Fixed-Combination Eye Drops Based on Fluorometholone Nanoparticles and Bromfenac/Levofloxacin Solution Improve Drug Corneal Penetration

Abstract Background Adherence to chronic therapies is crucial to prevent the progression of disease, such as glaucoma. However, only a limited number of studies have investigated them using real-world data in Japan. This study aimed to evaluate Japanese patients’ adherence to fixed- and unfixed-combination eye drops as a second-line therapy for glaucoma in real-world practice. Methods This retrospective, non-interventional cohort study utilized a commercially available Japanese healthcare database (MinaCare database). Medical/pharmacy claims data were collected from 2011 to 2016. The primary endpoint was adherence to medications, assessed by proportion of days covered (PDC) with medication during a 12-month post-index period. Meanwhile, the secondary endpoints included the persistence rate. Results A total of 738 patients were included in this study: 309 and 329 in the fixed- and unfixed-combination cohorts, respectively. Prostaglandin analog (PG)/β-blocker (BB) was most commonly claimed in 241/309 (78.0%) patients in the fixed-combination cohort. In the unfixed-combination cohort, PG and BB were claimed in 130/329 (39.5%) patients, whereas PG and α2-agonist were claimed in 87/329 (26.4%) patients. Patients were more adherent to the fixed-combination than the unfixed-combinations (mean PDCs [SD], 79.1% [32.1] vs. 62.2% [38.0]; P < 0.0001). The proportion of patients with good adherence (PDC ≥ 80%) was also higher in the fixed-combination cohort (69.6%) than in the unfixed-combination cohort (48.6%) (P < 0.0001). During the 12-month post-index period, the persistence rate was higher in the fixed-combination cohort than in the unfixed-combination cohort (47.6% [95% confidence intervals (CI): 41.9–53.0] vs. 24.9% [95% CI: 20.4–29.7], P < 0.0001). Conclusions Japanese patients with glaucoma preferred the fixed-combination therapies over the unfixed-combination therapies. Hence, fixed-combination therapies would contribute to the improvement of adherence.

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A Comparative Analysis of the Efficacy and Safety of fixed Combinations of Latanoprost/Timolol vs Dorzolamide/Timolol in Primary Open Angle Glaucoma or Ocular Hypertension

Journal of Postgraduate Medicine Education and Research ◽

10.5005/jp-journals-10028-1039 ◽

2012 ◽

Vol 46 (4) ◽

pp. 172-176

Author(s):

Sukhsagar Ratol ◽

Rani Walia ◽

Mridu Chaudhry

Keyword(s):

Ocular Hypertension ◽

Primary Open Angle Glaucoma ◽

Fixed Combination ◽

Open Angle Glaucoma ◽

Eye Drops ◽

Open Angle ◽

Once Daily ◽

Group 2 ◽

Diurnal Iop ◽

Group 1

ABSTRACT Background Glaucoma is a leading cause of irreversible blindness. The fundamental problem in medical management of glaucoma is of patient compliance. An ideal drug or a drug combination is needed to slow the progression of this majorly symptomless disease. Aim To compare the efficacy and tolerability of the fixed combination latanoprost and timolol instilled once daily in the evening vs fixed combination of dorzolamide and timolol instilled twice daily in primary open angle glaucoma or ocular hypertension. Materials and methods A 12-week, randomized, open, parallel group study including 50 patients with primary open angle glaucoma or ocular hypertension was conducted at a tertiary care hospital. Patients were randomized to group 1, (fixed combination (FC) latanoprost and timolol eye drops, once daily in evening) and group 2, (FC dorzolamide and timolol eye drops, twice daily). At baseline, 2, 4 and 12 weeks, IOP was recorded at 9 AM and 12 noon. The difference in IOP reduction in two treatment groups from baseline to 12 weeks was the main outcome measure. Results Mean diurnal IOP was similar at baseline for both groups. Mean reduction in IOP from baseline to 12 weeks was 9.92 mm Hg (p = 0.001) in group 1 and 9.22 (p = 0.001) in group 2. The reduction in IOP in both groups 1 and 2 was statistically significant at all time intervals. There was a statistically significant advantage for group 1 at 12 weeks for both time readings (p = 0.013 and 0.002 respectively) as compared to group 2. Conclusion The fixed combination of latanoprost and timolol was more effective than that of dorzolamide and timolol in reducing mean diurnal IOP and both treatments were well tolerated. To confirm further such studies are required. How to cite this article Ratol S, Walia R, Chaudhry M. A Comparative Analysis of the Efficacy and Safety of fixed Combinations of Latanoprost/Timolol vs Dorzolamide/Timolol in Primary Open Angle Glaucoma or Ocular Hypertension. J Postgrad Med Edu Res 2012;46(4):172-176.

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Comparison of the intraocular pressure lowering effect of latanoprost and a fixed combination of timolol-pilocarpine eye drops in patients insufficiently controlled with beta adrenergic antagonists

British Journal of Ophthalmology ◽

10.1136/bjo.84.2.181 ◽

2000 ◽

Vol 84 (2) ◽

pp. 181-185 ◽

Cited By ~ 14

Author(s):

J.-P. Nordmann

Keyword(s):

Intraocular Pressure ◽

Fixed Combination ◽

Eye Drops ◽

Beta Adrenergic ◽

Lowering Effect ◽

Pressure Lowering ◽

Adrenergic Antagonists

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Effectiveness of a Preservative-Free Eye Drop, Cyclosporine 0.05% Emulsion, and Omega-3 Supplementation as a Fixed Combination in Dry Eye Disease – a Pilot Study

Current Trends in Ophthalmology ◽

10.18314/ctoy.v1i1.151 ◽

2018 ◽

Vol 1 (1) ◽

pp. 01-06

Author(s):

Tokko HA ◽

Al-Awadi A ◽

Somani S

Keyword(s):

Dry Eye ◽

Fixed Combination ◽

Case Series ◽

Secondary Outcome ◽

Combination Regimen ◽

Eye Drops ◽

Secondary Outcome Measure ◽

Omega 3 ◽

The Impact ◽

Preservative Free

Purpose: We aim to evaluate the impact of combining a preservative-free drop, cyclosporine 0.05% emulsion, and omega-3 oral supplementation on the signs and symptoms of dry eye in a typical ophthalmic practice.Design: A retrospective case series conducted on patients with dry eye disease.Methods: Patients diagnosed with dry eye in a typical ophthalmology practice were initiated on a fixed combination regimen which included a preservative-free eye drop (I-DROP ® PUR GEL, I-MED pharma), cyclosporine 0.05% ophthalmic emulsion, and oral omega-3 supplement(Dry Eye Omega Benefits®, PRN)for 3 monthsconsecutively. The primary outcome measured was a symptom score using the Canadian Dry Eye Assessment Tool (CDEA). Secondary outcome measure was Non-invasive Keratograph Break-up Time (NIKBUT). Primary and secondary outcomes measured at baseline and 3 months following intervention were compared.Results: Thirty-six patients were included with a female male ratio of 2.6:1 and average age of 64.Patient symptoms improved significantly following the intervention as demonstrated by a lower CDEA score during the second visit compared to the first visit (16.11 vs. 19.50, respectively) (p< .05). NIKBUT scores were also significantly improved as demonstrated by a higher score during the second visit compared to the first in both the right (13.18 vs. 11.44) (p< .05) and left (14.62 vs. 12.78) (p< .01) eyes, respectively.Conclusion: A fixed combination of preservative-free eye drops, cyclosporine 0.05% and omega-3 supplementation may be an effective first line treatment option in alleviating symptoms and improving signs of patients suffering from dry eye.

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Comparison of adherence and persistence between fixed and unfixed topical combination glaucoma therapies using Japanese healthcare/pharmacy claims database: a retrospective non-interventional cohort study

10.21203/rs.3.rs-47479/v1 ◽

2020 ◽

Author(s):

Chikako Shirai ◽

Nobushige Matsuoka ◽

Toru Nakazawa

Keyword(s):

Cohort Study ◽

Real World ◽

Fixed Combination ◽

Japanese Patients ◽

Eye Drops ◽

Combination Therapies ◽

Real World Data ◽

Healthcare Database ◽

Pharmacy Claims ◽

Persistence Rate

Abstract Background Adherence and persistence with chronic therapies is crucial to prevent disease progression, such as in glaucoma. However, only a limited number of studies have reported them using real-world data in Japan. This study aimed to evaluate Japanese patients’ adherence and persistence to fixed- and unfixed-combination eye drops as a second-line therapy for glaucoma in real-world practice.Methods This retrospective, non-interventional cohort study utilized a commercially available Japanese healthcare database (MinaCare database). Medical/pharmacy claims data were collected from 2011 to 2016. The primary endpoint was adherence to medications, assessed by proportion of days covered (PDC) with medication during a 12-month post-index period. Meanwhile, the secondary endpoints included the persistence rate.Results A total of 738 patients were included in this study: 309 and 329 in the fixed- and unfixed-combination cohorts, respectively. Prostaglandin analog (PG)/β-blocker (BB) was most commonly claimed in 241/309 (78.0%) patients in the fixed-combination cohort. In the unfixed-combination cohort, PG and BB were claimed in 130/329 (39.5%) patients, whereas PG and α2-agonist were claimed in 87/329 (26.4%) patients. Patients were more adherent to the fixed-combination than the unfixed combinations (mean PDCs [SD], 79.1% [32.1] vs. 62.2% [38.0]; P < 0.0001). The proportion of patients with good adherence (PDC ≥ 80%) was also higher in the fixed-combination cohort (69.6%) than in the unfixed-combination cohort (48.6%) (P < 0.0001). During the 12-month post-index period, the persistence rate was higher in the fixed-combination cohort than in the unfixed-combination cohort (47.6% [95% confidence intervals (CI): 41.9–53.0] vs. 24.9% [95% CI: 20.4–29.7], P < 0.0001).Conclusions Japanese patients with glaucoma preferred the fixed-combination therapies over the unfixed-combination therapies. Hence, fixed-combination therapies would contribute to the improvement of adherence.

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Evaluation of cyclodextrins for enhancing corneal penetration of natamycin eye drops

Journal of Pharmacy And Bioallied Sciences ◽

10.4103/0975-7406.94128 ◽

2012 ◽

Vol 4 (5) ◽

pp. 29 ◽

Cited By ~ 5

Author(s):

Anjali Badhani ◽

Prashant Dabral ◽

Vinod Rana ◽

Kumud Upadhyaya

Keyword(s):

Eye Drops ◽

Corneal Penetration

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Corneal penetration of diclofenac from a fixed combination of diclofenac-gentamicin eyedrops

Journal of Cataract & Refractive Surgery ◽

10.1016/s0886-3350(98)80230-7 ◽

1998 ◽

Vol 24 (10) ◽

pp. 1365-1370 ◽

Cited By ~ 5

Author(s):

Hanspeter E. Killer ◽

François X. Borruat ◽

Bruno K. Blumer ◽

Carl P. Herbort ◽

Arthur Jauch

Keyword(s):

Fixed Combination ◽

Corneal Penetration

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Three-month evaluation of dorzolamide hydrochloride/timolol maleate fixed-combination eye drops versus the separate use of both drugs

Japanese Journal of Ophthalmology ◽

10.1007/s10384-012-0186-8 ◽

2012 ◽

Vol 56 (6) ◽

pp. 559-563 ◽

Cited By ~ 7

Author(s):

Kenji Inoue ◽

Minako Shiokawa ◽

Michitaka Sugahara ◽

Masato Wakakura ◽

Shoichi Soeda ◽

...

Keyword(s):

Fixed Combination ◽

Eye Drops ◽

Timolol Maleate ◽

Dorzolamide Hydrochloride

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Corneal Penetration of Low-Dose Atropine Eye Drops

Journal of Clinical Medicine ◽

10.3390/jcm10040588 ◽

2021 ◽

Vol 10 (4) ◽

pp. 588

Author(s):

Henning Austermann ◽

Frank Schaeffel ◽

Ute Mathis ◽

Verena Hund ◽

Frank Mußhoff ◽

...

Keyword(s):

Aqueous Humor ◽

High Performance ◽

Low Dose ◽

Ex Vivo ◽

Therapeutic Window ◽

Eye Drops ◽

Liquid Liquid Extraction ◽

Liquid Chromatography Tandem Mass ◽

Ex Vivo Study ◽

Corneal Penetration

Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid–liquid extraction followed by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10−8 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children’s eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.

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