Comparative study between efficacy of Excimer light with topical Tacrolimus 0.1% versus excimer light with topical Bimatoprost 0.01% in treatment of facial Vitiligo.

Loss and absence of melanocytes due to a number of factors is responsible for vitiligo; known to be the commonest disorder of pigmentation. The aim of the current work was to compare the efficacy and safety of excimer light with topical tacrolimus ointment 0.1% versus excimer light with topical bimatoprost gel 0.01% in treatment of facial vitiligo. The study was carried out on 48 patients presented with facial vitiligo. The patients were divided randomly using sealed envelope method into two groups (24 patients each). Group 1 were treated with excimer light plus topical tacrolimus ointment 0.1% and group 2 treated with excimer light plus topical bimatoprost gel 0.01%. Clinical improvement based on the quartile grading scale at the end of treatment did not show any statistically significant difference between groups. The majority of subjects in both groups experienced good to excellent improvement. Only 20.9% of patients in group 1 and 33.3% of subjects in group 2 achieved less than 50% repigmentation (p = 0.889). Our study demonstrated that 0.01% topical bimatoprost gel in combination with excimer light is considered safe and effective as treatment of nonsegmental facial vitiligo with comparable results to 0.1% tacrolimus.

Eyelash serums: A comprehensive review.

BACKGROUND: Eyelash serums, both prescription and over-the-counter, are gaining popularity for enhancing the appearance of eyelashes through various biologically active molecules. Categorized into prostaglandin analogs and non-prostaglandin analogs, these serums claim increased strength, length, luster, and thickness. Current United States law also requires no efficacy or safety assessments by the Food and Drug Administration before approving products for consumer use, potentially posing health risks for patients seeking over-the-counter eyelash enhancements. AIMS: Our aims include exploring proposed benefits and adverse effects associated with eyelash serums, while providing evidence-based clinical recommendations on their use. We aim to contribute valuable insights to the understanding of eyelash serums and their respective safety considerations. METHODS: The authors conducted a comprehensive electronic search across databases including PubMed, Embase, Cochrane Central, and Google Scholar to evaluate eyelash serum ingredients. Articles were evaluated by two independent researchers for relevance, and the ingredients discussed were analyzed and given clinical recommendations for eyelash serums based off the Oxford Centre for Evidence-Based Medicine. RESULTS: Results highlight bimatoprost's efficacy, supported by numerous studies evaluating safety and adverse effects. Other prostaglandin ingredients show potential benefits, but further studies are encouraged to enhance the understanding of respective safety profiles. While non-prostaglandins ingredients show promising data, more studies are needed due to a lack of formal evidence in eyelash serum use. CONCLUSION: As the cosmeceutical market for eyelash serums is growing, dermatologists need to be knowledgeable about evidence-based information regarding prescription and over-the-counter eyelash serum products before making recommendations to patients.

Preservative-Free Bimatoprost 0.01% Ophthalmic Gel for Glaucoma Therapy: A Phase III Randomized Controlled Trial.

PRCIS: Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension. Improved tolerability, in particular conjunctival hyperemia, was also observed. PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%). DESIGN: Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration. METHODS: Patients with glaucoma or ocular hypertension were randomized after a 7-week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was changed from baseline in IOP at week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia. RESULTS: The mean changes from baseline in IOP at week 12 in the PFB 0.01% gel and PB 0.01% were -9.72±2.97 and -9.47±3.06 mm Hg, respectively, at 8 am , -9.41±3.03 and -9.19±3.12 mm Hg at 10 am , and -8.99±3.36 and -8.54±3.44 mm Hg at 4 pm . Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at week 12 based on predetermined criteria (upper 95% CI margin of 1.5 mmHg at all time points). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at week 6 (20.1% vs. 29.3%, respectively) and week 12 (18.3% vs. 30.4%, respectively). CONCLUSIONS: PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at weeks 6 and 12.

The Effect of Bimatoprost Implant on Glaucoma Patients: An Observational Study.

PRCIS: In this retrospective study of glaucoma patients receiving the bimatoprost implant at Duke Eye Center, the number of topical intraocular pressure-lowering medications was significantly reduced through 12 months after the implant. PURPOSE: To study the effects of the bimatoprost implant on intraocular pressure (IOP) and the need for topical IOP-lowering medications in glaucoma patients in the clinical practice setting. PATIENTS AND METHODS: Patients who received the bimatoprost implant at Duke Eye Center from November 2020 to October 2021 were identified. Exclusion criteria included addition of other IOP-lowering medications concurrent with the implant and <1 month of follow-up. The change in IOP and number of topical IOP-lowering medications from baseline to months 1, 3, 6, 9, and 12 after the implant was calculated. Subgroup analysis was performed for different glaucoma severities. RESULTS: A total of 63 patients and 92 eyes were included (mean age 77.8 ± 10.1 years). Glaucoma severity ranged from mild (11%), moderate (30%), to severe (54%). There was a nonsignificant decrease in IOP at all timepoints. The mean number of topical IOP-lowering medications significantly decreased by 0.81, 0.75, 0.63, 0.70, and 0.67 at month 1, 3, 6, 9, and 12, respectively (all P < 0.001). There was no significant change in the total number of medications, including the bimatoprost implant. When divided by glaucoma severity, the reduction in the number of topical medications was significant at 1, 3, and 6 months for mild/moderate disease and at 1 month for severe disease. During the follow-up period, 19 eyes underwent additional laser or surgical procedures, 68% of which had a history of prior incisional glaucoma surgery. CONCLUSIONS: The bimatoprost implant may reduce the need for topical IOP-lowering agents over a 1-year period, especially in mild to moderate-stage glaucoma. The efficacy of the implant may be more limited in severe glaucoma, and further work is needed to characterize its long-term effects.

The role of fractional laser-assisted drug delivery in enhancing the efficacy of topical bimatoprost solution in the treatment of alopecia areata: An intra-patient comparative randomized clinical trial.

BACKGROUND: Transepidermal drug delivery is a novel therapeutic technique to boost efficacy of topical drugs. AIM: In this clinical trial we evaluate the efficacy of the combination of fractional carbon dioxide (FCO2) laser and bimatoprost solution compared to bimatoprost alone in the treatment of alopecia areata. METHODS: This is a prospective intra-patient comparative randomized clinical trial on 20 patients with alopecia areata. In each participant two patches were chosen to randomly receive either topical 0.03% bimatoprost solution (twice a day for 12 weeks) alone or in combination with FCO2 laser (every 2 weeks for 12 weeks). Then response to treatment was evaluated by the measurement of the severity of alopecia tool score system (SALT) score, percentage of hair regrowth, physician assessment and patients' satisfaction. RESULTS: SALT score was reduced significantly during treatment sessions and after a 3-month follow-up in both treatment groups (p = 0.000). The mean percentage of improvement in SALT score in the combination therapy and monotherapy groups were 46.43 ± 4.35% and 21.16 ± 4.06% at the end of the study and 46.42 ± 5.75% and16.11 ± 3.10% at the end of the follow-up period, respectively (p = 0.000). A general linear model of two-way analysis demonstrated a significantly superior outcome in the combination therapy group compared to the monotherapy group during time (F1.6, 13.2 = 43.8. p = 0.000). CONCLUSION: Fractional ablative laser can be considered as an assistant method for enhancing of efficacy of topical drugs especially in refractory cases of patchy alopecia areata.

Combined microneedling with topical vitamin D3 or bimatoprost versus microneedling alone in the treatment of alopecia areata: A comparative randomized trial.

INTRODUCTION: Alopecia areata (AA) is a challenging disease with variable treatment outcomes. Hair follicles express vitamin D receptors. Therefore, vitamin D3 may be promising for AA treatment through immunomodulatory mechanisms. The efficacy of bimatoprost in scalp AA treatment was reported by few studies. OBJECTIVE: To evaluate the efficacy and safety of microneedling (MN) with topical vitamin D3 versus MN with bimatoprost in comparison with MN alone in the treatment of localized AA. PATIENTS AND METHODS: Seventy-five patients with localized AA were divided into three groups. The first group: 25 patients were treated with MN alone. The second group: 25 patients treated with MN combined with topical vitamin D3. The third group: 25 patients treated with MN combined with bimatoprost solution. The response was evaluated clinically and dermoscopically. RESULTS: At the end of the study, all groups showed a statistically significant decrease in the SALT score compared to the baseline. The clinical response (regrowth scale): vitamin D and bimatoprost groups showed a statistically significant higher regrowth scale compared to MN alone group (p-value = 0.000). After treatment, hair regrowth was significantly higher in MN combined with bimatoprost than in MN combined with topical vitamin D3. However, after 3 months of follow-up, there was no statistically significant difference between both groups. Side effects were mild and transient in all groups. CONCLUSION: Topical vitamin D3 and bimatoprost combined with MN are safe and effective therapeutic options for localized AA.

Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia.

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM-TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM-TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 µM BIM, equivalent to 10 µM minoxidil. Moreover, BIM-TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM-TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM-TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM-TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2).

OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). RESULTS: Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2-7.4, 6.5-7.8, and 6.1-6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. CONCLUSIONS: The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. CLINICALTRIALS. GOV IDENTIFIER: NCT02250651.

Efficacy of bimatoprost for the treatment of primary open-angle glaucoma: A protocol of systematic review and meta-analysis.

BACKGROUND: Bimatoprost has been reported to treat primary open-angle glaucoma (POAG) effectively. However, up-to-date, no systematic review has specifically addressed the efficacy and safety of bimatoprost for the treatment of POAG. Therefore, this study will propose to appraise the efficacy and safety of bimatoprost for the treatment of POAG. METHODS: We will perform a systematic search in MEDLINE, EMBASE, CINAHI, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception up to the March 1, 2020. We will include randomized controlled trials (RCTs) for evaluating the efficacy and safety of bimatoprost for the treatment of POAG. Primary outcome is the mean intraocular pressure (IOP) reduction from baseline to the endpoint, and change in best corrected visual acuity. Secondary outcomes are contrast sensitivity, rate of progression of glaucoma, quality of life, and incidence of adverse events. Study quality will be examined by Cochrane Collaboration tool, and strength of evidence will be evaluated by Grading of Recommendations Assessment Development and Evaluation tool. RESULTS: This proposed study will outline the current RCTs to assess the efficacy and safety of bimatoprost for the treatment of POAG. CONCLUSION: The findings of this study will confirm whether bimatoprost is beneficial to patients with POAG. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040118.

Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1).

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-µg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations. DESIGN: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. PARTICIPANTS: Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout. METHODS: Study eyes received bimatoprost implant 10 µg (n = 198) or 15 µg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit. MAIN OUTCOME MEASURES: Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). RESULTS: Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-µg implant, 15-µg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-µg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-µg implant) and 21.8% (15-µg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit. CONCLUSIONS: Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-µg implant over the 15-µg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.

The Antiglaucoma Agent and EP2 Receptor Agonist Omidenepag Does Not Affect Eyelash Growth in Mice.

Purpose: The present study investigated the effects of the antiglaucoma agent and selective E2 receptor agonist omidenepag isopropyl (OMDI) on eyelash growth in comparison with a prostaglandin analog (prostamide receptor agonist) in mice. Methods: Four-week-old female mice (C57BL/6J) were divided into 3 groups of n = 10 each. The groups were administered 3 µL of 0.003% OMDI solution, the vehicle (negative control), or a 0.03% bimatoprost solution (positive control) on the upper eyelids of the right eyes once daily for 14 days. On the 15th day, all animals were euthanized, and the upper eyelids with eyelashes were fixed with 10% neutral formalin. Eyelashes were evaluated for number, length, and thickness using a stereomicroscope. Specimens were then paraffin-embedded and stained with hematoxylin and eosin, followed by microscopic examination to assess eyelash morphology and growth cycle. Results: Eyelash number (143.5 ± 6.7/eyelid), thickness, and percentage of dermal papilla in the anagen phase in the OMDI group were similar to those observed in the vehicle group (eyelash number, 144.2 ± 5.7/eyelid). In contrast, eyelash number (166.7 ± 7.0/eyelid), thickness, and the percentage of dermal papilla in the anagen phase were significantly greater in the bimatoprost group compared with those of the vehicle group. Conclusions: Unlike existing prostaglandin analogs, our findings indicate that OMDI has no effect on eyelash growth in mice, suggesting that it may be a promising antiglaucoma agent with a reduced number of adverse effects.

Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release.

A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.

Matrix Metalloproteinases and Glaucoma Treatment.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect.

The efficacy of the fixed combination of latanoprost and timolol versus other fixed combinations for primary open-angle glaucoma and ocular hypertension: A systematic review and meta-analysis.

BACKGROUND: Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their target intraocular pressure (IOP). Currently, there are several FC therapies available for the treatment of glaucoma. The FC of latanoprost/timolol (LTFC) is a commonly used FC. Here, we conducted systematic review to compare the IOP-lowering effects of LTFC with other FCs for patients with POAG and OHT. MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized-controlled clinical trials and cross-over studies. The outcomes were mean IOP and IOP fluctuation after one month of treatment. Meta-analysis was carried out using RevMan (version 5.1) software. After conducting meta-analyses, we rated the quality of each meta-analysis as high, moderate, low, or very low using the "GRADE" system. RESULTS: We included 16 trials in this meta-analysis. Moderate-quality meta-analysis showed that LTFC had a comparable mean IOP to that of a fixed combination of travoprost and timolol (TTFC) [mean difference (MD): 0.07 mmHg] and a fixed combination of dorzolamide and timolol (DTFC) [MD: -0.31 mmHg], and it also had a comparable IOP-fluctuation effect compared to that of TTFC [MD: 0.13 mm Hg] and DTFC [MD: 0.25 mmHg]. Compared to the fixed combination of bimatoprost and timolol (BiTFC), moderate-quality evidence showed a higher mean IOP in the LTFC group [MD 0.76 mmHg], whereas low-quality meta-analysis showed higher IOP fluctuation [MD 1.09 mmHg] in the LTFC group. CONCLUSIONS: LTFC is as effective as TTFC and DTFC, but worse than BiTFC in controlling mean IOP and IOP fluctuation for POAG or OHT patients. The quality of our meta-analyses was assessed as moderate, with the exception of one low-quality analysis that compared the IOP fluctuation of LTFC and BiTFC.

Fixed-combination Bimatoprost/Brimonidine/Timolol in Glaucoma: A Randomized, Masked, Controlled, Phase III Study Conducted in Brazil☆.

PURPOSE: Many patients with open-angle glaucoma eventually require >2 medications to lower their intraocular pressure (IOP). Fixed-combination ophthalmic solutions can be advantageous in patients who require multiple medications, but the number of fixed combinations combining 3 complementary IOP-lowering agents remains limited. This study assessed the efficacy and safety of a triple fixed combination (TFC) of bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% ophthalmic solution in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT), compared with a dual fixed combination (DFC) of brimonidine 0.2%/timolol 0.5%. METHODS: Patients with a baseline IOP of 23-34 mm Hg in both eyes and no history of IOP-lowering procedures were eligible for participation in this multicenter, double-masked, randomized, Phase III study. After washout of previous treatment (if applicable), patients were randomized to receive TFC or DFC twice daily in each eye for 3 months. The primary efficacy variable was the change from baseline in mean IOP in the worse eye at week 12 in the modified intent-to-treat (mITT) population. TFC was superior to DFC if the treatment difference (TFC - DFC) favored TFC at week 12 (P ≤ 0.05; 2-sample t test). Secondary and sensitivity analyses were also performed. Safety, including adverse events, was assessed at all visits. FINDINGS: The mITT/safety population included 185 patients (TFC, n = 90; DFC, n = 95). TFC superiority was demonstrated at all postbaseline visits (all, P < 0.001) through week 12 (week 12 treatment difference: ─2.17 mm Hg; 95% CI, ─3.12 to ─1.22). While treatment-related conjunctival hyperemia was more frequent with TFC than with DFC (47.8% vs 23.2%; P < 0.001), consistent with the additional presence of bimatoprost in TFC, most cases were mild and the numbers of patient discontinuations at week 12 were similar between the TFC and DFC groups (11 [12.2%] vs 7 [7.4%] patients; P = 0.266). No unexpected adverse events were reported. IMPLICATIONS: Compared with DFC, TFC provided superior IOP lowering throughout the primary efficacy period. An acceptable tolerability profile was observed through 12 months of use of TFC, offering an effective therapeutic option in patients with POAG or OHT who require multiple medications to control their IOP. Additional studies are required for the assessment of the long-term effects of TFC. ClinicalTrials.gov identifier: NCT01217606.

Bimatoprost Imprinted Silicone Contact Lens to Treat Glaucoma.

Bimatoprost is widely used for the management of glaucoma. Currently, it is delivered via eye drop solution, which is highly inefficient due to low bioavailability. To control the release of ocular drugs, contact lenses are used by scientists. However, the conventional soaking method showed high burst release due to absence of any efficient controlling membrane. The objective of the paper was to apply molecular imprinting technology to improve the loading of bimatoprost from the soaking solution and to sustain the release of drug from the contact lens. The bimatoprost was loaded by conventional soaking method (BT-SM) and compared with the molecular imprinted contact lenses (BT-MP). The loading of bimatoprost by molecular imprinting technology affect the swelling of the contact lens; however, the batch BT-MP-10 did not showed significant alterations. The uptake study showed improvement in the bimatoprost loading by molecular imprinting technology in comparison to the conventional soaking technology. The in vitro bimatoprost release data showed improvement in the bimatoprost release rate profiles with BT-MP contact lenses (up to 36-60 h) lenses in comparison to BT-SM contact lenses (up to 24-36 h). The in vivo rabbit tear fluid data with BT-MP batch showed improvement in the bimatoprost retention time in comparison to BT-SM contact lens and eye drop solution. The rabbit model failed to respond bimatoprost; thus, the efficacy studies need to be conducted on canines or human primates. The paper revealed the potential of using molecular imprinting technology to improve the uptake of bimatoprost and to achieve sustain release kinetics without altering the swelling, transmittance and folding endurance properties of the contact lens.

Maximizing Panfacial Aesthetic Outcomes: Findings and Recommendations From the HARMONY Study.

BACKGROUND: Aesthetic medicine has evolved from targeting individual treatment areas to a global approach of panfacial rejuvenation. HARMONY was the first clinical study to systematically demonstrate positive physical and psychosocial impacts of panfacial treatment. OBJECTIVE: Provide evidence-based guidance on treatment strategies to help maximize outcomes in patients seeking panfacial rejuvenation. MATERIALS AND METHODS: Study sites with the lowest (n = 2) and highest (n = 2) improvements based on FACE-Q Satisfaction with Face Overall scores were analyzed to understand differences in treatment strategy that may contribute to incrementally greater patient satisfaction. RESULTS: The highest scoring sites exhibited greater improvement in all patient-reported outcomes and investigator-assessed measures related to dermal filler treatment compared with the lowest scoring sites. The highest sites favored lateral malar augmentation and used less volume medially versus the lowest sites. In the lower face, the highest sites used greater volumes and more HYC-24L than HYC-24L+. Initial treatment volumes were more conservative at highest than lowest sites; greater volumes were used by highest sites in touch-up treatments. CONCLUSION: Product usage trends common to the highest scoring sites (including injection volume, injection sites, and product selection) may provide guidance on best practices for a panfacial approach to aesthetic treatment to maximize patient satisfaction.

Comparison of the efficacy and safety of using 0.01% versus 0.03% bimatoprost for the treatment of eyebrow hypotrichosis: A randomized, double-blind, split-face, comparative study.

BACKGROUND: Previous studies have proven the efficacy and safety of 0.01% and 0.03% bimatoprost for the treatment of eyebrow hypotrichosis; however, there is no comparison study between both concentrations. AIMS: To compare the efficacy and safety between 0.01% and 0.03% bimatoprost for the treatment of eyebrow hypotrichosis. PATIENTS/METHODS: This prospective, randomized, double-blind, split-face clinical study was conducted in 30 patients with eyebrow hypotrichosis. Each side of eyebrow of individual patients was randomly assigned for 0.01% and 0.03% bimatoprost, applied on each eyebrow once daily. Eyebrow density, diameter, the Global Eyebrow Assessment scale, 7-point rating scale, and patient satisfaction were evaluated. Side effects were also recorded. RESULTS: Both 0.01% and 0.03% bimatoprost significantly improved eyebrow density and diameter (P < .05), although there were no statistically significant differences in changes in eyebrow density and diameter from baseline between both concentrations (P = .96 and .84, respectively). Additionally, patients significantly preferred 0.03% bimatoprost in terms of clinical improvement and satisfaction (P = .04 and .003, respectively). CONCLUSIONS: Both 0.01% and 0.03% bimatoprost are effective and safe for the treatment of eyebrow hypotrichosis. Bimatoprost 0.03% is superior to its 0.01% counterpart, albeit without statistical significance.

24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients.

OBJECTIVE: The objective of this study was to evaluate the safety and intraocular pressure (IOP)-lowering effects over 24 months of biodegradable bimatoprost sustained-release implant (Bimatoprost SR) administration versus topical bimatoprost 0.03% in patients with open-angle glaucoma (OAG). METHODS: This was a phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. At baseline following washout, adult patients with OAG (N = 75) received Bimatoprost SR (6, 10, 15, or 20 µg) intracamerally in the study eye; the fellow eye received topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or single repeat administration with implant was permitted. The primary endpoint was IOP change from baseline. Safety measures included adverse events (AEs). RESULTS: At month 24, mean IOP reduction from baseline was 7.5, 7.3, 7.3, and 8.9 mmHg in eyes treated with Bimatoprost SR 6, 10, 15, and 20 µg, respectively, versus 8.2 mmHg in pooled fellow eyes; 68, 40, and 28% of pooled study eyes had not been rescued/retreated at months 6, 12, and 24, respectively. AEs in study eyes that occurred ≤ 2 days post-procedure typically were transient. After 2 days post-procedure, overall AE incidence was similar between study and fellow eyes, with some events typically associated with topical prostaglandin analogs having lower incidence in study eyes. CONCLUSIONS: Bimatoprost SR showed favorable efficacy and safety profiles up to 24 months, with all evaluated dose strengths demonstrating overall IOP-reducing effects comparable to those of topical bimatoprost. Targeted and sustained delivery of bimatoprost resulted in protracted IOP lowering, suggesting that Bimatoprost SR may represent a transformational new approach to glaucoma therapy. Clinicaltrials.gov identifier: NCT01157364.