Effect of bimatoprost sustained-release intracameral implant on intraocular pressure and medication burden in patients with prior glaucoma surgery.

The present retrospective study evaluated intraocular pressure (IOP) and medication burden after bimatoprost sustained-release (bimatoprost SR, Durysta, Allergan) implantation in patients with glaucoma. A secondary objective was to examine an effect of bimatoprost SR in a subset of patients with prior minimally invasive and incisional glaucoma surgery. A retrospective chart review of 122 eyes that received bimatoprost SR by 6 glaucoma specialists at Wills Eye Hospital between March 2020 and September 2021 was performed. One hundred and eighteen eyes from 84 patients had a reduction in IOP (18.5±5.7mmHg vs. 16.0±5.4mmHg, P<0.01) and required fewer glaucoma medications (2.1±1.4 vs. 1.2±1.2, P<0.01) after bimatoprost SR implantation. In 41 eyes from 31 patients who previously underwent glaucoma surgery (including iStent, goniotomy, trabeculectomy, Xen Gel Stent, or tube shunt surgery), medication burden was decreased after bimatoprost SR implantation (1.9±1.3 vs. 1.0±1.0, P<0.001). These data suggest that bimatoprost SR is an efficacious treatment modality for glaucoma, even in post-surgical patients.

Comparative study of the efficacy and safety of topical minoxidil 2% versus topical bimatoprost 0.01% versus topical bimatoprost 0.03% in treatment of eyebrow hypotrichosis: a randomized controlled trial.

Eyebrows are an important feature of facial identity and communications in human beings as well as an important eye defense shield from dust and foreign bodies. To compare the efficacy and safety between 0.01%, 0.03% bimatoprost and minoxidil 2% in gel formulations for eyebrow enhancement. Sixty eligible subjects were female or male, aged 18 years or older with eyebrow hypotrichosis, defined as either a Grade 1 or 2 on the Global Eyebrow Assessment (GEBA) scale. Patients were randomized into 3 groups using block randomization. Group a (20 patients) applied topical 0.03% bimatoprost gel once daily onto both eyebrows, group b (20 patients) applied topical 0.01% bimatoprost gel once daily onto both eyebrows while group c (20 patients) applied topical minoxidil 2% gel once daily onto both eyebrows. A significant improvement in GEBA score was reported in all the three groups after treatment (P ≤ 0.001); however, there was no statistically significant difference between the three groups (P1 = 0.091; P2 = 0.102; P3 = 0.663). Bimatoprost is equally efficacious as minoxidil in enhancement of eyebrows with a more favorable response produced by the 0.03% concentration.

A randomized clinical trial comparing three fixed combinations of bimatoprost with timolol in patients with open-angle glaucoma or ocular hypertension.

OBJECTIVE: To compare the efficacy and safety of two fixed combination, preservative-free eye drops (bimatoprost 0.01% in combination with either timolol 0.1% or 0.5%) in a gel formulation, with bimatoprost 0.03%/timolol 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: Phase II, randomized, investigator-masked, multicenter, 3-arm parallel group (Eudract No. 2017-002823-46). Eighty-six patients aged ≥18 years with OAG or OHT, with intraocular pressure (IOP) initially controlled for at least 6 months by a combination therapy of a dual prostaglandin and timolol or insufficiently controlled by first-line monotherapy were included. Patients were randomized to receive T4030a (bimatoprost 0.01%/timolol 0.1%; N = 29), T4030c (bimatoprost 0.01%/timolol 0.5%; N = 29) or bimatoprost 0.03%/timolol 0.5% (N = 28), administered once daily in the evening for 12 weeks. Primary endpoint was defined as change in IOP from day 1 to week 12 measured at 08:00 (±1 h). Further efficacy, safety and pharmacokinetic endpoints were assessed as secondary outcomes. RESULTS: The mean change in IOP from baseline to week 12 was -9.8 ± 2.1 mmHg for T4030a, -10.1 ± 2.5 mmHg for T4030c and -10.0 ± 2.8 mmHg for bimatoprost 0.03%/timolol 0.5%. All treatments were well tolerated with no safety issues identified in any group. In patients treated with T4030a, the systemic concentration of timolol was significantly lower after 12 weeks than in patients treated with T4030c or bimatoprost 0.03%/timolol0.5%. CONCLUSIONS: These study results suggest that the preservative-free ophthalmic formulation of T4030a (bimatoprost 0.01%/timolol 0.1%) can be regarded as a useful tool in the therapeutic management of OAG and OHT.

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.

Periocular invasive melanoma manifestation in a patient using bimatoprost: case report and literature review.

Prostaglandin F2a 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 in situ) 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.

Do Prostaglandin Analogue Lash Lengtheners Cause Eyelid Fat and Volume Loss?

BACKGROUND: Prostaglandin analogues (PGAs; a first-line antiglaucoma treatment) have been remarketed as popular eyelash-lengthening serums due to their lash-lengthening and lash-thickening side effects. Periorbital volume loss is now a well-established side effect of topical PGAs used to treat glaucoma (prostaglandin-associated periorbitopathy) but has not, to date, been listed as a potential side effect of lash-lengthening serums containing PGAs. OBJECTIVES: The aim of this study was to identify whether periorbital fat/volume loss is seen in users of PGA lash lengtheners. METHODS: This investigation comprised a case report and an informal randomized controlled study comparing "before-and-after" color photographs displayed on the websites of manufacturers of PGA-containing lash lengtheners (PGALLs) (ie, containing bimatoprost, norbimatoprost, isopropyl cloprostenate, dechloro-dihydroxy-difluoro-ethylcloprostenolamide, or methylamido-dihydro-noralfaprostal) vs 2 control groups: non-PGALLs (NPGALL) and false eyelashes (FLs). Expert and layperson blinded graders used a purpose-designed grading system to identify subtle signs of periorbital fat/volume loss over time. RESULTS: A 35-year-old female developed thin, wrinkled, darker skin, and periorbital hollowing after 10 months of treatment with Lash Boost (Rodan & Fields, San Francisco, CA), containing isopropyl cloprostenate, which reversed 6 months after discontinuation. Fifteen "before-and-after" pairs of photographs (PGALL, n = 10; NPGALL, n = 3; FL, n = 2) were graded by 5 graders (3 expert, 2 layperson). Mean grading score was 8.2 (of 19) in the PGALL group, 2.3 in the NPGALL group, and 3.2 in the FL group. PGALL scores were significantly higher than scores in the NPGALL (P < 0.001) and FL (P = 0.017) groups. CONCLUSIONS: Review of commercial "before-and-after" photographs suggests that PGALL users develop changes compatible with prostaglandin-associated periorbitopathy. Consumers must be aware of the possibility of periorbital volume loss prior to commencing treatment with PGALLs. Often the customer-facing product ingredient list contains no mention of PGAs.

Topical bimatoprost in the treatment of eyelash loss in alopecia totalis and universalis: A prospective, open-label study.

Bimatoprost is a synthetic prostaglandin structural analogue used among other indications to increase eyelash growth. The aim of this prospective, open-label study was to evaluate the safety and efficacy of topical bimatoprost in the treatment of eyelash loss in alopecia areata totalis (AT) and universalis (AU). Study subjects applied ophthalmic bimatoprost (0.3 mg/ml) solution to the eyelid margins once nightly for at least 12 weeks (mean treatment period was 30.6 weeks). A total of 16 out of 17 subjects completed the study. Only the subjects with eyelashes present at baseline experienced an increase in eyelash length and thickness. No new eyelash regrowth was induced. In patients with AT and AU topical bimatoprost affected existing eyelashes, but failed to induce regrowth of new eyelashes.

Granulomatous uveitis and choroidal detachment in a patient after topical treatment with Bimatoprost: A case report.

BACKGROUND: Bimatoprost 0.03% is an intraocular pressure (IOP) lowering prostaglandin analog with different adverse side effects such as potential ocular inflammatory effect and ocular hyperemia. CASE PRESENTATION: We report a case of 80-year-old woman diagnosed with bilateral glaucomatous uveitis, and choroidal detachment in the left eye after topical bimatoprost administration. During the patient's hospitalization, Bimatoprost treatment was discontinued and local steroid therapy was administrated. After 1 week we reported a marked improvement of visual acuity, IOP measurement was 12 mmHg in both eyes. Anterior segment examination showed complete resolution of conjunctival and pericheratic hyperemia with significant reduction of endothelial precipitates in both eyes. CONCLUSIONS: In our case, the anterior granulomatous uveitis occurred in both pseudophakic eyes and the choroidal detachment (CD) in the eye that previously had trabeculectomy. Probably the scar tissue of the trabeculectomy allowed a better penetration of the Bimatoprost or a greater sensitivity due to an altered trabecular tissue. This work confirms that the onset physiopathology mechanism of granulomatous uveitis and CD following instillation of Bimatoprost remains uncertain.

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.

Ocular Surface Disease in Glaucoma Patients Randomized to Benzalkonium Chloride-Containing Latanoprost and Preservative-Free Bimatoprost.

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to receive BAK-containing latanoprost (Xalatan) or preservative-free bimatoprost (Lumigan PF). Intraocular pressure (IOP), basal Schirmer's test, noninvasive keratograph tear-breakup time (TBUT), conjunctival redness score (R score), OSD index (OSDI), and corneal Oxford staining were recorded and compared between the 2 groups at 1-month and 4-month visits. The influence of BAK was analyzed by a generalized estimating equation model. Results: We enrolled 74 and 76 eyes treated with latanoprost and bimatoprost, respectively. The IOP decreased in both groups, although greater reduction was observed for latanoprost (13.95 vs. 15.42 mmHg, P = 0.0264). There was a significantly negative association between tear flow and latanoprost use (ß = -0.763, P = 0.0243). The first and average TBUT did not show intergroup differences, but the area with unstable tear film increased with latanoprost use and showed marginal significance at 4-month visit (9.33% vs. 5.94% P = 0.055). In both groups, OSDI decreased, whereas Oxford stain increased over time, and R scores showed improvement after transient increase in the first month. The bimatoprost group had significantly worse conjunctival hyperemia, whereas a negative association with conjunctival hyperemia was revealed for latanoprost use (R score-bulbar nasal: ß = -0.045, P = 0.0423). Conclusions: BAK-containing latanoprost was associated with decreased tear secretion and may be associated with tear-film instability, whereas bimatoprost was associated with worse conjunctival hyperemia. Ocular surface side effects should be considered when prescribing BAK-containing medication to glaucoma patients.

Proposal of a simple grading system integrating cosmetic and tonometric aspects of prostaglandin-associated periorbitopathy.

ABSTRACT: The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ±â€Šstandard deviation, 69.9 ±â€Š14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ±â€Š5.4 mm Hg) than grades 0 (15.0 ±â€Š5.1 mm Hg, P = .032) and 1 (14.5 ±â€Š4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ±â€Š3.2 mm Hg) than the other 3 grades (1.3-1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ±â€Š0.8) and bimatoprost (2.0 ±â€Š0.7) than latanoprost (1.0 ±â€Š0.8, P < .001 for both comparisons) and tafluprost (1.0 ±â€Š0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ±â€Š0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard ß = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (-0.18) and omidenepag (-0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.

Revisiting the Safety of Prostaglandin Analog Eyelash Growth Products.

BACKGROUND: The FDA approved bimatoprost ophthalmic solution 0.03% for treatment of eyelash hypotrichosis in 2008. Consumer concern persists regarding potential side effects of this product. OBJECTIVE: To identify gaps in the safety information associated with the use of prostaglandin eyelash growth products. MATERIALS AND METHODS: Literature searches were performed using PubMed, Embase, and Nexis Uni databases without restriction to publication date, language, or study setting. RESULTS: The literature pertaining to bimatoprost for treatment of eyelash hypotrichosis is dominated by industry-sponsored clinical trials. Study design choices create gaps in our understanding of the clinical safety of these products. CONCLUSION: Because of study design choice, clinical trials of bimatoprost for eyelash growth may have systematically underreported the incidence of drug application discomfort and prostaglandin-associated periorbitopathy. The risk of increased iris pigmentation remains inadequately investigated. Consequently, there is an ongoing need to educate and monitor patients who choose to use these products.

Effects of topical prostaglandin drops on angiogenesis in an in ovo chick chorioallantoic membrane model.

BACKGROUND: To investigate the effects of bimatoprost, latanoprost and travoprost on angiogenesis in the chick chorioallantoic membrane (CAM) model in ovo. MATERIALS AND METHODS: Fifty fertilized specific-pathogen-free chick eggs were used in this preclinical, prospective, experimental embryo study. Eggs were randomly distributed into 5 groups of ten eggs. Eggs were placed in the incubator after disinfection of their shells with alcohol and monitored appropriate temperature and humidity. On the 3rd day of incubation, a small window was opened on the eggshell. Bimatoprost in group 1, latanoprost in group 2, travoprost in group 3, bevacizumab in group 4, phosphate-buffered-saline (PBS) used in group 5 was applied by injection to CAM. The sterile film was glued onto the broken part of the shell and the eggs were placed in the incubator again. On the 8th day of incubation, eggs were opened and vascular structures on CAMs were examined. Digital photographs were taken, analysed in the ImageJ open source image processing software and differences between groups were evaluated. Thereafter, VEGF (Vascular endothelial growth factor) levels were measured appropriately in the embryo samples. RESULTS: All embryos in the prostaglandin groups and the PBS control group were observed to have life signs confirmed by heart rate. In 8 embryos in the bevacizumab group, no life signs were confirmed, while 2 embryos with life signs showed severe hypoplasia. Vascular density, number of vessels and VEGF levels in the bimatoprost, latanoprost and travoprost groups, there were statistically significantly higher than the PBS control group. CONCLUSION: This study demonstrates that topical prostaglandin drops increase angiogenesis in the chick CAM model in ovo.

Uveitis and cystoid macular oedema secondary to topical prostaglandin analogue use in ocular hypertension and open angle glaucoma.

BACKGROUND: Of the side effects of prostaglandin analogues (PGAs), uveitis and cystoid macular oedema (CME) have significant potential for vision loss based on postmarket reports. Caution has been advised due to concerns of macular oedema and uveitis. In this report, we researched and summarised the original data suggesting these effects and determined their incidence. METHODS: Preferred Reporting Items for Systematic review and Meta-Analyses guidelines were followed. Studies evaluating topical PGAs in patients with ocular hypertension or open angle glaucoma were included. MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, LILACS and ClinicalTrials.gov were searched between 1946 and 2019. Experimental studies, animal studies and randomised studies with other intraocular pressure-lowering eye drops were excluded. RESULTS: 214 studies (28 232 patients) met the inclusion criteria. Using prospective data, the incidence of uveitis and CME among PGA users were 62/28 232 (0.22%) and 25/28 232 (0.09%), respectively. A higher frequency of both uveitis and CME were found among latanoprost users compared with bimatoprost. There were 21 case studies reporting CME including 48 eyes in 43 patients. 47 of 48 eyes (97.9%) had previous incisional ocular surgery. 8 eyes were re-challenged, of which 7 (87.5%) recurred. 7 case studies reported uveitis in 15 eyes of 10 patients. 7 of 15 eyes (46.7%) were either pseudophakic or aphakic. 6 eyes were re-challenged, and all 6 (100%) recurred. CONCLUSIONS: Cases of uveitis or CME revealed a confounding effect of ocular surgery, aphakia or subluxed intraocular lens. PGAs may be used in non-surgical patients without concern of causing CME or uveitis. The incidences of PGA-associated CME and uveitis are rare with limited prospective studies on the cause-effect relationship.

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.

Bimatoprost Implant: First Approval.

Bimatoprost implant (Durysta™), developed by Allergan, is a sustained-release drug delivery system containing bimatoprost, a prostaglandin analogue with ocular hypotensive activity. The implant, administered intracamerally, involves the use of a biodegradable, solid polymer drug delivery system for slow, sustained drug release, designed to lower intraocular pressure (IOP) over a 4- to 6-months period. In March 2020, bimatoprost implant received its first approval, in the USA, for use to reduce IOP in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). Allergan's clinical development programme for bimatoprost implant is ongoing. This article summarizes the milestones in the development of bimatoprost implant leading to this first approval for use in the reduction of IOP in patients with OAG or OHT.

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.