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The American Journal of Managed Care Nov 2023Dry eye disease (DED) is one of the most common ocular surface disorders. All DED involves an imbalance between tear production and evaporation. Most cases of DED are... (Review)
Review
Dry eye disease (DED) is one of the most common ocular surface disorders. All DED involves an imbalance between tear production and evaporation. Most cases of DED are driven by excessive evaporation, which is often associated with meibomian gland dysfunction (MGD). In evaporative DED, a deficient tear film lipid layer is believed to lead to increased tear evaporation, inflammation, and ocular surface damage. Most prescription treatments for DED address signs and symptoms by targeting tear production and/or inflammation, but they do not address excessive evaporation. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO™; Bausch + Lomb) is a water-free, single-ingredient, preservative-free prescription eye drop that directly targets tear evaporation and is approved by the FDA to treat the signs and symptoms of DED. Results from preclinical studies indicate that PFHO has a high oxygen carrying capacity, may reduce friction on blinking, and spreads quickly over the tear film surface to form a monolayer that inhibits evaporation. These effects can lead to stabilization of the tear film to promote ocular surface healing. Further, PFHO was detected in tears for at least 6 hours in a rabbit pharmacokinetic study, and results indicate that it may improve lipid layer thickness and quality. In 2 pivotal phase 3 trials in patients with DED and clinical signs of MGD (GOBI [NCT04139798] and MOJAVE [NCT04567329]), treatment with PFHO consistently met primary efficacy end points related to DED signs and symptoms (total corneal fluorescein staining and eye dryness, respectively) and was well tolerated. Compared with use of hypotonic saline solution, instillation of PFHO led to significant improvements in signs and symptoms in as early as 2 weeks. In a long-term, open-label safety extension study, efficacy of PFHO was sustained over 12 months, and the safety profile was consistent with those of previous studies. Clinical trial results indicate that treatment with PFHO effectively and consistently reduces the signs and symptoms of DED.
Topics: Animals; Humans; Rabbits; Ophthalmic Solutions; Dry Eye Syndromes; Inflammation; Lipids
PubMed: 37930231
DOI: 10.37765/ajmc.2023.89464 -
PloS One 2022To evaluate the concentrations of brimonidine and timolol in the vitreous and aqueous humors after instillation of a 0.1% brimonidine tartrate and 0.5% timolol... (Clinical Trial)
Clinical Trial
Brimonidine and timolol concentrations in the human vitreous and aqueous humors after topical instillation of a 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution: An interventional study.
PURPOSE
To evaluate the concentrations of brimonidine and timolol in the vitreous and aqueous humors after instillation of a 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution.
METHODS
This single-arm open-label interventional study included patients with macular holes or idiopathic epiretinal membranes who were scheduled for vitrectomy. Written informed consent was obtained from all participants. A 0.1% brimonidine tartrate and 0.5% timolol fixed-combination ophthalmic solution was administered topically twice daily for 1 week preoperatively. The vitreous and aqueous humors were sampled before vitrectomy, and brimonidine and timolol concentrations were quantified using liquid chromatography-tandem spectrometry. This study was registered with the Japan Registry of Clinical Trials (jRCT, ID jRCTs051200008; date of access and registration: April 28, 2020). The study protocol was approved by the University of Fukui Certified Review Board (CRB) and complied with the tenets of the Declaration of Helsinki.
RESULTS
Eight eyes of eight patients (7 phakic eyes and 1 pseudophakic eye) were included in this study. The mean brimonidine concentrations in the vitreous and aqueous humors were 5.04 ± 4.08 nM and 324 ± 172 nM, respectively. Five of the eight patients had brimonidine concentrations >2 nM in the vitreous humor, which is necessary to activate α2 receptors. The mean timolol concentrations in the vitreous and aqueous humors were 65.6 ± 56.0 nM and 3,160 ± 1,570 nM, respectively. Brimonidine concentrations showed significant positive correlations with timolol concentrations in the vitreous humor (P < 0.0001, R2 = 0.97) and aqueous humor (P < 0.0001, R2 = 0.96).
CONCLUSIONS
The majority of patients who received a 0.1% brimonidine tartrate and 0.5% timolol topical fixed-combination ophthalmic solution showed a brimonidine concentration >2 nM in the vitreous humor. Brimonidine and timolol may be distributed in the ocular tissues through an identical pathway after topical instillation.
Topics: Humans; Aqueous Humor; Brimonidine Tartrate; Ophthalmic Solutions; Timolol; Vitreous Body
PubMed: 36454807
DOI: 10.1371/journal.pone.0277313 -
Scientific Reports Jul 2021Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we... (Comparative Study)
Comparative Study Randomized Controlled Trial
Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.
Topics: Aged; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Humans; Intention to Treat Analysis; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Treatment Adherence and Compliance; Treatment Outcome
PubMed: 34294842
DOI: 10.1038/s41598-021-94574-x -
Chemical & Pharmaceutical Bulletin 2023Benzalkonium chloride (BAC) is a useful preservative for ophthalmic solutions but has some disadvantageous effects on corneal epithelium, especially keratinocytes....
Benzalkonium chloride (BAC) is a useful preservative for ophthalmic solutions but has some disadvantageous effects on corneal epithelium, especially keratinocytes. Therefore, patients requiring the chronic administration of ophthalmic solutions may suffer from damage due to BAC, and ophthalmic solutions with a new preservative instead of BAC are desired. To resolve the above situation, we focused on 1,3-didecyl-2-methyl imidazolium chloride (DiMI). As a preservative for ophthalmic solutions, we evaluated the physical and chemical properties (absorption to a sterile filter, solubility, heat stress stability, and light/UV stress stability), and also the anti-microbial activity. The results indicated that DiMI was soluble enough to prepare ophthalmic solutions, and was stable under severe heat and light/UV conditions. In addition, the anti-microbial effect of DiMI as a preservative was considered to be stronger than BAC. Moreover, our in vitro toxicity tests suggested that DiMI is safer to humans than BAC. Considering the test results, DiMI may be an excellent candidate for a new preservative to replace BAC. If we can overcome manufacturing process issues (soluble time and flushing volume) and the insufficiency of toxicological information, DiMI may be widely adopted as a safe preservative, and immediately contribute to the increased well-being of all patients.
Topics: Humans; Benzalkonium Compounds; Ophthalmic Solutions; Preservatives, Pharmaceutical; Epithelium, Corneal
PubMed: 37394604
DOI: 10.1248/cpb.c23-00115 -
International Journal of Nanomedicine 2022Untreated ocular infections can damage the unique fine structures of the eye with possible visual impairments and blindness. Ciprofloxacin (CIP) ophthalmic solution is...
INTRODUCTION
Untreated ocular infections can damage the unique fine structures of the eye with possible visual impairments and blindness. Ciprofloxacin (CIP) ophthalmic solution is prescribed as first-line therapy in ocular bacterial infections. Natamycin (NT) ophthalmic suspension is one of the progenitors in ocular antifungal therapy. Nanostructured lipid carriers (NLCs) have been widely examined for ocular penetration enhancement and distribution to deeper ocular tissues. The objective of the current study was to prepare NLCs loaded with a combination of CIP and NT (CIP-NT-NLCs) and embed them in an in-situ gelling system (CIP-NT-NLCs-IG). This novel formulation will target the co-delivery of CIP and NT for the treatment of mixed ocular infections or as empirical treatment in case of limited access to healthcare diagnostic services.
METHODS
CIP-NT-NLC and CIP-NT-NLC-IG formulations were evaluated based on physicochemical characteristics, in vitro release, and ex vivo transcorneal permeation studies and compared against commercial CIP and NT ophthalmic eye drops.
RESULTS AND DISCUSSION
NLCs formulation (0.1% CIP and 0.3% NT) showed particle size, polydispersity index, and zeta potential of 196.2 ± 1.2 nm, 0.43 ± 0.06, and -28.1 ± 1.4 mV, respectively. Moreover, CIP-NT-NLCs showed entrapment efficiency of 80.9 ± 2.9 and 98.7 ± 1.9% for CIP and NT, respectively. CIP-NT-NLCs-IGformulation with 0.2% w/v gellan gum demonstrated the most favorable viscoelastic characteristics for ocular application. CIP-NT-NLCs and CIP-NT-NLCs-IG formulations exhibited a sustained release pattern for both drugs over 24 h. Moreover, CIP-NT-NLCs and CIP-NT-NLC-IG formulations showed 4.0- and 2.2-folds, and 5.0- and 2.5-folds enhancement in ex vivo transcorneal permeability of CIP and NT, respectively, compared to the control formulations.
CONCLUSION
The results suggest that this dual nanoparticulate-based in-situ gelling drug delivery system can serve as a promising topical delivery platform for the treatment of ocular infections.
Topics: Ciprofloxacin; Drug Carriers; Drug Liberation; Eye Infections; Gels; Humans; Lipids; Nanostructures; Natamycin; Ophthalmic Solutions; Particle Size
PubMed: 35611213
DOI: 10.2147/IJN.S360740 -
Journal of Ocular Pharmacology and... May 2019Effective glaucoma therapy relies to a great extent on the patients' ability to regularly self-administer eye drops. This study aimed to assess self-reported...
Effective glaucoma therapy relies to a great extent on the patients' ability to regularly self-administer eye drops. This study aimed to assess self-reported nonadherence and to identify potential barriers to adherence in glaucoma patients. Participants completed a 16-item questionnaire, designed to examine nonadherence rate and assess the therapy experience. Inclusion criteria stipulated treatment duration of at least 1 year. Nonadherence was defined as missing ≥5% of the prescribed pressure-lowering eye drops doses. In total, 201 glaucoma patients aged 24-88 years were included. Mean treatment duration was 9.4 years. Nonadherence was reported by 30.3% of participants and 69.7% were reported to be adherent. Individuals who experienced side effects reported higher levels of nonadherence than those who did not (37.6% vs. 18.4%; = 0.004). Eye drops with preservatives were used by 84.1% of participants, 11.9% were on combined preservative and preservative-free treatment, and 4.0% on preservative-free medication only. Self-reported nonadherence levels were 32.0%, 25.0%, and 12.5%, respectively, for each of these groups. Men reported higher rates of nonadherence than women (36.8% vs. 24.5%; = 0.066). Age, social status, history of migration, severity of disease, and fear of blindness were not associated with significant differences in nonadherence levels. Nonadherence with glaucoma therapy is a significant barrier to therapeutic success for approximately one-third of patients. Nonadherence may be reduced if side effects are avoided. Preservative-free products may provide adherence benefits. The patient experience should be a key consideration when selecting appropriate treatments, to reduce nonadherence and optimize outcomes.
Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Female; Germany; Glaucoma; Humans; Injections, Intraocular; Male; Middle Aged; Ophthalmic Solutions; Patient Compliance; Patient Reported Outcome Measures; Preservatives, Pharmaceutical; Surveys and Questionnaires; Young Adult
PubMed: 30897019
DOI: 10.1089/jop.2018.0134 -
Acta Ophthalmologica Mar 2022The aim of this article is to discuss how physiology and anatomical background affect the effectiveness of implant-dependent microinvasive glaucoma surgery (MIGS).... (Review)
Review
The aim of this article is to discuss how physiology and anatomical background affect the effectiveness of implant-dependent microinvasive glaucoma surgery (MIGS). First, we provide a micro view of aqueous outflow and tissue behaviour. Second, we review studies exploring the mechanisms of the pressure-lowering effect of MIGS, as well as tissue behaviour during aqueous flow and tissue motion. We also describe and classify microinvasive surgical procedures and the most important types of implants, as well as their mechanisms of action, implantation techniques and efficacy. Further, we summarize the indications and surgical results presented in recent studies, providing an evidence-based update on novel and emerging MIGS techniques for the treatment of open-angle glaucoma. These data can help surgeons to personalize the management of glaucoma and to choose the best MIGS option for individual glaucoma patients.
Topics: Glaucoma Drainage Implants; Glaucoma, Open-Angle; Humans; Latanoprost; Minimally Invasive Surgical Procedures; Ophthalmic Solutions
PubMed: 33988310
DOI: 10.1111/aos.14906 -
Chemical Research in Toxicology Jun 2021Graphene family nanomaterials (GFNs) are rapidly emerging for ocular applications due to their outstanding physicochemical properties. Since the eyes are very sensitive... (Review)
Review
Graphene family nanomaterials (GFNs) are rapidly emerging for ocular applications due to their outstanding physicochemical properties. Since the eyes are very sensitive organs and the contact between the eyes and GFNs in eye drops, contact lenses, intraocular drug delivery systems and biosensors and even the workers handling these nanomaterials is inevitable, it is necessary to investigate their ocular toxicities and physiological interactions with cells as well as their toxicity mechanisms. The toxicity of GFNs can be extremely affected by their physicochemical properties, including composition, size, surface chemistry, and oxidation level as well as dose and the time of exposure. Up to now, there are several studies on the and toxicity of GFNs; however, a comprehensive review on ocular toxicity and applications of GFNs is missing, and a knowledge about the health risks of eye exposure to the GFNs is predominantly unspecified. This review highlights the ocular applications of GFNs and systematically covers the most recent advances of GFNs' physicochemical properties, and ocular toxicity, and the possible toxicity mechanisms as well as provides some perspectives on the potential risks of GFNs in material development and biomedical applications.
Topics: Eye; Graphite; Humans; Nanostructures; Ophthalmic Solutions
PubMed: 34041903
DOI: 10.1021/acs.chemrestox.0c00340 -
BMJ Open Aug 2023Evaporative dry eye (EDE) is common and can lead to ocular pain, decreased visual quality and reduced quality of life. Intense pulsed light (IPL) and 3% diquafosol...
Protocol for a parallel assignment prospective, randomised, comparative trial to evaluate the safety and efficacy of intense pulsed light (IPL) combined with 3% diquafosol (DQS) ophthalmic solution in dry eye syndrome.
INTRODUCTION
Evaporative dry eye (EDE) is common and can lead to ocular pain, decreased visual quality and reduced quality of life. Intense pulsed light (IPL) and 3% diquafosol ophthalmic solution have been found to be beneficial in reducing signs and symptoms of dry eye.
METHODS AND ANALYSIS
A randomised clinical trial will be performed at He Eye Specialist Hospital in Shenyang. 360 dry eye disease patients will be equally divided randomly into the IPL group, DQS group (3% diquafosol ophthalmic solution eye-drops) and IPL+group (IPL combined with 3% diquafosol eye-drops). All groups will be followed up for 4 weeks. The primary outcome measures will be the non-invasive tear break-up time and the Ocular Surface Disease Index change from the baseline. The secondary outcome measures willincludeconjunctival and cornea staining with fluorescein and lissamine, meibomian gland function and secretion quality, tear film lipid layer score, tear meniscus height, conjunctival hyperemia (redness score) changes . Adverse events also will be monitored and documented.
DISCUSSION
This study aimed to assess whether the combination of IPL with 3% diquafosol ophthalmic solution (study group), IPL+ (study group), is more effective than IPL (active control group) or DQS (active control group) in participants with EDE.
ETHICS AND DISSEMINATION
Management of dry eye with IPL combined with 3% diquafosol ophthalmic solution, registered on 23 January 2023. Ethics approval number: IRB (2022) K029.01. The study's findings will be shared regardless of the effect's direction.
TRIAL REGISTRATION NUMBER
NCT05694026.
Topics: Humans; Male; Dry Eye Syndromes; Lacerations; Ophthalmic Solutions; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 37643847
DOI: 10.1136/bmjopen-2023-073055 -
The American Journal of Managed Care Oct 2023Dry eye disease (DED) is a common condition in which tear film abnormalities result in a damaging cycle of tear hyperosmolarity, desiccating stress, inflammation, and...
Dry eye disease (DED) is a common condition in which tear film abnormalities result in a damaging cycle of tear hyperosmolarity, desiccating stress, inflammation, and ocular surface injury. In a healthy tear film, meibum produced by the meibomian glands forms a lipid layer that stabilizes the tear film and protects against aqueous tear evaporation. Excessive tear evaporation due to a deficient lipid layer is believed to be the most common cause of DED, and most evaporative DED is associated with meibomian gland dysfunction (MGD); this highlights the pathophysiologic importance of the dysfunctional tear lipid layer. Current treatments for DED may be used to supplement hyperosmolar aqueous tears, lubricate the ocular surface, increase meibum flow, decrease inflammation, promote tear production, or otherwise decrease clinical signs of ocular surface damage and/or improve symptoms. Until now, no prescription eye drop has directly addressed the excessive evaporation that occurs in most patients with DED. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO™; Bausch + Lomb) is a preservative-free eye drop that has demonstrated the ability to form a long-lasting barrier that inhibits evaporation in preclinical studies. FDA approval of PFHO was based on results from 2 pivotal clinical trials (GOBI [NCT04139798] and MOJAVE [NCT04567329]) in patients with DED and clinical signs of MGD which demonstrated consistent improvements in both signs and symptoms of disease, with a safety profile similar to that of saline eye drops. PFHO is the first and only FDA-approved eye drop that directly targets tear evaporation in patients with DED, thereby promoting ocular surface healing and providing symptomatic relief.
Topics: Humans; Dry Eye Syndromes; Inflammation; Lipids; Meibomian Glands; Ophthalmic Solutions; Clinical Trials as Topic
PubMed: 37844320
DOI: 10.37765/ajmc.2023.89448