This study investigates the interaction of two approved and one newly developed latanoprost formulation with in vitro and in silico models of the tear film and tear film lipid layer (TFLL). Latanoprost, a prostaglandin analogue used for intraocular elevated pressure treatment, is topically delivered by nanocarriers within aqueous solutions or emulsions. The study focuses on the impact of these carriers on drug interactions with the tear film and their effect on the TFLL. Three different types of latanoprost carriers, micellar, nanoemulsion, and polymer-based, were compared, and each revealed distinct interaction patterns with the TFLL. Surface pressure kinetics demonstrated a rapid increase for the benzalkonium chloride formulation and a slow rise for the preservative-free variants. Visualization of the acellular in vitro TFLL model revealed different patterns of incorporation for each formulation, indicating unique interaction mechanisms. Molecular dynamics simulations further revealed different mechanisms of drug release in the TFLL between micellar and nanoemulsion formulations. In-depth examination highlighted the role of triglyceride molecules in replenishing the nonpolar layer of the TFLL, which suggests potential improvements in ocular surface compatibility by adjusting the quality and concentration of the oily phase. These findings suggest the potential for optimizing latanoprost formulations by tuning the oily phase-to-surfactant ratio and selecting suitable surfactants.
- MeSH
- antihypertenziva terapeutické užití MeSH
- glaukom * farmakoterapie MeSH
- latanoprost terapeutické užití MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oči * MeSH
- systémy cílené aplikace léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
UNLABELLED: PURPOSE : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.
- MeSH
- antihypertenziva škodlivé účinky MeSH
- benzoáty * MeSH
- beta-alanin analogy a deriváty MeSH
- bimatoprost terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- glaukom s otevřeným úhlem * diagnóza farmakoterapie MeSH
- latanoprost škodlivé účinky MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oční hypertenze * diagnóza farmakoterapie MeSH
- oční roztoky MeSH
- prospektivní studie MeSH
- timolol škodlivé účinky MeSH
- tonometrie oční MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Cíl: Cílem této studie bylo ověřit možné změny konvenčně nediagnostikované nasální části zorného pole u pacientů s diagnózou včasného primárního glaukomu s otevřeným úhlem (PGOÚ) s vysokou tenzí. Materiál a metody: Vyšetření vzdálené nasální části zorného pole bylo provedeno u 30 nemocných (60 očí) s počínajícím PGOÚ (preperimetrické stadium změn). Soubor tvořilo 16 žen (průměrného věku 46,5 let) a 14 mužů (průměrného věku 44,7 let). U všech očí bylo zjištěno glaukomovým programem (rychlý prahový program v rozsahu 50 stupňů nasálně a 22 stupňů temporálně) přístrojem Medmont M700 fyziologické zorné pole. Zraková ostrost byla 1,0 s případnou korekcí menší nebo rovnou ±3 dioptrie, a kromě glaukomového onemocnění neměli jinou oční vadu. Zorné pole bylo následně vyšetřeno stejným přístrojem posunutím fixačního bodu o 40 stupňů temporálně (prostorově adaptabilní program) a současným otočením hlavy o 10 stupňů nasálně. Celkem bylo zahrnuto 89 vyšetřovacích bodů s použitím flicker podnětů a rozsahem 0–120 stupňů nasálně. Výsledky: U všech očí byla zjištěna deprese vzdálené periferie nasální části zorného pole v rozsahu od 50 do 95 stupňů, při normální zorném poli vyšetřeným glaukomovým programem. Závěr: Při normálním zorném poli vyšetřeném rychlým prahovým glaukomovým programem byly u všech nemocných PGOÚ zjištěny změny v distální části nasální periferie zorného pole.
Aim: The aim of this study was to examine possible changes in the conventionally undiagnosed nasal visual field in patients diagnosed with early primary open angle glaucoma. Material and Methods: Examination of the far nasal part of the visual field was performed in 30 patients (60 eyes) with early stage of primary open angle glaucoma (preperimetric stage of changes). The cohort consisted of 16 women (mean age 46.5 years) and 14 men (mean age 44.7 years). In all eyes, the glaucoma program (rapid threshold program of 50 degrees nasally and 22 degrees temporally) was performed with the Medmont M700 instrument to determine the physiological visual field. Visual acuity was 1.0 with a possible correction less than or equal to ±3 diopters and they had no other ocular defect except glaucoma disease. The visual field was subsequently examined with the same instrument by moving the fixation point 40 degrees temporally (spatially adaptive program) and simultaneously turning the head 10 degrees nasally. A total of 89 examination points were included using flicker stimuli and a range of 0–120 degrees nasally. Results: The far nasal limit of the visual field reached 100° in 13.33% of eyes, 105° in 20% of eyes and up to 110° in 66.67% of eyes. Conclusion: In all eyes, depression of the distal periphery of the nasal part of the visual field was found to range from 50 to 95 degrees, with a normal visual field examined by the glaucoma program.
- MeSH
- časná diagnóza MeSH
- glaukom s otevřeným úhlem diagnóza MeSH
- glaukom * diagnóza MeSH
- lidé MeSH
- optická koherentní tomografie MeSH
- testy zrakového pole metody MeSH
- zraková pole MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinická studie MeSH
Úvod: Měření nitroočního tlaku (NOT) u pacientů s endokrinní orbitopatií (EO) může být obtížné a zavádějící zejména u pacientů s diplopií a deviací oka nasálně či do hypotropie. I pacientům bez diplopie v primárním pohledovém směru a na první pohled bez patrné poruchy motility je však nutno věnovat při měření NOT dostatečnou pozornost. Cíl studie: Porovnat shodu měření NOT u pacientů s EO v inaktivní fázi pomocí tří rozdílných typů tonometrů: iCARE rebound tonometeru, Goldmannova aplanačního tonometru (AT) and bezkontaktního tonometru (BT). Materiál a metodika: Do studie bylo zařazeno celkem 98 očí 49 dospělých pacientů v inaktivní fázi EO (36 žen, 13 mužů) ve věku 19 až 70 let (medián 55,0). Všichni pacienti měli potvrzenou tyreopatii, anamnézu proběhlé lehké až středně těžké EO, nevykazovali žádné známky aktivního onemocnění a neměli diplopii při pohledu vpřed. Kromě komplexního oftalmologického vyšetření byl změřen NOT pomocí BT, iCARE a AT. Výsledky měření byly porovnány a statisticky zpracovány. Výsledky: Průměrný NOT měřený pomocí AT byl 18,1 ±2,4 mmHg (13–25 mmHg), pomocí BT 22,3 ±5,0 mmHg (13–35 mmHg) a pomocí iCARE 18,0 ±2,4 mmHg (13,3–26 mmHg). Pomocí Blant-Altmanovy analýzy jsme zjistili, že střední rozdíl mezi AT a iCARE byl -0,1 ±1,16 mmHg (limit shody -2,4 až 2,1), mezi AT a BT 4,2 ±3,6 mmHg (limit shody -2,8 až 11,2) a mezi iCARE a BT -4,3 ±3,7 mmHg (limit shody -11,6 až 2,9). Mezi AT a iCARE nebyl zjištěn statisticky významný rozdíl (p = 1,000). Na druhé straně jsme potvrdili statisticky významný rozdíl mezi AT and BT (p < 0,0001) i mezi iCARE a BT (p < 0,0001). Závěr: Dle našich výsledků u pacientů s EO v inaktivní fázi může BT výrazně nadhodnocovat hodnoty NOT ve srovnání s AT a iCARE. Hodnoty získané pomocí iCARE tonometru u těchto pacientů ale byly srovnatelné se zlatým standardem AT.
Introduction: Intraocular pressure (IOP) measurement in patients with thyroid-associated orbitopathy (TAO) can be difficult and misleading, particularly in patients with diplopia and eye deviation (esotropia or hypotropia). However, when measuring IOP, it is also necessary to pay sufficient attention to TAO patients without diplopia in primary gaze direction and without motility disorder that might not be readily apparent. Purpose: The aim of this study was to evaluate the accuracy of measurement of intraocular pressure (IOP) using three different types of tonometers: the rebound tonometer (iCARE), the Goldmann applanation tonometer (GAT) and the non-contact airpuff tonometer (NCT) in patients with inactive TAO. Materials and Methods: A total of 98 eyes of 49 adult patients with TAO were examined. The study group included 36 females and 13 males, with an age range of 19–70 years and a median age of 55.0. All the patients had evidence of thyroid disease, a history of mild to moderate TAO, no clinical signs or symptoms of active disease, and no diplopia in direct gaze direction. In addition to a comprehensive eye examination, all the patients underwent measurement of intraocular pressure with three tonometers: NCT, iCARE, and GAT. The measurements with these three devices were compared. Results: The mean IOP was 18.1 ± 2.4 mmHg (range 13–25 mmHg) with GAT, 22.3 ±5.0 mmHg (range 13–35 mmHg) with NCT, and 18.0 ±2.4 mmHg (range 13.3–26 mmHg) with iCARE. The mean difference between the GAT and iCARE measurements (using the Bland-Altman analysis) was -0.1 ±1.16 mmHg (limits of agreement -2.4 to 2.1). The mean difference between the GAT and NCT measurements was 4.2 ±3.6 mmHg (limits of agreement -2.8 to 11.2). The mean difference between the iCARE and NCT measurements was -4.3 ±3.7 mmHg (limits of agreement -11.6 to 2.9). No significant difference was found between GAT and iCARE (p = 1.000). However, there was a significant difference between GAT and NCT (p < 0.0001), as well as between iCARE and NCT (p < 0.0001). Conclusions: In patients with TAO, NCT significantly overestimates IOP values compared to the GAT and ICare. By contrast, the iCARE rebound tonometer provides IOP measurements comparable to the gold standard GAT in these patients.
- MeSH
- diplopie MeSH
- glaukom etiologie MeSH
- Gravesova oftalmopatie * diagnóza MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oční hypertenze MeSH
- tonometrie oční metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinická studie MeSH
- MeSH
- chirurgie operační metody MeSH
- diferenciální diagnóza MeSH
- farmakoterapie metody MeSH
- glaukom s otevřeným úhlem diagnóza terapie MeSH
- glaukom s uzavřeným úhlem diagnóza etiologie terapie MeSH
- glaukom * diagnóza klasifikace terapie MeSH
- laserová terapie metody MeSH
- lidé MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND/OBJECTIVES: Adverse effects of topical glaucoma medications (TGMs) may include development of ocular adnexal disorders. We undertook a study to determine the effect of TGMs on the risk of developing lacrimal drainage obstruction (LDO) and eyelid malposition. SUBJECTS/METHODS: All patients 66 years of age and older in Ontario, Canada initiating TGM and all patients diagnosed with glaucoma/suspected glaucoma but not receiving TGM from 2002 to 2018 were eligible for inclusion in this retrospective cohort study. Using validated healthcare administrative databases, cohorts were identified with TGM and no TGM patients matched 1:2 on sex and birth year. The effect of TGM treatment on risk of surgery for LDO and lid malpositions was estimated using Kaplan-Meier and Cox proportional hazards models. RESULTS: Cohorts included 122,582 patients in the TGM cohort and 232,336 patients in the no TGM cohort. Among the TGM cohort there was decreased event-free survival for entropion (log-rank P < 0.001), trichiasis (P < 0.001), and LDO (P = 0.006), and increased ectropion-free survival (P = 0.007). No difference in ptosis-free survival was detected (P = 0.78). For the TGM cohort there were increased hazards for entropion (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.12-1.37; P < 0.001), trichiasis (HR 1.74, 95% CI 1.57-1.94; P < 0.001), and LDO (at 15 years: HR 2.39, 95% CI 1.49-3.85; P = 0.004), and a decreased hazard for ectropion (HR 0.89, 95% CI 0.81-0.97; P = 0.008). No association between TGM treatment and ptosis hazard was detected (HR 0.99, 95% CI 0.89-1.09; P = 0.78). CONCLUSIONS: TGMs are associated with an increased risk of undergoing surgery for LDO, entropion, and trichiasis.
- MeSH
- blefaroptóza * MeSH
- ektropion * etiologie chirurgie MeSH
- entropion * diagnóza etiologie chirurgie MeSH
- glaukom * komplikace MeSH
- lidé MeSH
- oční víčka MeSH
- retrospektivní studie MeSH
- trichiáza * komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- dupilumab,
- MeSH
- alergická konjunktivitida diagnóza farmakoterapie MeSH
- atopická dermatitida * komplikace MeSH
- biologická terapie MeSH
- glaukom chemicky indukované terapie MeSH
- hormony kůry nadledvin škodlivé účinky terapeutické užití MeSH
- humanizované monoklonální protilátky aplikace a dávkování farmakologie MeSH
- keratokonus diagnóza terapie MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- oči patologie transplantace účinky léků MeSH
- oční symptomy * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
PRCIS: Deep sclerectomy (DS) with the Esnoper Clip drainage implant in patients with uncontrolled primary open angle glaucoma (POAG) achieved a complete success rate of 87.2% at the 1-year follow-up. PURPOSE: To investigate the efficacy and safety of DS followed by Esnoper Clip implantation in patients with uncontrolled POAG. MATERIALS AND METHODS: In a prospective, consecutive, interventional study, we investigated 39 eyes of 35 patients with uncontrolled POAG who underwent DS with Esnoper Clip implantation. Complete ophthalmologic examinations including corrected visual acuity and intraocular pressure (IOP), were performed preoperatively, and at 1 day, at 1 week as well as at 1, 3, 6, 9, and 12 months postoperatively. Moreover, any goniopunctures and glaucoma medications required postoperatively were noted. RESULTS: The mean preoperative IOP was 20.8±5.2 mm Hg and it decreased to 13.9±3.1 mm Hg at 1 year postoperatively ( P <0.001). The number of glaucoma medications decreased from 2.9±0.7 preoperatively to 0.3±0.8 after 1 year ( P <0.001). The complete success rate (IOP≤21 mm Hg without glaucoma medication) and the qualified success rate (IOP ≤21 mm Hg with or without glaucoma medication) were 87.2% and 94.9%, respectively. Goniopuncture was performed in 33.3% of cases. No significant corrected visual acuity changes were registered at the final follow-up. Perioperative complications consisted of 3 micro-perforations of the trabeculo-descemet membrane. Postoperative complications included: hyphema (6 eyes), hypotony (6 eyes), shallow anterior chamber (3 eyes), choroidal detachment (4 eyes)-all of which were resolved without surgical intervention during the first postoperative month-and conjunctival dehiscence, which required resuture (2 eyes). CONCLUSION: Deep sclerectomy with the Esnoper Clip implant was safe and effectively lowered IOP in patients with uncontrolled POAG.
Glaucoma is a leading cause of blindness worldwide, with elevated intraocular pressure being a major risk factor for its development and progression. First-line treatment for glaucoma relies on the administration of prostaglandin analogs, with latanoprost being the most widely used. However, before latanoprost reaches the cornea, it must pass through the tear film and tear film lipid layer (TFLL) on the ocular surface. Given the significant lipophilicity of latanoprost, we hypothesize that TFLL could, to a certain extent, act as a reservoir for latanoprost, releasing it on longer time scales, apart from the fraction being directly delivered to the cornea in a post-instillation mechanism. We investigated this possibility by studying latanoprost behavior in acellular in vitro TFLL models. Furthermore, we employed in silico molecular dynamics simulations to rationalize the experimental results and obtain molecular-level insight into the latanoprost-TFLL interactions. Our experiments demonstrated that latanoprost indeed accumulates in the TFLL models, and our simulations explain the basis of the accumulation mechanism. These results support the hypothesis that TFLL can serve as a reservoir for latanoprost, facilitating its prolonged release. This finding could have significant implications for optimizing glaucoma treatment, especially in the development of new drug delivery systems targeting the TFLL.
- MeSH
- antihypertenziva terapeutické užití MeSH
- glaukom * farmakoterapie MeSH
- latanoprost terapeutické užití MeSH
- lidé MeSH
- nitrooční tlak MeSH
- počítačová simulace MeSH
- rohovka MeSH
- slzy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
