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Investigative Ophthalmology & Visual... Mar 2023The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix...
PURPOSE
The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix metalloproteinase (MMP) gene expression in cells from human aqueous outflow tissues.
METHODS
MMP gene expression by human trabecular meshwork (TM), scleral fibroblast (SF), and ciliary muscle (CM) cells exposed to 10 to 1000 µM bimatoprost or 0.1 to 10 µM BFA (intraocular concentrations after intracameral bimatoprost implant and topical bimatoprost dosing, respectively) was measured by polymerase chain reaction array.
RESULTS
Bimatoprost dose-dependently upregulated MMP1 and MMP14 mRNA in all cell types and MMP10 and MMP11 mRNA in TM and CM cells; in TM cells from normal eyes, mean MMP1 mRNA levels were 62.9-fold control levels at 1000 µM bimatoprost. BFA upregulated MMP1 mRNA only in TM and SF cells, to two- to three-fold control levels. The largest changes in extracellular matrix (ECM)-related gene expression by TM cells derived from normal (n = 6) or primary open-angle glaucoma (n = 3) eyes occurred with 1000 µM bimatoprost (statistically significant, ≥50% change for 9-11 of 84 genes on the array, versus 1 gene with 10 µM BFA).
CONCLUSIONS
Bimatoprost and BFA had differential effects on MMP/ECM gene expression. Dramatic upregulation in MMP1 and downregulation of fibronectin, which occurred only with bimatoprost at high concentrations observed in bimatoprost implant-treated eyes, may promote sustained outflow tissue remodeling and long-term intraocular pressure reduction beyond the duration of intraocular drug bioavailability. Variability in bimatoprost-stimulated MMP upregulation among cell strains from different donors may help explain differential long-term responses of patients to bimatoprost implant.
Topics: Humans; Intraocular Pressure; Matrix Metalloproteinase 1; Glaucoma, Open-Angle; Tonometry, Ocular; Sclera; Bimatoprost
PubMed: 36877514
DOI: 10.1167/iovs.64.3.15 -
Veterinary Ophthalmology Jul 2018To determine the effect of a bimatoprost sustained-release intracameral implant (Bimatoprost SR) on episcleral venous pressure (EVP) in normal dogs. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the effect of a bimatoprost sustained-release intracameral implant (Bimatoprost SR) on episcleral venous pressure (EVP) in normal dogs.
METHODS
Normotensive beagle dogs were randomized to receive Bimatoprost SR 30 μg (n = 7) or sham injection (needle insertion only, n = 7) in one eye on day 1. EVP was measured with an episcleral venomanometer through day 65. Episcleral aqueous outflow vessels were identified using fluorescence imaging following intracameral injection of indocyanine green in one additional animal. A separate cohort of dogs that had been trained for conscious intraocular pressure (IOP) measurements received Bimatoprost SR 30 μg (n = 8) in one eye; IOP was evaluated through day 66.
RESULTS
Baseline mean EVP was 10.0 mmHg in the Bimatoprost SR group and 10.4 mmHg in the sham group. Eyes treated with Bimatoprost SR exhibited a transient increase in mean EVP that peaked at day 8, followed by a decrease to levels below baseline. From day 29 to day 65, the change in mean EVP from baseline ranged from -2.4 to -3.9 mmHg (P < 0.05 vs. sham). Baseline mean IOP in eyes treated with Bimatoprost SR was 14.9 mmHg, and a steady IOP reduction was maintained through day 66. Bimatoprost SR-treated eyes exhibited a selective, sustained dilation of aqueous outflow vessels that was not observed in sham-treated eyes.
CONCLUSIONS
In normal dogs, Bimatoprost SR was associated with a transient increase in EVP followed by a sustained decrease. Changes in EVP were accompanied by a sustained dilation of aqueous outflow vessels.
Topics: Animals; Bimatoprost; Dog Diseases; Dogs; Drug Implants; Female; Injections, Intraocular; Intraocular Pressure; Sclera; Venous Pressure
PubMed: 29457333
DOI: 10.1111/vop.12522 -
Dermatologic Surgery : Official... Sep 2010Many women desire prominent eyelashes. In December 2008, bimatoprost ophthalmic solution 0.03% was approved for the treatment of hypotrichosis of the eyelashes in the... (Review)
Review
BACKGROUND
Many women desire prominent eyelashes. In December 2008, bimatoprost ophthalmic solution 0.03% was approved for the treatment of hypotrichosis of the eyelashes in the United States.
OBJECTIVE
To review eyelash physiology and the proposed mechanisms by which the topical pros-tamide product bimatoprost enhances eyelash growth.
METHODS AND MATERIALS
Clinical and preclinical studies pertaining to the efficacy, safety, and mechanisms of action of bimatoprost are presented.
RESULTS
Treatment with bimatoprost increases the percentage of eyelash follicles in anagen at any one time. This probably accounts for its ability to lengthen lashes. Bimatoprost-induced stimulation of melanogenesis appears to result in darker lashes and, at the same time, appears to increase the size of the dermal papilla and hair bulb, affecting lash thickness and fullness. Such effects, largely demonstrated in animal studies, are consistent with the results of a recent Food and Drug Administration phase III clinical trial. The favorable safety profile of bimatoprost in human subjects is probably secondary to the limited exposure of ocular tissues resulting from topical application at the base of the upper lashes.
CONCLUSION
By influencing the eyelash hair cycle and follicles, bimatoprost ophthalmic solution 0.03% is a safe and effective means of enhancing eyelash growth. Dr. Cohen has served as a consultant and clinical trial participant for Allergan, Inc.
Topics: Amides; Bimatoprost; Cloprostenol; Eyelashes; Humans
PubMed: 20384750
DOI: 10.1111/j.1524-4725.2010.01522.x -
Orbit (Amsterdam, Netherlands) Feb 2023Prostaglandin F analogs (PGAs) are considered efficacious in the first-line treatment of glaucoma. They have however been associated with a number of periocular side... (Review)
Review
Prostaglandin F analogs (PGAs) are considered efficacious in the first-line treatment of glaucoma. They have however been associated with a number of periocular side effects. We present a case of periocular hyperpigmentation and progression to lentigo maligna melanoma (LMM) in a patient using bimatoprost eye drops. We conducted a literature review regarding the etiology and pathophysiology of periocular pigmentation in this setting.A 71-year-old female Caucasian patient with open-angle glaucoma using bimatoprost exclusively in her right eye noticed an ipsilateral lower eyelid/upper cheek area dark lesion after commencing treatment. Examination demonstrated a heterogeneously pigmented lesion. Excisional biopsy demonstrated extensive lentigo maligna (melanoma with superficially invasive malignant melanoma in the lesion center. The patient underwent successful staged excision and reconstruction. Literature review has demonstrated case reports supporting periocular hyperpigmentation; however, there has been no description of progression to periocular lentigo maligna and melanoma in a patient using bimatoprost.
Topics: Female; Humans; Aged; Hutchinson's Melanotic Freckle; Bimatoprost; Glaucoma, Open-Angle; Melanoma; Skin Neoplasms; Eyelids; Hyperpigmentation; Melanoma, Cutaneous Malignant
PubMed: 34320913
DOI: 10.1080/01676830.2021.1955392 -
AAPS PharmSciTech Dec 2021Currently, glaucoma is managed by frequent instillation of bimatoprost eye drop therapy, which showed very poor ocular bioavailability. Contact lens is widely used as...
Currently, glaucoma is managed by frequent instillation of bimatoprost eye drop therapy, which showed very poor ocular bioavailability. Contact lens is widely used as medical device to improve the drug retention on the ocular tissues. However, the traditional methods of drug loading in the contact lens matrix showed high burst release and changes the optophysical properties of the contact lens material. In this paper, a novel bimatoprost-loaded silica shell nanoparticles-laden soft contact lenses were developed to achieve sustain drug delivery without altering the optophysical properties of the contact lens. Silica-shell nanoparticles were prepared using octyltrimethoxysilane (OTMS) and microemulsion. Traditional soaking method (SM-BT), direct bimatoprost loading method (DL-BT), and microemulsion-laden contact lens (ME-BT) were developed for comparison. The silica shell-coated nanoparticles-laden soft contact lenses (SiS-BT) showed improved swelling, transmittance, oxygen permeability, and lysozyme adherence compared to SM-BT, DL-BT, and ME-BT lenses. The DL-BT and ME-BT batch showed high bimatoprost lost/leaching during extraction and sterilization steps, with low cumulative drug release. Also, SiS-BT lens showed sustain bimatoprost release for 96 h. In a rabbit tear fluid model, the SiS-BT lens showed high bimatoprost concentration for 72 h compared to ME-BT lens and eye drop therapy. Based on histopathological studies of cornea, the SiS-BT lens was found to be safe for human applications. The data demonstrated the novel application of silica shell nanoparticles to deliver bimatoprost from the contact lens for extended period of time without altering the optophysical properties of the contact lens.
Topics: Animals; Bimatoprost; Contact Lenses, Hydrophilic; Drug Delivery Systems; Glaucoma; Nanoparticles; Rabbits; Silicon Dioxide
PubMed: 34950994
DOI: 10.1208/s12249-021-02199-0 -
Scientific Reports Apr 2023Bimatoprost ophthalmic solution 0.03% (PGF2α analogues) combined with narrowband ultraviolet B (NB-UVB) was reported to be an effective treatment for vitiligo. To... (Randomized Controlled Trial)
Randomized Controlled Trial
Bimatoprost ophthalmic solution 0.03% (PGF2α analogues) combined with narrowband ultraviolet B (NB-UVB) was reported to be an effective treatment for vitiligo. To investigate the efficacy and safety of treatment for non-segmental/segmental vitiligo compared among bimatoprost ophthalmic solution 0.01% combined with NB-UVB phototherapy, bimatoprost monotherapy, and placebo. This single-blind randomized controlled study enrolled stable Thai vitiligo patients with at least three similarly sized lesions in the same anatomical area. The treatment duration was 6 months with 1- and 2-month post-treatment follow-ups. The 3 selected lesions on each patient were randomized to receive combination therapy, monotherapy, or placebo. The Vitiligo Area Scoring Index (VASI) was used to evaluate lesion response. Of the 25 initially enrolled subjects, 19 patients were analyzed. There were 13 and 6 non-segmental and segmental vitiligo cases, respectively. Eight and 11 cases had face/neck and non-face/neck lesions, respectively. Non-segmental vitiligo and non-face/neck vitiligo patients in the combination group had significant improvement in VASI score at 3 months, 6 months, and at the 2-month follow-up. No side effects were observed/reported. Bimatoprost combination therapy was shown to be safe and effective for treating Thai patients with non-segmental vitiligo in non-face/neck areas of the body.
Topics: Humans; Vitiligo; Bimatoprost; Single-Blind Method; Ultraviolet Therapy; Treatment Outcome; Combined Modality Therapy; Ophthalmic Solutions
PubMed: 37081101
DOI: 10.1038/s41598-023-32591-8 -
Journal of Biomaterials Science.... Aug 2021Contact lenses are ideally suited for sustained ocular drug delivery to bypass the issues associated with eye drop therapy. However, drugs such as bimatoprost loaded by...
Contact lenses are ideally suited for sustained ocular drug delivery to bypass the issues associated with eye drop therapy. However, drugs such as bimatoprost loaded by the conventional soaking method show poor drug uptake, high burst release, and altered critical lens properties. In this study, the effect of gold nanoparticles (GNPs) on bimatoprost loading/uptake from the soaking solution and its release kinetics from the lens was investigated. In one method, GNP solutions of varying strength were loaded into the bimatoprost soaking solution (mM-SS batches), and in another method, the GNPs were included in the contact lens matrix during casting (mM-GN-L batches). The GNPs were spherical with average size of 21.1 nm and -20.1 mV zeta potential. The swelling, oxygen permeability, and optical transmittance of the lens were improved compared to those of the lens drug-loaded by the conventional soaking method (SM-L). The mM-GN-L batches showed significant improvement in drug uptake from the soaking solution compared to the SM-L and mM-SS batches. The studies showed relatively low burst and sustained bimatoprost release up to 72 h compared to 24 h with the SM-L batch. The ability to sustain drug release improved proportionally with an increase in the amount of GNPs in the lens. The presence of GNPs lowered protein adherence. The GNP-laden lenses were deemed safe in ocular irritation and histopathology reports (rabbit model). Further, they showed higher drug retention in the rabbit tear fluid compared to the SM-L lens. In conclusion, the presence of GNPs in contact lenses increased drug uptake from the soaking solution, and improved the and release kinetics without affecting the critical properties of the contact lenses for therapeutic application.
Topics: Animals; Bimatoprost; Contact Lenses; Drug Delivery Systems; Drug Liberation; Gold; Metal Nanoparticles; Rabbits
PubMed: 33980134
DOI: 10.1080/09205063.2021.1927656 -
Dermatologic Surgery : Official... May 2016Eyebrow loss may have substantial negative functional and social consequences. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Eyebrow loss may have substantial negative functional and social consequences.
OBJECTIVE
Evaluate the safety and efficacy of bimatoprost 0.03% in subjects with eyebrow hypotrichosis.
METHODS
This multicenter, double-masked study randomized adult females or males with eyebrow hypotrichosis to receive bimatoprost 0.03% twice (BID) or once daily (QD) or vehicle BID for 7 months. Primary endpoint was overall eyebrow fullness at Month 7. Secondary endpoints included eyebrow fullness (mm), darkness (intensity units), and subject satisfaction with treatment. Safety was also assessed.
RESULTS
At Month 7, the proportion of subjects with improvement was significantly higher in bimatoprost groups versus vehicle (both, p < .001). Improvements occurred in both bimatoprost groups versus vehicle after Month 1 and continued through follow-up; eyebrow fullness and darkness improved as early as Months 2 and 1, respectively (both, p < .001). Greater satisfaction was reported with bimatoprost versus vehicle at Month 2 and all subsequent time points. Overall, 38.1%, 42.4%, and 35.5% of subjects in the bimatoprost BID, QD, and vehicle groups, respectively, experienced ≥1 treatment-emergent adverse event (TEAE). Most frequent TEAEs were similar across groups. No skin or iris hyperpigmentation or conjunctival hyperemia occurred.
CONCLUSION
Bimatoprost 0.03% BID and QD is safe, well tolerated, and effective for eyebrow hypotrichosis.
Topics: Adult; Aged; Aged, 80 and over; Bimatoprost; Cosmetic Techniques; Double-Blind Method; Eyebrows; Female; Humans; Hypotrichosis; Male; Middle Aged; Patient Satisfaction; Treatment Outcome
PubMed: 27124878
DOI: 10.1097/DSS.0000000000000755 -
Journal of Glaucoma Sep 2023This retrospective study found a statistically significant reduction in mean intraocular pressure (IOP) and the number of medications after intracameral Bimatoprost...
PRCIS
This retrospective study found a statistically significant reduction in mean intraocular pressure (IOP) and the number of medications after intracameral Bimatoprost sustained release (SR) injection in patients with glaucoma. A history of selective laser trabeculoplasty (SLT) did not impact treatment outcomes.
PURPOSE
To determine outcomes of Bimatoprost SR on IOP and the number of topical IOP-lowering medications in patients with glaucoma. A secondary objective was to determine the outcomes of Bimatoprost SR in patients with a prior history of SLT.
METHODS
Retrospective case series. One hundred eighteen eyes from 84 patients that received Bimatoprost SR by 6 glaucoma specialists at Wills Eye Hospital from March 2020 to September 2021 were examined. The intervention was a single injection of intracameral Bimatoprost SR. The main outcome measures included IOP and the number of medications.
RESULTS
The most recent mean follow-up time for all eyes was 27.8 ± 18.6 weeks. The mean posttreatment IOP at the most recent follow-up of 16.6 ± 5.3 mm Hg was significantly lower than the mean under-therapy pretreatment IOP of 18.5 ± 5.7 mm Hg for all eyes ( P < 0.01). The mean posttreatment number of medications at the most recent follow-up of 1.3 ± 1.3 decreased compared with the number of pretreatment medications of 2.1 ± 1.4 for all eyes ( P < 0.01). Analysis of multilevel models controlling for demographic variables demonstrated a statistically significant reduction in IOP and number of medications posttreatment ( P < 0.01). A prior history of SLT (n = 54) had no impact on treatment for both IOP and the number of medications ( P > 0.1 for both).
CONCLUSIONS
Intracameral Bimatoprost SR reduced IOP and decreased the number of medications. Prior history of SLT did not impact Bimatoprost SR treatment outcomes.
Topics: Humans; Bimatoprost; Retrospective Studies; Intraocular Pressure; Delayed-Action Preparations; Antihypertensive Agents; Glaucoma; Trabeculectomy; Treatment Outcome; Laser Therapy
PubMed: 37523637
DOI: 10.1097/IJG.0000000000002271 -
Ophthalmology Sep 2003
Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Lipids; Ocular Hypertension; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic
PubMed: 13129903
DOI: 10.1016/S0161-6420(03)00849-2