least 6 months and with a best-corrected visual acuity of 20/100 or better, were studied. The patients were asked to instill an artificial tear drop using their accustomed technique while being video recorded. The patients viewed the recordings, and the errors in their drop instillation method were pointed out. This was followed by an educational session on proper drop instillation technique. After 30 minutes, patients were videotaped instilling drops to ascertain the effect of the educational session. The variables compared were: number of drops instilled, number of drops reaching the ocular surface, and the number of times the tip of the medication bottle touched the eye or ocular adnexa.Results: Before the instruction session, patients squeezed an average of 1.5 ± 0.9 drops from the bottle, and the average number of drops reaching the conjunctival fornix was 0.9 ± 0.7. The tip of the bottle touched the ocular adnexa in 29/45 (64.4%) patients. After the education session, the patients squeezed an average of 1.2 ± 0.5 drops and an average of 1.2 ± 0.4 drops reached the conjunctival fornix. The tip of the bottle touched the ocular adnexa in 13/45 (28.9%) patients. With proper instructions, the percentage of patients that instilled just one drop on the eye increased from 66 to 82%.Conclusion: A single educational session on the proper use of topical drops improves the successful instillation of eye drops. However, it was not determined whether the patients will retain the improved instillation technique for long-term or if the intervention results in only a short-term improvement.How to cite this article: Lazcano-Gomez G, Castillejos A, Kahook M, Jimenez-Roman J, Gonzalez-Salinas R. Video-graphic Assessment of Glaucoma Drop Instillation. J Curr Glaucoma Pract 2015;9(2):47-50.

Novel primary epithelial cell toxicity assay using porcine corneal explants.

The purpose of this study was to develop a novel primary epithelial cell toxicity assay using porcine corneal explant and evaluate the assay using benzalkonium chloride (BAK). Circular corneal explants were trephined from the peripheral cornea of porcine eyes using 2-mm biopsy punches, and placed on 6-well culture dishes with a culture medium. After incubation for 12 hours, 50 μL of BAK at 0.00001%, 0.0001%, 0.001%, or 0.01% was applied to each well for 2 minutes. After washing, explants were cultured for another 24 hours, then epithelial outgrowth was photographed and measured. Corneal immunohistochemical characteristics were evaluated by cytokeratin (CK) 3, CK12, and ZO-1. Cell toxicity was evaluated by WST-8 assay, Ki-67 staining, and TUNEL assay. Epithelial cells migrated outward concentrically from the corneal explant as time elapsed and were positive for CK3, CK12, and ZO-1. The outgrowth rate decreased significantly with 0.0001%, 0.001%, and 0.01% BAK compared with the phosphate-buffered saline (PBS) control (P < 0.01), and the decrease was BAK concentration dependent. Numbers of viable cells and Ki-67-positive cells also decreased significantly with 0.01% BAK compared with the PBS control (P < 0.05). TUNEL-positive cells were present in the epithelial outgrowth. Moreover, TUNEL-positive cell density tended to increase with 0.01% BAK compared with the PBS control (P = 0.14) and 0.00001% BAK (P = 0.081). Our novel toxicity assay using porcine corneal explant is simple and reflects the effect of single and short-duration instillation of eye drops. The method is useful for evaluation of corneal toxicity at low concentrations of BAK.

Evaluation of the efficacy and safety of a new device for eye drops instillation in patients with glaucoma.

ObjectiveThis study evaluated the efficacy and safety of a new device (Eyedrop®) designed for eye drop instillation in patients with and without glaucoma.MethodsThis prospective study included consecutive patients with glaucoma and healthy participants. After a complete eye examination and determination of baseline intraocular pressure (IOP), topical hypotensive medication was introduced in both eyes, and the Eyedrop® delivery device (a plastic device in which the bottle with eye drops is inserted) was made available to all participants (with video and written instructions) for use in one eye, randomly chosen. In the second phase, all patients were evaluated by an experienced examiner for IOP determination, investigation of possible associated side effects, and ease of instilling eye drops (by a visual analog scale [VAS]; 0–10).ResultsThirty two participants (mean age 42.3±16.2 years) were evaluated. Of these, 44% had glaucoma. There was no significant difference in mean IOP variation when comparing the eye using (−3.9±2.9 mmHg) or not using the device (−3.3±2.6 mmHg; P=0.36). The subjective rating of the facility of drops instillation was significantly higher with the Eyedrop® applicator (VAS =7.6±1.6) than without it (VAS =6.2±1.8; P<0.01), with a higher frequency of positive device-related evaluations (VAS score >5) among participants without prior experience with eye drop instillation (78.6% [11/14]) versus those already experienced (66.7% [12/18]). No difference in the frequency of side effects or in the distribution pattern of fluorescein between eyes was observed (P≥0.63).ConclusionEyedrop® received a better subjective response regarding the ease of instillation of hypotensive eye drops compared to traditional instillation, especially in patients with no previous experience with eye drops. Using the device did not result in any loss of hypotensive effect or increase in the frequency of side effects.

Difficulties with self instillation of eye drops and its impact on intraocular pressure in glaucoma patients

Aims: Prevalence of glaucoma increases with age and this potentially blinding condition requires regular instillation of eye drops. But with aging itself and accompanying co-morbidities, self instillation of eye drops gets affected. This study was designed to study the subjective difficulties associated with self instillation of eye drops in glaucoma patients and to quantitatively assess their impact on intraocular pressure (IOP). Settings and Design: Prospective interventional study at primary eye care center. Materials and Methods: A total of 69 persons diagnosed with glaucoma or ocular hypertension (OHT), who were self instilling their eye drops, were included in this study. Patients were interviewed for subjective difficulties being faced during self instillation using a formatted questionnaire. The patients were then subjected to assisted eye drop instillation for 4 weeks. The change IOP and consumption of eye drop bottles were compared between self installation and assisted instillation periods. Statistical Analysis: Paired t-test was applied at 5% significance level to compare pre and post interventional change of parameters. Results: Fifty three percent of patients reported subjective difficulties while self instilling their eye drops. Non-compliance was self-reported in 18% of the patients. The IOP dropped by 10-13% (P-value < 0.0001) and consumption of eye drop bottles was 14% (P-value < 0.0001) higher during self instillation. Conclusion: Assisted eye drop instillation may be beneficial to achieve better IOP control.

Difficulties of daily tasks in advanced glaucoma patients - a videotaped evaluation

Objetivo O objetivo deste trabalho foi avaliar objetivamente, com registro em video, as dificuldades dos pacientes com glaucoma avancado na colocacao de colirios hipotensores e na realizacao de tarefas do cotidiano. Metodos Realizou-se um estudo prospectivo observacional em pacientes com glaucoma avancado e perda visual. Os dados foram coletados durante 5 meses e posteriormente aplicados questionarios (questoes demograficas, qualidade de vida, autoadministracao de colirios e aderencia ao tratamento) e realizadas entrevistas e gravacoes das tarefas em video (autoadministracao dos colirios, leitura, subir e descer escadas, deambular em espacos apertados e pavimentos irregulares). Realizou-se avaliacao oftalmologica com registro em formulario pre-definido e pesquisou-se a correlacao entre os defeitos de campos visuais e as limitacoes dos pacientes. Resultados Com 25 participantes foram abtidos um total 12 horas de video.Todos os doentes afirmaram ser capaz de colocar os colirios hipotensores e 68%afirmaram nunca ter falhado na instilacao do colirio. No entanto, 20% nao conseguiram instilar uma unica gota no olho. Setenta e dois por cento (72%) dos pacientes afirmaram nunca tocar o frasco no olho, porem 40% afirmaram tocar. Houve dificuldade moderada nas atividades, especialmente ao deambular em espacos com obstaculos e em pavimentos irregulares. Alguns pacientes apresentaram mecanismos proprioceptivos de adaptacao a baixa visao (como tatear o degrau com o pe). Houve uma correlacao entre a severidade dos defeitos de campo visual e maior limitacao nas atividades. Conclusao Os portadores de glaucoma avancado tem consideravel dificuldade nas atividades da vida diaria e na instilacao de colirios, frequentemente com percepcao deficiente. Alguns pacientes apresentam adaptacoes proprioceptivas para superar parte da limitacao visual.

Bronchoconstriction following instillation of phenylephrine eye drops in premature infants with bronchopulmonary dysplasia: two cases report

Premature infants requiring an ophthalmic examination or even surgery for retinopathy of prematurity (ROP) have a high prevalence of co-existing bronchopulmonary dysplasia (BPD). Reactive airway is one of the clinical presentations of BPD. We report two cases of bronchoconstriction following instillation of mydriatic eye drops. One occurred during induction of anesthesia for laser photocoagulation and the other before screening of ROP. The most likely cause in each case was phenylephrine eye drops. We recommend that the minimal dosage of phenylephrine needed to attain proper mydriasis should be instilled to infant patients, and the possibility of bronchoconstriction occurrence kept in mind, especially for infants with low body weight with BPD.

Recent Advances in Management of Dry Eye and our Experience with Autologous Serum Eye Drops in Treatment of Severe Dry Eyes

Normal sight is dependent on moist ocular surface. Dry eye is a condition Occurring due to inadequate tear volume or function. Treatment depends on Severity of dry eyes; normally it is treated by artificial tears, severe dry eye Can also be treated by autologous serum eye drops. To assess the efficacy of autologous serum eye drops in severe dry eyes a Prospective case study was conducted in patients attending the cornea Clinic of Department. Of Ophthalmology, Santosh medical college and hospital, Ghaziabad, Based on history, clinical examination findings, follow up of 28 eyes of 16 Patients at 4 weeks and 8 weeks after starting the autologous serum eye Drops along with artificial tears and on the basis of age, sex, subjective Symptomatic grading and objective score was done- Autologous serum eye Drops instillation in severe dry eye patients improved the symptomology (the Subjective scores) as well as improvement in signs (objective improvement).

HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr−/− mice

HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr−/−) mice. In three-week-old male Vldlr−/− mice, HL-217 (1.5 or 3mg/ml) was administered twice per day for 4weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr−/− mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC50=38.9±0.7μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.

Hybrid formulations of liposomes and bioadhesive polymers improve the hypotensive effect of the melatonin analogue 5-MCA-NAT in rabbit eyes.

For the treatment of chronic ocular diseases such as glaucoma, continuous instillations of eye drops are needed. However, frequent administrations of hypotensive topical formulations can produce adverse ocular surface effects due to the active substance or other components of the formulation, such as preservatives or other excipients. Thus the development of unpreserved formulations that are well tolerated after frequent instillations is an important challenge to improve ophthalmic chronic topical therapies. Furthermore, several components can improve the properties of the formulation in terms of efficacy. In order to achieve the mentioned objectives, we have developed formulations of liposomes (150–200 nm) containing components similar to those in the tear film and loaded with the hypotensive melatonin analog 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT, 100 µM). These formulations were combined with mucoadhesive (sodium hyaluronate or carboxymethylcellulose) or amphiphilic block thermosensitive (poloxamer) polymers to prolong the hypotensive efficacy of the drug. In rabbit eyes, the decrease of intraocular pressure with 5-MCA-NAT-loaded liposomes that were dispersed with 0.2% sodium hyaluronate, 39.1±2.2%, was remarkably higher compared to other liposomes formulated without or with other bioadhesive polymers, and the effect lasted more than 8 hours. According to the results obtained in the present work, these technological strategies could provide an improved modality for delivering therapeutic agents in patients with glaucoma.

PO-0713 Systemic Effects Of Anticholinergic – Sympathomimetic Eye Drops During Screening For Retinopathy Of Prematurity

<h3>Background and aims</h3> Anti cholinergic and sympathomimetic eye drops are widely used to achieve mydriasis. Normally systemic effects of these eye drops are ignorable but adverse events in preterm infants are reported. In this study during routine screening for retinopathy of prematurity (ROP), preterm infants were searched for the systemic effects of eye drops. <h3>Methods</h3> The standard protocol was to instil 3 drops per eye which is a mixture of short acting tropicamide 0.5% with long acting cyclopentolate 1% and phenylephrine 2.5% ophtalmic solution in equal volumes. Each drop instilled at a 15 min interval before examination. Body temperature, heart rate, respiration, blood pressure, spO2, presence of flashing were recorded three times; before the instillation of eye drops, just before the examination and after an hour. Parents were informed about the adverse side effects and presence of complaints were asked after 24 h with the telephone interview. Data were analysed by 2 two-way ANOVA and independent samples t-test. <h3>Results</h3> Forty eight (27 male+21 female) infants with birth weight 1498 ± 432(720–2500)g and gestational age 31,7 ± 3.3(25–37)weeks were examined at postmentruel age of 41.95 ± 4.74(34–58) weeks. Body temperature rised subsequently with each eye drop (p = 0.023). The change in other physiologic parameters were not statistically significant. Apnea over10 seconds were developed in 9 infants. Within 24 h gastrointestinal symptoms developed in 8, discomfort/sleeplessness in 22, hyperemia/discharge from the eye in 20 infants. <h3>Conclusion</h3> It was concluded that doctors must be aware of the the systemic effects of mydriatic eye drops used in screening examination for ROP and parents have to be informed about these effects.

Visualization of tear film thickness after eyedrop instillation

AbstractAbstract not provided

Ocular tolerability and efficacy of a cationic emulsion in patients with mild to moderate dry eye disease – A randomised comparative study

The purpose of this study was to compare the safety and efficacy of a new cationic emulsion (CE) with a formulation of polyvinyl alcohol and povidone (PVA-P) for the treatment of mild to moderate dry eye disease. This was a multicenter, open-label, comparative study. Patients were randomised to receive CE (Cationorm) or PVA-P (Refresh) (1:1). The following objective criteria were assessed to compare the two eye drops: tear Break-up Time (TBUT), Schirmer's test, lissamine green staining (Van Bijsterveld score), corneal fluorescein staining (Oxford scale) and oculopalpebral examination, on D7 and D28 (end of study). At these visits, ocular symptoms and safety were also assessed. Seventy-nine patients were randomised: CE: 44 patients; PVA-P: 35 patients. At D28, improvement was significantly better for TBUT [CE: 1.7 ± 2.4 s; PVA-P: 0.6 ± 1.8 s; P=0.015] and for the Van Bijsterveld score [CE: -1.4 ± 1.2; PVA-P: -0.9 ± 1.2; P=0.046] in the CE group. The same applied for the palpebral erythema score (P=0.023), overall efficacy assessed by the investigators (P<0.001), and symptoms not related to eye drop instillation (P=0.021). Improvement was observed from D7. No difference was observed between the two treatments with regard to ocular safety. These results suggest that in patients with mild to moderate dry eye, Cationorm, in addition to its moisturizing and lubricating properties, also helps stabilize the tear film due to its oily component. This study demonstrates the benefit of this new pharmaceutical form for the treatment of mild to moderate dry eye disease.

Preparation and in vitro–in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis

The objective of this study was to explore the potential of the nanostructured lipid carriers (NLCs) modified with chitosan oligosaccharide lactate (COL) for topical ocular application. Ofloxacin (OFX) loaded NLCs were prepared by microemulsion or high shear homogenization methods. For combination of NLCs Compritol HD5 ATO was used as solid lipid, oleic acid as liquid lipid, Tween 80 as surfactant, ethanol as co-surfactant. The optimum NLCs was modified with 0.75% COL. The properties of NLCs in the absence or presence of OFX (0.3%) were characterized as zeta potential, particle size, viscosity and pH, TEM, drug loading, encapsulation efficiency and anti-microbial properties. Ex-vivo penetration/permeation studies were performed with rabbit cornea in Franz-diffusion cells. The penetration rate of OFX from NM-COL4OFX and NH-COL4OFX were significantly higher than commercial solution. Based on the selected formulations, in vivo tests were carried out by eye-drop instillation of NLCs in rabbit. The addition of COL improved the preocular residence time, controlled the drug release and enhanced the corneal bioavailability. In conclusion, OFX COL modified NLCs prepared by high shear homogenization method could be offered as a promising strategy for ocular drug delivery.

Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.

The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP) was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a promising system for glaucoma management.

The effect of the Thai “Eye Drop Guide” on success rate of eye drop self-instillation by glaucoma patients

Abstract Background: Noncompliance can mislead clinicians regarding the efficacy of therapy and result in more aggressive, but inappropriate treatment. Improper techniques used for eye drop instillation frequently occurs in chronic glaucoma patients. The Thai Eye Drop Guide (EDG) device has been developed to ensure precise instillation. However, whether the EDG is more effective than the traditional technique when careful instructions for both techniques are given is still unknown. Objective: To compare success rates of eye drop self-instillation by chronic glaucoma patients using a traditional technique and the EDG when careful instructions for both are given. Methods: Fifty-nine chronic glaucoma patients were instructed to instill eye drops using the EDG or a traditional technique in a randomized sequence. A two week practice period was assigned before groups were crossed-over. The instillation performance was VDO recorded after each practice period. Three criteria of success: time taken to instill an eye drop into the eye; instillation of only one drop; and without the bottle tip touching lids, lashes, periocular tissues, or the other hand, were scored by three independent readers from video-records. The readers were blinded to the sequence to which the patients were randomized. Results: There were no significant differences in success rates between the EDG and traditional technique (61.0% and 66.1% respectively, p = 0.607) and the number of drops dispensed per application (median of 1 drop in both groups, p = 0.89). The time taken to instill eye drops with the EDG was significantly longer than using the traditional technique (median of 19 and 9 s respectively, p &lt; 0.001). Older age (p = 0.049, OR 4.23) and more education (p = 0.025, OR 0.19) were found to be significantly associated with failure of the EDG. Conclusion: EDG is not more effective than a traditional technique in terms of improving dispensing accuracy and decreasing the drops dispensed per application even when careful instructions are given. The results suggest that, if good instructions are provided, experienced glaucoma patients can improve their eye drop instillation performance.

Nanomedicine for glaucoma: sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops.

Glaucoma is a chronic progressive optic neuropathy that is characterized by optic nerve changes and visual field loss. Elevated intraocular pressure (IOP) is the main modifiable risk factor. Chronic instillation of daily eyedrops to lower IOP is the primary treatment of choice, although it requires patient adherence and correct performance. We have developed a nanoliposome drug delivery system for the longer term delivery of latanoprost. In the present open-label, pilot study, the safety and efficacy of a single subconjunctival injection of liposomal latanoprost was evaluated in six subjects with a diagnosis of either ocular hypertension (OHT) or primary open-angle glaucoma (POAG). Subconjunctival injection of liposomal latanoprost was well tolerated by all six subjects. From a baseline IOP of 27.55 ± 3.25mmHg, the mean IOP decreased within 1h to 14.52 ± 3.31mmHg (range 10-18mmHg). This represented a mean decrease of 13.03 ± 2.88mmHg (range 9-17mmHg), or 47.43 ± 10.05% (range 37-63%). A clinically and statistically significant IOP reduction (≥20% IOP reduction, P = 0.001 to 0.049) was observed through 3months after injection. The nanomedicine reported here is the first nanocarrier formulation that has an extended duration of action in humans, beyond a couple of weeks. The findings in this study open up a new treatment modality, which will greatly enhance patient compliance and improve treatment outcomes. The current study provides the evidence and support for further clinical studies of liposomal latanoprost in the treatment of glaucoma.